Catherine Nelson-Piercy, MA, FRCP

Consultant Obstetric Physician

Guy’s & St Thomas’ NHS Foundation Trust

Queen Charlotte’s Hospital

London, UK

Joanna Girling, MA, MRCP, FRCOG

Consultant Obstetrician & Gynaecologist

West Middlesex University Hospital

Isleworth, UK

British Library Cataloguing in Publication Data

Nelson-Piercy, Catherine

Maternal medicine in clinical practice

1. Obstetrics - Examinations, questions, etc. 2. Obstetrics - Case studies

I. Title II, Girling, Joanna

618.2 0076

ISBN-10: 1-84628-563-1

e-ISBN-10: 1-84628-582-8

ISBN-13: 978-1-84628-563-9

e-ISBN-13: 978-1-84628-582-0

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Preface

Medical problems in pregnancy are common. They are responsible

for much maternal and fetal morbidity and mortality. Recognition of

the importance of maternal medicine is now reflected in the content

of the membership exam of Royal College of Obstetricians and

Gynaecologists (MRCOG), core training and higher training in both

obstetrics and medicine.

Originally, this book was intended to be a collection of multiple

choice questions, data interpretation and short answer questions, and

model essay answers in obstetric medicine to help the trainee prepare

for the MRCOG part 2. However, we appreciate that different

trainees prepare and learn in different ways and that much practical

maternal medicine is learnt after passing the MRCOG and member-

ship exam of the Royal College of Physicians (MRCP). It was Tom

Holland who had the idea to produce a collection of case studies to

illustrate common problems in obstetric medicine and it was Ian

Greer who had the idea to publish the case reports that trainees had

written as part of their RCOG special skills module in maternal med-

icine. We are indebted to both.

So the finished product gives the trainee many different

approaches to obstetric medicine. The extended matching ques-

tions require a large breadth of theoretical knowledge. The short

answers and data interpretation require a systematic approach to a

clinical problem. Most of the case reports, which range from eso-

teric to more mundane, are derived from real cases and all are

accompanied by a brief literature review to further broaden the

learning experience. Because the cases are real, the management

described is not always perfect and is sometimes controversial. We

have decided to leave in many of these unresolved issues to prompt

the reader to think about, and read around, the topic. For this rea-

son, key references used by the trainees in writing their case

reports have been included. By contrast, the model essay answers

provide a template of ideal management, as one would describe in

an exam.

We hope that there is something for everyone and that trainees

and, indeed, consultants will be able to “test themselves” using the

Contents

Contributors

Multiple Choice Questions

1.1

Pre-existing Hypertension

1.2

Pregnant Women with Pre-existing Hypertension

1.3

Pre-eclampsia

1.4

Maternal Supraventricular Tachycardia

1.5

Prophylaxis of Endocarditis

1.6

Thromboembolic Disease in Pregnancy

1.7

Deep Vein Thrombosis

1.8

Treatment Options for Diabetes in Pregnancy

1.9

Women with Established Diabetes

1.10

Gestational Diabetes

1.11

Postnatal Care of Women with Diabetes

1.12

Thrombocytopenia

1.13

Folate Supplementation

1.14

Neuropathies and Palsies in Pregnancy

1.15

Epilepsy

1.16

Cerebral Vein Thrombosis

1.17

Eclampsia

1.18

Thyroid Dysfunction

1.19

Postpartum Thyroiditis

1.20

Pituitary Hormones

1.21

Prolactinomas in Pregnancy

1.22

Erythema Nodosum

1.23

Rheumatoid Arthritis

1.24

Inflammatory Bowel Disease

1.25

Ulcerative Colitis

1.26

Hyperemesis Gravidarum

1.27

The Liver in Pregnancy

1.28

Acute Fatty Liver of Pregnancy (AFLP)

1.29

Hepatitis C Infection

1.30

Sclerosing Cholangitis in Pregnancy

1.31

Tuberculosis in Pregnancy in UK

1.32

Radiation

1.33

Phenylketonuria in Pregnancy

1.34

Psychiatry

viii

CONTENTS

Extended Matching Questions

2.1 Hypertension

2.2 Heart Sounds and Murmurs

2.3 Anaemia

2.4 Chest Pain

2.5 Causes of Adrenal Dysfunction

2.6 Connective Tissue Disease

2.7 Liver Disease

Short Answer Questions/Data Interpretation/

Clinical Scenarios

3.1

Hypertension and Proteinuria

3.2

Hypertension and Proteinuria

3.3

Postpartum Breathlessness

3.4

Fetal Tachycardia

3.5

Abdominal Pain and Anaemia

3.6

Abnormal Blood Gases

3.7

Abdominal Pain and Abnormal Liver Function

3.8

Diabetes

3.9

Facial Weakness

Essay Questions

4.1

Mitral Valve Replacement

4.2

Sickle Cell Disease

4.3

Hyperthyroidism

4.4

Diabetes

4.5

Polyuria and Polydypsia

4.6

Systemic Lupus Erythematosus

4.7 Deep Venous Thrombosis

4.8

Jaundice

4.9

Chicken Pox

Case Studies

5.1 Sickle Cell Disease

5.2 Hyponatraemia

5.3 Ischaemic Heart Disease

102

5.4 Cardiac Transplant

104

5.5 Postpartum Eclampsia

106

5.6 Hyperemesis Gravidarum

109

5.7 Postpartum Cerebral Haemorrhage

114

5.8 Hypokalaemia

116

5.9 Hepatitis A

119

Contributors to the Case Studies

Catherine Calderwood, MA CANTAB, MRCOG

Consultant Obstetrician and Gynaecologist

Simpson Centre for Reproductive Health

Royal Infirmary of Edinburgh and

St John’s Hospital, Livingston, UK

Sonji D. Clarke, MBBS, MRCOG

Consultant Obstetrician and Gynaecologist

Guy’s and St Thomas’ Hospitals Foundation Trust

London, UK

Douglas P. Dumbrill, FCOG(SA), MRCOG

Consultant Obstetrician and Gynaecologist

112 Vincent Pallotti Medical Centre

Alexander Road

Pinelands 7405

Capetown, South Africa

Tom Holland, MBBS

Research Fellow

Early Pregnancy and Gynaecology Assessment Unit

King’s College Hospital

London, UK

Wunmi Ogunnoiki, MRCOG

Consultant Obstetrician and Gynaecologist

Maidstone Hospital

Maidstone, UK

Daghni Rajasingam, MBBS, MRCOG

Locum Consultant Obstetrician and Gynaecologist

Guy’s & St Thomas’ Hospital

London, UK

Vijayan Valayatham, MD, MRCOG

Consultant Obstetrician and Gynaecologist

Likas Women and Child Hospital

Sabah, Malaysia

Chapter 1

Multiple Choice Questions

You should answer each statement as true [T] or false [F].

1.1 PRE-EXISTING HYPERTENSION

(a) Pre-existing hypertension always presents before

20 weeks’

gestation.

(b) Endocrine causes of pre-existing hypertension include

hyperaldosteronism.

in pregnancy should have their serum potassium and creatinine

measured.

(d) Renal disease can present with hypertension and proteinuria that

is indistinguishable from pre-eclampsia.

(e) In pregnant women with pre-existing hypertension, the risk

of superimposed pre-eclampsia is related to the degree of

hypertension.

Answers

(a) F

(b) T

(d) T

(e) T

Explanation

(a) Because the physiological fall in blood pressure in the first

trimester can lead to a normal booking blood pressure, a high pre-

pregnancy blood pressure could be masked and only present

when there is a physiological rise in the third trimester.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

(b) Endocrine causes of hypertension include Conn’s syndrome,

other causes of hyperaldosteronism

(e.g. bilateral adrenal

hyperplasia), Cushing’s syndrome and phaeochromocytoma.

(c)

This is to screen for hyperaldosteronism, which causes

hypokalaemia, and pre-existing renal impairment. It is important

to remember the physiological fall in serum creatinine that occurs

early in gestation.

(d) Proteinuria present before 20 weeks is indicative of underly-

ing renal disease, but if there is no record of urinalysis in

early pregnancy and a women presents with hypertension

and proteinuria, it could be difficult to differentiate pre-

eclampsia from underlying renal disease. It should be

remembered that the former is much more common and that

pre-eclampsia might rarely present at very early gestations

(18-24 weeks). If abnormal liver function or thrombocytope-

nia are present, this points towards pre-eclampsia more than

renal disease.

(e)

Pregnant women with severe hypertension, defined as a diastolic

blood pressure

110 mmHg at

20 weeks’ gestation, have a 40%

risk of superimposed pre-eclampsia.

1.2 PREGNANT WOMEN WITH PRE-EXISTING

HYPERTENSION

(a) Women with pre-existing hypertension are at increased risk of

placental abruption.

(b) Diuretic therapy should be discontinued before conception in

women with pre-existing hypertension.

tension than other women with pre-eclampsia.

(d) Antihypertensive therapy must be continued throughout

pregnancy in women with pre-existing hypertension.

(e) Women with pre-existing hypertension should not breastfeed

if switched back to angiotensin-converting enzyme

(ACE)

inhibitors after delivery.

Answers

(a) T

(b) F

(d) F

(e) F

1. MULTIPLE CHOICE QUESTIONS

Explanation

(a)

Women with pre-existing hypertension are at increased risk of

placental abruption, even if they do not develop superimposed

pre-eclampsia.

(b) There is no need to discontinue diuretics before conception; they

are not thought to be teratogenic. The reason why diuretics

are normally discontinued in pregnancy is because they could

confound the picture in pre-eclampsia, causing volume depletion

in an already vasoconstricted state. They can be safely used in

pregnancy to treat pulmonary oedema, fluid overload and benign

intracranial hypertension.

(c)

There is no reason why women with pre-existing hypertension

would develop proteinuria at earlier gestations. If they have

underlying renal disease, they might already have significant pro-

teinuria before the development of pre-eclampsia, making pre-

eclampsia more difficult to diagnose.

(d) Because blood pressure usually falls in the first half of pregnancy,

even in hypertensive women, this might enable the temporary

withdrawal of antihypertensive therapy, especially in women who

only require a low dose of one drug to control their hypertension

outside pregnancy. It is usual to need to reinstitute antihyperten-

sive therapy later in pregnancy, particularly after 28 weeks, when

the physiological effect is for blood pressure to increase again.

(e)

Although ACE inhibitors are contraindicated in pregnancy, they

can be safely used by breastfeeding mothers.

1.3 PRE-ECLAMPSIA

(a) Pre-eclampsia can cause disseminated intravascular coagulopathy

(DIC).

(b) If pre-eclampsia necessitates delivery prior to 34 weeks’ gesta-

tion, screening for antiphospholipid syndrome is indicated.

agents in the puerperium.

(d) Use of low-dose aspirin does not reduce pre-eclampsia.

(e) Pre-eclampsia predisposes to pulmonary oedema.

Answers

(a) T

(b) T

(d) F

(e) T

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Explanation

(a) DIC is an unusual, but recognised, complication of pre-eclampsia.

It can occur in up to 20% of cases of HELLP (haemolysis, elevated

liver enzymes, low platelets) syndrome, but is more common if

there is placental abruption or haemorrhage from other causes.

(b) The diagnostic criteria for antiphospholipid syndrome include

one or more premature births (

34 weeks’ gestation), with nor-

mal fetal morphology, due to pre-eclampsia or severe placental

insufficiency.

60% of women with pre-eclampsia, and more commonly in those

who antenatally have heavy proteinuria or severe hypertension or

require antihypertensive agents or preterm delivery.

(d) Meta analyis of large randomised, controlled trials shows that

low dose aspirin [75 mg daily] reduces the risk of developing

pre-eclampsia by 19% [1].

(e) Women with pre-eclampsia have leaky capillaries and hypoal-

buminaemia. They are, therefore, particularly vulnerable to fluid

overload and pulmonary oedema, which most commonly presents

postpartum but can occur antenatally.

1.4 MATERNAL SUPRAVENTRICULAR TACHYCARDIA

The following drugs would be appropriate and safe to treat a maternal

supraventricular tachycardia (SVT) at 27 weeks’ gestation:

(a) Verapamil

(b) Digoxin

(d) Amiodarone

(e) Flecanide

Answers

(a) T

(b) T

(d) F

(e) T

Explanation

The first-choice therapy for SVT is usually nonpharmacological, using

vagal manoeuvres such as carotid sinus massage, eyeball pressure or

1. MULTIPLE CHOICE QUESTIONS

sudden immersion of the face in cold water. If medical therapy is

needed, adenosine is the first-line treatment, but if cardioversion does

not result with intravenous adenosine, alternative options include vera-

pamil. For prevention of further attacks, the first choice in pregnancy

would be a beta-blocker such as propranolol or sotalol.

(a)

Verapamil is not teratogenic. Oral use to prevent SVT in preg-

nancy is safe, although the intravenous formulation should be

avoided or used with caution because of the risk of profound

maternal hypotension. It should not normally be used in con-

junction with beta-blockers. This would not, therefore, be the

ideal choice for the acute management of SVT.

(b)

Digoxin crosses the placenta readily but is not teratogenic. There

is extensive experience of its use in pregnancy. Higher doses

might be needed because of increased renal excretion in preg-

nancy. Digoxin reduces conductivity within the atrioventricular

node. It is particularly useful to control the ventricular response

in atrial fibrillation, but would not be the ideal choice for acute

management of SVT.

(c)

Adenosine is the treatment of choice for terminating paroxysmal

SVT and usually leads to rapid reversion to sinus rhythm. Once

conservative manoeuvres to induce vagal stimulation (such as

carotid sinus massage and the Valsalva manoeuvre) have been

tried without success, adenosine should be administered by rapid

intravenous injection in increments every

1-2 minutes. The

starting dose is 3 mg, followed by 6 mg and then the maximal

bolus dose of 12 mg. Adenosine should be given only if cardiac

monitoring facilities are available. Adenosine use in pregnancy is

safe and the half-life is only 7-10 seconds. Side effects, such as

chest pain and dyspnoea, are therefore short-lived.

(d)

Amiodarone is used to treat SVT and ventricular tachycardia.

Given intravenously, it acts rapidly and is used when other drugs

are ineffective or contraindicated. Amiodarone does not cause

myocardial depression, but is contraindicated in pregnancy.

Amiodarone structurally resembles thyroid hormones and

contains iodine. Up to 15% of patients develop amiodarone-

induced hypothyroidism or hyperthyroidism. Both amiodarone

and its active metabolite, desmethylamiodarone, cross the pla-

centa. The risk of fetal or neonatal hypothyroidism and growth

restriction is up to 20%. Amiodarone is highly lipid-soluble and

crosses readily into breast milk. Because it has a very long half-life,

breast milk could contain substantial amounts of amiodarone, even

if discontinued before delivery.

(e)

Flecanide is widely used for the treatment of fetal tachycardia.

On the basis of limited literature, which includes case reports of

first-trimester exposure, its use in pregnancy seems safe. There

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

are far more data regarding, and is more confidence in, its use in

the second and third trimesters. It is used to treat arrhythmias

associated with Wolff-Parkinson-White (WPW) syndrome and

similar conditions with accessory pathways. It would not be the

drug of first choice to treat SVT.

1.5 PROPHYLAXIS OF ENDOCARDITIS

The following require antibiotic prophylaxis for endocarditis during

delivery:

(a) Ventricular septal defect (VSD)

(b) Atrial septal defect

(d) Bicuspid aortic valve

(e) WPW syndrome

Answers

(a) T

(b) F

(d) T

(e) F

Explanation

(a) If a VSD is untreated, the risk of endocarditis is significant.

Appropriate antibiotic prophylaxis during delivery is as follows:

intravenous amoxicillin (amoxycillin), 2 g (or intravenous van-

comycin, 1 g in patients who are allergic to penicillin) and intra-

venous gentamicin,

120 mg (1.5 mg/kg body weight) at the

induction of anaesthesia or at the onset of labour or ruptured

membranes, followed by oral amoxicillin 6 hours later.

(b) Isolated ostium secundum atrial septal defects do not constitute

a risk for endocarditis.

and antibiotic prophylaxis is mandatory.

(d) Many of these patients are not diagnosed, but a bicuspid aortic

valve is a common underlying feature in fatal cases of endocardi-

tis in pregnancy in the Report on Confidential Enquiries into

Maternal Deaths [2].

(e) An accessory pathway in itself is not an indication for prophylaxis

of endocarditis. In practice, some women with WPW syndrome

1. MULTIPLE CHOICE QUESTIONS

have associated structural congenital heart defects or the pathway

might have arisen as a result of the surgical correction of congenital

heart disease.

1.6 THROMBOEMBOLIC DISEASE IN PREGNANCY

(a) D-dimer measurement is more useful in the management

of thromboembolic disease in pregnancy than outside pregnancy.

(b) Heparin-induced thrombocytopenia (HIT) is associated with an

increased risk of thrombosis.

osteopenia than unfractionated heparin (UH).

(d) An epidural should not be sited for at least 12 hours after a dose

of UH.

(e) Warfarin should not be taken during lactation.

Answers

(a) F

(b) T

(d) F

(e) F

Explanation

(a) D-dimers are commonly increased in normal pregnancy because

of the prothrombotic tendency. The diagnosis of thrombo-

embolic disease should be made on the basis of clinical findings

and imaging results.

(b) HIT is extremely rare in pregnancy if a LMWH is used. With

UH, it occurs most commonly in the first 10 days of treatment.

HIT is part of an allergic response in which platelets are con-

sumed and thrombosis initiated. If HIT occurs, heparin must be

discontinued and an alternative treatment sought (e.g. aspirin

and stockings for women at low risk, danaparoid for women at

higher risk and, possibly, warfarin for those at highest risk of

thromboembolic disease).

at 0.04% of all pregnancies, but is probably lower than this. UH

has a 2% risk of an osteoporotic fracture.

(d) UH has a short half-life, and therefore anaesthetists are usually

prepared to site an epidural 4 hours after a thromboprophylactic

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

dose. Most anaesthetists require a 12-hour window after a throm-

boprophylactic dose of a LMWH and a 24-hour window for a

treatment dose of a LMWH.

(e) Warfarin is safe to use in breastfeeding women.

1.7 DEEP VEIN THROMBOSIS

(a) Deep vein thrombosis (DVT) is twice as common in pregnant

women compared with women who are not pregnant.

(b) DVT is more common in the third trimester than the first.

left.

(d) Venous ulceration is occasionally caused by DVT.

(e) Patients with DVT have a 1% risk of development of a pulmonary

embolus.

Answers

(a) F

(b) F

(d) F

(e) T

Explanation

(a) In pregnancy the risk of thromboembolic disease is six fold

greater than the nonpregnant population.

(b) The increase in thromboembolic events starts early in the first

trimester and is not related to gestational age. The risk increases

again in the puerperium because of the increased likelihood of

immobilization, dehydration, infection and pelvic trauma. All three

arms of Virchow’s triad are fulfilled, namely stasis secondary to

vasodilatation and pressure from the gravid uterus, increased

coagulation factors (as part of the body’s adaptation to minimize

haemorrhage there is an oestrogen-driven increase in clotting-

factor production) and endothelial damage (especially during

miscarriage, termination, surgery for ectopic pregnancy and both

vaginal and Caesarean delivery).

of the anatomical arrangement of the pelvic veins, whereby the

left iliac vein is compressed by the right iliac artery as it arises

1. MULTIPLE CHOICE QUESTIONS

from the aorta, which is itself to the left of the inferior vena

cava.

(d)

Following DVT, women should wear a full-length support

stocking for 2 years, in order to minimize the relatively high risk

of venous insufficiency and, consequently, venous ulceration.

This risk is generally quoted as between 5% and 10%.

(e)

Pulmonary embolus is a leading cause of maternal mortality.

Although the absolute incidence is low, thromboprophylaxis and

correct treatment of acute DVT are important for minimizing

this risk.

1.8

TREATMENT OPTIONS FOR DIABETES IN

PREGNANCY

(a)

Gliclazide is teratogenic.

(b)

Angiotensin converting enzyme (ACE) inhibitors should be

stopped in the second trimester.

(c)

Folate (5 mg/day) should be taken before conception and for the

first trimester.

(d)

A basal bolus regimen gives better neonatal outcome than twice-

daily premixed insulin.

(e)

Postprandial testing of glucose enables tighter control of diabetes

than preprandial testing.

Answers

(a) F

(b) F

(d) T

(e) T

Explanation

(a) The leading cause of teratogenesis in diabetic pregnancy is poor

glycaemic control at conception. There are not extensive studies

on the use of sulphonylureas in the first trimester of pregnancy.

However, in clinical practice, preconception advice should be

based on achieving optimal diabetic control, and if this can be

done with gliclazide, then the drug does not need to be discon-

tinued until the pregnancy test is positive. For many women,

however, insulin therapy is required before conception, in order

to achieve adequate control.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

(b)

ACE inhibitors are taken by many women with diabetic renal dis-

ease to slow the disease progression. There is increasing evidence

of adverse fetal renal effects and major congenital malformation,

and so ideally they should be stopped prior to conception or as

soon as possible thereafter.

(c)

“High-dose” folate (5 mg/day) should be taken before conception

by women with established diabetes. This is a guideline from the

Scottish Intercollegiate Guidelines Network (SIGN) [4] and

Confidential Enquiry into Maternal and Child Health

(CEMACH). In the recent CEMACH survey of pregnancy in

women with established diabetes

2002-03 [5], only

40% of

women achieved this. As in earlier studies, neural tube defects

(NTDs) occurred about four times more often in diabetic preg-

nancy than expected in the general population. Other women at

increased risk of NTDs, such as those taking anticonvulsant

agents and those with a personal or family history of pregnancy

complicated by NTDs, should also take folate at this dose.

(d)

In diabetic pregnancy, neonatal outcome is influenced by struc-

tural anomaly, prematurity, growth restriction in the presence of

microvascular disease or pre-eclampsia, birth trauma secondary

to accelerated growth, neonatal hypoglycaemia, jaundice, poly-

cythaemia and left-ventricular hypertrophy. All of these can be

improved, or the risk reduced, by tight diabetic control. The

Diabetes Control and Complication Trial (DCCT) provided

useful information on the advantages of tight diabetic control in

pregnancy [6]. A basal bolus (short-acting insulin with each meal

and long-acting insulin overnight and/or each morning) gives better

control for most women than twice-daily premixed insulins, which

contain fixed ratios of short-acting and long-acting insulin.

(e)

There is some evidence that measurement of blood glucose levels

2 hours postprandially gives better control than premeal tests

[7]. The logic is that hyperglycaemia is the main determinant of

adverse neonatal outcome in diabetic pregnancy, and, therefore,

glycaemic control must include assessments when the levels are

highest. By recording these postmeal values, subsequent changes to

the insulin doses preceding meals can be made, with the aim of

enhancing control. By definition, premeal tests record the glucose

nadirs. Although it is important that these levels are also optimized,

these alone are no longer accepted as sufficient monitoring, which

must incorporate both premeal and postmeal measurements.

1.9

WOMEN WITH ESTABLISHED DIABETES

(a)

There is an increased risk of aneuploidy in the offspring of

diabetic women.

1. MULTIPLE CHOICE QUESTIONS

(b) The risk of structural congenital anomaly depends on glycaemic

control at conception in women with established diabetes.

risk of jaundice.

(d) The offspring are more likely to develop type 1 diabetes if the

mother has type 1 diabetes than if the father has type 1 diabetes.

(e) The risk of pre-eclampsia is increased in women with established

diabetes.

(f ) Heartburn can indicate autonomic neuropathy in women with

diabetes.

(g) Women with type 2 diabetes have a better pregnancy outcome

than those with type 1 diabetes.

Answers

(a) F

(b) T

(d) F

(e) T

(f) T

(g) F

Explanation

(a) Diabetes does not influence the risk of aneuploidy, which is largely

determined by maternal age. However, maternal response to an

aneuploid pregnancy could be affected by her diabetes - e.g. if her

own quality of life or life expectancy are impaired by diabetes, she

might feel it is less appropriate to have a handicapped child; her

decision to terminate an aneuploid pregnancy rather than allow

nature to take its inevitable course might be influenced by the diffi-

culties of achieving good diabetic control.

(b) There are good data that the glycosylated haemoglobin (HbA_1c)

level at conception has a strong influence on the risk of a struc-

tural anomaly in the fetus. If HbA_1c is normal, the risk of an

anomaly is the same as in the general population, approximately

2-3%. If HbA_1c is over 10%, the risk of an anomaly is at least 30%,

and possibly more. Because most structural anomalies occur in

the first 8 weeks of the pregnancy (e.g. NTDs at 5-6 weeks and

heart defects at 8 weeks), glycaemic control must be optimized

before conception.

proposed that fetal hyperinsulinaemia results in increased fetal

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

erythropoietin production, which in turn causes neonatal poly-

cythaemia. Breakdown of some of these excess red blood cells

and immature liver enzymes, for handling the bilirubin load, pre-

dispose these babies to jaundice. It is estimated that about 20%

develop jaundice.

(d)

In type 1 diabetes, the fetus has a higher chance of developing dia-

betes if the father is affected, rather than if the mother is affected.

The cumulative risk of developing diabetes by the age of 20

years for children with mothers who have type 1 diabetes is

1.4-5%, approximately 10-30 times greater than background.

The risk is only one-third of that if the father (rather than the

mother) has the disease. This is postulated to be because of

in-utero development of tolerance to pancreatic beta-cell

autoantigens if the mother has diabetes; it is not because of the

demise of susceptible fetuses. Interestingly, children whose

mothers have type 1 diabetes could have an increased risk of

type 2 diabetes, which is ascribed to fuel-mediated intrauterine

events causing fetal hyperinsulinism [8].

(e)

Women with established diabetes do have an increased inci-

dence of pre-eclampsia, and this is raised further if they have

pre-existing hypertension or diabetic renal disease.

(f)

Autonomic neuropathy is not a common problem in diabetic

pregnancy. However, it can cause postural hypotension and

delayed gastric emptying with severe nausea, vomiting and reflux

oesophagitis.

(g)

In the CEMACH report [5], the perinatal mortality was as high

for women with type 2 as those with type 1 diabetes.

1.10 GESTATIONAL DIABETES

(a) Women have a 50% risk of developing type 2 diabetes later in life.

(b) Women have a 75% chance of developing gestational diabetes in

a subsequent pregnancy.

(d) Shoulder dystocia can be predicted by antenatal ultrasound

measurements.

(e) Insulin should be continued until the baby is at least 12 hours

of age.

Answers

(a) T

(b) F

1. MULTIPLE CHOICE QUESTIONS

(d) F

(e) F

Explanation

(a)

Gestational diabetes can be considered a “stress test” of insulin

metabolism. In normal pregnancy, insulin production doubles

and peripheral insulin resistance develops, with the dual processes

“accelerated starvation” and “facilitated anabolism”. Women

who cannot make these metabolic changes are inherently more

likely to develop diabetes in later life. Being pregnant does not in

itself alter the risk of subsequent diabetes.

(b)

In subsequent pregnancies the chance of gestational diabetes

developing again is over 90%, unless there has been substantial

weight loss.

(c)

Women should have lifelong intentions to attain an ideal body

weight and exercise regularly, because both reduce insulin resist-

ance and so improve glucose metabolism.

(d)

Shoulder dystocia is difficult to predict. Serial antenatal ultra-

sound measurements showing accelerated growth indicate an

increased risk but has a low positive-predictive value, and the

absence of this picture has a poor negative-predictive value. It is

reasonable obstetric practice to have an experienced obstetrician

available for the delivery of all babies whose mothers have

required insulin during pregnancy.

(e)

Insulin requirements return to prepregnancy levels as soon as

delivery is complete. Insulin treatment should be discontinued

straight away, in order to avoid hypoglycaemia. If labour has

been rapid and delivery completed within the duration of action

of antenatally administered long-acting insulin, special care

should be taken to avoid hypoglycaemia.

1.11 POSTNATAL CARE OF WOMEN WITH DIABETES

Ms A is 29 years old. She has had type 1 diabetes mellitus since she

was 6 years old, which is generally well controlled, with no evidence

of end-organ damage; she is otherwise fit and well, and is a slim

nonsmoker. She has just delivered her first child after an intensely

managed, but largely uncomplicated, pregnancy and labour; she does

not want to conceive again for “ages”. You review her on the postnatal

ward on the morning after her spontaneous vaginal delivery:

(a) She can take enalapril, even if she continues with breastfeeding.

(b) She can use the combined oral contraceptive pill (COCP) once

breastfeeding is complete.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

her normal nonpregnant dose.

(d) Depot Provera is relatively contraindicated because of the diabetes.

(e) She does not require postnatal thromboprophylaxis.

Answers

(a) T

(b) F

(d) T

(e) T

Explanation

(a)

Enalapril is an ACE inhibitor used in patients with diabetes to

slow deterioration of renal function. It seems to be safe in lactation

and can be started soon after delivery, as required. The drug

should not be prescribed during pregnancy because it affects the

fetal renal tract, causing impaired nephron migration in the first

trimester and fetal renal artery vasoconstriction in the second half

of pregnancy, with consequent oligohydramnios and its associated

complications. It is also teratogenic [3].

(b)

The World Health Organization (WHO) lists the use of the

COCP in women with diabetes of 20-years’ duration or more as

category 3/4 - i.e. either the risks outweigh the advantages of use

(category 3) or the use is absolutely contraindicated (category 4).

The combined hormonal contraceptive patches (e.g. Evra) fall

under the same classification as the COCP.

(c)

Insulin regimens are normally approximately 25% less during

breastfeeding compared with the usual nonpregnant dose. Lacta-

tion requires around 1000-1500 kcal/day. In addition, breastfeeding

women are more active at night than when they are not breast-

feeding and therefore must avoid hypoglycaemia.

(d)

The WHO lists use of depot Provera as category 3. The concerns

relate to the increased risk of cardiovascular complications. The

potential for unpredictable return of fertility following use of depot

Provera is a further disadvantage: women with diabetes should

achieve optimal diabetic control before conception, and need a form

of contraception that enables their fertility to return to normal

quickly when it is discontinued. Contraception is important for this

lady, and should be reliable. She could consider the progesterone

1. MULTIPLE CHOICE QUESTIONS

only pill (POP) if she can manage the strict regimen (although using

Cerazette obviates this because it has a 12-hour window, rather than

the 3-hour window of other POPs) or a progestogen implant (e.g.

Implanon), progestogen-releasing intrauterine system

(e.g.

Mirena) or copper intrauterine contraceptive device. The low and

steady dose of progestogen from these two hormonal options does

not increase the risk of cardiovascular complications [9].

(e) Thromboprophylaxis should be considered for women with

diabetes during pregnancy and the puerperium. This patient

does not seem to have any additional risk factors for thrombosis

(she is slim, young and a nonsmoker), and she had an uncompli-

cated vaginal delivery. Therefore, she does not need postnatal

thromboprophylaxis.

1.12 THROMBOCYTOPENIA

The following can cause a maternal platelet count less than 100

10⁹

platelets/l in pregnancy:

(a) Human immunodeficiency virus (HIV)

(b) Thrombosis

(d) Endometritis

(e) Alloimmune thrombocytopenia

Answers

(a) T

(b) F

(d) T

(e) F

Explanation

(a) HIV can present with anaemia, leucopenia, thrombocytopenia or

pancytopenia. A low platelet count at booking should always

prompt consideration of HIV.

(b) A low platelet count is not a feature of acute thrombosis. A high

platelet count could cause thrombosis.

the development of DIC and consumption of clotting factors or

after blood transfusion.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

(d) Any cause of sepsis, either antenatal or postnatal, could be asso-

ciated with thrombocytopenia.

(e) Alloimmune thrombocytopenia is a cause of fetal, not maternal,

thrombocytopenia. The maternal platelet count is normal in this

condition.

Other causes of thrombocytopenia in pregnancy include gestational

thrombocytopenia, pre-eclampsia, antiphospholipid syndrome,

immune thrombocytopenic purpura (ITP), thrombotic thrombocy-

topenic purpura (TTP) and haemolytic uraemic syndrome (HUS).

1.13 FOLATE SUPPLEMENTATION

The following conditions are indications for treatment with folic acid

(5 mg/day) in pregnancy:

(a) Hereditary spherocytosis

(b) Sulfasalazine therapy

(d) Vegetarian diet

(e) Sickle cell disease

Answers

(a) T

(b) T

(d) F

(e) T

Explanation

(a) Any haemolytic anaemia could lead to folate deficiency. Both sickle

cell disease and hereditary spherocytosis are haemolytic anaemias.

(b) Sulfasalazine has antifolate actions and is a dihydrofolate reduc-

tase inhibitor. It is, therefore, associated with an increased risk of

NTDs, oral clefts and cardiovascular defects. Folate (5 mg/day)

supplementation is recommended throughout pregnancy.

increased risk of congenital malformations, particularly NTDs,

and folate-deficiency anaemia.

(d) Vegetarians are not usually folate-deficient as fruit and vegetables

are folate-rich unless they have been over cooked.

(e) See part (a).

1. MULTIPLE CHOICE QUESTIONS

1.14 NEUROPATHIES AND PALSIES IN PREGNANCY

The following nerves might be affected by neuropathies or palsies in

pregnancy:

(a) Lateral cutaneous nerve of the thigh

(b) Optic nerve

(d) Hypoglossal nerve

(e) Median nerve

Answers

(a) T

(b) F

(d) F

(e) T

Explanation

(a) The lateral cutaneous nerve of the thigh, supplying sensation to

the outer aspect of the thigh, might be compressed by the gravid

abdomen as the nerve passes behind or through the inguinal

ligament, medial to the anterior superior iliac spine.

(b) The optic nerve is not affected by neuropathies or palsies in

pregnancy.

(VIIth cranial) nerve, is more common in pregnant women than

nonpregnant women. Oedema around the nerve causes compres-

sion as it exits the skull through the stylomastoid foramen, some-

times in association with herpes virus infection.

(d) The hypoglossal nerve, or XIIth cranial nerve, supplies the

muscles of the tongue and is no more commonly affected in preg-

nancy than outside pregnancy.

(e) Compression of the median nerve as it passes through the carpal

tunnel is well recognised as a common complication of pregnancy,

possibly related to oedema.

1.15 EPILEPSY

(a) Free drug levels of carbamezepine fall during pregnancy.

(b) The recommended preconceptual dose of folic acid for women

taking anticonvulsants is the same as that for women with a

previous child with a NTD.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

breastfeed.

(d) Vigabatrin is not teratogenic.

(e) The risk of epileptic seizures increases intrapartum.

Answers

(a) T

(b) T

(d) F

(e) T

Explanation

(a)

Because of the increased blood volume and resulting increased

volume of distribution, in addition to increased excretion of

drugs through the liver and kidney, free drug levels of most

antiepileptic drugs fall in pregnancy. For many women car-

bamezepine does not have a narrow therapeutic window and so

dose changes are not necessarily needed. Conversely, increases in

lamotrigine dose are frequently required.

(b)

Women taking antiepileptic drugs before conception and in early

pregnancy are advised to take folic acid (5 mg/day) to reduce the

risk of NTDs and other abnormalities, such as cardiovascular and

urogenital malformations.

(c)

Negligible amounts of sodium valproate are found in breast milk.

Only 1-10% of valproate is transferred from plasma to breast milk,

and the maximum amount received by the baby is likely to be 3% of

a therapeutic dose. Breastfeeding should, therefore, be encouraged.

(d)

Vigabatrin is teratogenic in animals and humans, and it should be

avoided if possible in pregnancy.

(e)

Women with epilepsy are more likely to have seizures around the

time of delivery. This is related to several factors, including

hyperventilation, lack of absorption of drugs from the gastroin-

testinal tract during labour (which can be minimised by adminis-

tering drugs intravenously or rectally), stress and lack of sleep at

the end of pregnancy. The risk of seizures is about 1-2% during

labour and 1-2% in the first 24 hours postpartum.

1.16 CEREBRAL VEIN THROMBOSIS

(a) Cerebral vein thrombosis might present with convulsions.

(b) Usually, cerebral vein thrombosis occurs in the third trimester.

1. MULTIPLE CHOICE QUESTIONS

(d) In the UK, cerebral vein thrombosis is the commonest throm-

botic cause of maternal death in the puerperium.

(e) If headache is associated with hemiparesis, cerebral vein throm-

bosis should be considered.

Answers

(a) T

(b) F

(d) F

(e) T

Explanation

Cerebral vein thrombosis is uncommon (incidence, approximately 1 in

10,000 pregnancies per year), but associated with a high mortality. Most

fatal cases (about 1 fatal case/year in the UK) related to pregnancy occur

in the puerperium. Patients usually present with headache, which might

be associated with seizures, impaired consciousness and signs of raised

intracranial pressure, with vomiting and photophobia fever and leuco-

cytosis are not uncommon, and the differential diagnosis for cerebral

vein thrombosis therefore often includes meningitis and encephalitis.

One-third to two-thirds of patients have focal signs, such as hemipare-

sis. Venous infarction and intracerebral bleeding can result from

obstruction of the collateral circulation. Differential diagnoses include

eclampsia, subarachnoid haemorrhage and herpes encephalitis.

Diagnosis is made by computerised tomography scanning (CT) to

detect intracerebral bleeding, although magnetic resonance imaging

(MRI), especially venous angiography MRI, best shows venous clots.

Treatment with heparin is controversial because the risk of intracere-

bral bleeding might be increased, but clot formation is prevented.

Evidence suggests outcome is better with heparin therapy.

1.17 ECLAMPSIA

(a) Eclampsia is always preceded by hyperreflexia or drowsiness.

(b) The (maternal) outcome in eclampsia is related to gestation.

(d) In the UK, most patients with eclampsia have their first fit at

home.

(e) Maternal mortality from eclampsia in the UK is 10%.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Answers

(a) F

(b) T

(d) F

(e) F

Explanation

(a) Eclampsia might not be preceded by any classical features of

pre-eclampsia, and there is no relationship between the presence

of hyperreflexia and clonus and the development of eclampsia.

There could be preceding headache or neurological symptoms or

signs, but not necessarily.

(b) Both antepartum and preterm eclampsia are independent risk

factors for a severe maternal outcome.

prophylaxis of eclampsia, but high serum concentrations can

result in loss of tendon reflexes (

5 mmol/l) and neuromuscular

paralysis (

7.5 mmol/l).

(d) The British Eclampsia Survey [10] showed 75% of patients have

their first fit in hospital.

(e) Maternal mortality from eclampsia is approximately 2%.

1.18 THYROID DYSFUNCTION

When considering the treatment of thyroid dysfunction in pregnancy,

the following medications should be avoided:

(a) Thyroxine in the first trimester.

(b) Propranolol in the first trimester.

(d) Carbimazole at all gestations.

(e) Propylthiouracil (PTU) at term.

Answers

(a) F

(b) F

(d) F

(e) F

1. MULTIPLE CHOICE QUESTIONS

Explanation

(a)

Thyroxine is not only safe in the first trimester, but it is also

important for fetal neurological development. Children whose

mothers had untreated or undertreated hypothyroidism in the

first trimester have a greater risk of neurodevelopmental delay

than those whose mothers were correctly treated with thyroxine

or were euthyroid. Beyond the first trimester, placental changes

prevent significant thyroxine from crossing unless the fetus is

athyrotic [11].

(b)

Propranolol use is safe in the first trimester. Although atenolol

might cause growth restriction if given in the first trimester, this

has not been shown with propranolol and, in any case, it would

not be a reason to withhold beta-blockers from a thyrotoxic

patient.

(c)

Iodine crosses the placenta, and radioactive iodine destroys

developing thyroid tissue. The Royal College of Physicians’

(RCP) guidelines recommend that it is avoided in the 4 months

before conception and during pregnancy and lactation. People

who are given radioactive iodine should avoid nonessential close

personal contact with pregnant women and babies for up to 27

days, depending on the dose administered [12].

(d)

Carbimazole and PTU can both be used with confidence

throughout pregnancy when clinically indicated. They are not

teratogenic, and any link with the very rare aplasia cutis is either

extremely weak or co-incidental. There is also evidence that they

each reduce the risk of teratogenesis that untreated, or under-

treated, thyrotoxicosis brings with it [13]. Contrary to earlier

dogma, sophisticated experiments on isolated term placental lob-

ules show that carbimazole does not cross the placenta more

readily than PTU. Both drugs carry a small risk of fetal hypothy-

roidism, so should be given at the lowest dose to maintain a clin-

ically euthyroid state with the free thyroxine concentration (fT₄)

at the upper end of normal for pregnancy.

(e)

See (d).

1.19 POSTPARTUM THYROIDITIS

(a) Postpartum throiditis usually presents within 6 weeks of delivery.

(b) Symptoms of hyperthyroidism are common in postpartum

thyroiditis.

(d) Hypothyroidism usually resolves by 6 months postpartum.

(e) There is a high risk of recurrence in future pregnancies.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Answers

(a) F

(b) F

(d) F

(e) T

Explanation

(a)

Postpartum thyroiditis is a subacute destructive autoimmune

condition that is strongly related to antiperoxidase antibodies and

occurs in the first year postpartum. It can present as hyperthy-

roidism, hypothyroidism or, most often, a purely biochemical

phenomenon; the prevalence in clinical practice is much lower

than the 2-17% described in clinical trials.

In clinically apparent cases, any or all of the three phases can

occur: hyperthyroidism at 1-3 months postpartum, hypothy-

roidism at 3-8 months postpartum, and euthyroidism by 1 year

postpartum.

(b)

Hyperthyroidism is usually asymptomatic.

(c)

If treatment is required, it is treatment of the symptoms

themselves

- e.g. beta-blockers for tachycardia and tremor.

Thionamides are not needed because the thyrotoxic picture is due

to increased release of preformed thyroxine from the damaged

thyroid, rather than excess formation of thyroxine.

(d)

The hypothyroid phase is more likely to be symptomatic than the

hyperthyroid phase, requiring treatment, although the symptoms

might be vague and difficult to distinguish from other postnatal

problems. Treatment is with thyroxine. In most cases, the autoim-

mune process has subsided by 12 months postpartum and the thy-

roid gland has returned to normal: thyroxine should be withdrawn

when the baby is 1 year old.

(e)

Follow-up thyroid tests are important because a small proportion

of women have permanent hypothyroidism and 5% of women

each year subsequently develop it; 70% of women get postpartum

thyroiditis following subsequent pregnancies [14,15].

1.20 PITUITARY HORMONES

The following can be said of pituitary hormones in pregnancy:

(a) The placenta secretes adrenocorticotropic hormone (ACTH).

(b) Levels of basal growth hormone (GH) are unchanged.

1. MULTIPLE CHOICE QUESTIONS

(d) Follicle stimulating hormone (FSH) and luteinizing hormone

(LH) levels are increased.

(e) The placenta secretes antidiuretic hormone (ADH).

Answers

(a) T

(b) T

(d) F

(e) F

Explanation

(a) The placenta does secrete ACTH, although pituitary secretion is

unchanged.

(b) Levels of basal growth hormone secretion from the pitu-

itary are unchanged, although the placenta secretes placental

GH and human placental lactogen, which is closely related

to GH.

so that levels 10-fold greater than those of nonpregnancy are

encountered. Levels fall rapidly postpartum, unless breastfeeding

commences.

(d) FSH and LH secretion are suppressed by the high levels of

oestrogen in pregnancy and levels are usually undetectable.

(e) The placenta secretes vasopressinase, which metabolises ADH,

occasionally producing diabetes insipidus because of ADH defi-

ciency in late pregnancy.

1.21 PROLACTINOMAS IN PREGNANCY

(a) Microprolactinomas should be managed by continuation of

dopamine agonists.

(b) Enlargement of the tumour might present with headache.

testing.

(d) Cabergoline is contraindicated in pregnancy.

(e) Women with prolactinomas should be advised against breastfeeding.

Answers

(a) F

(b) T

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

(d) F

(e) F

Explanation

(a) Women with microprolactinomas can usually discontinue

dopamine agonists in pregnancy as the risk of expansion of the

tumour is very small.

(b) Other symptoms might include visual-field defects.

than microprolactinomas. Visual field testing is performed to

detect any tumour expansion upwards, causing compression of

the optic nerve or chiasm.

(d) Both bromocriptine and cabergoline can be safely taken in

pregnancy and are usually electively continued in women with

macroprolactinomas.

(e) There is no reason why women with prolactinomas should not

breastfeed, although lactation might be suppressed in those

taking dopamine agonists.

1.22 ERYTHEMA NODOSUM

Erythema nodosum is associated with the following:

(a) Streptococcal sore throat

(b) SLE

(d) Histoplasmosis

(e) Chlamydial infection

Answers

(a) T

(b) F

(d) T

(e) T

Explanation

Erythema nodosum is a painful or tender nodule over the shin that is

dusky red, purple or blue and fades over several weeks. It is most

1. MULTIPLE CHOICE QUESTIONS

common in young women and can be idiopathic. It is also associated

with tuberculosis, sarcoidosis, inflammatory bowel disease and drugs

(including OCP, NSAIDs and sulphonamides).

1.23 RHEUMATOID ARTHRITIS

(a) The pregnancy outcome is related to disease activity.

(b) ESR is a useful marker of disease activity in pregnancy.

(d) Methotrexate should be stopped as soon as the pregnancy test is

positive.

(e) Sulfasalazine reduces the speed of disease progression and is safe

in pregnancy.

Answers

(a) F

(b) F

(d) F

(e) T

Explanation

(a) Women with rheumatoid arthritis might experience some

improvement in their symptoms during pregnancy, although up

to one-quarter will continue to have severe symptoms. Unlike

other autoimmune conditions, there is no evidence that disease

activity influences pregnancy outcome, which is generally good

unless there is hypertension, secondary antiphospholipid syn-

drome (APS) (uncommon), or significant joint problems that

limit hip abduction (for vaginal delivery) or neck extension (for

general anaesthetic).

(b) Outside pregnancy, disease activity can be monitored by eleva-

tion of ESR. However, normal pregnancy is associated with a

modest elevation of ESR too, readings of 50 to 100 mm/hour

being normal depending on the gestational age and haemoglobin

concentration [16]. CRP should be used instead, because it is not

influenced by pregnancy and, unlike SLE, disease activity does

affect it.

pregnancy for all women with rheumatoid arthritis, because

upper cervical spine involvement makes intubation for general

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

anaesthetic hazardous. Cervical spinal cord compression is rare,

but constitutes a neurosurgical emergency. It might present

as increased difficulty walking unrelated to joint disease, leg

weakness, or loss of bowel or bladder control.

(d)

Drug therapy is often one of the greatest challenges in pregnant

women with rheumatoid arthritis. Analgesia should ideally be

given with paracetamol-based drugs; if these are inadequate,

NSAIDS can be considered in the first half of the pregnancy, but

not thereafter because of the risks of fetal renal artery

vasoconstriction and premature closure of the ductus arteriosus.

Disease-modifying antirheumatic drugs (DMARDS) slow disease

progression, but are often used in conjunction with symptomatic

treatment because alone they frequently only achieve partial

improvement and this is not immediate. Methotrexate, sul-

fasalazine, leflunamide and ciclosporin have all been shown to slow

the rate of progressive joint damage. However, methotrexate is a

folate antagonist that should be stopped at least 3-6 months before

conception. Conception while taking methotrexate is associated

with an increased risk of NTDs and other skeletal abnormalities.

(e)

Sulfasalazine is safe in pregnancy, but high-dose folate (5 mg daily)

must also be prescribed because the drug has an antifolate action.

1.24 INFLAMMATORY BOWEL DISEASE

The following might be seen as complications of inflammatory bowel

disease in pregnancy:

(a) Ascending cholangitis

(b) Erythema nodosum

(d) Erythema multiforme

(e) Iron-deficiency anaemia

Answers

(a) T

(b) T

(d) T

(e) T

Explanation

(a) Ascending cholangitis is a recognised complication/association of

both Crohn’s disease and ulcerative colitis.

1. MULTIPLE CHOICE QUESTIONS

(b) Erythema nodosum might be seen in association with inflamma-

tory bowel disease.

neous preterm labour.

(d) Skin manifestations of inflammatory bowel disease include

erythema nodosum, erythema multiforme and pyoderma gan-

grenosum. Erythema multiforme is an acute mucocutaneous

hypersensitivity reaction, and its most common form is associated

with symmetrical target lesions on the extremities.

(e) Inflammatory bowel disease might cause a normochromic normo-

cytic anaemia of chronic disorder, a microcytic anaemia of iron

deficiency secondary to blood loss or a macrocytic picture because

of malabsorption of vitamin B12 from the terminal ileum.

1.25 ULCERATIVE COLITIS

Consider the following for a woman with ulcerative colitis who is

pregnant:

(a) She should aim to stop aminosalicyclates, if possible.

(b) She has previously had a pancolectomy and, following formation

of an ileal pouch, is fully continent; she should aim for a vaginal

delivery if obstetric conditions permit.

(d) Backache should be investigated thoroughly.

(e) Her offspring do not have an increased risk of developing the

condition.

Answers

(a) F

(b) T

(d) T

(e) F

Explanation

(a) Maintenance of remission is important in ulcerative colitis: flares are

most common in the first trimester or if treatment is inappropriately

reduced or stopped. Aminosalicyclates, such as mesalazine, can be

administered as foam enemas, suppositories or tablets. They are safe

in pregnancy, and should only be stopped if it is certain that the dis-

ease is fully quiescent. Folate (5 mg daily) should be taken with

aminosalicylates, because they have an antifolate action.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

(b)

Caesarean section (LSCS) is usually best avoided in women with

inflammatory bowel disease, especially if they have had bowel

surgery, because the operation can be technically difficult, with an

increased risk of trauma to local structures, including the bowel

and bladder. In addition, women with active inflammatory bowel

disease have an increased risk of thrombosis, and therefore their

peripartum risk of a thromboembolic event should be minimized.

Typical nonobstetric indications for LSCS might include active

perianal disease if there is a risk of fistula formation, severe per-

ineal scarring with reduced elasticity and faecal incontinence. Ileal

pouches per se are not usually an indication for LSCS. However, it

is clearly important that obstetric factors that could impair func-

tion of the pouch (e.g. prolonged second stage of labour and third-

degree tear) and provoke incontinence are avoided.

(c)

Prednisolone administration in pregnancy is generally safer than a

severe relapse, and should be used to treat flares of ulcerative colitis.

Maternal side effects of steroid courses lasting longer than 2-3 weeks

include hypertension, hyperglycaemia and Addisonian collapse if

additional doses are not prescribed during stressful episodes (such as

labour). In addition, if chickenpox develops, there is an increased

incidence of the serious complications of this infection, including

pneumonitis and encephalitis: women should have their immune sta-

tus checked. There is not an increased risk of parvovirus infection.

(d)

Backache in pregnancy has a broad differential diagnosis, and

is often benign. In a woman with ulcerative colitis consider

ankylosing spondylitis and vertebral collapse because of steroid-

induced osteoporosis.

(e)

Clustering of cases occurs, and is more common in certain ethnic

groups.

1.26 HYPEREMESIS GRAVIDARUM

The following intravenous fluids are appropriate in the management

of hyperemesis gravidarum:

(a) Hartmann’s solution

(b) Double-strength normal saline

(c)

5% dextrose solution

(d) 10% dextrose solution

(e) Normal saline

Answers

(a) T

(b) F

1. MULTIPLE CHOICE QUESTIONS

(d) F

(e) T

Explanation

Women with prolonged recurrent vomiting are usually hypona-

traemic and volume-depleted. They are prone to both Wernicke’s

encephalopathy, because of thiamine deficiency, and central pontine

myelinolysis, because of severe hyponatraemia or its overzealous

correction. Therefore, hyponatraemia should be corrected slowly with

normal saline rather than double-strength saline, or Hartmanns’ solution

which contains physiological amounts of sodium. Dextrose (either 5% or

10%) solution contains no sodium ions and therefore exacerbates any

hyponatraemia. Furthermore, solutions containing a high concentration

of dextrose can precipitate Wernicke’s encephalopathy if administered

before thiamine replacement.

1.27 THE LIVER IN PREGNANCY

(a) Blood flow to the liver increases.

(b) Placental alkaline phosphatase is heat stable.

(d) Spider naevi do not suggest chronic liver disease.

(e) Increased production of albumin occurs.

Answers

(a) F

(b) T

(d) T

(e) F

Explanation

(a) In pregnancy, the circulating volume increases by about 50%,

with a large part of this increase going to the uteroplacental

circulation, kidneys and breasts. The absolute amount of blood

going to the liver remains unchanged. As a percentage of cardiac

output, it falls from 35% to 29% by late pregnancy.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

(b)

Alkaline phosphatase is produced by the liver, the placenta and

bone. In pregnancy, placental production increases, especially in

the third trimester, so that by term, total levels might be three

times the upper limit of normal. Liver and placental isoenzymes

can be distinguished by heat treatment to 60ºC for 10 minutes,

which destroys the liver isoenzyme (and, in adults, small amount

of bone isoenzyme): in clinical practice, the amount by which the

alkaline phosphatase assay falls after heat treatment can usually

be considered to be the liver component.

(c)

The size of the liver is unchanged in pregnancy, but it usually

occupies a more superior and posterior position, such that if it is

palpable, there is usually significant pathology.

(d)

The characteristic lesions of chronic liver disease include spider

naevi, palmar erythema and peripheral oedema, but each of these

is common in normal pregnancy, the first two signs reflecting

raised circulating oestrogen levels.

(e)

Although liver production of some proteins increases in preg-

nancy, such as coagulation factors and hormone-binding proteins,

albumin production is unchanged. Circulating albumin concen-

trations fall in normal pregnancy because of haemodilution.

1.28 ACUTE FATTY LIVER OF PREGNANCY (AFLP)

(a) AFLP usually presents near term.

(b) There is a 25% recurrence risk in some families.

(d) Hypoglycaemia can occur.

(e) Hyperuricaemia is a feature of AFLP.

Answers

(a) T

(b) T

(d) T

(e) T

Explanation

(a) AFLP typically presents in the third trimester.

(b) Some cases of AFLP are caused by long-chain hydroxyacyl

co-enzyme A dehydrogenase (LCHAD) deficiency, a homozygous

1. MULTIPLE CHOICE QUESTIONS

long-chain fatty-acid metabolic problem occurring in the fetus.

The fetal abnormal fatty-acid metabolites cross into the maternal

circulation and overwhelm the maternal heterozygote capacity,

resulting in the clinical scenario of AFLP. In these families, there

is a 25% recurrence risk as for other autosomal recessive condi-

tions, although the severity is variable. In most women, the aeti-

ology is unclear and the risk of recurrence is low.

(c)

Pruritus is a nonspecific feature of many types of liver disease,

including AFLP. It is important that obstetricians do not immedi-

ately assume that itching in pregnancy is because of obstetric

cholestasis.

(d)

Liver failure results in impaired mobilization of glucose from the

liver during fasting. In AFLP, regular blood glucose measure-

ments should be made, and low results treated with intravenous

high-concentration glucose.

(e)

Hyperuricaemia is a feature of severe liver disease; in AFLP, the

raised uric acid level is out of proportion with the features of pre-

eclampsia, which are usually mild.

1.29 HEPATITIS C INFECTION

(a)

80% of infected individuals become chronic carriers of hepatitis C.

(b) 10% of hepatitis C carriers develop hepatoma.

the mother is also HIV positive.

(d) Caesarean section should be offered to reduce the risk of fetal

infection.

(e) Lactation is best avoided in women with hepatitis C infection.

(f) Sexual transmission of hepatitis C is common.

Answers

(a) T

(b) F

(d) F

(e) F

(f) F

Explanation

(a) Hepatitis C is an RNA virus transmitted by blood and blood

products, which is therefore common among intravenous drug

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

abusers. At least 80% of infected people become carriers and

develop chronic liver disease.

(b)

Cirrhosis develops in approximately 20% of hepatitis C carriers

over 10 years, and of these, around 10% develop primary hepato-

cellular carcinoma.

(c)

Overall, materno-fetal vertical transmission is rare, but it seems

to depend on the viraemic load. Transmission in HIV-positive

women is higher, and this might reflect the propensity for higher

viraemic loads.

(d)

In HIV-negative hepatitis-C-positive women, there is no benefit

in offering Caesarean section. However, if the viraemic load is

very high, delivery by Caesarean section has been suggested to

protect the neonate from infection: this area needs further study.

(e)

In HIV-negative women, breastfeeding should be encouraged.

Horizontal transmission of hepatitis C within the family seems to

be rare.

(f)

Hepatitis C is common among those with haemophilia and intra-

venous drug abusers. It is, however, not common in prostitutes,

homosexual men and those attending sexual-health clinics, making

sexual transmission unlikely.

1.30 SCLEROSING CHOLANGITIS IN PREGNANCY

(a)

25% of patients with sclerosing cholangitis in pregnancy have

inflammatory bowel disease.

(b) Sclerosing cholangitis should be part of the differential diagnosis

for obstetric cholestasis.

cholangitis.

(d) Antimitochondrial antibodies might be positive in patients with

sclerosing cholangitis in pregnancy.

(e) Ursodeoxycholic acid (UDCA) is a potential treatment for

sclerosing cholangitis.

Answers

(a) F

(b) T

(d) F

(e) T

1. MULTIPLE CHOICE QUESTIONS

Explanation

(a)

Primary sclerosing cholangitis is a chronic liver disease charac-

terized by fibrosis and inflammation in the intrahepatic and

extrahepatic bile ducts. Of patients with sclerosing cholangitis,

75% have inflammatory bowel disease, usually ulcerative colitis;

screening of asymptomatic patients with inflammatory bowel

disease can detect an early phase of abnormal liver

biochemistry.

(b)

Symptoms include fluctuating pruritus (and hence the differential

diagnosis in pregnancy includes obstetric cholestasis), jaundice,

fever and biliary colic.

(c)

Typically, liver function tests show a raised alkaline phosphatase

level. However, in pregnancy, alkaline phosphatase might be

three times the upper limit of normal, and therefore in this cir-

cumstance this is not such a helpful test, unless heat treatment or

isoenzyme assay are available.

(d)

The diagnosis is made in the presence of antinuclear cytoplasmic

antibodies antimitochondrial antibodies suggest primary biliary

cirrhosis, and typical cholangiogram and biopsy features.

(e)

UDCA causes some transient improvement in liver function, but

does not seem to alter long-term prognosis. Ultimately, liver

transplantation is required.

1.31 TUBERCULOSIS IN PREGNANCY IN UK

(a) TB in pregnancy is more common in Asian and African immi-

grants than in indigenous women.

(b) Extrapulmonary TB is rare compared with pulmonary TB.

(d) Antituberculous medication, including rifampicin, should not be

used in the first trimester of pregnancy.

(e) Most cases of tuberculosis (TB) in pregnancy are associated with

HIV infection.

Answers

(a) T

(b) F

(d) F

(e) F

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Explanation

(a)

The prevalence of TB in UK is rising. In most UK populations,

TB is typically found in recently arrived immigrants from the

Asian subcontinent or Africa.

(b)

Symptoms are often atypical or reported late, and the diagnosis

can be challenging. Nonspecific abdominal or back pain, lym-

phadenopathy and respiratory symptoms should be considered

seriously, especially in high-risk women. Extrapulmonary TB is

common in pregnancy, accounting for more than 50% cases in

two recent UK series [17].

(c)

Chest X-ray helps to diagnose pulmonary TB and, with fetal

shielding is safe. Serial sputa or early morning urine samples lead

to a microbiological diagnosis and correct sensitivities. A Heaf

test, consisting of a six-point, disposable puncture apparatus that

is activated through a small amount of purified protein derivative

of Mycobacterium tuberculosis (PPD), placed on the flexor surface

of the left forearm can be used safely in pregnancy: a negative

result of discrete induration at the puncture sites is classified as

grade 0 or 1 (maximum, grade 4) and implies that further investi-

gation is not required. HIV-positive patients might have a delayed

response, and false negatives are more common in this population.

(d)

Antituberculous medication should be used at whatever gestation

of pregnancy the diagnosis of TB is made. Common regimens

include rifampicin, isoniazid, ethambutol and pyrazinamide, all of

which are safe throughout pregnancy and lactation.

(e)

In UK, most pregnant women with TB are HIV negative.

1.32 RADIATION

(a) Almost all man-made radiation results from diagnostic medical

exposures.

(b) A single PA chest X-ray is equivalent to approximately 3 days of

natural background radiation.

fatal childhood cancer.

(d) The threshold for gross fetal malformation caused by X-ray

exposure in the first trimester is equivalent to 20 abdominal X-

rays.

(e) The risk of heritable effects because of fetal irradiation (i.e.

effects that could be passed on to the descendants of the unborn

child) is similar to the increased risk of childhood cancers that

irradiation causes.

1. MULTIPLE CHOICE QUESTIONS

Answers

(a) T

(b) T

(d) F

(e) T

Explanation

(a)

Man-made radiation accounts for 15% of the total radiation bur-

den, of which 97% results from diagnostic medical procedures

[18 RCR London 1995].

(b)

A chest X-ray gives an effective dose of 0.002 mSv and a fetal

dose of

0.001 mGy. The units of radiation can be confusing:

Grays (Gy) are the absorbed dose of ionizing radiation, where

1 Gy

1 J of energy being imparted to 1 kg of matter (previ-

ously called a Rad), and Sieverts (Sv) are a dose-equivalent of

1 J/kg (previously called the rem), where the dose-equivalent is

the measure of effects of radiation on living organisms. Sieverts

are calculated as the absorbed dose in Gy multiplied by the rela-

tive biological effectiveness - e.g. alpha radiation causes 20 times

more biological damage than beta radiation. Humans can absorb

up to 0.25 Sv without any immediate effect; 1 Sv causes radiation

sickness and

8 Sv is fatal.

(c)

The baseline risk of childhood cancer in the first 15 years of life

is 1 in 650, and half of these cases (1 in 1300) are fatal. It is esti-

mated that fetal exposure to X-rays increases the risk of fatal

cancer in childhood by 1 in 33,000 per 1 mGy exposure. A pelvic

CT scan gives an approximate fetal radiation dose of 25 mGy,

which increases the risk of fatal childhood cancer to 1 in 1320. By

contrast, an abdominal X-ray gives a fetal radiation dose of

1.4 mGy, or an excess fatal childhood cancer risk of 1 in 24,000.

Modern radiology departments can calculate the dose of radiation

used in individual procedures if inadvertent exposure has occurred

or determine the average amount applied in their department if a

procedure is contemplated in pregnancy. The risk applies across

the whole pregnancy, but is lower if it occurs in the first 6 weeks.

Although exposure should always be minimized, if a procedure is

likely to benefit the woman, in most cases the additional child-

hood cancer risk is unlikely on its own to be a reason to terminate

the pregnancy.

(d)

Fetal malformation, severe mental retardation and intrauter-

ine death are the principal deterministic effects of external

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

irradiation that can occur if the level of radiation is suffi-

ciently high. In the first trimester, the minimal dose for fetal

malformation is estimated at 500 mGy, which is equivalent to

360 abdominal X-rays (mean dose/procedure, 1.4 mGy), or 20

CT scans of the pelvis. There is the possibility of a non-

threshold-type response in relation to mental retardation,

interpreted as the loss of 30 intelligence quotient (IQ) points

for each Gy of X-ray or gamma-ray exposure. However, even

for a high-dose procedure, such as a CT scan of the pelvis, this

represents, at most, the loss of

1 IQ point. In practice, radi-

ation doses resulting from most diagnostic procedures do not

present a substantial risk to an individual pregnancy.

(e)

The risk of heritable disease is estimated at 1 in 42,000 per

mGy exposure. This includes disease of varying severity, and

so direct comparison with fatal cancer risks is unhelpful.

However, the absolute risks are similar, although the conse-

quences are potentially very different. An abdominal X-ray

carries a risk of heritable disease of

1 in 30,000 and a CT

scan of the pelvis has a risk of 1 in 1700. Because these risks

are small, both absolutely and in comparison with back-

ground risks, inadvertent or unavoidable diagnostic proce-

dures are not sufficient grounds alone to advise termination

of a pregnancy.

1.33 PHENYLKETONURIA IN PREGNANCY

(a) The fundamental metabolic problem in phenylketonuria (PKU)

is failure to metabolise tyrosine to phenylalanine.

(b) If the pregnant woman does not take the correct treatment, the

risk to her child of severe intellectual handicap is over 90%.

pregnancy.

(d) Breastfeeding is encouraged in most women.

(e) Pre-eclampsia is more common in women with PKU.

Answers

(a) F

(b) T

(d) T

(e) F

1. MULTIPLE CHOICE QUESTIONS

Explanation

Ideally, women with PKU should have prepregnancy advice so that

they conceive with phenylalanine levels as low as possible (target

level,

0.6 mmol/l). This needs considerable encouragement and

support, including expert dietetic input. In pregnancy, blood levels of

phenylalanine should be measured at least every few weeks, which

can usually be done at home using a capillary sample placed onto card

and posted to the laboratory directly. Vomiting in early pregnancy

and intercurrent infection must both be treated carefully and thor-

oughly because they could provoke a catabolic state in which the

mother’s own protein stores are broken down, increasing phenyla-

lanine levels despite strict dietary compliance.

(a)

PKU is an autosomal recessive condition in which 1 of 40 muta-

tions in the phenylalanine hydroxylase gene results in inability to

metabolise phenylalanine to tyrosine. In infancy, it is diagnosed

by the Guthrie heel-prick test at the end of the first week of

life. Phenylalanine is present is most natural proteins, which

must therefore be withdrawn from the diet and replaced by an

amino-acid substitute without phenylalanine. Failure to do so

from birth to at least adolescence, when neurological development

is complete, results in severe mental handicap.

(b)

In pregnancy, a woman with PKU must take a strictly low-

phenylalanine diet. Failure to do so results in increased circulating

levels, which cross the placenta and cause irreversible intrauterine

damage, including severe intellectual handicap in

90%, micro-

cephaly in

70% and congenital heart disease, especially tetralogy

of Fallot, in

10% of offspring.

(c)

There is a significant risk of congenital heart defect.

(d)

Assuming the baby does not have homozygous PKU similar to

his/her mother, the risk of which is about 1% if the father’s car-

rier status is unknown, breastfeeding should be encouraged. This

is because the neonate has the metabolic capacity to deal with the

extra phenylalanine load in the mother’s milk.

(e)

Pregnancy complications other than the adverse fetal effects out-

lined above are not more common than expected.

1.34 PSYCHIATRY

(a) In the UK, more women die from suicide than hypertensive

disease of pregnancy.

(b) A women is five times more likely to commit suicide in the first

3 months postpartum than outside pregnancy.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

outside pregnancy.

(d) A woman with a family history of bipolar disease has a one in

three risk of puerperal psychosis.

(e) Puerperal psychosis affects 2 in 10,000 pregnancies.

(f) Most cases

(95%) of puerperal psychosis occur in the first

postnatal month.

(g) A woman with a history of puerperal psychosis has a 10% risk of

recurrence after a future pregnancy.

(h) A woman with puerperal psychosis is more likely to be a profes-

sional or from a higher social class.

Answers

(a) T

(b) T

(d) T

(e) F

(f) F

(g) F

(h) T

Explanation

(a) In the Confidential Enquiry into Maternal Deaths, 2000-02 [2],

60 women died from psychiatric causes and a further 28 women

died from suicide; when the Office of National Statistics data are

linked with childbirths in the preceding year, a further 42 and 32

cases, respectively, were identified. There were 14 hypertensive

deaths in the same survey.

(b) The annual suicide rate is around 3.3 per 100,000 women, but the

rate is five times higher in the postnatal period; if a woman has

puerperal psychosis, her risk of suicide is 3 per 1000, which is

100 times greater than in the nonpregnant female population.

in pregnancy, almost 80% are violent deaths, which is the same as

for male suicide.

(d) A family history of bipolar disease and a family history of

puerperal psychosis are both very strong predictors of puerperal

psychosis. Therefore, such histories should be sought, and appro-

priate management plans put in place.

1. MULTIPLE CHOICE QUESTIONS

(e) Puerperal psychosis affects 2 in 1000 pregnancies. Each unit

should therefore have a robust relationship with their liaison

psychiatrists.

(f) Of the total cases of puerperal psychosis, 50% of cases occur in

the first 7 days after delivery, 75% of cases occur by day 16 and

95% of cases occur by day 90.

(g) If a woman has a history of puerperal psychosis, her risk of

recurrence is 50%. The recurrence risk is also 50% if she has a

history of schizophrenia, bipolar disorder, severe unipolar disorder

or severe postnatal depression.

(h) Typically, women who suffer puerperal psychosis are profes-

sional women, including doctors, teachers, lawyers.

REFERENCES

Duley L, Henderson-Smart DJ, Knight M, King JF. Cochrane

Pregnancy and Childbirth Group Antiplatelet agents for pre-

venting pre-eclampsia and its complications. Cochrane Database

of Systematic Reviews. 3, 2006.

Why Mothers Die 2000-02: Report on Confidential Enquiry into

Maternal Deaths in the United Kingdom, 2004.

Cooper WO et al. Major congenital malformations after first

trimester exposure to ACE inhibitors. New Engl J Med 2006;

354: 2443-51.

Guidelines no55 @ www.sign.ac.uk/guidelines (accessed 13/10/6)

Confidential Enquiry into Maternal and Child Health, Pregnancy

in Women with type 1 and type 2 diabetes, 2002-03 [2005].

Diabetes control and complication trial research group. The

effect of intensive treatment of diabetes on the development of

long-term complications in insulin dependent diabetes. N Engl J

Med 1993; 329: 977-86.

de Veciano M et al. Postprandial versus preprandial glucose

monitoring in women with gestational diabetes mellitus requir-

ing insulin therapy. N Engl J Med 1995; 333: 1237-41.

Weiss PA et al. Long term follow up of infants of mothers with

type 1 diabetes. Evidence for hereditary and nonhereditary trans-

mission of diabetes and precursors. Diabetes Care 2000; 23:

905-11.

Medical eligibility criteria for contraceptive use, 3rd edn (2004).

http://www.who.int (accessed 10/10/06)

10. The British Eclampsia Survey Douglas KA, Redman CW.

Eclampsia in the United Kingdom. Br Med J 1994; 309: 139-400.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

11. Haddow JE et al. Maternal thyroid deficiency during pregnancy

and subsequent neuropsychological development of the child.

N Engl J Med 1999; 341: 549-55.

12. Lazarus J. Guidelines for the Use of Radioiodine in the

Management of Hyperthyroidism: A Summary Prepared by the

Radioiodine Audit Subcommittee of the Royal College of

Physicians on Diabetes and Endocrinology and the Research

Unit of the Royal College of Physicians. J R Coll Physicians Lond

1995; 29: 464-69.

13. Momotani N et al. Maternal hyperthyroidism and congenital

malformation in the offspring. Clin Endocrin 1984; 20: 695-700.

14. Othman S et al. A long term follow up of postpartum thyroiditis.

Clin Endocrinol 1990; 32: 559-64.

15. Lazarus JH et al. Clinical aspects of recurrent postpartum

thyroiditis. Br J Gen Pract 1997; 47: 305-08.

16. Van den Broe NR and Letsky EA. Pregnancy and the erythrocyte

sedimentation rate. Br J Obstet Gynaecol 2001; 108: 1164-7.

17. Kothari A et al. Tuberculosis and pregnancy - results of a study

in a high prevalence area of London. Eur J Obstet Gynaecol and

Repod Biol 2006; 126: 48-55.

18. Making the best use of a Department of Clinical Radiology,

Guidelines for Doctors,

3rd edn. The Royal College of

Radiologists, London; 1995.

Chapter 2

Extended Matching Questions

2.1 HYPERTENSION

The following women have all presented with hypertension in preg-

nancy. Choose the most likely diagnosis from the list below:

(a)

Phaeochromocytoma

(b)

Pregnancy-induced hypertension

(c)

Reflux nephropathy

(d)

Cushing’s syndrome

(e)

Pre-eclampsia

(f)

Conn’s syndrome

(g)

Renal artery stenosis

(h)

Coarctation of the aorta

(i)

Systemic lupus erythematosus (SLE)

(j)

Essential hypertension

At 11 weeks’ gestation, a 34 year old primiparous woman is found

to have a booking blood pressure of 126/74 mmHg and normal

urinalysis. At 39 weeks’ gestation, she is found to have a blood

pressure of 144/96 mmHg; urinalysis shows trace proteinuria and

glycosuria.

At 11 weeks’ gestation, a 22 year old primiparous woman is found to

have a booking blood pressure of 164/102 mmHg and normal uri-

nalysis. Serum creatinine is 66 mol/l and serum potassium is

3.2 mmol/l.

At 11 weeks’ gestation, a 30 year old primiparous woman is found

to have a booking blood pressure of 152/94 mmHg and urinaly-

sis shows 2

protein and 3

blood. Serum creatinine is 159

mol/l and serum potassium is 4.6 mmol/l.

At 11 weeks’ gestation, a 29 year old primiparous woman is found

to have a booking blood pressure of 132/76 mmHg and normal

urinalysis. At 35 weeks’ gestation, she is found to have a blood

pressure of 154/98 mmHg; urinalysis shows 2

proteinuria.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

5. At 11 weeks’ gestation, a 19 year old primiparous woman is found

to have a booking blood pressure of 160/104 mmHg and urinaly-

sis shows 3

protein. Serum creatinine is 132 mol/l and serum

potassium is 4.1 mmol/l.

Answers

(b)

(f)

(i)

(e)

(c)

Explanation

1. New-onset hypertension in the late third trimester in the

absence of significant proteinuria is most likely to be pregnancy-

induced hypertension. In pregnancy, 1

glycosuria is common

and nonpathological.

2. Pre-existing hypertension with co-incident hypokalaemia suggests

an underlying diagnosis of hyperaldosteronism.

3. Pre-existing hypertension with renal impairment and both

haematuria and proteinuria points to a diagnosis of underlying

renal disease. Haematuria would favour a diagnosis of SLE.

4. New-onset hypertension in the third trimester with new-onset

proteinuria is most likely to be pre-eclampsia.

5. Pre-existing hypertension with renal impairment and protein-

uria points to a diagnosis of underlying renal disease. This is

most likely to be because of reflux nephropathy. SLE is also

possible.

2.2 HEART SOUNDS AND MURMURS

The following women are all found to have a heart murmur or added

sound. Choose the most likely auscultatory abnormality from the list

below:

(a) Early diastolic murmur

(b) Mid-systolic click

(d) Pan-systolic murmur

(e) Late-systolic murmur

(f) Third heart sound

(g) Opening snap

2. EXTENDED MATCHING QUESTIONS

(h)

Venous hum

(i)

Mid-diastolic murmur

(j)

Fourth heart sound

A Somalian primiparous woman at 27 weeks’ gestation presents

to an obstetric day assessment unit with orthopnoea.

A multiparous woman on an obstetric high-dependency unit,

who presented with breathlessness 2 weeks after delivery by

Caesarean section. Echocardiogram confirms the diagnosis of

peripartum cardiomyopathy.

A 30 year old primiparous woman with a bioprosthetic aortic-valve

replacement 20 years previously presents with breathlessness at

30 weeks’ gestation.

A 33 year old American is referred at 16 weeks’ gestation with a

history of palpitations. She brings the results of previous inves-

tigations, which include an echocardiogram showing posterior

movement of one mitral valve cusp during systole.

A 20 year old woman with hypertension discovered at booking at

14 weeks’ gestation is found to have radiofemoral delay.

Answers

(i)

(d) or (f)

(a)

(b)

(e)

Explanation

1. Orthopnoea because of pulmonary oedema in an immigrant

with mitral stenosis secondary to rheumatic fever. Pulmonary

oedema has been precipitated by the increased cardiac output

and tachycardia at this gestation. An opening snap might also

be heard.

2. Peripartum cardiomyopathy is a dilated cardiomyopathy leading

to, in this case, mitral regurgitation, causing a pan-systolic murmur

and a gallup rhythm or third heart sound.

3. This is aortic regurgitation because of a failing prosthetic heart

valve.

4. This is mitral valve prolapse.

5. This is coarctation of the aorta that could cause a mid-to-late

systolic murmur.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

2.3 ANAEMIA

The following women have presented with anaemia. Please choose

the most appropriate cause of their anaemia.

(a)

Autoimmune haemolytic anaemia because of SLE

(b) Autoimmune haemolytic anaemia (AIHA) because of methyl-

dopa administration

(c)

HELLP syndrome

(d) Blood loss

(e)

Iron deficiency

(f)

Sickle cell disease

(g)

Coeliac disease

(h) Hereditary spherocytosis

(i)

Alpha thalassaemia trait

(j)

Pernicious anaemia

A 38 year old multiparous woman with hypothyroidism pres-

ents with dyspepsia and shortness of breath on exercise at 30

weeks’ gestation. She has a megaloblastic anaemia and parietal

cell antibodies.

A 24 year old multiparous woman with a 1-year history of

abdominal pain and steatorrhoea is found to have a booking

haemoglobin (Hb) concentration of 9.1 g/dl, high MCV and nor-

mal MCHC. A blood film shows hypersegmented neutrophils.

An 18 year old primiparous woman presents at 23 weeks’ gesta-

tion with a Hb concentration of 9.3 g/dl, low MCV, low MCHC

and platelet count of 540

10⁹ platelets/l.

A 40 year old multiparous woman presents at 33 weeks’ gestation

with hypertension and abdominal pain. She is found to be anaemic,

with a Hb concentration of 8.9 g/dl, normal MCV and normal

MCHC 5 days after admission. A blood film shows spherocytes,

her reticulocyte count is high and a Coombs’ test is positive.

An 18 year old primiparous woman presents at 23 weeks’ gestation

with a Hb concentration of 9.3 g/dl, low MCV, normal MCHC

and platelet count of 234

10⁹ platelets/l.

Answers

( j)

(g)

(d)

(b)

(i)

2. EXTENDED MATCHING QUESTIONS

Explanation

Megaloblastic anaemia because of a failure of absorption of vitamin

B12 and consequent vitamin B12 deficiency because of perni-

cious anaemia. Autoimmune gastritis leads to destruction of pari-

etal cells and lack of intrinsic factor, which is essential for vitamin

B12 absorption. Pernicious anaemia is associated with atrophic

autoimmune hypothyroidism.

Macrocytic normochromic anaemia. Megaloblastic anaemia

because of a failure of absorption of folate due to coeliac disease.

Hypersegmented neutrophils are characteristic in the peripheral

blood in megaloblastic anaemia. Bone marrow aspiration would

show megaloblasts (large erythroblasts with immature nuclei).

This woman has a microcytic hypochromic anaemia, of which the

commonest cause would be iron deficiency. However, the raised

platelet count suggests recent blood loss.

This woman has a normocytic normochromic anaemia. The

presence of spherocytes in the blood film support a diagnosis of

haemolytic anaemia. The direct antiglobulin test (DAT; Coombs’

test) detects autoantibodies on the surface of the red blood cells

and, if positive, indicates an autoimmune haemolytic anaemia. In

hereditary spherocytosis, Coombs’ test is negative and the osmotic

fragility test is positive. Methyldopa is a well-recognised cause of

AIHA and is a common drug choice for treatment of hypertension

in pregnancy.

This woman has a microcytic normochromic anaemia, making an

alpha thalassaemia trait a more likely diagnosis than iron deficiency

(when all the indices are reduced). These individuals are normal-

ly asymptomatic but could become anaemic during pregnancy, in

which case they should receive iron and folate supplements.

2.4

CHEST PAIN

A pregnant woman has “chest pain”. Match the following clinical

scenarios to the diagnoses below:

(a) Pulmonary embolus

(b) Myocardial infarction

(d) Tietze’s syndrome

(e) Rib fracture

(f) Reflux oesophagitis

(g) Angina

(h) Amniotic fluid embolus

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

(i)

Tuberculosis (TB)

(j)

Pneumothorax

A 40 year old woman at term in uncomplicated labour suddenly

becomes dyspnoeic and develops central chest pain before colla-

psing; during the resuscitation, you notice extensive bruising.

A 40 year old woman at term in uncomplicated labour suddenly

becomes dyspnoeic and develops central chest pain before colla-

psing; during the resuscitation, you are told that she has been

hypertensive for several years.

A 40 year old woman at term in uncomplicated labour suddenly

becomes dyspnoeic and develops central chest pain before col-

lapsing; during the resuscitation, you notice that she has Q-waves

in lead III of the electrocardiogram (ECG).

On chest examination, the trachea is central, there is dullness to

percussion and whispering pectoriloquy.

On chest examination, the trachea is deviated to the left and, at the

left apex, there is dullness to percussion and whispering pectoriloquy.

On chest examination, the trachea is deviated to the right and

there is reduced air entry on the left, with hyper-resonance on

percussion.

On chest examination, there is tenderness when the thorax is

compressed.

On chest examination, there is tenderness over the costochondral

margins.

Answers

(h)

(b)

(a)

(c)

(i)

(j)

(e)

(d)

Explanation

1. Amniotic fluid embolus is a rare complication of pregnancy,

typically occurring during otherwise uncomplicated labour. If

fetal squames are found in central blood or maternal sputum, this

supports the diagnosis. Typically, the presentation is sudden

collapse requiring resuscitation; the condition has a high mortality

2. EXTENDED MATCHING QUESTIONS

rate. DIC is a common complication, and could reveal itself as

bruising or bleeding.

Although myocardial infarction is rare in pregnancy, its frequency

is gradually increasing, as more women with risk factors for car-

diovascular disease become pregnant. During pregnancy, the extra

work of the heart increases markedly in the first trimester and then

again in labour. Once the diagnosis has been considered, it can be

confirmed by measuring blood troponin levels, ECG changes and

cardiac enzyme changes, which evolve in the normal way.

Pulmonary embolism is the leading direct cause of maternal

mortality in the UK and should always be considered when a

pregnant woman collapses. The classic ECG changes of an S-wave

in lead I and a Q-wave plus inverted T-wave in lead III of the

ECG are nonspecific and can occur in normal pregnancy.

When examining the respiratory system, the trachea must be

palpated to establish whether it is pulled towards an area of fibrosis

or scarring, or deviated away from a large pneumothorax or pleural

effusion. Asymmetry of chest-wall expansion can also give a clue to

the site of the pathology, in addition to percussion, which will be

dull in consolidation, stony dull in pleural effusion and might be

hyper-resonant in pneumothorax. Air entry might be reduced if

there is a large pneumothorax or effusion. Tactile vocal fremitus

(the ability to feel sounds vibrating through to the chest wall with a

hand laid flat, palm downwards, on the chest) and whispering pec-

toriloquy (whispered sounds heard distinctly through a stethoscope

held over the area of pathology) occur with pneumonia and fibrosis.

These findings are typical of pneumonia.

TB typical affects the apices of the lung and causes fibrosis which

draws the trachea across towards the affected side.

These findings are typical of pneumothorax.

Localized pain on chest wall compression suggests the possibili-

ty of rib fracture.

Tietze’s syndrome is also known as “costochondritis” and results

from inflammation in the cartilage that joins rib to sternum.

2.5 CAUSES OF ADRENAL DYSFUNCTION

From the causes of adrenal dysfunction listed below, choose the most

appropriate diagnosis in the following clinical scenarios:

(a) Addison’s disease

(b) Conn’s syndrome

(d) Adrenal carcinoma

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

(e)

Lymphocytic hypophysitis

(f )

Sheehan’s syndrome

(g)

Phaeochromocytoma

(h) Exogenous steroid therapy adrenal suppression

(i)

Radiotherapy

( j)

Congenital adrenal hyperplasia

A 32 year old women presents to the infertility clinic with a history

of secondary infertility and amenorrhoea. She describes lethargy

and loss of libido. On closer questioning, she admits to symptoms

of depression following failure to breastfeed her first child who was

born by emergency Caesarean section 13 months previously.

A 30 year old primiparous woman attends Day Assessment Unit

(DAU) at 28 weeks’ gestation because she has been experiencing

daily palpitations for

3 months. These are accompanied by

extreme anxiety. Her booking blood pressure at 11 weeks’ gesta-

tion was 138/94 mmHg. She has no family history of hypertension.

Her blood pressure on admission to the DAU is 124/68 mmHg but

during the CTG recording (10 minutes later) her blood pressure is

documented as 158/102 mmHg.

A 23 year old women with brittle asthma complains of dizziness

3 hours after a normal vaginal delivery with minimal blood loss.

You review her on the postnatal ward and find her blood pressure

to be 84/53 mmHg. Her heart rate is 76 bpm, lochia is normal

and her Hb concentration is 11.5 g/dl.

A 36 year old multiparous woman book for antenatal care at 14

weeks’ gestation. You find her blood pressure to be 154/98 mmHg;

she has 3

glycosuria, a body mass index of 38 and you notice

bruises on all four limbs and marked, purple abdominal striae. Her

ACTH level, requested by the endocrine registrar 1 week previ-

ously, is below the normal range for a nonpregnant woman.

A 28 year old women with type 1 diabetes mellitus collapses 12

hours following a ventouse delivery at 39 weeks’ gestation. Her

blood pressure is

88/60 mmHg, her Hb concentration is

13.1 g/dl, serum sodium level is 132 mmol/l, serum potassium is

5.3 mmol/l and blood glucose is 3.3 mmol/l. Following delivery,

her insulin sliding scale was adjusted to half the rate of insulin

compared with labour and was discontinued following breakfast

1 hour before the collapse. She has received no insulin since.

Answers

(f)

(g)

(h)

2. EXTENDED MATCHING QUESTIONS

(d)

(a)

Explanation

Sheehan’s syndrome classically presents as a failure to lactate. It is

caused by pituitary infarction following postpartum haemorrhage.

Subsequent features include a failure to resume menstruation, loss

of secondary sexual characteristics, hypothyroidism (where the

thyroid stimulating hormone

(TSH) is inappropriately low

despite reduced free low fT₄ level) and adrenal insufficiency.

Phaeochromocytoma could present with fluctuating or labile

hypertension, and hypertension might occur in the supine posi-

tion because of the pressure of the gravid uterus on the tumour.

Tachycardia and anxiety are caused by the intermittent secretion

of catecholamines from the tumour.

Endogenous production of corticosteroids from the adrenal

glands is suppressed if exogenous steroids are given in high doses

for prolonged periods of time. This woman with brittle asthma

was receiving prednisolone (30 mg/day) for most of her pregna-

ncy but no supplementary parenteral steroids were given to cover

the stress of her labour, and because she arrived on the post natal

ward at 10 a.m., she has missed the morning drug round. Women

taking oral steroids should be given intravenous hydrocortisone

50 mg 6 hourly from the onset of labour until 24 hours after

delivery.

This woman has typical features of Cushing’s syndrome. This is

more likely to be because of adrenal, rather than pituitary, caus-

es in pregnancy. An adrenal cause is confirmed by the low ACTH

level, which is suppressed because of excess corticosteroid pro-

duction by the adrenal tumour. Pituitary Cushing’s syndrome

would be more likely if the ACTH level was high (although

levels are higher in any case during pregnancy because of placen-

tal production).

Addison’s disease because of autoimmune destruction of the adre-

nal glands is more common in women with type I diabetes. This

woman has collapsed because of mineralocorticoid insufficiency,

which is probably compounded by the relative volume depletion of

labour and delivery. She was on a sliding scale, and was likely to be

receiving intravenous 5% or 10% dextrose solution rather than

saline, further exacerbating sodium depletion. Her blood glucose

level is low, despite receiving no insulin, because insulin require-

ments are reduced with corticosteroid insufficiency. Her blood

glucose is, however, not low enough to explain the collapse.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

2.6 CONNECTIVE TISSUE DISEASE

Consider the following connective tissue disorders and match them

with the most appropriate clinical scenario from the list below:

(a)

Sarcoid

(b) SLE

(c)

APS

(d) Rheumatoid arthritis

(e)

Normal pregnancy

(f)

Sjogren’s syndrome

(g)

(h) Ankylosing spondylitis

(i)

Osteoarthritis

At booking, a 35 year old woman gives a history of haematuria

and proteinuria. She also has a past medical history of photo-

sensitive facial erythema and arthralgia.

A 25 year old pregnant woman presents with dyspnoea. She has a nor-

mal chest X-ray, normal oxygen saturation and raised ACE levels.

At booking a 39 year old gives a history of stiff joints in her

hands, which fluctuates and often completely resolves; she is also

found to have a mild normocytic anaemia.

A 22 year old woman’s first baby is born with a facial rash that

resolves after a few months. The paediatricians question the

mother and discover that she has dry mouth and gritty eyes.

A 40 year old pregnant woman presents with dyspnoea and

painful red eyes; she has a restrictive lung picture, with reduced

transfer factor and granulomata on pleural biopsy.

A 29 year old with a history of bloody diarrhoea and abdominal

pain develops a stiff lower back during pregnancy.

Answers

(b)

(e)

(d)

(f )

(a)

(h)

Explanation

1. This lady has SLE. Butterfly rash and photosensitivity are typical

of SLE, which can manifest as abnormalities in every body system,

2. EXTENDED MATCHING QUESTIONS

and frequently also includes nonspecific symptoms, such as

fatigue and fever. It is nine times more common in women than

men, and is especially prevalent in black women, affecting 1 in 250.

Women with SLE need close surveillance in pregnancy, especially if

their disease is active. Those women with hypertension or renal

involvement have an increased risk of pre-eclampsia; they should

have antiphospholipid antibodies and the extractable nuclear anti-

gens, anti-Ro and anti-La measured (see below), because these

might have a direct bearing on the pregnancy outcome.

These can each be features in a normal pregnancy. The subjective

feeling of dyspnoea is common in pregnancy. Usually, the absence

of any associated clinical features (cardiovascular or respiratory)

and the clear onset of symptoms during the pregnancy should

enable appropriate reassurance. Some groups of women, especial-

ly those recently arrived from overseas, have a higher risk of a vari-

ety of medical problems (including congenital and rheumatic heart

disease and TB) and might warrant a lower threshold for investiga-

tion of dyspnoea in pregnancy. Depending on the clinical scenario,

it might be appropriate to perform a chest X-ray, an ECG, arteri-

al blood gases, etc. Serum ACE levels are helpful in the diagnosis of

sarcoidosis outside pregnancy, but are rarely measured after con-

ception because they are frequently raised in normal pregnancy.

Rheumatoid arthritis most commonly occurs in women aged between

30 and 50 years and follows a relapsing and remitting course.

Typically, the small joints of the hand are painful and stiff, espe-

cially in the morning, and appear warm, tender and swollen. There is

often associated malaise and some extra-articular involvement. Sero-

positivity for rheumatoid factor is found in 70% of these patients.

The facial rash is neonatal cutaneous lupus, which occurs in 5%

of the babies whose mothers are anti-Ro or anti-La positive: 2%

of such women will have a fetus with congenital heart block,

which could manifest in utero as fetal bradycardia, hydrops fetal-

is or intrauterine death. Treatment has limited success, but may

include steroids and plasmapheresis; ultimately, delivery is

required, although the neonate could require long-term pacing.

In both cases, the risk of recurrence in a subsequent pregnancy is

around 16-44%. Anti-Ro and anti-La can occasionally occur in

asymptomatic women. More commonly there is an associated

connective tissue disorder: they occur in 70% of women with

Sjogren’s syndrome and 10% of women with rheumatoid arthri-

tis and SLE. In this case, the diagnosis is Sjogren’s syndrome.

This lady has sarcoidosis. The major causes of granulomata in

lung tissue are TB and sarcoidosis, the former causing cavitating

lesions. The other respiratory findings in sarcoidosis include

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

bihilar lymphadenopathy, widespread ground glass shadowing,

restrictive lung defect and pulmonary hypertension. On lung

function testing, this patient would have a decreased total lung

capacity, reduction in both FEV1 and FVC, and decreased gas

transfer. The latter might be useful for early diagnosis and assess-

ment of progression of diseases of the lung parenchyma, such as

pulmonary fibrosis, asbestosis and sarcoidosis.

6. Ankylosing spondylitis is associated with inflammatory bowel

disease, which is the likely diagnosis here. Although isolated anky-

losing spondylitis is much more common in men than women, this

is not true when it is associated with other conditions. This

woman needs investigation of her gastrointestinal symptoms.

2.7 LIVER DISEASE

From the causes of abnormal liver function tests (LFT) listed below,

choose the most appropriate diagnosis to fit the following clinical sce-

narios:

(a) Acute fatty liver of pregnancy (AFLP)

(b) Obstetric cholestasis (OC)

(d) Acute hepatitis A

(e) Chronic hepatitis B

(f) Dubin-Johnson syndrome

(g) Drug reaction

(h) Acute cholecystitis

(i) Crigler-Najjar syndrome

(j) Liver haematoma

(k) Normal pregnancy

(l) Post-Caesarean section

(m) Primary biliary cirrhosis (PBC)

(n) Nonalcoholic steatohepatitis (NASH)

(o) Gilbert’s syndrome

(p) Haemolysis

(q) Pre-eclampsia

(r) Sclerosing cholangitis

Mrs X is at 35 weeks’ gestation. She presents with RUQ pain, fever,

nausea and malaise. Her blood pressure is 140/90 mmHg and her

urine shows 1

proteinuria.

1. Her temperature is 37.6 C, ALT is 300 iu/ml, WBC is 28

10⁹/l,

urate is 692 mol/l, RBG is 3.6 mmol/l and platelet count is

153

10⁹/l.

2. Her temperature is 39.3 C, ALT is 60 iu/ml, WBC is 21

10⁹/l,

urate is 350 mol/l, RBG is 6.8 mmol/l and platelet count is

221

10⁹/l.

2. EXTENDED MATCHING QUESTIONS

3. Her temperature is 37.2 C, ALT is 60 iu/ml, WBC is 12

10⁹/l,

urate is 400 mol/l, RBG is 5.3 mmol/l and platelet count is 100.

Mrs Y is has not booked and is around 32 weeks’ gestation. She pres-

ents with pruritus, malaise and reduced fetal movements. Her ALT

is 250 iu/ml.

4. Her ultrasound shows a small, fibrotic liver.

5. Her liver ultrasound shows diffuse architectural change, and on

liver biopsy, portal tract infiltration and granulomata are

observed.

6. Her liver ultrasound is normal.

Mrs W has had an upper respiratory tract infection, which was treat-

ed by her GP. She makes a good recovery, and shortly after, attends an

antenatal clinic. At the clinic, she is thought by her midwife to look yel-

low, so LFTs are performed.

7. Her bilirubin is 32 mol/l, ALT is 270 iu/ml and urine dipstick

bilinogen large.

8. Her bilirubin is 10 mol/l, ALT is 23 iu/ml and urine dipstick

small urobilinogen.

9. Her bilirubin is 51 mol/l (unconjugated, 47 mol/l and conju-

gated, 4 mol/l), ALT is 19 iu/ml and urine large urobilinogen.

Mrs Z attends your obstetric medicine clinic with the following:

10. An episode of bloody, painful diarrhoea, and she is found to have

a significantly raised alkaline phosphatase (

1000 iu/l).

11. Type 2 diabetes, obesity and raised gamma-glutamyl transferase

(70 iu/l).

12. Hereditary spherocytosis, and you also find that her bilirubin is

mol/l.

Answers

1. (a)

2. (h)

3. (c)

4. (e)

5. (m)

6. (b)

7. (g)

8. (k)

9. (o)

10. (r)

11. (n)

12. (p)

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Explanation

There is a broad differential diagnosis if abnormal LFTs are encoun-

tered in pregnancy. It is important to remember that the reference

range quoted by the laboratory for transaminases, bilirubin and

gamma-glutamyl transferase are approximately 20% lower and alka-

line phosphatase up to three times greater in pregnancy than outside

pregnancy [1]. After delivery, LFTs return to the nonpregnant range,

but could initially increase substantially in the first few days, espe-

cially if delivery is by Caesarean section [2].

Mrs X represents a typical, and possibly confusing, presentation

in late pregnancy.

AFLP often presents as a nonspecific illness with low-grade

temperature, marked leucocytosis and hyperuricaemia beyond that

which is usually seen in pre-eclampsia. Blood pressure and urinary

protein levels might suggest pre-eclampsia, but the degree of abnor-

mality of the LFTs is usually out of keeping with the apparently mild

pre-eclampsia. Typically, LFTs deteriorate rapidly, so whenever the

diagnosis is considered, LFTs should be repeated after 6 hours.

Unlike other forms of pregnancy-specific liver dysfunction (i.e.

HELLP syndrome, pre-eclampsia obesteric cholestasis and hyper-

emesis gravidarum), liver failure might develop with hypoglycaemia,

because of the inability of the liver to store glycogen, and a coagu-

lopathy, because of impaired hepatic production of clotting factors,

especially factor II (prothrombin), which has the shortest half-life of

all the coagulation factors. AFLP is best treated by prompt delivery.

If there is no obvious and sustained improvement in liver function,

transfer the patient to a hepatic intensive care unit for specialist liver

support and consideration of urgent liver transplantation.

Acute cholecystitis can present at any gestation of pregnancy.

Typically, there is severe right upper quadrant pain, with fever, sys-

temic upset and tenderness, especially on inspiration, in the right

hypochondrium. There could be history of intolerance to fatty foods,

which in pregnancy might be confused with heartburn secondary to

hormone-induced incompetence of the oesophageal sphincter. The

diagnosis is supported by significant fever, bacteraemia, thickening

of the gallbladder wall on ultrasound, usually with gallstone(s), and

a dilated biliary tract. Near-term management is usually supportive,

with analgesia, antibiotics and control of fever. Although cholecys-

tectomy can be carried out in pregnancy, it is best delayed until after

the acute episode, and unless remote from term, until after delivery.

HELLP syndrome typically presents near term or in the early

puerperium with right upper quadrant pain secondary to liver capsule

oedema, pre-eclampsia, which seems mild, and the biochemical

2. EXTENDED MATCHING QUESTIONS

parameters that fulfil the acronym (as described above). The main-

stay of treatment is delivery for the antenatal patient, combined

with supportive management. There is some evidence that steroids

might ameliorate the course of the disease. These can be considered

in unusual cases that continue to deteriorate postpartum [3, 4].

Patients who have not been booked are more likely to have sig-

nificant obstetric and/or medical problems than women who

booked in the first trimester.

This scenario is chronic hepatitis B carriage with cirrhosis. She

needs to have blood taken to assess her e-antigen status and viral

load. Lamivudine might be of value for reducing her chance of pro-

gressing to end-stage liver failure. Her baby needs vaccination

against hepatitis B at delivery and gamma-globulin if she is a high

infectivity carrier. Her partner must have his hepatitis B status

checked. Depending on the likely route of transmission, she needs

to be tested for other viral infections, including hepatitis C and

human immunodeficiency virus (HIV). She needs referral to a

hepatologist.

Primary biliary cirrhosis is 10 times more common in women than

men, and typically presents in the fourth or fifth decade of life with

pruritus and abnormal LFTs, especially a raised alkaline phos-

phatase level. The diagnosis is established by finding antimito-

chondrial antibodies, which should be measured in every pregnant

woman with unexplained itching and elevated liver enzymes. Liver

biopsy, which may be deferred until after delivery, will typically

demonstrate granulomata.

Obstetric cholestasis occurs in around

1 in 160 pregnancies.

Typical symptoms are pruritus, often with general tiredness or

malaise. It is a diagnosis of exclusion. Therefore, in addition to

the normal ultrasound, she needs a viral and autoimmune screen.

Drug reactions are a common cause of abnormal LFTs. Co-amoxiclav

is one of the commonest causes. It is important to identify the

drug responsible and discontinue it: usually the LFTs will then

return to normal range.

This is normal. Clearly, the midwife was mistaken in her concern

about “looking yellow”.

Gilbert’s syndrome is a benign, familial cause of unconjugated

hyperbilirubinaemia, which affects up to 7% of the population. It

is due to reduced levels of the hepatocyte membrane enzyme that

takes up unconjugated bilirubin and conjugates it (thereby ren-

dering it water-soluble). Fasting, intercurrent infection and preg-

nancy can each cause bilirubin levels to increase, and could result

in clinically apparent jaundice. The unconjugated fraction of

bilirubin is over 90% of the total bilirubin, and other LFTs are

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

normal. The reticulocyte count is normal, excluding haemolysis.

The condition is benign and does not usually warrant further

investigation. Treatment is only of the precipitating factor.

10. This patient has inflammatory bowel disease, most likely ulcera-

tive colitis (UC). The raised alkaline phosphatase level is because

of primary sclerosing cholangitis (PSC), a chronic fibrosing liver

disease, with inflammatory destruction of bile ducts. Of people

with sclerosing cholangitis, 75% have UC; 2.5-7.5% people with

ulcerative colitis develop PSC.

11. NASH is common in obese individuals, and might form part of

the spectrum of insulin-resistant conditions or the metabolic syn-

drome. Its presentation is very different from, and it is not relat-

ed to, AFLP.

12. Hereditary spherocytosis is an autosomal dominant cause of

haemolytic anaemia, affecting 1 in 5000 northern Europeans.

Typically, the blood film shows spherocytes and reticulocytes, and

anaemia might also be present. The direct Coombs’ test is nega-

tive, thereby excluding autoimmune haemolysis. Bilirubin is pre-

dominantly unconjugated, and is raised because of the breakdown

of haemoglobin in excess of the liver uptake mechanisms.

REFERENCES

1. Girling JC, Dow E, and Smith JH. Liver function tests in pre-

eclampsia: The importance of comparison with a reference range

derived for normal pregnancy. Br J Obstet Gynaecol 1997; 104:

246-50.

2. David A, Kotecha M, and Girling JC. Factors influencing post-

natal liver function tests. Br J Obstet Gynaecol 2000; 107: 1421-26.

3. Magann EF, Perry KG Jr, Meydrech EF, Harris RL, Chauhan SP,

Martin JN Jr. Postpartum corticosteroids: accelerated recovery

from the syndrome of hemolysis, elevated liver enzymes, and low

platelets

(HELLP). Clinical Trial. Journal Article. American

Journal of Obstetrics & Gynecology 1994; 171: 1154-8.

4. Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin RW,

Martin JN Jr. Antepartum corticosteroids: disease stabilization in

patients with the syndrome of hemolysis, elevated liver enzymes,

and low platelets (HELLP). American Journal of Obstetrics &

Gynecology 1994; 171: 1148-53.

Chapter 3

Short Answer Questions/Data

Interpretation/Clinical Scenarios

3.1 HYPERTENSION AND PROTEINURIA

You are asked to review a 39 year old woman on the antenatal ward. She

is 33 weeks into her first ongoing pregnancy. She suffered a miscarriage

at 9 weeks’ gestation in her first pregnancy 2 years ago. She booked with

a blood pressure of 136/78 mmHg and urinalysis was negative. Her

antenatal course has been uneventful and she had a normal anomaly scan

at 20 weeks. She was admitted from the antenatal clinic 3 days ago

because she was found to have 1

proteinuria and her blood pressure

was 148/96 mmHg. Since admission, her blood pressure has ranged

from 132-154 mmHg systolic and 86-104 mmHg diastolic. She has

received no treatment since admission. Blood tests performed on admis-

sion revealed the following results:

Haemoglobin (Hb): 13.1 g/dl

Platelet:

152

10⁹/l

Creatinine:

mol/l

ALT:

23 iu/l

AlkP:

210 iu/l

Bilirubin:

mol/l

Albumin:

25 g/l

Uric acid:

0.39 mmol/l

The midwife is concerned because the 24-hour urine collection result

has come back as 6.2 g protein/24 hours.

1. What is the diagnosis?

2. What other investigations would you arrange?

3. What treatment would you give?

4. What would you tell the woman?

Answers

1. The diagnosis is pre-eclampsia. This woman has new-onset

hypertension and significant proteinuria. The diagnosis is further

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

supported by relatively high haemoglobin, suggesting haemocon-

centration, uric acid that is above the normal range for 33 weeks’

gestation and serum creatinine that is also higher than expected at

33 weeks’ gestation.

Other appropriate investigations would include an ultrasound scan

of the fetus to assess fetal growth and liquor volume, umbilical

Doppler/regular CTGs to monitor fetal well-being, serial blood

tests to monitor platelet count, renal function and serum albumin,

and liver function tests. At 33 weeks’ gestation, minor abnormalities

in blood chemistry might prompt delivery, for example:

Platelet:

100

10⁹/l

Serum albumin:

20 g/l

ALT/AST:

above the normal range for pregnancy

Creatinine:

100

mol/l

Whether to treat this (moderate) level of hypertension in pregnancy is

controversial. A blood pressure above

170/110 mmHg should

definitely be treated, but there is no evidence that lower levels are

immediately harmful to the mother, and overzealous control of blood

pressure could risk jeopardizing uteroplacental perfusion and the

fetus. Treating blood pressure will reduce the risk of episodes of

severe hypertension that could be harmful or lead to delivery that

would not otherwise be indicated. On balance, begin treatment with

methyldopa, 250 mg three times daily. The Royal College of

Obstetricians and Gynaecologists (RCOG) [1] guidelines also recom-

mend the use of antenatal steroids to induce fetal lung maturation at

gestations of up to 34-36 weeks. Therefore, also prescribe two doses

of betamethasone, 12 mg 12 hours apart. Because of the risks of age

(39 years), nephrotic range proteinuria, pre-eclampsia and relative

immobility in hospital, thromboprophylaxis with thromboembolic

deterrent stockings and low molecular weight heparin (e.g. enoxa-

parin, 40 mg subcutaneously daily) should be commenced.

The woman should be informed of the diagnosis; explain pre-

eclampsia to her. She should be advised to remain in hospital until

delivery and that delivery is likely to be required within the next 2-3

weeks. The rationale for antenatal steroids, thromboprophylaxis and

antihypertensives should be explained and the plan for monitoring

both her and her baby discussed. She should be informed of the

“symptoms” of pre-eclampsia (headache and epigastric pain) and

placental abruption (vaginal bleeding and abdominal pain) and

advised to inform a midwife or doctor if she experiences these or any

reduction in fetal movements. She should be offered counselling

from a neonatologist and a visit to the neonatal unit. She has an

increased risk of delivery by Caesaeran section, so this should be

discussed and an anaesthetic review arranged.

3. DATA INTERPRETATION/CLINICAL SCENARIOS

3.2 HYPERTENSION AND PROTEINURIA

A 24 year old multiparous woman is admitted to the antenatal ward

at 29 weeks’ gestation with a blood pressure of 152/92 mmHg and 4

proteinuria. She is asymptomatic apart from oedema affecting her

fingers, face and legs. An ultrasound scan reveals a normally grown

fetus and normal liquor volume. Her booking blood pressure was

104/68 mmHg and urinalysis at 11 weeks’ gestation was negative.

Blood tests on admission show the following:

Hb:

12.4 g/l

WBC:

5.1

10⁹/l

Platelet:

175

10⁹/l

Uric acid:

0.33 mmol/l

Urea:

4.2 mmol/l

Creatinine:

mol/l

ALT:

23 iu/l

Albumin:

25 g/l

A 24-hour urine collection reveals 6.5 g of protein. She receives two

doses of betamethasone, 12 g intramuscularly and is treated with

methyldopa 500 mg three times daily. After one week, her blood pres-

sure is 130-140/84-96 mmHg. She remains asymptomatic and blood

chemistry results are as follows:

Hb:

11.3 g/l

WBC:

17.2

10⁹/l

Platelet:

140

10⁹/l

Uric acid:

0.35 mmol/l

Urea:

6.4 mmol/l

Creatinine:

mol/l

ALT:

28 iu/l

Albumin:

22 g/l

A repeat 24-hour urine collection shows 13.9 g of protein.

1. What is the likely cause of leucocytosis?

2. Do you think this women needs to be delivered? Explain your

answer.

Answers

1. This patient has new-onset hypertension and proteinuria. The

diagnosis is pre-eclampsia, which is supported by the relative

haemoconcentration, a uric acid level that is high for this gestation,

a falling platelet count and a rising creatinine. Although not

abnormal outside pregnancy, a serum creatinine of 87

mol/l is

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

above the normal limit for the third trimester of pregnancy

(normal, 70-75

mol/l).

The patient has been appropriately admitted to hospital, but

her fetus is well grown, her blood pressure is well controlled on

methyldopa and she is asymptomatic. Leucocytosis is likely to be

due to betamethasone therapy. At this gestation, every effort

should be made to prolong the pregnancy and gain fetal maturity.

Although she has heavy proteinuria, this in itself is not an indica-

tion for delivery. With this degree of proteinuria, she is likely to

become more hypoalbuminaemic.

Conservative management should be continued, with regular

(alternate day) monitoring of blood pressure, platelet count,

serum creatinine and liver function tests, in addition to appropri-

ate monitoring of the fetus. Possible indications for delivery

include the following:

● Platelet:

100

10⁹/l

● Creatinine:

100

mol/l

● ALT/AST:

50 iu/l

● Albumin:

20 g/l

● Symptoms, such as epigastric or right upper quadrant pain, or

severe headache.

● Inability to control the blood pressure with maximal doses of

three antihypertensive drugs.

● Fetal compromise.

In practice, there is no absolute cut-off point for the above blood test

results that is applicable at all gestational ages. The closer to term the

pregnancy, the less abnormal the result that could prompt delivery. In

general, it is a balance between the risks of prematurity, a failed induc-

tion of labour and emergency Caesarean section, or an elective

Caesarean section and the risks to the mother (developing a crisis relat-

ed to pre-eclampsia such as HELLP syndrome, eclampsia, pulmonary

oedema, renal impairment and placental abruption) and the fetus (pla-

cental abruption and intrauterine death) if the pregnancy is continued.

3.3 POSTPARTUM BREATHLESSNESS

You are asked to review a 36 year old Ghanaian woman on the postna-

tal ward. She had her fifth normal delivery 1 day previously and has

complained to the midwives that she feels breathless. She had an

uneventful pregnancy until 20 weeks’ gestation when she required iron

supplements for anaemia. At 36 weeks’ gestation, her blood pressure

was noted to be elevated (155/100 mmHg), having been normal at

3. DATA INTERPRETATION/CLINICAL SCENARIOS

booking (135/85 mmHg). She was treated with methyldopa, 250 mg

three times daily, which was stopped at delivery. She did not develop

proteinuria and pre-eclampsia; bloods were persistently normal. She

developed hypertension in the late third trimester of her last two preg-

nancies but has no significant past medical history of note. On closer

questioning, she denies chest pain, has no cough and tells you the

breathlessness has been getting gradually worse since delivery and that

last night she was very breathless, except when she was breastfeeding

her baby.

On examination, she is obese (her weight at booking was 120 kg) and

apyrexial, with regular monitoring of blood pressure and alternate day

platelet. Her jugular venous pressure (JVP) is not raised, there is no

right ventricular heave, the apex is at the anterior axillary line and she

has a gallup rhythm with a loud systolic murmur. There are bilateral

fine crepitations at the bases of both lung fields. Mild ankle oedema is

present, but no sacral oedema. Abdominal examination reveals a well-

contracted uterus and no organomegaly.

1. What is the likely diagnosis?

2. What investigations would you request?

3. What would you expect these investigations to show?

4. Justify your subsequent management plan.

Answers

1. The breathlessness is most likely to be due to pulmonary oedema.

The history is suggestive of orthopnoea (possibly relieved by sit-

ting up to breastfeed). She is tachycardic and tachypnoeic, and has

bibasal crackles, all of which support a diagnosis of pulmonary

oedema. The differential diagnosis of postpartum pulmonary

oedema includes peripartum cardiomyopathy, which is the most

likely diagnosis. The risk factors in this case are obesity, multipar-

ity and pregnancy-induced hypertension. The findings of an

enlarged heart, systolic murmur (because of mitral and/or tricuspid

regurgitation secondary to ventricular dilation) and gallup rhythm

also support the diagnosis.

There is long differential diagnosis for pulmonary oedema,

including primary valvular causes, such as mitral regurgitation and

mitral stenosis. The latter would cause a mid-diastolic murmur that

might be overlooked in the presence of a tachycardia of 120 bpm.

The other important cause to exclude is iatrogenic fluid overload.

The differential diagnosis of breathlessness postpartum must

include pulmonary embolism, but in the absence of chest pain and

with the above clinical examination findings, this is unlikely.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Appropriate investigations would include the following:

Electrocardiogram (ECG).

Echocardiogram.

Chest X-ray.

Arterial blood gases.

Full blood count (FBC).

Urea and electrolytes.

Serum creatinine.

Liver function tests.

In peripartum cardiomyopathy, the echocardiographic

features

include the following:

Global dilation of all four heart chambers.

Left-ventricular dysfunction.

The absence of any other cause of heart failure.

The diagnostic criteria are as follows:

Left-ventricular ejection fraction of

45%

Fractional shortening of

30%

Left-ventricular end diastolic pressure (LVEDP) of

2.7 cm/m²

The chest X-ray would show cardiomegaly and pulmonary

oedema. The arterial blood gases might show hypoxia. It is impor-

tant to repeat the

“pre-eclampsia bloods” because pulmonary

oedema could be a result of undiagnosed pre-eclampsia and hypoal-

buminaemia, although the history does not suggest this.

Cardiomyopathy with right heart involvement could cause

deranged liver function tests because of “back pressure”, but the

transaminases are likely to be slightly abnormal after a normal

delivery in any case. A FBC should be performed, especially

because of her prior anaemia, grand multiparity and, therefore,

her risk of postpartum haemorrhage, because unrecognised heavy

bleeding at delivery could result in anaemia, which might exacerbate

her dyspnoea and tachycardia.

She should be referred to a cardiologist. Initial management

involves oxygen therapy, if hypoxic, and diuretics to treat the pul-

monary oedema. Because she is postpartum, it is appropriate to

start an angiotensin-converting enzyme (ACE) inhibitor. ACE

inhibitors, although contraindicated in pregnancy, are safe to use in

breastfeeding mothers. Treatment is started at a low dose and

increased gradually if the blood pressure allows. Worsening heart

failure and hypotension are indications for inotropes. Because one of

the greatest risks in peripartum cardiomyopathy relates to throm-

botic events, prophylactic heparin should be started immediately.

Cardiac transplantation might be the only option in severe cases

3. DATA INTERPRETATION/CLINICAL SCENARIOS

that are unresponsive to conventional and full-supportive

management. Most maternal deaths occur close to presentation.

About 50% of patients have spontaneous and full recovery.

The patient should be counselled about contraception and future

pregnancy. The prognosis depends on whether there is normalization

of the left-ventricular size and function within 6 months of delivery.

Mortality is increased in those with persistent left-ventricular dys-

function. Women should be counselled against further pregnancy if

the left-ventricle size and function do not return to normal, because

there is a significant risk of recurrence (40-50%) and mortality (20%)

[2]. The recurrence risk in women whose hearts return to normal size

and function is lower (20%). However, the contractile reserve might

be impaired, even if the left-ventricle size and function are normal.

Subsequent pregnancies require high-risk collaborative care.

Therefore, adequate effective contraception is important in all women

until cardiology follow-up can differentiate the high-risk women

from the moderate-risk women.

3.4 FETAL TACHYCARDIA

You are phoned by a midwife in a community clinic who is seeing a

woman at 28 weeks gestation whose baby has a tachycardia of

180 bpm, measured using a hand-held sonicaid. The midwife tells

you that the woman is taking tablets for a “thyroid problem”.

1. What are the causes of fetal tachycardia?

2. How would decide whether this is fetal thyrotoxicosis?

3. How would you treat fetal thyrotoxicosis?

Answers

Fetal thyrotoxicosis is uncommon. The fetal risk is proportional to the

level of maternal thyrotropin receptor-stimulating antibody. Beyond

20-24 weeks’ gestation, the fetal thyroid can respond to this passively

acquired antibody. Fetal thyrotoxicosis could present with intrauter-

ine death premature delivery, craniosynostosis and impaired intellec-

tual development or any of the features discussed below.

1. Fetal tachycardia should be confirmed on a CTG.

Transient tachycardia might be due to fetal movements and appear

as sustained accelerations on the CTG.

True fetal tachycardia might be due to the following:

● Infection.

● Fetal distress/placental insufficiency.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

● Administration of maternal drugs, such as beta-sympathomimetics.

● Fetal tachyarrythmia, especially supraventricular tachycardia,

possibly associated with cardiac anomaly.

● Fetal thyrotoxicosis.

The features that suggest fetal thyrotoxicosis fall into two cate-

gories. First, the absence of other causes of tachycardia (e.g. no

evidence of maternal infection or chorioamnionitis) and lack of

relevant medication or a normal CTG apart from tachycardia, with

no decelerations and normal variability and no other obvious cause

for placental insufficiency, such as pre-eclampsia or abruptio pla-

centae. Second, there might be specific features in the history or

examination that point to fetal thyrotoxicosis, for example:

● Maternal thyrotoxicosis, either active or previously treated with

radioactive iodine or surgery, such that there might still be cir-

culating thyrotropin receptor-stimulating antibodies.

● Increased fetal movements, intrauterine growth restriction

(IUGR) with oligohydramnios or goitre with polyhydramnios.

● Fetal hydrops points to longstanding tachycardia, but not

specifically to fetal thyrotoxicosis.

The ultimate diagnosis of fetal hyperthyroidism is made by

cordocentesis. This is only justified if there is sufficient clinical

evidence to make the diagnosis likely, but insufficient evidence to

make it certain, and prematurity precludes delivery. There are

well-defined reference ranges for fetal thyroid function against

which the results can be compared. Cordocentesis is more reliable

than amniocentesis for assessing fetal thyroid status.

In this case, which is remote from term, treatment would be

with carbimazole, orally administered to the mother: as it crosses

the placenta it will suppress fetal thyroid activity. The dose is

titrated against fetal tachycardia and movements. If the mother

becomes clinically hypothyroid, she must also take thyroxine,

which does not cross the placenta and so does not affect fetal thyroid

function. Further cordocenteses can be considered, depending on

the response to treatment and the gestational age. At delivery, cord

thyroid function tests should be preformed, and a paediatric review

initiated.

All women with active thyrotoxicosis or a history of Graves’

disease that was treated by radioactive iodine or surgery should

have TSH receptor-stimulating antibodies measured in early

pregnancy. Those with a positive titre should be offered fetal

monitoring after 24 weeks’ gestation, perhaps in the form of

maternal assessment of fetal movements, regular measurement

of fetal heart rate and a growth scan in the third trimester. Cord

3. DATA INTERPRETATION/CLINICAL SCENARIOS

blood should be taken and a paediatric follow-up arranged, espe-

cially if the woman is taking antithyroid medication, which could

have masked the effect of the antibodies in utero.

3.5 ABDOMINAL PAIN AND ANAEMIA

A 27 year old Nigerian woman attends the day assessment unit at

22 weeks’ gestation complaining of abdominal pain. She has not

booked, having returned from a 4 month stay in Nigeria 2 weeks pre-

viously. This is her third pregnancy; she had two uncomplicated

pregnancies 1 year and 3 years ago, respectively, both within the UK,

where she has been resident for 8 years. She tells you that she visited

her local accident and emergency (A E) department 3 days previ-

ously because of the abdominal pain and was told she had a urinary

tract infection and prescribed amoxicillin (amoxycillin). The pain

was no better, prompting her visit to the day assessment unit. While

in Nigeria, she had felt tired and purchased some iron supplements.

On examination, she is apyrexial and her heart rate is 76 bpm; the

uterine size is consistent with the gestational age. She is tender in the

right hypochondrium and has 1

proteinuria. Her blood pressure is

128/76 mmHg. You review her results from the A E department and

notice that her Hb concentration was 9.2 g/dl and MCV was 86 fl. A

urine culture was negative. You repeat the FBC: her Hb concentra-

tion is now

7.8 g/dl WBC and platelet count are normal.

Biochemistry is normal apart from a bilirubin level of 54

mol/l and

a serum albumin level of 19 g/l. You organize an upper abdominal

ultrasound, which reveals a normal liver, gall bladder and pancreas.

There is mild hydronephrosis on the right, a normal kidney on the

left and splenomegaly (16 cm).

1. Discuss the differential diagnosis and your management plan.

Answers

1. This woman has a normocytic anaemia and splenomegaly. The

most likely diagnosis is malaria. Differential diagnoses include

haemolytic anaemia, acute viral infection, portal hypertension and

myeloproliferative disease. The raised bilirubin level suggests

haemolysis; the falling Hb concentration suggests that this is

acute. Investigation should include a peripheral blood smear to

look for malarial parasites.

Peripheral parasitaemia over 2% should be regarded as severe

disease. Other investigations, if malaria is not confirmed, include

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

a blood film, a Coombs’ test for haemolytic anaemia and a retic-

ulocyte count. Leukaemia is unlikely because of the normal

WBC. Pre-eclampsia and HELLP syndrome are unlikely because

of the normal blood pressure, normal platelet count and normal

transaminases. Pre-eclampsia does not cause splenomegaly.

A mild hydronephrosis is normal in pregnancy, but because of

proteinuria, the midstream urine (MSU) should be repeated.

Proteinuria occurs in malaria.

Plasmodium falciparum is responsible for the most severe

disease in malaria. Immigrants from sub-Saharan Africa who

have lived in the UK and return intermittently to Africa are likely

to be nonimmune. Pregnant women, with little or no immunity,

are at increased risk of developing severe disease compared with

nonpregnant women. Maternal and perinatal mortality are

increased. Pregnant women with malaria should be admitted for

treatment because of their increased risk of hypoglycaemia and

severe disease. Treatment depends on the Plasmodium type and

the pattern of drug resistance in Nigerian malaria. Expert advice

should be sought. Quinine is the drug of choice for P. falciparum.

There is a particular risk of severe hypoglycaemia. Oral therapy is

10 mg/kg body weight three times daily for a minimum of 5 days,

until clearance of parasitaemia. Intravenous therapy is 20 mg/kg

body weight over 4 hours, followed by 10 mg/kg body weight over

4 hours three times daily.

If P. falciparum malaria is confirmed, management should

include admission for treatment with intravenous quinine. The

risks from severe disease in pregnancy include hypoglycaemia

(particularly with intravenous quinine treatment), severe anaemia

(this women’s Hb concentration is falling fast), pulmonary oede-

ma (the albumin level is already low), hyperpyrexia and cerebral

malaria. In pregnancy, parasites sequester in the placenta, where

infection might be very heavy. Malaria increases the risk of

second-trimester miscarriage, premature labour and low birth

weight. The Hb concentration and platelet count should be

checked regularly. Blood glucose should be monitored initially

and then every 2 hours when quinine is first commenced. ECG

monitoring is advised during intravenous quinine administration

because it could cause atrial fibrillation, conduction defects and

heart block. A single treatment dose of pyrimethamine-sulfadoxine

is given following parasite clearance. This patient should be

counselled regarding the likely decline in her immunity to malaria

because she is resident in the UK. If she wishes to return to an

endemic area, such as Nigeria, she should take antimalarial

prophylaxis in the same way as any UK resident.

3. DATA INTERPRETATION/CLINICAL SCENARIOS

3.6 ABNORMAL BLOOD GASES

Look at the arterial blood gas result performed at 28 weeks’ gestation

in a woman with dyspnoea, and answer the following questions:

pH:

7.38

HCO₃: 14 mmol/l

pCO₂:

2.7 kPa

pO₂:

14 kPa

1. Interpret the results.

2. Describe the changes that happen to pCO₂ in normal pregnancy.

3. Look at the results below and calculate the anion gap:

Na: 139 mmol/l

4.5 mmol/l

Cr: 120

mol/l

8.7 mmol/l

Cl:

107 mmol/l

4. In the light of the calculated anion gap, give three causes for the

arterial blood gas (ABG) results.

Answers

1. This is a compensated metabolic acidosis: the pH is normal, but the

bicarbonate concentration is low (normal range, 20-22 mmol/l), and

the pCO₂ is low as a compensatory move to maintain neutrality.

2. The pCO₂ falls in normal pregnancy secondary to increased

respiration. The nonpregnant normal range is usually 4.5-6 kPa;

in pregnancy it is typically 3.5-4.5 kPa.

3. The anion gap defines the unmeasurable anions that maintain

electro-neutrality. The calculation is as follows:

[Na K]

[HCO₃

Cl]

(i.e. 143.5

121

22.5)

The normal anion gap is 6-12. Therefore, this acidosis is caused

by an acid other than hydrochloric acid.

4. This is a compensated metabolic acidosis with a raised anion gap.

Three causes to consider are as follows:

a. Diabetic ketoacidosis - check the history for diabetes; test urine

for ketones; measure blood sugar; and treat aggressively with

intravenous rehydration using normal saline and intravenous

insulin and potassium (to lower the glucose level and prevent

hypokalaemia, because insulin carries potassium ions into cells).

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

b. Salicyclate poisoning - check the history for aspirin use or risk

factors for deliberate overdose; and measure the salicyclate level.

c. Lactic acidosis - check the history and clinical examination find-

ings for causes of and features of lactic acidosis (e.g. hypotension

and septic shock; drugs, including metformin and antiretroviral

agents, especially nucleoside reverse transcriptase inhibitors in

highly active antiretroviral therapy (HAART)); and measure lac-

tate levels; treat or remove the underlying cause.

3.7 ABDOMINAL PAIN AND ABNORMAL

LIVER FUNCTION

A woman who is 37 weeks into her first pregnancy complains of

feeling generally unwell for 3 days, with right upper quadrant pain.

She has no other localizing symptoms and has never been ill before.

On examination, she is afebrile and her pulse is 80 bpm and blood

pressure is 140/90 mmHg; there is trace protein on urine dipstick

analysis. These are her initial blood results:

ALT:

150 iu/l

AST:

120 iu/l

Bilirubin:

mol/l

Albumin:

28 g/l

Creatinine:

mol/l

Sodium:

138 mmol/l

Potassium:

4.2 mmol/l

Urea:

3.4 mmol/l

Urate:

0.68 mmol/l

1. List your first three differential diagnoses.

2. List the first three maternal investigations you would order, and

briefly justify each.

3. You repeat the liver function tests 6 hours later. The results are

shown below:

ALT:

786 iu/l

AST:

669 iu/l

Bilirubin: 27

mol/l

Albumin: 27 g/l

What is your provisional diagnosis? Outline your immediate

management.

ANSWERS

(a) HELLP syndrome.

3. DATA INTERPRETATION/CLINICAL SCENARIOS

(b) Acute fatty liver of pregnancy (AFLP).

(a) A FBC with film: a low platelet count would suggest PET or

HELLP syndrome; intravascular haemolysis, as indicated by frag-

mented red blood cells on the film, would suggest HELLP syn-

drome; a raised WBC would suggest a infective cause, but a very

high WBC supports AFLP.

(b) Clotting: abnormal clotting, especially prolonged INR would

support incipient acute liver failure for which there are a large

number of causes, but in this scenario AFLP must be strongly

considered. Prothrombin is the clotting factor with the shortest

half-life and, therefore, is the first to be affected when there is

reduced liver manufacture. Abnormal clotting can also reflect DIC

in association with HELLP syndrome.

impaired ability of the failing liver to release glucose from glycogen

breakdown or to make glucose form other sources, such as lactate

and amino acids. Hypoglycaemia must not be overlooked, because

otherwise it can cause impaired consciousness and even death.

The rapid deterioration in the liver function tests makes AFLP

the most likely, and the most dangerous, diagnosis. Management

is based on the following:

(a) Confirming the diagnosis.

(b) Delivering the baby.

At this point, if not already performed, blood should be taken for a

viral hepatitis screen to include hepatitis A, B and C, cytomegalovirus,

Epstein-Barr virus and human immunodeficiency virus (HIV). The

renal function, glucose, clotting and FBC measurements should be

repeated, and a group and save performed, in case delivery is required

by Caesarean section or a bleeding diathesis ensues. The history

should be checked carefully to ensure no medication, travel, contacts

or past problems have been overlooked, and a thorough examination

repeated, especially checking for signs of chronic liver disease.

AFLP affects 1 in 10,000 pregnancies and has a high case fatality

ratio for both mother and baby. The best way to halt the disease

process is to deliver the baby, which not only helps the maternal

condition, but also removes the baby from a potentially hostile envi-

ronment. Usually, delivery is initially attempted vaginally, and,

pleasingly, induction of labour is often swift. If Caesarean section is

necessary, for fetal or maternal reasons, the major issue of concern is

the potential bleeding problems that can arise from performing

major surgery in someone with incipient liver failure: whenever

possible, a decision to perform Caesarean section should be made

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

sooner rather than later, although in clinical practice this can be very

difficult.

The paediatricians must be alerted to the likely maternal diagnosis

of AFLP: in some cases, maternal AFLP is because of homozygosity

of long-chain hydroxyacyl-Co A dehydrogenase deficiency (LCHAD)

in the baby, the excess unmetabolised fetal fatty acids saturating the

reduced (heterozygous) maternal enzyme level and resulting in acute

liver failure; the baby needs investigation and a special diet devoid of

long-chain fatty acids. Women in this situation have a 25% risk of

recurrence of AFLP if they stay in the same partnership.

Women with AFLP can progress very rapidly to acute liver failure.

They must be nursed very carefully, with hourly observations of all

vital signs, careful observation for bleeding diathesis (e.g. bruising or

bleeding, either spontaneously or from sites of minor trauma, such as

venepuncture) and impaired conscious levels, capillary glucose meas-

urements every 2 hours, and regular liver function tests with clotting

measurements. Venous access should be secured with large-bore can-

nulae, and it is often sensible for a central line to be sited while clot-

ting is still normal, to enable safe delivery of large quantities of 50%

dextrose solution, which can be irritating to small peripheral veins.

Usually, women should be managed on the delivery suite until the

baby is born and then transferred to the most appropriate intensive

care bed afterwards.

A multidisciplinary approach is important, including experienced

obstetricians, anaesthetists, haematologists and hepatologists. If liver

function continues to deteriorate, early contact with the regional liver

transplant centre is vital: they are an invaluable source of advice on

further investigation (e.g. whether other causes of liver failure, such

as paracetamol overdose, Wilson’s disease, alpha 1 antitrypsin defi-

ciency, etc, must be considered) and management, and, if appropri-

ate, can take over care as soon as delivery is expedited. They usually

recommend an infusion of N-acetyl cysteine.

AFLP can be a frightening experience for the woman and her fam-

ily, and so all efforts must be made to ensure that they are fully

informed about what is happening. They will need follow-up, both to

re-explain the events surrounding delivery and to consider future

pregnancies.

3.8 DIABETES

A woman with longstanding diabetes attends your antenatal endocrine

clinic. She is 12 weeks’ pregnant. In her only other pregnancy, 7 years

ago, she had a Caesarean section at 30 weeks’ gestation for severe

3. DATA INTERPRETATION/CLINICAL SCENARIOS

pre-eclampsia; her son weighed 1.4 kg and is now well after a stormy

course in the neonatal intensive care unit (NICU). She has back-

ground retinopathy, renal impairment (nonpregnant creatinine level,

170

mol/l) and hypertension. She has excellent diabetic control,

with a glycosylated haemoglobin (HbA_1c) at the upper limit of normal;

she takes enalapril for hypertension.

1. What baseline tests do you do today; give one rationale for each

test?

2. What is her risk of the following:

(a) Renal deterioration

(b) Developing pre-eclampsia

3. List three ways you might be able to distinguish pre-eclampsia

from a deterioration in renal function.

Answers

The following baseline tests today should be done today:

(a) Blood pressure measurement - uncontrolled hypertension is a

predictor of poor pregnancy outcome, with increased risk of

renal deterioration, IUGR and prematurity.

(b) Antiphospholipid screening - although diabetic renal disease

is a strong risk factor for recurrent severe, early onset pre-

eclampsia, this does not preclude other important causes.

vital, especially as there is a substantial risk of premature delivery.

In addition, an early check for major anomalies is important.

(d) Baseline assessment of renal function - to give accurate advice

regarding outcome of the pregnancy, and as a baseline value.

(e) Baseline measurements of platelet count and liver function -

against which to compare subsequent results if pre-eclampsia

supervenes.

(f) Dilated fundoscopy - if the retinopathy has progressed and

there is now proliferative retinopathy, this needs active treat-

ment to protect visual acuity.

(g) Urine analysis for proteinuria and protein to creatinine ratio -

to characterise renal involvement and acts as a baseline level if

it progresses later in the pregnancy.

Advice regarding risks is based on the fact that she has moderate renal

impairment (i.e. a serum creatinine level between 125

mol/l and 250

mol/l) and hypertension, with previous early onset pre-eclampsia.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

The risks will be approximately as follows:

(a) Renal deterioration:

25%

(b) Pre-eclampsia:

50%

3. The following help to distinguish pre-eclampsia from renal

deterioration:

Falling platelet count in pre-eclampsia.

Abnormal liver function tests in pre-eclampsia.

Rising uric acid level.

Worsening hypertension, increasing proteinuria, deteriorating renal

function and placental insufficiency (IUGR and oligohydramnios)

occur in both diabetic renal disease and pre-eclampsia and cannot be

used to distinguish the two conditions.

3.9 FACIAL WEAKNESS

A pregnant woman presents with recent, sudden-onset, unilateral

facial weakness.

1. What is the differential diagnosis?

2. What aspects of the history and examination help to establish

which of your differential diagnoses are correct?

3. Discuss the symptoms and signs that might be associated with the

most common cause of facial weakness in pregnancy?

4. Outline the treatment options.

Answers

1. This is a VIIth nerve palsy. The differential diagnosis is either an

upper motor neurone lesion (UML) or a lower motor neurone

lesion (LML).

2. In a UML, frontalis and obicularis oris are spared, so that she will

be able to close her eye and furrow her brow. A UML is rarely

isolated, so the history and examination will usually localize other

neurological deficits, especially in the long tracts or other cranial

nerves. A LML causes weakness of all the muscles of the face, so

that eye closure, including blinking, and furrowing of the brow are

lost.

3. Bell’s palsy is the commonest cause of facial weakness in pregnancy.

Outside pregnancy there are 2 in 10,000 cases per year, but it is

more common in pregnancy, presumably because of compression

associated with oedema as the nerve passes through the narrow,

3. DATA INTERPRETATION/CLINICAL SCENARIOS

bony canal of the mastoid process. The following are common and

should be sought:

● Pain in or behind the ear, with or without the typical rash of her-

pes zoster.

● Numbness on the affected side of the face.

● Loss of taste on ipsilateral anterior two-thirds of the tongue.

● Hyperacusis.

Less commonly, Bell’s palsy can be associated with sarcoidosis,

Lyme disease, demyelination or space-occupying lesions.

Treatment should include the following:

(a) Protection of the cornea from particles in the air (because of

the loss of the blink reflex) and from damage by bedclothing

while sleeping: an eye patch is advised until the eye recovers.

(b) Use of articial tears for corneal dryness.

good recovery from 80% to 97%, by reducing the oedema.

Ideally, it is started within 72 hours of onset, although some

improvement has been recorded if the drug is started up to 7

days after onset. The dose is usually 1 mg/kg body weight,

with a maximum dose of 80 mg, for 1 week, and then it is

tapered and stopped during the next 7 days.

(d) Even if there is no clinical evidence of herpes infection, aci-

clovir should be started, 800 mg five times daily for 5 days, as

herpes is thought to be a common aetiological factor in Bell’s

plasy.

It is important to explain that this is not a stroke and reassure the

patient that there is a good chance of full recovery.

The following are useful websites:

http://www.bellspalsy.org.uk website accessed 17/10/06: UK-based

website of the Bell’s Palsy association, with useful information for

sufferers of Bell’s Palsy.

REFERENCES

1. RCOG Green top Guideline no 10A Management of severe

pre-eclampsia/eclampsia March 2006.

2. Elkayam U, Tummala P, Rao K. Maternal and fetal outcomes of

subsequent pregnancies in women with peripartum cardiomy-

opathy. New Engl J Med 2001; 344: 1567-71.

Chapter 4

Essay Questions

4.1 MITRAL VALVE REPLACEMENT

Discuss the management of a 23 year old primiparous woman with

a metal Starr-Edwards mitral valve replacement who is receiving

maintenance therapy with warfarin and who presents at 5 weeks’

gestation.

Model Answer

The optimal management of women with metal heart-valve replace-

ments in pregnancy is controversial because the interests of the

mother and the fetus are in conflict. These women require life-long

anticoagulation and this must be continued in pregnancy because of

the increased risk of thrombosis. Thrombosis could involve the valve

itself or lead to embolic phenomena, including transient ischaemic

attacks and cerebrovascular accidents. Warfarin crosses the placenta

and is associated with warfarin embryopathy if given between 6 weeks’

and 12 weeks’ gestation. The risk of teratogenesis is about 5%.

Warfarin is also associated with an increased risk of miscarriage, still-

birth and fetal intracerebral haemorrhage. There is some evidence

that the adverse fetal effects of warfarin are related to the dose

required to maintain the maternal INR over 2, with doses of warfarin

in excess of 5mg associated with higher risks of teratogenesis, mis-

carriage and stillbirth. Heparin, whether unfractionated heparin

(UH) or low-molecular-weight heparin (LMWH), is associated with

increased risks of valve thrombosis and embolic events, even in full

anticoagulant doses, compared with warfarin. However, because it

does not cross the placenta, there are no adverse effects on the fetus.

The risk of valve thrombosis and embolic events is also related to

both the site and the type of valve prosthesis. Thus, valves in the

mitral position are associated with a higher risk than those in the aor-

tic position. Also, the newer bi-leaflet valves (e.g. Carbomedics) have a

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

lower thrombotic risk than older, first-generation ball-and-cage valves

(e.g. Starr-Edwards) or Bjork-Shiley valves. Other issues that must be

considered are the risk of premature labour and the possibility of

urgent delivery in a mother who is fully warfarinized.

The safest option for this mother is to continue warfarin through-

out pregnancy. This is because she has a thrombogenic valve in the

mitral position. The control of the warfarin therapy should be

extremely tight, avoiding periods of undercoagulation or overcoagula-

tion and maintaining the INR between 2.0 and 3.5. This will necessi-

tate very regular visits to an anticoagulation clinic. Other management

strategies include replacing warfarin with high-dose subcutaneous or

intravenous UH or a subcutaneous LMWH, either from 6-12 weeks’

gestation to avoid warfarin embryopathy or throughout the preg-

nancy. Full-dose intravenous UH is obviously not practical for

prolonged periods, but some pregnancies in women with metal valves

can be managed on full anticoagulant doses of LMWH (e.g. enoxa-

parin, 1 mg/kg body weight/twice daily).

Whichever management option is chosen, warfarin should be

discontinued and substituted with heparin 10 days before delivery to

enable clearance of warfarin from the fetal circulation. For delivery

itself, heparin therapy is decreased or interrupted. Warfarin is recom-

menced 2-3 days postpartum. Heparin can be discontinued once the

INR reaches 2.0 or greater. In the event of bleeding or the need for

urgent delivery in a fully anticoagulated patient, warfarin can be

reversed with fresh frozen plasma (FFP) and vitamin K, and heparin

with protamine sulphate. However, vitamin K should be avoided if

possible because it renders the woman extremely difficult to antico-

agulate with warfarin after delivery. Women with metal valve replace-

ments all require prophylaxis of endocarditis with antibiotics during

delivery, regardless of the mode of delivery.

When this woman presents at 5 weeks’ gestation, she should be

fully counselled about the risks and benefits of the various therapeu-

tic options to both her and her baby. If, despite directive counselling

advising her to continue warfarin throughout pregnancy, she prefers

to replace warfarin with a LMWH, this should be achieved before

6 weeks’ gestation if possible. She should be taught how to self-

administer the heparin injections. Low-dose aspirin

(75 mg/day)

could be added as an extra antithrombotic agent. She should be advised

of the potential risks of all strategies, and if she elects to continue

with warfarin, serial ultrasound scans should be offered because of

the risk of warfarin embryopathy and intracerebral haemorrhage in

the baby. She should be advised to attend hospital immediately if she

goes into labour or develops any new symptoms. If the underlying

need for her mitral valve replacement relates to congenital heart

4. ESSAY QUESTIONS

disease, she should be offered fetal cardiology scanning to exclude

congenital heart disease in the fetus. Postpartum, she should be

reassured that breastfeeding is safe with both heparin and warfarin

therapy. Future contraception should be discussed.

4.2 SICKLE CELL DISEASE

Describe your counselling and antenatal management plan for a

32 year old primiparous women with sickle cell disease who is

12 weeks’ pregnant.

Model Answer

Sickle cell disease is a genetic haemolytic anaemia. There are several

forms of sickle cell disease, of which the most common are sickle cell

anaemia (SS), haemoglobin SC disease and sickle beta-thalassaemia

(S thal) disease. Women with sickle cell disease have an increased risk

of morbidity, both maternal and perinatal, and mortality in preg-

nancy. These risks relate to an increased predisposition to both

pre-eclampsia and growth restriction. There is also an increased risk

of sickle cell crises in pregnancy, which most commonly cause bone

pain. Sickle cell crises can be precipitated by infection, dehydration,

hypoxia, cold and acidosis.

Management should occur in a joint clinic, or in conjunction, with

a haematologist who has expertise in the management of sickle cell

pregnancies and begins with a detailed past medical history. Women

with SS have a chronic haemolytic anaemia, but most are generally

healthy between episodes of crisis, the frequency of which is enor-

mously variable. However, some women have retinopathy, leg ulcers,

renal involvement and previous strokes. Having established the

woman’s baseline health status, explain the increased risk of crises in

pregnancy and the need for her to present to hospital to have these

aggressively managed. Reassure her regarding the safety of opiate

analgesia in pregnancy if it is required to treat sickle cell crises. She

should also be advised to avoid well-known precipitants (cold and

dehydration) and attend hospital to have any intercurrent infection

treated rapidly. She should be offered echocardiography, because

asymptomatic pulmonary hypertension (PHT) occurs in up to 30% of

people with sickle cell disease: PHT has a 30-50% mortality rate in

the puerperium.

The genetics of sickle cell disease should be explained and

electrophoresis recommended for her partner, to ascertain the risk of

her carrying a fetus with SS, SC disease or S thal disease. If she has

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

SS and her partner has a sickle cell trait, the risk of her fetus having

SS is 50%. Prenatal diagnosis with chorionic villus sampling (CVS)

or amniocentesis can be offered.

The obstetric risks of miscarriage, uteroplacental insufficiency

and pre-eclampsia should be explained, in addition to the need for

regular antenatal visits and serial ultrasound scans of the fetus to

monitor growth. Many women with SS are offered elective delivery

at 38 weeks’ gestation to avoid the (small) risk of late intrauterine

death. Therefore, and because of the increased risk of pre-eclampsia

and IUGR, the rate of Caesarean section is increased. Women with

SS and SC disease are also at increased risk of thromboembolic

events and should receive prophylactic LMWH after a Caesarean

section, if admitted with a sickle cell crisis or for any other reason. She

should have an antenatal appointment with an obstetric anaesthetist to

discuss the benefits of regional analgesia for both vaginal delivery and

Caesarean section. In labour, she should have good analgesia and be

well hydrated, usually with intravenous fluids.

All women with sickle cell disease should receive folic acid (5 mg)

throughout pregnancy because they have a haemolytic anaemia and

therefore their folate requirements are high. Because they have under-

gone “autosplenectomy”, they also require prophylactic penicillin,

which should be continued or started in pregnancy.

The role of exchange transfusion for SS in pregnancy is very contro-

versial. There is some evidence that routine exchange transfusion reduces

the risk of sickle cell crises, by reducing the percentage of Haemoglobin

S. However, the risk of transfusion reactions in those who have received

multiple transfusions is high and some say prohibitive. Other strategies

include the use of “top-up” transfusions for severe anaemia only.

If a crisis does occur in pregnancy, it should be managed in

hospital with intravenous fluids and analgesia. A rigorous search for,

and treatment of, underlying infective precipitants is indicated.

When a crisis presents with chest pain, this could represent infection,

infarction or pain related to “sickling” alone, or more commonly a

combination of all three factors.

In summary, this is a high-risk pregnancy and thus advice to the

patient and antenatal care should reflect the need for increased sur-

veillance of both mother and fetus.

4.3 HYPERTHYROIDISM

You are asked to review a 29 year old nurse in the first trimester of

pregnancy, whose blood tests suggest hyperthyroidism. Discuss the

clinical differential diagnosis, prognosis and management options;

explain your rationale.

4. ESSAY QUESTIONS

Model Answer

In broad terms, the differential diagnosis includes deterioration or

relapse of previously diagnosed thyroid disease, newly diagnosed

autoimmune thyrotoxicosis, gestational or biochemical thyrotoxicosis

related to hyperemesis gravidarum, molar pregnancy and other rarer

causes of thyrotoxicosis, including thyroiditis, malignancy, solitary

active nodule and fictitious thyrotoxicosis.

A detailed history and examination should help in reaching the

correct diagnosis. If she has previously had Graves’ disease, she

could be experiencing a relapse. Relapse is not infrequent in the first

trimester, and is thought to reflect the altered maternal immune state:

clinical disease activity follows the titre of thyrotropin receptor- stim-

ulating antibodies, which increases in the first trimester. If she is cur-

rently taking antithyroid medication, relapse could also be because of

impaired absorption secondary to pregnancy-associated vomiting or

inappropriate cessation of tablets

(commonly on the basis of

unfounded concern about teratogenesis). A completely new diagnosis

of autoimmune thyrotoxicosis is uncommon in early pregnancy,

because untreated disease is associated with reduced libido and fertil-

ity. The presence of vomiting and associated symptoms points to

hyperemesis gravidarum (HG), which is the commonest cause of

hyperthyroidism in the first trimester in women who do not give a

prepregnancy history of thyroid disease; rarely, nausea and vomiting

are a dominant feature in autoimmune thyroid disease, and care

should be taken to distinguish the two conditions.

The clinical symptoms and signs of thyrotoxicosis and pregnancy

can be similar, and should be interpreted carefully. Weight loss

despite a good diet, failure of tachycardia to settle with Valsalva

manoeuvre and onycholysis are helpful indicators of active hyperthy-

roidism. Eye signs and pretibial myxoedema do not reflect the activ-

ity of Graves’ disease. Other symptoms and signs of thyrotoxicosis

are not useful clinical discriminators between pregnancy and hyper-

thyroidism: fatigue, anxiety, emotional lability, heat intolerance,

sweating, warm extremities and amenorrhoea are common in both.

Vomiting is occasionally a feature of hyperthyroidism, so care

must be taken to separate it from the more common HG. The pres-

ence of a small goitre is common in pregnancy. But, a large goitre or

a palpable thyroid nodule could point to the diagnoses of multinodu-

lar goitre, toxic nodular adenoma or even thyroid malignancy. In

this case, a thyroid ultrasound might be helpful: cystic lesions in

association with hyperthyroidism make malignancy unlikely.

However, if there are solid nodules, fine-needle aspiration (FNA)

can, and indeed should, be safely employed during pregnancy to

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

exclude malignancy. Radioactive iodine-uptake tests are contraindi-

cated in pregnancy (as discussed later). If the FNA result is benign,

she requires treatment with antithyroid medication in the usual way

(see below). If the FNA result is malignant, she should be offered

surgery. If, however, the report is “cellular”, the management choices

are more difficult because it could still be a malignant nodule: high-

dose thyroxine, to suppress tumour growth, should not be employed

in this woman because she has clinical hyperthyroidism.

The presence of thyroid autoantibodies supports a diagnosis of

autoimmune hyperthyroidism, but is not sufficiently specific to con-

firm it. Similarly, a family history of thyroid disease supports this as

a possible diagnosis.

The prognosis of the hyperthyroidism depends on its cause and

how quickly thyroid dysfunction can be controlled. A number of

observational studies in women with autoimmune thyrotoxicosis sug-

gest that if hyperthyroidism remains poorly controlled, both maternal

and fetal complications, such as thyroid storm, congestive cardiac fail-

ure, hypertensive disease of pregnancy, premature labour, small for

gestational age infants and stillbirth, seem to be increased. The out-

come is worse in pregnancies in which thyroid disease is never con-

trolled, compared with those in which euthyroidism is achieved, but

both of these patient groups have poorer outcomes than pregnancies

in which thyroid disease is controlled before conception [1]. Although

these studies might be flawed with confounding variables, and lack

appropriate control subjects, it seems sensible to achieve control as

soon as possible. If this nurse has a relapse or new diagnosis of hyper-

thyroidism, she should take either carbimazole or propylthiouracil

(PTU). Recent evidence shows that these drugs are equally effective in

pregnancy, without evidence of teratogenicity or fetal hypothy-

roidism, unless large doses are used: older literature, which imply

there are risks of aplasia cutis and high placental transfer with PTU,

but not carbimazole, are now discredited [2,3]. Indeed, depending on

how early in the first trimester this woman is, use of antithyroid med-

ication might reduce her risk of teratogenesis compared with women

who do not become euthyroid during the first trimester [4]. Thyroid

surgery can be performed in pregnancy, although it is usually reserved

for women who have a symptomatic goitre, malignant disease or failed

medical treatment. Radioactive iodine is absolutely contraindicated in

this woman: iodine crosses the placenta and is actively taken up by the

fetal thyroid once it begins functioning at around 8-10 weeks’ gesta-

tion; radioactive iodine irreversibly destroys the fetal thyroid, with

devastating consequences.

Biochemical hyperthyroidism is common in HG and has a good

prognosis. In approximately 40% of women with HG, there is a raised

4. ESSAY QUESTIONS

free thyroxine

(fT₄) level and/or suppressed thyroid-stimulating

hormone (TSH) level, sometimes with a very high fT₄

level

(80 pmol/l). The usual clinical picture of a woman with hyperemesis is

someone who is listless, tired and washed out, which is not a common

scenario in other forms of thyrotoxicosis. There are no goitre, tremor or

eye signs; if present, tachycardia is secondary to dehydration, weight loss

is secondary to poor nutritional intake and warm peripheries is

secondary to the vasodilatation of pregnancy; the symptoms are clearly

of recent onset and do not antedate the pregnancy. If there is clinical

doubt concerning the differential diagnosis of thyroid dysfunction, the

absence of thyroid antiperoxidase, antithyroglobulin autoantibodies and

TSH receptor antibodies supports the diagnosis of hyperemesis.

Treatment of hyperemesis is centred on correcting the metabolic

insults of prolonged vomiting and preventing further vomiting. There

is no place for the use of antithyroid medication in hyperemesis: the thy-

roid abnormality is not usually long lasting. If antithyroid drugs are

used for the treatment of human chorionic gonadotrophin (HCG)-

induced hyperthyroidism [5], they are either ineffective or required in

extremely high doses to achieve biochemical euthyroidism [6] (which

might result in sufficient transplacental passage to cause fetal hypothy-

roidism). Thyroid function tests must be monitored serially, to ensure

that they resolve as hyperemesis settles: clearly, if they do not, alternative

explanations for the abnormality must be sought [7].

As part of the investigations of this nurse, a pelvic ultrasound

examination is invaluable. Both multiple pregnancy and molar preg-

nancy are more likely to be associated with hyperemesis and hyper-

thyroidism. Details of her history, including ethnicity, past obstetric

history, assisted conception and family history, could point to

increased risk of either of these events. In the case of a molar preg-

nancy, the general prognosis clearly depends on the histological

assessment, but is likely to be good, even if she has choriocarcinoma

because it is usually highly responsive to methotrexate-based

chemotherapy. The first line of management involves surgical evacu-

ation of the uterus. Depending on the severity of the symptoms of

hyperthyroidism, she might also need supportive measures, such as

rehydration, antipyretics and beta-blockade. Usually, the symptoms

will regress following surgery.

If the clinical picture is unusual, especially if there is a poor

response to treatment, the possibility of Munchausen’s disease, with

self-administration of large amounts of thyroxine tablets should be

considered. This is a difficult diagnosis to establish, and should be

approached sensitively.

In summary, the most likely differential diagnosis is autoim-

mune thyroid disease or HG, although other less common causes of

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

hyperthyroidism must be considered. Management should be based

on a careful history and examination, probably involving an endocri-

nologist, or a physician or obstetrician with an interest in the medical

problems of pregnancy.

4.4 DIABETES

Explain the points that should be discussed during prepregnancy

counselling of women with diabetes. Which of these do you consider

to be the most important, and why? How can you encourage women

to adopt these measures?

Model Answer

The principles of diabetic management in pregnancy relate to the

effect of the pregnancy on the diabetes and the effect of the diabetes

on the mother and baby.

Pregnancy affects diabetes by increasing the insulin requirement,

accelerating diabetic eye and renal diseases

(usually temporarily,

unless microvascular disease is already advanced), exacerbating

hypertension, increasing the incidence of hypoglycaemia and lower-

ing the threshold at which diabetic ketoacidosis occurs.

Diabetes affects the pregnancy by increasing the likelihood of mis-

carriage, major structural anomaly, pre-eclampsia, prematurity, birth

trauma, Caesarean section, admission to neonatal intensive care and

the so-called “minor problems” of pregnancy, such as thrush, heart-

burn, peripheral oedema, carpal tunnel syndrome and urinary tract

infection [8].

Many of these problems can be minimized by achieving exemplary

diabetic glycaemic control before conception and maintaining this

throughout pregnancy. This is the most important principle in the

management of diabetic pregnancy. If diabetic control is good

at conception, with premeal values less than ~6 mmol/l, 2-hour

postmeal levels less than ~8 mmol/l and glycosylated haemoglobin

(HbA_1c) within the normal range, the outcome for the pregnancy in

relation to miscarriage and structural anomaly is comparable with

the general population, which is 20% and 3%, respectively. However,

if a pregnancy is not planned, and conception occurs when control

is less tight than this, the frequency of these outcomes increases

approximately in relation to the level of control; for example, if

HbA_1c is over 10%, the risks are around 75% and 30-50%, respec-

tively. The cornerstone of management in diabetic pregnancy is,

4. ESSAY QUESTIONS

therefore, preconceptual planning. Target glucose measurements

must be set, and the patient assisted in attaining them by optimizing

her diet, exercising regularly and adjusting her treatment. Women

on oral hypoglycaemic agents might need to add in, or switch to,

insulin. Blood pressure should also be brought under tight control

before conception, either using agents that are safe in pregnancy or

by advising the woman to stop them as soon as a pregnancy test is

positive. If she is taking cholesterol-lowering agents, she must be

advised to stop these before pregnancy. Low-dose aspirin, for pro-

phylaxis against pre-eclampsia, should be discussed so that the

woman knows the rationale and when to commence it. General

health issues pertinent to pregnancy must be discussed, including

smoking, alcohol intake, rubella immunity, haemoglobinopathy

screening, risks of aneuploidy and high-dose folate supplementa-

tion. Women should be given a contact point for accessing the ante-

natal endocrine services as soon as they are pregnant.

One of the major challenges in the care of young women with

diabetes is to know how best to deliver this information to them, in a

format that is acceptable and achievable. There are likely to be many

different solutions, depending on local populations, but in most cases,

preconceptual clinics must be promoted by a broad multidisciplinary

team in a variety of settings and, possibly, in different local languages.

This could include any health professional who comes into contact

with women with diabetes, such as adult and adolescent endocrinology

services, obstetric professionals, primary care teams, pharmacists and

social services. Fundamental to the success of preconceptual care is

contraception, which should be reliable and acceptable, in addition to

quickly reversible when discontinued and safe in relation to diabetes.

4.5 POLYURIA AND POLYDYPSIA

A 34 year old primiparous women presents to the day assessment unit

at 36 weeks’ gestation complaining of excessive thirst and polyuria.

You take a thorough history and establish that she is drinking up to

10 l of water daily. She is also passing vast quantities of urine and

says that she wakes every 1 hour at night to pass urine.

Explain your differential diagnosis and outline what investigations

you would perform.

Model Answer

The differential diagnosis of polyuria includes diuretic therapy,

hyperglycaemia (diabetes mellitus), hypercalcaemia, hypokalaemia

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

and diabetes insipidus (DI). In the absence of hyperglycaemia, the

most likely diagnosis is DI. The incidence DI in pregnancy is

approximately the same as in the nonpregnant female population

(i.e. 1 in 15,000).

DI is caused by a relative deficiency of vasopressin (antidiuretic

hormone [ADH]). There are four types, as follows:

Central - (cranial) due to deficient production of ADH from the pos-

terior pituitary.

Nephrogenic - duetoADH resistance and most commonly associated with

chronic renal disease.

Transient

- due to increased vasopressinase production by the

placenta or decreased vasopressinase breakdown by the liver. This

form of DI is found in association with pre-eclampsia and

HELLP syndrome or acute fatty liver of pregnancy (AFLP), and

regresses after delivery.

Psychogenic - resulting from compulsive drinking of water and con-

sequent polyuria.

Pregnancy could unmask previously subclinical DI. In those with

established DI, there is a tendency to deterioration during pregnancy.

The most likely diagnosis in this case is either unmasking of previous

subclinical cranial DI, transient DI related to pregnancy or compul-

sive drinking of water.

The patient should be admitted to confirm and document the

extent of polyuria and polydypsia. Urea, electrolytes, serum glucose

and calcium should be checked. Paired samples of plasma and urine

should be sent for estimation of osmolality.

The fundamental problem in DI is failure to concentrate the urine

(because of deficient ADH). Confirmation of a diagnosis of DI is

straightforward if the plasma osmolality (

295 mOsm/kg) or serum

sodium (

145 mmol/l) is inappropriately raised in the presence of

polyuria and a low urine osmolality (

300 mOsm/kg). This excludes

compulsive drinking of water. However, often the plasma osmolality

is normal (remembering that in pregnancy the upper limit of normal

falls from about 285 mOsm/kg to 275 mOsm/kg). If fluid intake can

be restricted so that plasma osmolality increases, an inability to con-

centrate the urine confirms a diagnosis of DI. In nonpregnant

women, diagnosis is conventionally with a fluid-deprivation test, in

which the patient is not allowed to drink for 15-22 hours, during

which time serial weights, urine and plasma osmolalities are meas-

ured. Following dehydration and a loss of 3-5% of body weight,

ADH is stimulated and urine concentration occurs in those without

DI and in those with psychogenic DI. In pregnancy, such dehydra-

tion is potentially hazardous and a “short” water deprivation test

4. ESSAY QUESTIONS

(e.g. overnight) might be all that is required to demonstrate an

increasing urine osmolality (

700 mOsmol/kg should be considered

normal) with normal plasma osmolality, and thus exclude cranial and

nephrogenic DI.

To differentiate between cranial and nephrogenic DI, adminis-

tration of a synthetic analogue of vasopressin desmopressin (10-20

intranasally) is used. This will result in concentration of urine in cra-

nial DI, and to a greater extent in patients without DI, but not in those

with nephrogenic DI (who remain polyuric). Desmopressin use is safe

for diagnosis or treatment of DI in pregnancy.

A confirmed or suspected diagnosis of new-onset DI in pregnancy

should prompt a search for pre-eclampsia and AFLP, in particular.

4.6 SYSTEMIC LUPUS ERYTHEMATOSUS

A woman with systemic lupus erythematosus (SLE) comes to see you

for prepregnancy advice. She is taking prednisolone (5 mg/day), ran-

itidine (300 mg/day) for reflux oesophagitis and codydramol for pain.

She is otherwise well. She has never been pregnant.

What advice would you give her?

Model Answer

Advice to a woman with SLE would relate to the effect of the autoim-

mune condition on her pregnancy, both from her and from her baby’s

perspective, the effect of being pregnant on the SLE and the safety of

medication during pregnancy and lactation. It is also important to

cover general issues, including rubella immunity, haemoglobinopathy

status, folate supplementation and smoking cessation.

Establish how the SLE has affected her, in particular whether there

is renal involvement or hypertension, thrombocytopenia or other

haematological problems, neurological problems

(especially psy-

chosis), a history of previous thromboembolic episodes and her

autoantibody profile. Women with SLE have an increased risk of pre-

eclampsia, the magnitude of the risk being determined by the extent of

renal involvement and hypertension. Additional monitoring of blood

pressure, proteinuria and fetal growth, including uterine artery wave-

form assessment should be advised. There is also a place for advising

low-dose aspirin (75 mg daily), which in a recent meta-analysis was

shown to reduce perinatal mortality, in addition to the incidence of pre-

eclampsia. If she has had a major flare of SLE recently, especially a

renal flare, she should be advised to delay pregnancy for 6 months.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

The most important antibodies to consider are those related to the

antiphospholipid syndrome, anticardiolipin and lupus anticoagulant,

and anti-Ro and anti-La. If she has positive antiphospholipid antibod-

ies on two occasions at least 6 weeks apart, she has an increased risk of

first and second trimester miscarriage, intrauterine growth restriction,

pre-eclampsia and later pregnancy loss. In women who have had recur-

rent first trimester loss in association with antiphospholipid antibodies,

the correct management would be low-dose aspirin plus a thrombo-

prophylactic dose of a LMWH. In this woman who has not had any

obstetric disasters (or successes), the role of heparin is less certain, and

the decision should therefore be based on joint discussion with the

woman. Heparin-induced thrombocytopenia is extremely rare with

LMWH, as is the risk of symptomatic vertebral collapse because of

heparin-associated osteopenia (0.04%). Because she is taking pred-

nisolone, she could already be at risk of osteoporosis, and it might be

worth performing a prepregnancy baseline bone densitometry scan

before deciding on the use of heparin.

Anti-Ro and anti-La antibodies have a 2% risk of causing congenital

heart block and a 5% risk of causing neonatal cutaneous lupus. Once

one pregnancy has been affected, the risk in a subsequent pregnancy

rises to 20%. The fetal heart rate should be monitored from 14 weeks’

gestation: heart block is not thought to occur before then, because the

conducting system is not sufficiently developed. Preferably, monitor-

ing should allow assessment of the atrial and ventricular rates, using M-

mode Doppler imaging, which is present on most modern ultrasound

machines used in antenatal departments. If there is a discrepancy

between the atrial and the ventricular rates, or a fetal bradycardia is

detected, referral should be made to a specialist unit. Intrauterine treat-

ment is rarely successful, and early delivery could be indicated. In

severe cases, hydrops fetalis might develop.

Autoimmune conditions can flare in the first trimester and post-

partum, and are often relatively quiescent during the rest of the preg-

nancy. Women should conceive when they are in remission, and not

within 6 months of a renal flare. SLE could deteriorate in the second

half of pregnancy, and this can sometimes present confusion with

pre-eclampsia if hypertension and proteinuria are worsening. In the

postnatal period, women should accept all constructive help at home

and be prepared to adjust their medication if a flare occurs. Flares

can be especially distressing at this time if they involve the hands so

that handling the baby is difficult.

The weight gain of pregnancy might make weight-bearing joints

more painful, although in some women this is counterbalanced by an

increased range of movement, presumably because of hormonally

driven relaxation or softening of tissues surrounding them.

4. ESSAY QUESTIONS

Prednisolone is safe in pregnancy, and the woman must be advised

to continue it. Placental metabolism ensures that very little reaches

the fetus, especially at this low dose [5 mg daily]. There are reassur-

ing data about the lack of teratogenesis: reports suggesting that

steroid do cause teratogenesis were confounded by the underlying

conditions requiring treatment, the use of unconventional steroids

and very diverse, and apparently unrelated, congenital abnormalities.

There are a number of important maternal issues regarding pred-

nisolone use in pregnancy, as follows:

● Steroid-induced hypertension could be confused with pre-eclampsia;

blood pressure should be monitored more closely than normal.

● Steroid-induced glycaemia increases the risk of gestational

diabetes. There should be a lower threshold for looking for diabetes.

● Adrenal suppression means that additional steroids should be given

to cover stressful events, such as labour and delivery, significant

antepartum haemorrhage, etc. This is usually hydrocortisone,

50 mg intravenously four times daily from the onset of the “stress”

until 24 hours after the event is complete.

● Steroids and pregnancy each increase the risk of varicella pneu-

monitis if chickenpox develops. Women taking steroids who do not

know if they have had chickenpox should have their immunity

checked. If they are susceptible, they should avoid cases of chick-

enpox and immediately seek advice regarding the use of varicella

zoster immunoglobulin (VZIG) and/or aciclovir if exposure occurs.

Ranitidine is safe in all trimesters of pregnancy and should be contin-

ued. Indigestion in pregnancy might exacerbate any pre-existing symp-

toms and make interpretation of steroid-induced gastritis difficult.

Codydramol is safe to continue. Constipation in pregnancy might be

worsened by the codeine component. Women should be warned of this,

and might consider a trial of paracetamol alone. She must be warned

against using a nonsteroidal anti-inflammatory drug (NSAID) as an

alternative, because it could cause fetal renal artery vasoconstriction or

premature closure of the patent ductus arteriosus (PDA).

Give her general prepregnancy advice, including folate supplemen-

tation, smoking cessation and reducing alcohol intake in pregnancy. Offer

screening for thalassaemia and sickle cell disease, rubella and diabetes,

and take baseline measurements of renal and liver function and a full

blood count. Depending on her age, issues regarding trisomy 21 should

be discussed. Ensure that a letter summarizing all the issues discussed

is sent to the patient and copied to the other teams involved in her care,

including the rheumatologists and the general practitioner (GP). Give

her a contact telephone number and the opportunity to return if further

queries arise or as soon as she conceives.

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

4.7 DEEP VENOUS THROMBOSIS

You are asked to make a management plan for a woman who is

weeks’ pregnant and has just been diagnosed with a large

iliofemoral deep vein thrombosis (DVT). Discuss your options and

any difficulties you perceive.

Model Answer

Management of acute DVT at term can be challenging, because

labour and delivery increase the risk of further thrombosis, but anti-

coagulation can restrict analgesia and increase the risk of haemor-

rhage and haematoma.

This patient must be fully assessed. Risk factors for thrombosis

must be reviewed (e.g. age, obesity, concurrent medical problems,

family and personal histories, immobility, etc) and minimized where

possible (e.g. maintaining mobility, treating infection and stopping

smoking). The obstetric history must also be reviewed, and any

further obstetric problems that might influence delivery should be

identified; the likelihood of a vaginal delivery should be assessed.

Any previous partograms should be reviewed. Ideally, a Caesarean

section should be avoided because this increases the risk of thrombo-

sis through the attendant pelvic vein trauma, immobility, dehydration

and infection. However, an emergency Caesarean increases these risks

more than an elective Caesarean, the latter also has a potential advan-

tage over the former because there can be a minimal delay in admin-

istration of anticoagulation.

A thrombophilia screen should be carried out, preferably before

the initiation of anticoagulation. Although this might be difficult to

interpret accurately in pregnancy and in the presence of a thrombus,

it is important to attempt to identify high-risk thrombophilic states,

such as antithrombin deficiency, homozygosity for factor V Leiden

and multiple heterozygous states: a family history of thrombosis or

identification of these high-risk states in a first-degree relative is

important. Antithrombin deficiency is the most thrombogenic throm-

bophilic state, and specialized advice for this condition should be

sought from a haematologist. The precise risk will depend on the

antithrombin level and whether the defect is qualitative or quantita-

tive; antithrombin infusions might be required during delivery.

The acute management options include anticoagulation with a

LMWH (e.g. enoxaparin, 1 mg/kg body weight subcutaneously twice

daily), full-length support stockings on both legs and analgesia.

Assessment of fetal well-being with CTG could be indicated; if labour

4. ESSAY QUESTIONS

seems imminent, a cervical assessment must be performed. Warfarin

is absolutely contraindicated because it crosses the placenta and anti-

coagulates the fetus, carrying a risk of fetal haemorrhage; its half-life is

too long to enable safe management of delivery.

The management plan for labour is to stop anticoagulation for the

minimum amount of time possible, maintain hydration (possibly with

an intravenous crystalloid infusion) and keep mobility unrestricted.

Regardless of the mother’s current wishes for regional analgesia, this

option should be kept open, especially in a primiparous woman, so that

unexpected obstetric problems in labour can be managed safely and

without recourse to general anaesthesia, which itself increases immo-

bility and infection, and thus the risk of thrombosis. Women who have

had several deliveries before without regional blockade might feel confi-

dent in their ability to undergo labour without it, but even they cannot

predict unexpected obstetric complications; these women also have an

increased risk of postpartum haemorrhage, which is more easily

managed if anticoagulation has been appropriately suspended. Most

anaesthetists will not insert an epidural within 24 hours of a treatment

dose of a LMWH, which could pose a problem if spontaneous onset of

labour occurs shortly after administration of a dose. Women must be

advised not to inject if they have any sense that labour is starting, but

instead to attend the hospital for an assessment. As a result of this

concern, alternative options might be considered, including changing to

UH, inducing labour or performing a planned Caesarean section. Each

option has distinct pros and cons, as follows:

UH - this drug was the standard treatment in pregnancy before the

development of LMWHs. However, its use is cumbersome because it

requires continuous intravenous infusion in high doses and regular

monitoring to adjust the dose. Full anticoagulation with an activated

partial thromboplastin time (APTT) twice control is often difficult to

achieve. By comparison, LMWH has a standard weight-dependent

dose, with twice-daily self-administration by the patient, and does not

require dose monitoring. However, UH has a shorter half-life so an

epidural can usually be sited within 4 hours of discontinuing the infu-

sion; it is also readily reversed with protamine sulphate if obstetric

haemorrhage or emergency Caesarean are required.

Induction of labour - this offers some control of when labour com-

mences, so that the woman does not enter labour after injecting

heparin. However, if the cervix is unfavourable and prostaglandin (PG)

is required, great care must be taken to ensure that dehydration, immo-

bility and pelvic vein trauma from repeated vaginal assessment are

avoided while induction is taking place. Less than 50% of primiparous

women are likely to deliver within 24 hours of starting a PGE₂ induc-

tion. In a grandmultiparous woman, PGE₂ induction itself poses

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

several maternal and fetal risk factors, including haemorrhage, and so it

is usually avoided. It is unlikely, therefore, that PGE₂ induction would

offer many benefits to this patient. However, there might be a place for

serial cervical assessments and sweeps, which would enable monitoring

of the progress of the cervix and provide an indication of when a simple

ARM, and possibly Syntocinon, induction might be feasible. Ideally,

labour will not occur within the first week, because this is the approxi-

mate time the clot takes to stabilize and the risk of extension or

embolism takes to pass, and therefore it is best not to commence induc-

tion immediately in this patient.

Planned Caesarean section - as already discussed, LSCS is associ-

ated with an increased risk of thrombosis. However, if the likelihood of

a vaginal delivery is estimated to be low, a planned Caesarean section is

likely to be safer than an emergency Caesarean section, and so should

be considered. In this patient, ideally LSCS should be performed at

least 39 weeks’ gestation, to ensure that the clot is as stable as possible,

and LSCS should be avoided while the leg remains clinically painful

and swollen. If elective LSCS is decided on, the evening dose of

LMWH should be omitted; the period of “nil by mouth” should be

kept to the minimum accepted by the anaesthetist and the Caesarean

should be planned for as early in the morning as possible, keeping close

to the 24-hour window. Immobilization should be minimized, both

before and after surgery, close attention should be paid to haemostasis

and prevention of infection, and the treatment dose of LMWH should

be recommenced as soon as safely possible after surgery, usually 3 hours

after removal of the epidural catheter (although this will be longer if

there is an increased risk of haemorrhage).

After delivery, early mobilization and hydration must be encour-

aged. Anticoagulation usually needs to be continued for 6 months

following the event. In the puerperium, the woman can switch to war-

farin if she prefers. Both LMWH and warfarin are safe during lacta-

tion and both are effective at preventing further thrombosis. LMWH

has the advantage of stable dosing and does not require dose monitor-

ing. Warfarin is taken orally, but has a wide therapeutic dose range

that can vary within a patient. Therefore, it is important to monitor the

INR closely, to avoid accidental overdose

(with the risk of

haemorhage) or underdose (with the risk of recurrence). This usually

entails hospital- based blood tests two to three times weekly initially

and then one to two times weekly once the therapeutic window is

achieved. For many women, the initial attraction of an oral medication

is counterbalanced by the possibility of side effects and need for fre-

quent hospital visits while caring for a newborn baby.

Once treatment is complete, it is essential that future care is planned.

Oestrogen-containing contraception must be avoided, as should other

4. ESSAY QUESTIONS

high-risk scenarios, such as prolonged immobility, surgery and long-haul

flights; smoking should be stopped and a weight-reduction programme

started, if required. There should be a low threshold for thrombopro-

phylaxis if a high-risk situation is unavoidable. The thrombophilia screen

should be completed, if not already performed, and a plan for manage-

ment in future pregnancies should be made. If this was a first throm-

boembolic event in a woman with no family history, a negative throm-

bophilia screen and absence of other major and unavoidable risk factors,

the usual advice for a subsequent pregnancy would be to take aspirin

(75 mg/day) from conception and a thromboprophylactic dose of

LMWH (e.g. enoxaparin, 40 mg/day) for 6 weeks from delivery. All other

women must start a thromboprophylactic dose of LMWH as soon as they

know they are pregnant until the baby is 6 weeks old.

4.8 JAUNDICE

What are the most common causes of jaundice in pregnancy? How

would you differentiate them?

Model Answer

Jaundice could be due to a cause co-incidental to the pregnancy or to a

pregnancy-specific condition. Worldwide, the most common cause of

jaundice in pregnancy is acute viral hepatitis. Other relatively common

causes are acute cholecystitis, drug abuse (paracetamol and alcohol),

haemolysis (e.g. sickle cell disease or malaria) and cholestatic jaundice

secondary to drug use (most commonly co-amoxyclav). Pregnancy-

specific causes of jaundice include obstetric cholestasis, AFLP,

HELLP syndrome, pre-eclampsia, in which jaundice is rare before

20 weeks’ gestation, and HG, in which jaundice can occur in the first

half of pregnancy.

The cause of jaundice can usually be established by taking a thor-

ough history, performing a careful examination, ordering appropriate

investigations and then logically piecing it all together.

The gestational age should be established: if the woman is in the

first half of pregnancy, it is much less likely that the jaundice is due

to a pregnancy-specific cause. In the history, pruritus would point

towards obstetric cholestasis or the less common autoimmune condi-

tions of primary biliary cirrhosis or chronic active hepatitis; acute

viral hepatitis and AFLP can also cause pruritus. Epigastric or right

upper quadrant pain occurs in HELLP syndrome, AFLP and

pre-eclampsia, in addition to biliary colic from a wide range of

causes, including acute cholecystitis. Vague symptoms of malaise,

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

flu-like illness and nausea/vomiting are nonspecific and can occur

because of many causes of jaundice. Pale stools and dark urine imply

cholestasis, including OC, viral hepatitis and extrahepatic biliary tract

obstruction. The history might reveal previous episodes of jaundice,

risk factors for liver disease, such as drug use/abuse, including alcohol

and paracetamol, or a family history of liver disease (e.g. haemochro-

matosis, hereditary spherocytosis or Gilbert’s syndrome).

On examination, the patient might be febrile, suggesting a viral hep-

atitis, acute cholecystitis or even AFLP. There may be hypertension and

proteinuria, supporting one of the liver disorders in the spectrum of

hypertensive diseases of pregnancy. Excoriation supports the symptom

of pruritus; hepatomegaly, splenomegaly, ascites, lymphadenopathy and

signs of chronic liver disease must be sought. However, be aware that

spider naevi and palmar erythema are common in pregnancy and usu-

ally reflect the hyperoestrogenic state of pregnancy rather than chronic

liver dysfunction. Intrauterine growth restriction occurs in the hyper-

tensive disorders of pregnancy, but it is not expected with obstetric

cholestasis or other acute illnesses resulting in jaundice.

Liver function tests, including serum albumin, clotting time and bile

salt levels should be performed, in addition to a full blood count and film

(because haemolysis can result in jaundice). In cases where haemolysis

is a possibility, it is helpful to determine whether bilirubin is unconju-

gated (jaundice due to excess breakdown of haemoglobin, e.g. sickle cell

disease, hereditary spherocytosis and HELLP syndrome or reduced

ability to conjugate bilirubin e.g. Gilbert’s syndrome) or conjugated

(jaundice due to intrahepatic or extrahepatic causes). Renal function

incorporating urate and blood glucose must also be measured. These

results alone will not usually confirm a diagnosis, but can point to an

intrahepatic or extrahepatic clinical picture, depending on the relative

elevation of the transaminases, alkaline phosphatase and gamma

glutamyl transferase levels. A prolonged prothrombin time and

hypoglycaemia might suggest acute failure of hepatic synthesis; hypoal-

buminaemia suggests chronic synthetic dysfunction, but also occurs

with heavy proteinuria (e.g. pre-eclampsia). Remember that alkaline

phosphatase increases threefold by the third trimester of normal preg-

nancy because of placental production of a heat-stable isoenzyme. It

might be helpful to ask the laboratory to heat treat the sample to 60 C for

10 minutes and then rerun the assay: the difference between the first and

the second measurements represents the level of liver isoenzyme.

Relatively minor elevations in transaminases can occur in end-stage liver

disease, where there is massive hepatocellular damage and few surviving

hepatocytes. Elevated bile salt levels are a sensitive marker for cholesta-

sis but are not pathognomonic of one particular liver disease, nor are they

an essential diagnostic criterion for any condition.

4. ESSAY QUESTIONS

A viral hepatitis screen for hepatitis A, B and C, and in relevant

areas of the world hepatitis E, in addition to Epstein-Barr virus and

cytomegalovirus, should be requested because this will provide infor-

mation regarding an infective process; human immunodeficiency

virus (HIV) screening should be considered. A liver autoantibody

screen, incorporating antimitochondrial, anti-smooth muscle and

antinuclear cytoplasmic antibodies, should be considered if primary

biliary cirrhosis, autoimmune chronic active hepatitis or sclerosing

cholangitis form part of the differential diagnosis. Liver ultrasound

can be helpful, especially if extrahepatic obstruction is suspected (e.g.

cholelithiasis) or to diagnose features compatible with chronic liver

disease, such as hepatomegaly, splenomegaly, focal lesions, general

parenchymal disease, portal and hepatic vein patency or the presence

of varices, detection of ascites and lymphadenopathy. The presence

of liver steatosis is insufficiently specific or sensitive to clarify the

diagnosis. Liver biopsy might be considered, especially if coagulation

is normal, the diagnosis, and therefore management, is in doubt: this is

particularly true if the woman is preterm and delivery of the fetus is

being considered, because not all conditions will improve postnatally.

A multidisciplinary approach is likely to be needed, either to help

determination of the cause of jaundice or to help ongoing management.

4.9 CHICKEN POX

You are phoned by a GP. He has just seen a woman who is 12 weeks’

pregnant, and whose son has chickenpox. What advice should the

pregnant woman be given, and why? What are the risks of chicken-

pox in pregnancy?

Model Answer

At least 90% of adults born in the UK will be immune to chickenpox.

Among those who are unaware of previous exposure, approaching

90% will also be immune. If, however, she has only recently arrived in

the UK from tropical or subtropical regions, she is much less likely

to be immune (around 50%). The easiest way to establish immunity

is to ask whether she recollects having chickenpox. If she was

brought up in America or Japan, she might have had immunization

against chickenpox as part of the national immunization programme:

she should be asked about this too.

If she has not had chickenpox previously nor been vaccinated against

it, her GP should review her records for evidence of previous testing,

because some hospitals screen pregnant women who are unaware of

exposure for chickenpox immunity. Assuming there is no record of

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

immunity, there are two options. First, if she has had blood taken

recently, for example for her booking blood tests, the laboratory might

have a stored sample that could be tested. If stored serum is not avail-

able, 10 ml of clotted blood should be sent urgently to the laboratory,

marked “urgent, pregnant, close contact with chickenpox - please meas-

ure VZV IgG”. Most laboratories should be able to provide a result

within 24-48 hours if they are aware of the urgency of the sample.

Assuming that an enzyme-linked immunoassay or indirect immunoflu-

orescence test is used, there is a high degree of sensitivity.

In the interim, she should avoid close contact with pregnant

women who have not had chickenpox and neonates. She should also

report immediately if she develops clinical symptoms of chickenpox,

so that aciclovir can be considered (see below). In addition, her son

should see his GP to confirm that his rash is typical of varicella.

If she is not immune to chickenpox, she should have varicella zoster

immunoglobulin (VZIG) as soon as possible, up to 10 days after the first

contact with chickenpox, and only if this is before the rash appears;

VZIG is of no benefit once chickenpox has developed. She should be

asked whether she has had any other recent contact with chickenpox:

for example, does she know where her son contracted chickenpox, and

was she significantly exposed at the same time? This reduces the risk of

chickenpox from a household contact by about 40%. However, only

27% of women remain uninfected: 25% have a subclinical infection,

32% have mild disease, and the remainder have severe disease. There is

also some evidence that VZIG reduces the occurrence and severity of

fetal infection, fetal varicella syndrome and varicella of the newborn.

Other groups of patients who are at increased risk from chickenpox

include those who are immunocompromised (including those taking

immunosuppressive agents, such as steroids and symptomatic HIV-

positive individuals). Her medical history should be reviewed to ensure

she is not at higher risk than usual for pregnancy.

The risks of chickenpox relate to fetal, neonatal and maternal issues.

If chickenpox occurs before 13 weeks’ gestation, the risk of fetal vari-

cella syndrome is 0.4%, and if chickenpox occurs between 13 weeks’ and

20 weeks’ gestation the risk is 2% [9]; occasional cases have been reported

after 20 weeks’ gestation [10], but none beyond 28 weeks’ gestation. The

fetal problems are because of herpes zoster reactivation in utero rather

than fetal chickenpox per se, and occur mostly at less than 20 weeks’ ges-

tation because the fetus lacks the cell-mediated immunity required to

control reactivation until this gestation. The wide range of anomalies is

due to tissue and neuronal damage by secondary reactivation of the virus

in latently infected dorsal root ganglia, and may be external or internal.

Typical features include skin scarring in a dermatomal distribution,

limb hypoplasia, neurological abnormalities

(including bowel and

4. ESSAY QUESTIONS

bladder dysfunction, microcephaly, mental retardation and cortical

atrophy) and eye defects (microphthalmia, cataracts and chorioretinitis)

and reflect the damage to the fetal nervous system. Ultrasound assess-

ment of the fetus might detect polyhydramnios, hyperechogenic bowel,

hyperechogenic foci in the liver or hydrops fetalis, but these will not be

apparent for several weeks after maternal viraemia. Serial scans should

be organized. There is little place for invasive procedures: although

amniocentesis in the first half of pregnancy will detect varicella zoster

virus (VZV) DNA in about 8% cases, less than 50% of these fetuses will

be affected. The incidence of fetal viraemia increases with the length of

gestation, but does not reflect the risk to the fetus, because of the

increasing maturity of its immune system.

Varicella of the newborn (previously referred to as “congenital vari-

cella”) is due to vertical transmission. It is particularly severe if the

mother has chickenpox 7 days before or 2 days after delivery, because

protective maternal antibodies, which could cross the placenta, have

not formed but fetal viraemia is possible. Neonatal mortality may be as

high as 30%. Neonatal infection occurs in about 60% of babies whose

mothers are infected in the 28 days before delivery, but is more likely to

be subclinical if maternal infection occurs further from delivery

(because of the ameliorating effect of maternal antibodies). Herpes

zoster could occur in the first few months of life in babies whose

mothers have chickenpox during pregnancy, but this is usually benign.

Chickenpox in adults can be more severe than in children, and

there is some evidence that chickenpox in pregnancy increases the

risk of complications further, especially in the later stages of preg-

nancy. Pneumonitis occurs in about 8% of pregnant women: she

should be warned to report early if the symptoms of pneumonitis,

including cough, tachypnoea, dyspnoea, haemoptysis and chest pain,

occur, especially if she is at increased risk because of smoking or

chronic lung disease. Other complications of chickenpox include sec-

ondary skin sepsis, hepatitis, haemorrhagic rash and encephalitis;

mortality is estimated at 1-2%.

Aciclovir is thought to reduce the severity and duration of chick-

enpox in the pregnant woman, but only if it is given within 24 hours

of the onset of the rash: she must be told to make immediate contact

if chickenpox occurs and provided with details of who to contact at

weekends and where to attend. Aciclovir is now believed to be safe in

pregnancy. The aciclovir registry for reporting use of this drug in

pregnancy closed in 1998, after almost 1300 cases were reported,

with no evidence of adverse fetal effects. It is recommended that oral

aciclovir (800 mg five times daily) is taken for 7 days by women who

present within 24 hours of the onset of the rash and are beyond 20

weeks’ gestation. In women who are less than 20 weeks’ gestation, as

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

this woman is, aciclovir should be offered rather than recommended,

because of theoretical concerns relating to teratogenesis.

Intravenous aciclovir (10 mg/kg body weight three times daily)

should be used if varicella pneumonitis develops or there is evidence

of disease progression, such as continued cropping of the rash

beyond day 6, reappearance of fever after day 6, thrombocytopenia,

hepatitis or skin sepsis. If she does develop chickenpox, she should

be assessed every 24-48 hours to ensure that any early signs of com-

plications are detected.

REFERENCES

Millar LK et al. Low birth weight and pre-eclampsia in preg-

nancies complicated by hyperthyroidism. Obstet Gynecol 1994;

84: 946-9.

Momotani N et al. Effects of Propylthiouracil and methimazole

on fetal thyroid status in mothers with Graves’ hyperthyroidism.

J Clin Endocrin Metab 1997; 82: 3633-6.

Wing DA et al. A comparison of Propylthiouracil versus methi-

mazole in the treatment of hyperthyroidism in pregnancy. Am J

Obstet Gynecol 1994; 170: 90-5.

Momotani N et al. Maternal hyperthyroidism and congenital

malformation in the offspring. Clin Endocrin 1984; 20: 695-700.

Hershman JM. Role of human chorionic gonadotropin as a thy-

roid stimulator. J Clin Endo Metab 1992; 74: 258-9.

Chowdhury TA et al. A toxic testicle. Lancet 2000; 355: 2046.

Rodien P et al. Familial gestational hyperthyroidism caused by a

mutant thyrotropin receptor hypersensitive to human chorionic

gonadotropin. New Engl J Med 1998; 339: 1823-6.

Confidential Enquiry into Maternal And Child Health

(CEMACH). Type 1 and type 2 diabetes in pregnancy, 2005.

Enders G, Miller E, Cradock-Watson J et al. Consequences of

varicella and herpes zoster in pregnancy: a prospective study of

1739 pregnancies. Lancet 1994; 343: 1548-51.

10.

Drugs and Therapeutics Bulletin, ‘Chickenpox, pregnancy and

the newborn’ September 2005.

Chapter 5

Case Studies

5.1 SICKLE CELL DISEASE

Ms A was a 28 year old woman in her second pregnancy (she had one

previous termination of pregnancy) who booked-in at 19 weeks’ ges-

tation. She was known to have sickle cell disease (specifically sickle cell

anaemia [HbSS]), and her last crisis had occurred 3 years before this

pregnancy.

Her booking bloods were unremarkable. Her blood pressure and

haemoglobin (Hb) concentration were recorded as 90/60 mmHg and

8.1 g/dl, respectively, with an mean cell volume (MCV) of 87 fL.

At this visit, she was commenced on penicillin (250 mg/day), folate

(5 mg/day) and 4-weekly growth scans were organized.

Her first admission to hospital was a month later (at 23 weeks’ ges-

tation), when she was admitted for 6 days with a crisis (pain in her

back), which was possibly precipitated by a urinary tract infection.

She was initially treated with intravenous cefuroxime and thereafter

with oral clarithromycin. She received a 3-unit blood transfusion,

which co-incided with a symptomatic improvement.

Her second admission (for 12 days) occurred 2 weeks later (at

25 weeks’ gestation); again, she was treated for a crisis. She required

another 3-unit blood transfusion because her Hb concentration had

fallen to 6.8 g/dl. She required an opiate patient-controlled analgesia

(PCA) and was treated with intravenous fluids, cefuroxime, metron-

idazole and flucloxacillin.

During her third admission (at 30 weeks’ gestation for 7 days),

when she had chest pain and blood-stained sputum, she was treated

with intravenous antibiotics and a therapeutic dose (1 mg/kg body

weight/twice daily) of enoxaparin (until a ventilation/perfusion [V/Q]

lung scan was negative). Her blood cultures and sputum were nega-

tive and a further 2-unit transfusion was required.

Her fourth admission occurred within days of discharge from the

hospital. Her symptoms included worsening chest pain and shortness

of breath. On examination, there were crepitations and dullness

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

in the base of the right lung. She was treated with further intravenous

antibiotics for presumptive community-acquired pneumonia, but she

also had another inconclusive V/Q lung scan and was thus recom-

menced on a therapeutic dose of enoxaparin. She was discharged at

33 weeks’ gestation with oral antibiotics (clarithromycin, flucloxacillin,

cephadroxil and nystatin) and enoxaparin.

In total, she had seven ultrasound scans, which showed a small

baby (growth on the third centile), with normal liquor volume and

umbilical Doppler scan.

At 38 weeks’ gestation, she underwent induction of labour and

received two doses of vaginal prostaglandin. However, fetal distress

necessitated a Caesarean section under general anaesthetic. She deliv-

ered a 2.72 kg baby, with a pH of 7.22 and Apgar score of 5 and 9 at

1 minute and 5 minutes, respectively.

Discussion

Sickle cell disease results when there is a variant of the beta-globin

chain (a one amino-acid substitution of valine with glutamine). In

times of crises, which can be precipitated by a number of factors (e.g.

hypoxia, infection, cold, acidosis and dehydration), the red cell takes

on a characteristic, distorted shape. Because of this rigidity, it tends

to block small vessels, producing vaso-occlusive symptoms (pain) and

even infarction.

This patient last had a crisis 3 years before this pregnancy, but

during this pregnancy she developed three crises. This reflects the

increased complication rate and increased tendency to crises in

women with sickle cell disease who fall pregnant. They suffer from

chronic anaemia (Ms A’s booking Hb concentration was 8.1 g/dl),

because of chronic haemolysis, which is often asymptomatic. This is

because of the low affinity of sickle Hb (HbS) for oxygen, which

facilitates oxygen delivery to the tissues.

The possible effects of sickle cell disease on the pregnancy were

also reflected by the small, growth-restricted baby who could not

tolerate the stress of labour. This necessitated a Caesarean section.

Unexplained stillbirth is not uncommon in these patients because of

both impaired oxygen supply and sickling infarcts in the placental

circulation. Therefore, it is the unit policy to offer induction to all

women with sickle cell disease at 38 weeks’ gestation.

This pregnancy was complicated by frequent admissions with

crises and chest infections. It is often difficult to distinguish between

pneumonia, sickle chest syndrome and pulmonary embolism because

these conditions share similar signs and symptoms (tachypnoea,

pleuritic chest pain and leucocytosis) [1]. Early recourse to antibiotics

5. CASE STUDIES

and rehydration is important to prevent further morbidity and mor-

tality because most deaths are due to massive sickling following an

infection, which leads to a pulmonary embolism [2].

Ms A received three blood transfusions during this pregnancy.

Letsky [2] reported that the only consistently successful way to

reduce the incidence of complications from sickling is regular blood

transfusion at approximately 6-weekly intervals. This aims to dilute the

existing HbS, and by raising the Hb concentration, thus reduce the

stimulus to the bone marrow to produce more defective cells. This

policy does, however, expose the patient to the risks of multiple trans-

fusions (i.e. alloimmunization and infection) and it does not have uni-

versal acceptance.

At present, there is no effective long-term method of reducing the

lability of red cells in vivo. There is no evidence to support the use of

alkalis, hyperbaric oxygen, vasodilators, plasma expanders or antico-

agulation once the crisis is established. The best approach is meticu-

lous care and supportive therapy with adequate fluids, analgesia and

treatment of possible infection. Prophylactic antibiotics (e.g. peni-

cillin) are used because patients with sickle cell disease often have a

nonfunctioning spleen and penicillin affords protection against pneu-

mococcal septicaemia.

5.2 HYPONATRAEMIA

Ms B was a 29 year old primigravid who booked-in at 16 weeks’ ges-

tation. Her booking bloods were unremarkable. Her blood pressure

and Hb concentration were recorded as 100/60 mmHg and 11.2 g/dl,

respectively.

She had seven uneventful antenatal visits throughout which she had

a normal blood pressure and no abnormalities were found in her urine.

She self-presented at term in spontaneous labour, and in the ensu-

ing 48 hours, despite a prolonged latent phase, she delivered a 3.54 kg

infant with Apgar scores of 8 and 9 at 1 and 5 mins respectively. This

was facilitated by an instrumental delivery in theatre. She required an

epidural and Syntocinon for the last 12 hours of her labour. The

Syntocinon was infused (as per protocol) at an increasing rate of

1 mu/min and titrated to her contractions.

It was noted that she had only passed 70 ml of urine 5 hours after

the insertion of the epidural and urinary catheter, despite receiving

1500 ml of intravenous and oral fluids. The catheter was flushed and

a 500 ml fluid challenge was given. Her vital signs were stable. After

2 hours (at 7.30 a.m.), a baseline renal function test was performed

(Table 5.1).

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

TABLE 5.1. Serial urea and electrolytes

Time

7.30 a.m.

12.30 p.m.

8.10 p.m.

5.30 a.m.

Sodium, mmol/l

124

121

131

140

Creatinine, mol/l

131

110

Urea, mmol/l

4.7

5.4

5.7

4.6

Serum osmolality

262

Bicarbonate, mmol/l

Because of continuing oliguria, a further fluid challenge was admin-

istered at 10.30 a.m. Her serum osmolality was 262 mOsm/kg (normal

range, 275-285 mOsm/kg) and her urine osmolality was 338 mOsm/kg.

Further blood testing performed before ventouse delivery (at 12.30

p.m.) showed worsening renal function and hyponatraemia (Table 5.1).

With a presumptive diagnosis of “water intoxication” secondary to

Syntocinon administration, Ms B received treatment postoperatively

with fluid restriction (500 ml/12 hours). In the following 8 hours, a

massive diuresis occurred (6.5 l). By 17 hours postdelivery, her renal

function had significantly improved (Table 1) and she was discharged

home a day later.

Discussion

Hyponatraemia is the commonest electrolyte disturbance seen in a

general hospital population, occurring in

1% of all patients. It

is defined as a decrease in serum sodium concentration below the nor-

mal range (136-145 mmol/l), usually indicative of hypo-osmolality of

body fluid due to an excess of water relative to solute.

It has two principle causes, as follows:

1. Sodium depletion in excess of water or replacement of sodium

losses with water alone, for example in gastrointestinal and third-

space losses, sweating and dialysis/renal failure.

2. Dilutional hyponatraemia occurs if the water intake is in excess of

its output and usually implies impaired excretion. This occurs in

cases ranging from inappropriate secretion of antidiuretic hor-

mone (ADH) to those resulting from neuroendocrine, adrenal or

pituitary insufficiency.

The causes of the syndrome of inappropriate secretion of ADH

(SIADH) can broadly be divided into those secondary to malignancy

(tumours of the lung, pancreas or duodenum), central nervous system

disorders (meningitis, head injury or haemorrhage), chest disease

(tuberculosis or pneumonia) or metabolic disease (porphyria).

5. CASE STUDIES

101

Well-known complications of oxytocin include overstimulation of

the myometrium, resulting in tetanic contractions, fetal hypoxia or

occasionally uterine rupture. A lesser-known side effect is that it has

an ADH-like effect, leading to suppression of diuresis and features

including concentrated urine, hyponatraemia and low plasma osmo-

lality with no apparent dehydration or oedema. “Water intoxication”,

as it was called, was first reported in 1962 by Liggins [3]. This com-

plication occurred in women receiving large doses of oxytocin, most

commonly in those having midtrimester termination of pregnancy or

the induction of premature labour associated with fetal death in

utero. It usually involved large amounts of oxytocin in electrolyte-

free solutions administered over an extended time period, which

resulted in severe electrolyte derangements, convulsions, coma and

even death [4].

The pathogenesis involves progressive hyponatraemia and fluid

shifts from the extravascular to the intravascular compartment, with

resultant cerebral oedema. Transplacental passage can occur with

similar derangements in neonatal biochemistry [5]. Convulsions are

unlikely unless the fluid input exceeds output by

3 l in 24 hours,

and are, therefore, uncommon following oxytocin-induced labour

at term.

This patient, however, was given low doses of Syntocinon

(1 mu/min and then 2 mu/min) over a moderate time period (7 hours).

Even allowing for the small incremental dosage increases that

occurred with the step-up Syntocinon regimen, a low total dose of

oxytocin was infused. In retrospect, the two fluid challenges she

received probably exacerbated hyponatraemia.

Current labour ward protocols limit the use of oxytocin in terms

of concentration, duration of administration and type of additional

fluids. Stratton et al. [6] showed that patients who received co-infusions

of dextrose solution had significantly lower sodium levels compared

with patients who received electrolyte infusions

(normal saline).

Most units use Hartmann’s solution or normal saline for oxytocin

administration.

Correct use of the partogram limits the duration of the active

phase of labour; thus, rarely do patients “labour” for

24 hours in

hospital, minimizing oxytocin infusion times and risks.

A literature review using Medline revealed a predominance of

cases in the early 1970s and 1980s, with a paucity of new reports, sug-

gesting that water intoxication secondary to oxytocin administration

rarely occurs nowadays. However, clinicians should remain vigilant

to the possibility.

The primary treatment is recognition of the underlying cause (stopping

oxytocin) and thereafter restricting intake to 1000-1500 ml/ 24 hours.

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

This might seem an illogical step because of oliguria, but if the

diagnosis is correct, it will result in rapid improvement. Similar to

pre-eclampsia, the use of repeated blind fluid challenges should be

avoided in the labouring or postpartum patient unless volume deple-

tion or blood loss is suspected.

5.3 ISCHAEMIC HEART DISEASE

Ms C was a 32 year old caucasian woman. She was para 0

1, having

had a fetal loss at 23 weeks’ gestation 1 year previously. She attended

the obstetric medicine clinic at 7 weeks’ gestation, having been referred

by her general practitioner (GP).

In her past medical history, she had had a myocardial infarction

with coronary artery stenting aged 27, with ongoing angina, hyper-

cholesterolaemia, hypertension, asthma, oesophageal reflux and chronic

back pain.

She had conceived while taking aspirin, isosorbide mononitrate,

glyceryl trinitrate (GTN) spray, ramipril, simvastatin, montelukast,

omeprazole, codeine phosphate, diazepam, and beclomethasone and

salbutamol inhalers.

She was a current smoker of 40 cigarettes/day and was homeless

and living in a hostel. During investigation of the previous intrauter-

ine death, raised anticardiolipin antibodies were detected on two

occasions

8 weeks apart. She had an initial booking ultrasound that

showed a twin pregnancy.

There was a long discussion regarding her medication, and after

appropriate counselling, she was advised to stop simvastatin,

ramipril and omeprazole and to reduce codeine phosphate and

diazepam as much as possible. She was also referred to a smoking

cessation clinic. Her angiotensin-converting enzyme

(ACE)

inhibitor was changed to methyldopa and omeprazole was changed

to ranitidine. She was commenced on enoxaparin (40 mg once

daily) and folic acid

(5 mg/day), which was to be continued

throughout the pregnancy. She was understandably very anxious

regarding the pregnancy.

She returned for her booking appointment at 10 weeks’ gestation.

A repeat scan showed no fetal heart in one twin. Booking bloods were

taken, plus urea, electrolytes and urate measurements, which were

normal. Repeat anticardiolipin antibodies remained elevated.

A management plan was made for the pregnancy. She was to be

seen in the obstetric medicine clinic once per fortnight for blood

pressure measurement and urinalysis, and monitoring of her angina

symptoms, which she was at times reluctant to admit to. She was

offered serum screening at 16 weeks’ gestation.

5. CASE STUDIES

103

At her request she was commenced on high-dose vitamin C

(1 g/day) and vitamin E (400 iu/day) [7]. A fetal anomaly scan was

organized at

18 weeks’ gestation, with maternal uterine artery

Doppler estimation. Growth scans were planned from 24 weeks’ ges-

tation and delivery was planned by elective Caesarean section at

38-39 weeks’ gestation.

The pregnancy progressed uneventfully until 20 weeks’ gestation.

The fetal anomaly scan showed no anomalies in the fetus but there

was bilateral notching on the uterine artery Doppler scan. She man-

aged to cut down smoking to two to three cigarettes/day and the

social work department was involved regarding her housing situation.

She became increasingly stressed and complained of increasing

angina. Her isosorbide mononitrate was increased. Her anxiety grew

further around the time of her previous loss.

Growth scans estimated that the baby was growing between the

5th and the 50th centiles.

The woman complained of further episodes of angina, even on

minimal exertion and despite using her GTN spray. Her isosorbide

mononitrate was further increased. An echocardiogram was performed

at 36 weeks’ gestation. This showed a normal ejection fraction, with

good systolic function. An electrocardiogram (ECG) was normal. She

was reviewed by the obstetric anaesthetic team.

The planned elective Caesarean section was carried out at

38 weeks’

gestation.

Her low-molecular-weight heparin (LMWH) was stopped on the

day before the planned surgery. A combined spinal epidural was used

for analgesia and the Caesarean section was uncomplicated, with

400 ml blood loss. She delivered a live male infant, with a birth

weight of 2.95 kg.

Ms C recovered well from the Caesarean section and wished to

breastfeed. Unfortunately, varying advice was given over the safety of

her medication in breastfeeding. Breastfeeding did not establish eas-

ily and she bottle fed her son from 6 days of age. She continued on

enoxaparin (40 mg once daily) for 6 weeks postpartum. Her ACE

inhibitor and statin were restarted. At 6 weeks postpartum, both

mother and baby were well. She was considering a Mirena intrauter-

ine system (IUS) for future contraception, although she was not

currently with her partner. She was counselled regarding the risks of

a further pregnancy.

Discussion

This was a high-risk pregnancy in a woman with extensive medical

and social problems. She had significant risk factors and ischaemic

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

heart disease, with ongoing symptoms, despite her young age. It was

felt that her previous myocardial infarction was due to ischaemic

heart disease in the presence of underlying risk factors of hypercho-

lesterolaemia, hypertension and smoking rather than because of arte-

rial thrombosis from her antiphospholipid antibody syndrome

(APS). APS (late fetal loss in the presence of raised anticardiolipin

antibodies) also posed risks to the pregnancy, which could be reduced

by LMWH and low-dose aspirin. She conceived while receiving a

large number of drugs, for which there are minimal data on use in

pregnancy and breastfeeding.

There is very little literature on women with ischaemic heart

disease in pregnancy because until recently this was rare in women of

childbearing age [8,9].

The continued use of ACE inhibitors in pregnancy has been asso-

ciated with foetotoxicity (fetal renal failure and renal dysgenesis,

hypotension, oligohydramnios, pulmonary hypoplasia and hypocal-

varia). The risks are greatest during the second and third trimester

[10]. Women should change to an alternative antihypertensive pre

pregnancy. ACE inhibitors are safe to use while breastfeeding, but as

this case illustrates, this is not widely appreciated.

A recent multicentre study showed no increase in anomalies in the

fetus exposed to omeprazole in the first trimester [11]. Montelukast has

little safety data in human pregnancy; however, animal studies have

been reassuring (it has been categorized as US Food and Drug

Administration [FDA] pregnancy category B). In cases of severe asthma

requiring the use of montelukast during pregnancy, many clinicians con-

tinue this drug because the risks to the fetus of poorly controlled asthma

in the mother outweigh any potential risks of the drug.

APS has been extensively studied in pregnancy and there is good

evidence for the benefit of the use of both low-dose aspirin and

LMWH in these women, both to prevent early miscarriage and to

prevent thrombosis [12]. There is less evidence that it reduces the

risk of intrauterine growth restriction (IUGR) or late still birth.

5.4 CARDIAC TRANSPLANT

Mrs D was a 33 year old para 0

1 who attended for prepregnancy

counselling with her husband and mother. She had received a cardiac

transplant 10 years previously at the age of 24 following multiple

myocardial infarcts caused by thromboemboli. Postmyocardial

infarction, her left ventricular ejection fraction was

13% on an

echocardiogram. She was, therefore, placed on the cardiac transplant

waiting list and received a transplant

5 months after her initial

myocardial infarction. She had three episodes of rejection in the

5. CASE STUDIES

105

early period following her transplant, but these were all mild. She

had not had any other episodes of rejection.

She had been followed-up regularly at the transplant centre and

remained very well.

Her most recent coronary angiogram, performed a year earlier,

was normal with no evidence of allograft coronary artery disease. She

had also had an echocardiogram showing mild left-ventricular hyper-

trophy, but with good function. The right ventricle was normal. She

had a thickened aortic valve with mild aortic regurgitation and a

mildly thickened mitral valve with mild mitral regurgitation. An

ECG showed right bundle branch block.

Her current medication was as follows:

Ciclosporin A, 125 mg twice daily.

Azathioprine, 75 mg once daily.

Prednisolone, 5 mg once daily.

Atorvastatin, 10 mg at night had been stopped in preparation for

pregnancy.

A thrombophilia screen was negative and prepregnancy serum

creatinine was 116

mol/l.

A review of the literature was performed in order to advise her and

she was given a follow-up appointment for further discussion.

At her follow-up appointment, Mrs D reported a positive preg-

nancy test. Her booking blood pressure was

140/84 mmHg at

8 weeks’ gestation. Urinalysis showed 4

blood, 1

protein (she

reported some PV bleeding.) Baseline electrolytes, urate level and

ciclosporin A levels were performed. A 24-hour urine collection for

creatinine clearance and total protein estimation and an MSU were

also performed. Mrs D was commenced on aspirin (75 mg/day)

and folate (5 mg/day) to be continued throughout the pregnancy.

She had a normal nuchal translucency and first trimester scan.

Maternal uterine artery Doppler studies were arranged for

weeks’ gestation and showed a prediastolic “notch” and persistent

high-resistance waveform predictive of subsequent pre-eclampsia,

IUGR or placental abruption.

Mrs D had an uneventful antenatal course but delivered by

emergency Caesarean section at 36 weeks’ gestation in another unit

following an abruption. Mother and baby are well.

Discussion

The literature describes 57 pregnancies in 41 women postcardiac

transplantation. The overall reported incidence of miscarriage is

14%, with a preterm delivery rate at

37 weeks’ gestation of 30% and

an incidence of pre-eclampsia of 17.5% [13,14,15].

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

The main clinical issues for Mrs D were as follows:

Medication - there is evidence that ciclosporin A causes IUGR in

women who become pregnant while taking this drug. Therefore, the

lowest dose possible should be the aim. However, the maternal risks of

voluntarily ceasing the medication are very high and in the literature

three reported maternal deaths followed voluntary cessation of

immunosuppressants.

Renal impairment - baseline bloods were normal, with the excep-

tion of serum creatinine, which was raised (105

mol/l), although

this represented an appropriate pregnancy-related fall compared with

the preconception level (116

mol/l). Raised serum creatinine might

have been due, in part, to her excess muscle mass (she was an avid

weight-training enthusiast), in which case it should fall following ces-

sation of excessive exercise as she was advised, or it could have been

due to a degree of nephrotoxicity from ciclosporin A. If it was due to

nephrotoxicity, the development of pre-eclampsia was more likely.

This was the rationale behind starting aspirin therapy.

Measurement of resting pulse rate was important because

transplanted hearts are denervated and thus there is always a resting

tachycardia. It is important to document the patient’s normal heart rate.

She should also have an ECG because there might be minor abnormal-

ities, which are normal for her, and it is important to record this.

In the largest series of heart-transplant recipients with subsequent

pregnancy, maternal survival was 71% at 7.5 years [15]. In all other

case series, the mothers were described as healthy in the immediate

postpartum period. Reduced maternal survival while the child is still

young was also discussed with the couple.

This largest series reported 47 pregnancies in 35 women: 6 preg-

nancies ended in miscarriage and 6 ended in therapeutic abortion.

The incidence of preterm delivery at

37 weeks’ gestation was

43% and the mean birth weight was 2543 g

696 g. There were no

structural abnormalities reported in the infants. The incidence of

pre-eclampsia was 20% and allograft vasculopathy was 24%, which is

not higher than would be expected in any 1 year in a heart-transplant

patient who was not pregnant.

Nine women in this series died and, importantly, three of these

women had ceased taking their immunosuppressant therapy because

of concerns regarding the fetus.

5.5 POSTPARTUM ECLAMPSIA

Ms E was a 22 year old primigravid woman. She attended for routine

booking at 12 weeks’ gestation, at which time all investigations were

5. CASE STUDIES

107

normal. She was fit and well, with no significant past medical or family

history. Her booking blood pressure was 96/50 mmHg, and urinalysis

was negative. She received routine antenatal care and remained well

throughout her pregnancy; she was normotensive with no proteinuria

throughout.

At 41

3 weeks’ gestation she was admitted in spontaneous labour.

On admission, her blood pressure was recorded as 150/87 mmHg.

Labour progressed well, but at full dilation, following active push-

ing for 1 hour, the head was in a deflexed occipito-posterior position

with the vertex above the ischial spines, and a decision for emergency

Caesarean section was made. This was carried out uneventfully and a

live male infant weighing 3.3 kg was delivered in good condition.

Blood loss at the time of operation was estimated at 700 ml, with sub-

sequent blood loss of approximately 500 ml.

On day 1 post Caesarean section, she developed abdominal disten-

sion. Her blood pressure was recorded as 121/54 mmHg. An abdom-

inal X-ray was performed and this showed dilated loops of bowel

consistent with a paralytic ileus. She was thus transferred to the high-

dependency unit, where a nasogastric tube was inserted and intra-

venous fluids were commenced. Routine bloods were taken

(Table 5.2). She was found to be anaemic, with a Hb concentration of

8.4 g/dl and was transfused with two units of red blood cells. The fol-

lowing day, her abdominal distension was less. Her bowels opened

following an enema and there were some bowel sounds present.

On day 3 postnatally, she complained of a severe headache at

midnight; her blood pressure was recorded as 185/87 mmHg and she

was given 50 mg of pethidine intramuscularly because simple analge-

sia was inadequate. After 1 hour (on day 4 at 1 a.m.), the on-call reg-

istrar was called to see her urgently because she was having a

tonic-clonic convulsion. She was given facial oxygen and a magne-

sium sulphate (MgSO₄) bolus, followed by an infusion. The convul-

sion terminated after 10 minutes. In retrospect, on her chart her

blood pressure had been recorded as 178/81-185/90 mmHg since

5 p.m. that day. Urinalysis showed 2

proteinuria. Electrolytes,

urate, a full blood count, coagulation screen and liver function tests

were checked (Table 5.2).

Her blood pressure remained stable at about

126/78 mmHg.

Further bloods tests were repeated. A computed tomography (CT)

brain scan was performed the following day and reported as normal.

By day 5, she was feeling better and her ileus was improving. MgSO₄

infusion was stopped after 24 hours.

At 6 a.m. on day 6 post Caesarean section, the registrar was called

urgently to see her because she was having a further tonic-clonic

convulsion. She had not complained of any prodromal symptoms.

108

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

TABLE 5.2. Flow chart of Ms E’s blood test results

convulsion convulsion

Result

↓

Post-C/S

Day 2

Day 4

Day 6

Day 7

Day 8

Day 10

Day 12

Na, mmol/l

141

144

141

143

140

142

135

K, mmol/l

4.0

3.6

3.5

3.7

3.3

4.7

4.3

Urea mmol/l

2.9

4.6

7.4

10.6

12.4

9.9

5.7

Creatinine,

176

225

264

202

117

mol/l

Urate, mmol/l

0.40

0.69

0.71

0.58

0.42

Albumin, g/l

ALT, iu/l

Alkaline

188

179

149

159

142

143

phosphatase,

iu/l

ALT - alanine transaminase; C/S - Caesarean section; K - potassium; Na - sodium.

This convulsion terminated after 3 minutes. In retrospect, her blood

pressure had been recorded as 146/99 mmHg at 3 a.m. Repeat blood

tests were performed. She was commenced on atenolol, 50 mg once

daily. Her blood pressure was subsequently well controlled and she

had no further convulsions. However her renal function continued to

deteriorate (Table 5.2).

Her abdominal distension gradually reduced and she began eating

and drinking normally again. There were issues regarding bonding

with the baby: Ms E showed no interest in her son and wanted her

family to look after him at home. She was encouraged to have him

beside her as much as possible. She had regular reviews by obstetric

medicine and renal physicians. Her urine output remained excellent

despite deteriorating renal function. A renal scan was performed on

day 11. This was reported as showing normal kidneys of equal size,

slight pelvicaliceal system dilatation, probably because of incomplete

bladder emptying, and a postmicturition residual volume of 450 ml.

This scan result was discussed with the urologists and she was

allowed home with an in-dwelling catheter and plans for out-patient

review.

Her renal function improved (Table 5.2). She was well enough to

be discharged home on day 13, with the following discharge medica-

tion: ferrous sulphate (FeSO₄) 200 mg twice per day and atenolol

(50 mg once per day).

5. CASE STUDIES

109

When reviewed in the obstetric medicine clinic at 5 weeks postpar-

tum, she was well and normotensive (110/70 mmHg), and urinalysis

was clear. Her serum creatinine was 87

mol/l. Atenolol was discon-

tinued and GP follow-up was arranged. Urodynamic follow-up was

organized by the urology department.

Discussion

With improvements in antenatal care and both improved recognition

and earlier diagnosis of pre-eclampsia, in addition to earlier delivery

for those with severe pre-eclampsia, there seems to have been a shift

in the timing of eclampsia towards the postpartum period, perhaps

increasingly

48 hours post-delivery. Of eclamptic convulsions, 44%

occur postpartum.

More than one-third of women experience their first convulsion

before the development of hypertension and proteinuria. In the vast

majority of patients, at least one prodromal symptom is experienced.

In a recent study, 87% had headache, 44% had visual symptoms, 22%

had nausea or vomiting and 9% had epigastric pain [16].

Fortuitously, this woman remained an in-patient because she devel-

oped a paralytic ileus; she would otherwise have been discharged and

had the convulsion at home.

Her blood pressure was elevated both in the immediate postpar-

tum period and between her convulsions, but it remained untreated;

this was probably owing, in part, to the focus on her paralytic ileus

and, in part, because of being falsely reassured by the normal blood

profile on day 2 [17].

Her headache, severe enough to require opiate analgesia, should

have prompted further examination and investigation because it

heralded her first convulsion.

Her blood pressure was markedly elevated before her second

convulsion, although there were no prodromal symptoms.

MgSO₄ had been discontinued after 24 hours (as per protocol),

and it is difficult to predict which patients will develop recurrent con-

vulsions and require additional therapy [18].

Beware of the routine use of nonsteroidal anti-inflammatory

drugs (NSAIDs) following Caesarean section. This patient received

two doses of voltarol despite deteriorating renal function.

5.6 HYPEREMESIS GRAVIDARUM

Ms F was a 35 year old woman in her third pregnancy. In her first preg-

nancy, she had been admitted on four occasions with severe hyperemesis

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

and needed prolonged periods of hospitalization, in addition to regular

antiemetics until 33 weeks’ gestation. She terminated her second preg-

nancy because she could not face such severe hyperemesis again.

She was previously fit and well, but in the index pregnancy, she

experienced nausea and vomiting from her first missed period and pre-

sented to the hospital at 8 weeks’ gestation. On examination, she was

tachycardiac and had postural hypotension and ketonuria. Ms F was

admitted and treated with intravenous fluids and metoclopramide,

10 mg intramuscularly three times daily. A viable intrauterine preg-

nancy was confirmed on ultrasound scan; she improved on the above

therapy and was discharged 2 days later. In the subsequent 2 weeks, she

had three further admissions with hyperemesis gravidarum (HG). On

the third occasion, she was severely dehydrated, had lost 7 kg in weight

and was ketotic. She was admitted, rehydrated and given regular

cyclizine, 50 mg intravenously three times daily. Over the following

week, she improved and was sent home with oral antiemetics, folic acid

(5 mg) and thiamine hydrochloride (25 mg three times daily).

Her next admission was at 12 weeks’ gestation despite regular use

of oral cyclizine. She had lost a further 3 kg in weight and, again, had

ketones in her urine. Investigations revealed a raised free thyrox-

ine (fT₄) level, undetectable thyroid-stimulating hormone (TSH),

abnormal liver function with an alanine aminotransferase (ALT)

level of

70 iu/l and hypokalaemia (serum potassium, 3.1 mmol/l).

She was once again rehydrated with normal saline and potassium

chloride (40 mmol/l in each 1 l bag) and given domperidone, 60 mg

per rectum three times daily, cyclizine, 50 mg intravenously three

times daily and oral metoclopramide. Enoxaparin (40 mg) was given

daily for thromboprophylaxis. This time she was maintained on

intravenous fluids and parenteral anitemetics for 1 week. After 1 week,

she was still vomiting up to three times daily and was unable to drink

enough to avoid intravenous fluids. She was noted to be very

depressed by her husband and the nurses caring for her and was

requesting a termination of pregnancy.

The decision was made to undertake a trial of corticosteroid ther-

apy. This was begun as hydrocortisone, 100 mg intravenously twice

daily. After the first two doses, Ms F was able to tolerate oral fluids

and the intravenous fluids and antiemetics were discontinued.

Therapy was changed to prednisolone, 20 mg oral twice daily and she

was discharged. On review in clinic 1 week later, she had had no fur-

ther vomiting or nausea but still complained of “spitting”. Serum

electrolytes were normal, repeat liver function tests showed a normal

ALT level and a repeat thyroid function test showed resolving bio-

chemical thyrotoxicosis, with a free T₄ level just above the normal

range. The prednisolone dose was decreased to 15 mg twice daily.

5. CASE STUDIES

111

The dose was gradually weaned over the next month to 10 mg

twice daily. Ptyalism had resolved by 19 weeks’ gestation. An anomaly

scan of the baby was normal. Several times over the next 2 months

she attempted decreasing the steroid dose but would not tolerate

doses below 20 mg/day. If she reduced the dose to 15 mg/day, the

vomiting returned. She was thus maintained on a dose of 20 mg/day.

A glucose tolerance test at 28 weeks’ gestation was normal. At 30 weeks’

gestation, the prednisolone dose was successfully reduced to

15 mg/day and thereafter reduced by 5 mg every 2 weeks, such that

she was weaned off steroids by 36 weeks’ gestation.

At 39 weeks’ gestation, she presented in spontaneous labour

having ruptures her membranes. She vaginally delivered a healthy

female infant weighing 6 lbs 3 ozs. Postnatally, she was counselled

regarding the likely recurrence of hyperemesis in future pregnancies

and a plan was made to use corticosteroids at the first admission for

HG.

Discussion

This was a case of severe HG causing associated abnormal liver and

thyroid function. In her first pregnancy, symptoms had lasted until

the third trimester and, therefore, it was likely that this would happen

in any future pregnancy.

Nausea and vomiting occur commonly in pregnancy, usually

between the 6th and 16th week. In 20% of cases, it persists into the

second and third trimesters. Management involves reassurance, small,

frequent high-carbohydrate food and avoidance of large-volume drinks.

Acupunture, ginger and vitamin B6 might relieve symptoms. Other

causes of vomiting in pregnancy include the following:

Ear, nose and throat diseases, for example, labyrinthitis or Meniere’s

disease.

Acute fatty liver of pregnancy (AFLP; in the third trimester).

HELLP syndrome.

Gastrointestinal causes, for example, cholecystitis, pancreatitis, pep-

tic ulceration and, rarely, gastric cancer.

Metabolic/endocrine, for example, hypercalcaemia, Addison’s disease

and hyperparathyroidism.

Drugs, for example, opioids, iron therapy and antibiotics.

Psychological, for example, eating disorders.

If abdominal pain and tenderness is a marked feature, consideration

should be given to further investigation with endoscopy.

HG is defined as vomiting occurring before the 20th week of

pregnancy that is sufficient to cause dehydration, acidosis and a

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

minimum weight loss of 5%. Some definitions include the inability

to maintain the fluid and electrolyte balance without hospital admis-

sion. It occurs in about 0.5-1.5% of pregnancies and remains the

third most common cause for admission to hospital during preg-

nancy. Before the introduction of intravenous fluids, mortality from

HG was 159 deaths/1 million pregnancies. Complications of HG

include Wernicke’s encephalopathy, central pontine myelinosis

and peripheral neuropathy. Pneumomediastinum and oesophageal

rupture secondary to the mechanical forces of vomiting have been

described.

Meta-analysis of the available data showed a small reduction in the

risk of spontaneous miscarriage, stillbirth and preterm delivery in

women who experience HG. However, when HG is severe and asso-

ciated with maternal weight loss and repeated hospital admissions,

there is a slight increase in the incidence of IUGR. There is no

known increase in rate of congenital defects in vomiting pregnancies

compared with nonvomiting pregnancies.

The aetiology of HG remains elusive. It is believed that the

genetic variation in incidence is related to the presence of specific iso-

forms of human chorionic gonadotrophin (HCG) that cause HG

[19]. Elevated levels of oestrogen and progesterone have also been

implicated. Although high levels of oestrogen do cause slower intes-

tinal transit times, there are no studies showing a relationship

between severity of HG and oestrogen levels. Prospective cohort

studies have not shown any consistent relationship between proges-

terone levels and HG.

Thyroid hormone values deviate from the normal range in early

pregnancy, leading to gestational transient thyrotoxicosis

[20].

Although evidence supports a relationship between HCG and gesta-

tional transient thyrotoxicosis, the exact role of this in HG is obscure.

Overactivity of the adrenal cortex is also associated with HG, but it

is uncertain whether it has a role in its pathogenesis. Helicobacter

pylori infection was found in a significant number of patients with

HG in 11 prospective, case-controlled studies [21]. Liver function

abnormalities have been reported in about 67% of women with HG.

Elevations of aspartate aminotransferase (AST) or ALT levels can be

very dramatic, but return to normal with the cessation of vomiting

and the end of starvation.

Clinical assessment should include measurement of the pulse, lying

and standing blood pressures, urinalysis and weight, in addition to a

complete examination to exclude other causes of vomiting,

particularly infection. Further investigations should include urea and

electrolytes, liver function tests, thyroid function tests, and serum

phosphate, magnesium and calcium levels. A full blood count,

5. CASE STUDIES

113

midstream urine sample and blood glucose level should also be

determined.

Management of HG involves rehydration with intravenous fluids,

replacement of electrolytes, vitamins, antiemetics and cessation of oral

nutrition and fluids. Fluid replacement can be with either sodium

chloride (plus potassium, 20 mmol or 40 mmol) or Hartmann’s solu-

tion. Protracted vomiting is associated with Mallory-Weiss oesophageal

tears, Mendelson’s syndrome and jaundice. The neurological distur-

bances are a result of vitamin B1 deficiency. It is imperative that

thiamine hydrochloride (25-50 mg orally three times daily or as Pabrinex

intravenous weekly supplements) is prescribed in these cases, to avoid

Wernicke’s encephalopathy and Korsakov’s psychosis.

Antiemetic therapy is a mainstay of treatment, although no antiemetic

treatment is specifically licensed for use in pregnancy. Pyridoxine

hydrochloride (vitamin B6) and ginger have been shown to relieve

symptoms in severe HG.

Dopamine receptor antagonists can be used, including the

following: metoclopramide, domperidone, and phenothiazines.

These drugs are safe but can cause extrapyramidal side effects. Other

antiemetics that can be used include the following: cyclizine,

prochlorperazine, and chlorpromazine.

Ondansetron, a potent and highly selective type

3 serotonin

(5-hydroxytryptamine; 5-HT)receptor (5-HT₃) antagonist can be

used if all other antiemetics have failed. The safety of this drug has

not been sufficiently evaluated in large-scale trials. If management

has been optimal and there is no improvement, consideration might

be given to starting steroids (prednisolone, 20 mg twice daily or

hydrocortisone,

100 mg intravenously twice daily)

[22,23]. The

response is usually dramatic, but if there is no response, steroids

should be discontinued after 2-3 days. For those who respond to

steroids, it is important to continue the therapy after discharge and

wean the dose slowly. Usually, steroids will need to be continued in

reduced doses until such time as nausea and vomiting have abated.

With prolonged use of steroids in pregnancy, it is important to

monitor blood glucose levels.

Parenteral nutrition is only recommended if there is maternal

protein-calorie malnutrition and all other therapy has failed. Total

parenteral nutrition (TPN) is safe, with expert advice and monitor-

ing of maternal levels of nutrition. The fetus must be monitored with

serial growth scans, and there must be facilities to accommodate

preterm delivery available.

HG can be mild or severe, but most cases improve with optimal

management and termination is rarely required for medical reasons.

Early treatment of a recurrence is advised.

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

5.7 POSTPARTUM CEREBRAL HAEMORRHAGE

Ms G was a 34 year old para 2

5 with pre-existing renal disease and

hypertension who presented 7 days after a normal vaginal delivery with

sudden onset of right-sided weakness and loss of speech.

Her obstetric history was that of five miscarriages at

12 weeks’

gestation. Her sixth pregnancy was complicated by severe pre-

eclampsia, requiring induction at 29 weeks’ gestation. She had a

normal delivery of a live infant weighing 1.1 kg. Following this preg-

nancy, she was diagnosed with essential hypertension requiring

medication. She had a renal biopsy 3 years later to investigate renal

impairment and was diagnosed with Alport syndrome.

In the index pregnancy, her hypertension was controlled with

methyldopa, 750 mg three times daily. Aspirin was commenced to

reduce her significant risk of recurrent pre-eclampsia because of her

pre-existing renal disease and hypertension, and history of previous

early onset pre-eclampsia. A thrombophilia screen was negative.

Renal function remained stable with serum creatinine ranging

between 107-132

mol/l. She had pre-existing significant protein-

uria of

2.08 g/24 hours at the beginning of pregnancy, which

dropped to 1.24 g/24 hours towards the end of the pregnancy. Serial

scans confirmed normal fetal growth. There was no evidence,

clinically or from blood parameters, of superimposed pre-eclampsia.

She went into premature labour at 35 weeks’ gestation, with a vaginal

delivery of a live infant who had a birth weight of 2.2 kg. After delivery,

methyldopa was converted to atenolol, 50 mg/day and her blood

pressure remained stable. She was discharged home 2 days postpar-

tum. The last blood pressure recording before discharge was

138/86 mmHg.

She was re-admitted on day 7 postpartum, having had sudden

onset of headache, vomiting, one witnessed seizure, right-sided weak-

ness and loss of speech. She had been taking atenolol, 50 mg/day for

hypertension. Findings on examination were as follows: blood pres-

sure, 182/91 mmHg; heart rate, 60 bpm; sinus rhythm; and urinaly-

sis showed 4

proteinuria. Neurological assessment revealed a dense

right-sided hemiplegia with receptive and expressive dysphasia and a

Glasgow coma scale of 11/15. Abnormal parameters on her blood results

were as follows: ALT, 70 iu/l; and serum creatinine, 145

mol/l.

An urgent CT scan of the brain, with contrast, showed features

suggestive of intracerebral haemorrhage in the left frontal lobe, with

evidence of cerebral oedema.

She was transferred to a neurosurgical unit, where the haematoma

was evacuated. This was followed by a multidisciplinary package of care

on the stroke unit, involving the stroke physician, physiotherapist,

5. CASE STUDIES

115

speech and language therapist and clinical psychologist. She made

steady progress and was able to verbalize, saying a few words and

responding appropriately to commands, within 5 days of the event. Her

right leg regained power, but the right arm remained flaccid. Initially,

with some assistance, she was able to sit out of bed, started mobilizing

by day 10 and was able to walk without supervision by day 15. During

her admission, her baby was cared for at home by her mother.

She was discharged home 1 month after the event and was able to

communicate well, although slowly. She had residual right-hand

weakness. Power scores were 2-3 out of 5 in her right arm and 4 out

of 5 in her right leg. Her hypertension was well controlled with inda-

pamide and nifedipine. Follow-up arrangements were made with the

community physiotherapist, speech and language therapist and the

stroke clinic.

At her 1-year follow-up review in the stroke clinic, she had

regained normal power in her right upper and lower limbs and her

speech was back to normal. She had one episode of seizures and was

commenced on cabamazepine. Her hypertension was well controlled

with lisinopril, and simvastatin was added. She had an intrauterine

contraceptive device for contraception.

Discussion

Cerebrovascular disorders are uncommon and feared complications

of pregnancy. Collectively, they contributed to 15% of indirect mater-

nal deaths in the latest confidential enquiry into maternal deaths

survey. Most cases occur in the first week after delivery [24]. As high-

lighted in this case, there could be diagnostic confusion with eclampsia,

because of the common presentation of seizures, hypertension and

visual disturbance. Although Ms G had significant proteinuria at

presentation, this was because of previously diagnosed underlying renal

disease. Her mildly raised liver enzymes were probably a normal

physiological change in the puerperium. The seizure in this case was

secondary to the intracerebral bleed.

The association of pregnancy-related hypertension with stroke

during pregnancy and the puerperium is consistent in many studies

and with the known pathophysiology of cerebrovascular complications

of hypertension.

Blood pressure at discharge after delivery is not expected to be

predictive of the development of postpartum stroke. Therefore, a

longer period of closer monitoring of blood pressure as an in-patient

after delivery is unlikely to reduce the risk of postpartum stroke. The

finding of raised blood pressure after an intracerebral bleed is related

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

to the phenomenon of hypertension in response to seizures and

central neurological insult with resulting failure of cerebral autoreg-

ulation. Hypertension is thus a result and not a cause of most

cerebrovascular events.

Prompt neuroimaging studies, in addition to an elevated level of

suspicion and neurological consultation, as clearly demonstrated in

this case, are the key to diagnosis and an optimal prognosis. CT is usu-

ally the first imaging study performed because of its ready availability.

However, an initial negative result of the CT study and the presence of

a highly suggestive clinical history and physical findings suggest the

need for additional studies, such as magnetic resonance imaging (MRI)

and cerebral angiography, to confirm the appropriate diagnosis.

The morbidity and mortality associated with intracranial haemor-

rhage is high, with a risk of neurological or cardiovascular sequelae in

survivors and a need for close medical surveillance. Ms G made a

complete recovery from her hemiplegia but was left with seizures.

Patients who have had stroke in the past can be reassured that they

are unlikely to have a recurrence in pregnancy, unless they have an

obvious risk factor, such as APS or hypertension. The combined oral

contraceptive pill should be avoided because it carries a significant

risk of recurrence of stroke. Ms G was advised to seek prepregnancy

counselling before embarking on another pregnancy.

5.8 HYPOKALAEMIA

Mrs H was a 31 year old primigravida who presented at 26 weeks’

gestation with extreme lethargy such that she was virtually bed

bound. She had a diagnosis of Sjogren’s syndrome and was anti-Ro

and anti-La positive. Her pregnancy had been complicated by recur-

rent admissions for HG, and on each occasion she was noted to be

hypokalaemic (serum potassium, 2.4-3.1 mmol/l), which improved

with appropriate rehydration with normal saline and potassium chlo-

ride. However, at this admission she denied nausea or vomiting,

which had improved markedly since 20 weeks’ gestation.

Investigations revealed a serum potassium level of 2.9 mmol/l and

serum bicarbonate of 14 mmol/l. Retrospective review of biochemistry

results during the previous admissions showed that on each admission

she had been acidotic, with serum bicarbonate levels as low as 10 mmol/l.

Because persistent vomiting in HG usually causes a hypochloraemic

alkalosis (related to the loss of hydrochloric acid from the stomach),

alternative causes for the hypokalaemia were considered. Because of the

association of Sjogren’s syndrome with distal type 1 renal tubular

5. CASE STUDIES

117

acidosis (RTA), this was felt to be the most likely diagnosis. Urinary pH

was 9 when serum bicarbonate was 15 mmol/l. This was highly sugges-

tive of RTA.

Treatment was commenced with oral sodium bicarbonate, 1.8 g

three times daily and oral potassium citrate, 10 ml (28 mmol/l/10 ml)

three times daily. Within 1 week, she had normal energy levels and

felt enormously better. Within 2 weeks, her serum bicarbonate and

potassium levels were normal and potassium supplementation was

discontinued.

Mrs H was delivered by emergency Caesarean section for fetal dis-

tress at 38 weeks’ gestation; the birth weight of her infant was 3.1 kg.

Postpartum, the dose of bicarbonate was reduced to 1.2 g three times

daily. She was referred to a nephrologist for further management

postpartum.

Discussion

Hypokalaemia occurs in up to 20% of hospitalized patients but is only

clinically apparent in 5%. No pregnancy-specific incidence has been

reported. Hypokalaemia is a biochemical finding and is not a diagno-

sis in itself. It is almost always secondary to an underlying problem.

Hypokalaemia is frequently asymptomatic. Severe hypokalaemia

(serum potassium,

2.5 mmol/l) can cause muscle weakness and

fatigue. It rarely causes arrhythmia in patients without cardiac disease.

Despite the 50% increase in plasma volume and associated haemo-

dilution of pregnancy, the concentration of plasma electrolytes

remains unchanged compared with the nonpregnant state. The range

of normal serum potassium is 3.5-5.5 mmol/l. This phenomenon is

probably because of decreased excretion in pregnancy and net gain

from gastric absorption. In rat studies, fluctuations in maternal serum

potassium levels did not seem to have a deleterious effect on fetal

potassium levels.

Hypokalaemia has many causes. Acute hypokalaemia is most

commonly due to severe vomiting and/or diarrhoea. Chronic

hypokalaemia is most commonly due to diuretic use and hyperaldos-

teronism. A logical review of possible causes of potassium loss

should facilitate the correct diagnosis:

Renal losses:

● RTA

● Hyperaldosteronism

● Hypomagnesaemia

● Leukaemia

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Gastrointestinal losses:

● Vomiting or nasogastric suctioning

● Diarrhoea

● Enemas/laxatives

● Ileal loop

Drugs:

● Diuretics (except potassium-sparing diuretics)

● Beta-adrenoceptor agonists

● Steroids

● Aminophyllins

● Aminoglycosides

Transcellular shifts:

● Insulin

● Alkalosis

Reduced intake:

● Dietary deficiency, including malnutrition

● Parenteral nutrition

● Intravenous fluids lacking potassium

The following are pregnancy-specific/related causes:

Tocolysis with intravenous sympathomimetics, such as salbutamol [25].

Oral glucose load screening for gestational diabetes [26].

Abnormal cravings in pregnancy (pica), such as cravings for cola or

clay, and caffeine abuse in pregnancy [27,28,29].

A thorough search for the aetiology of hypokalaemia is required. It

will generally resolve with the treatment of its primary cause.

Supportive replacement therapy is, however, indicated in

5% of

patients, where the potassium level is

3 mmol/l. Oral therapy is usu-

ally sufficient. However, intravenous therapy might be indicated if

symptoms are severe, cardiac arrhythmias are present and oral intake

is not possible (vomiting or diarrhoea). Potassium supplementation is

safe in pregnancy. When hypokalaemia is refractory to treatment,

hypomagnesaemia should be suspected and corrected concurrently.

RTA is systemic acidosis due to the inability of the renal tubules to

maintain the acid-base balance. Type 4 RTA is the commonest form,

but it is associated with hyperkalaemia. RTA types 1 and 2 are associ-

ated with hypokalaemia. Type 2 (proximal) RTA is very rare. Type 1

(distal) RTA is usually secondary to systemic conditions such as dia-

betic ketoacidosis, liver disease, sickle cell anaemia and autoimmune

conditions, including Sjogren’s syndrome (as present in Mrs H),

thyrotoxicosis and systemic lupus erythematosus (SLE). It can be

sporadic, in which case it is usually an autosomal dominant familial

condition. Characteristically, there is failure to acidify the urine despite

5. CASE STUDIES

119

systemic acidosis. It is characterized by episodes of weakness and

paralysis and is accompanied by hypokalaemia, acidosis and hypocal-

caemia. Diagnosis is usually made following an acid-load test, during

which the patient takes an oral solution of ammonium chloride; if the

urine fails to acidify but the bicarbonate level falls, this is diagnostic of

RTA. Treatment is usually supportive with potassium, bicarbonate

and calcium supplementation during episodes.

During pregnancy, symptoms such as fatigue and lethargy can

mimic muscular weakness and make the diagnosis even harder to

reach. The ammonium load test is contraindicated in pregnancy

because acidosis can cause fetal distress. Untreated RTA can cause

severe weakness affecting labour and maternal well-being. Chronic

acidosis affects fetal bone growth, causing IUGR, and can cause car-

diotocographic changes. Potassium, bicarbonate and calcium supple-

mentation is safe in pregnancy. The potassium and bicarbonate

requirements are sevenfold and fourfold higher, respectively, in preg-

nancy than outside pregnancy.

In a review by Hardadottir et al. [30], RTA cases were associated

with IUGR, preterm labour and Caesarean section. Most cases of

RTA were secondary. It seems prudent to follow RTA pregnancies

with serial fetal growth scans and institute intrapartum cardiotoco-

graphic monitoring. Neonatal admissions were common in the above

mentioned series, and therefore paediatric colleagues should be

involved before delivery. If tocolysis is required, it is best to avoid

beta-sympathomimetics because they induce hyperglycaemia and

hypokalaemia.

In labour, attention should be paid to avoid potential precipitating

factors, including mental and physical stress, cold and carbohydrate

loads. Adequate analgesia should be administered, and an early

epidural might be ideal. Serum potassium should be monitored and

replaced as necessary, usually intravenously. The second stage of

labour can be shortened with assisted delivery if maternal exhaustion

or fetal distress supervenes. Glucose infusions should be avoided

because they can precipitate further hypokalaemia.

In the first 2 weeks of the puerperium, potassium, bicarbonate

and calcium supplementation usually decreases rapidly towards

prepregnancy doses. If the diagnosis has not been confirmed, the

ammonium load test can be completed postnatally.

5.9 HEPATITIS A

Mrs J, a 28 year old nulliparous woman at 34 weeks’ gestation, was

admitted with a history of worsening malaise, diarrhoea, nausea

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

and vomiting, and generalized itching. There was associated dark

urine, but no paleness of stools. Her pregnancy had being unevent-

ful apart from intermittent diarrhoea, presumed to be secondary to

her history of irritable bowel syndrome and managed with lop-

eramide. Her booking bloods at the beginning of the pregnancy,

were negative for human immunodeficiency virus

(HIV) and

hepatitis B. She was from South Africa and had been a resident in

the UK for 3 years. She worked as a secondary school teacher.

There was no history of recent travel, or use of herbal remedies or

hepatotoxic drugs.

On examination, she was afebrile and jaundiced, with normal blood

pressure and without proteinuria on urine dipstick assessment and

signs of chronic liver disease apart from telangectasia over the upper

chest and abdomen, which was associated with pregnancy. Abdominal

examination revealed no organomegaly and her fundal height was con-

sistent with gestational age. Fetal movements were normal and the car-

diotocograph (CTG) was reactive. Blood tests revealed a normal full

blood count, with Hb concentration of 12.5 g/dl, white blood cell

count of 9.6

10⁹ cells/l and platelet count of 198

10⁹ platelets/l.

Her renal function and random blood glucose were normal, but her

liver function was de-ranged (bilirubin, 98

mol/l; ALT, 769 iu/l;

alkaline phosphatase (AlkP), 185 iu/l; gamma-GT, 47 iu/l; and serum

albumin, 24 g/l). Her coagulation was normal.

She was transferred into a side room and barrier-nursed, with

institution of mainly supportive management, in addition to antihis-

tamines and vitamin K. Upper abdominal ultrasound revealed a

normal liver, gallbladder and spleen. Cultures of blood, urine and

sputum were negative.

Over the next 2 days, she gradually improved clinically, in addition

to biochemically (Table 3). Serum titres for hepatitis A revealed a

raised immunoglobulin (Ig) M consistent with acute hepatitis A

infection. Titres for hepatitis B and C were negative. Antimitochondrial

and anti-smooth muscle antibodies were negative. She was discharged

home after 1 week because she continued to improve.

She went into premature labour at 36 weeks’ gestation and had a

normal vaginal delivery of a male infant, weighing 2.8 kg. By 2 weeks

post delivery, her liver function had normalized.

Discussion

Liver disease in pregnancy can be subdivided into three types:

1. Liver disease peculiar to pregnancy, such as AFLP, obstetric

cholestasis, HG and pre-eclampsia.

5. CASE STUDIES

121

2. Intercurrent liver disease affecting pregnant women, such as viral

hepatitis and gall bladder disease.

3. The effect of pregnancy on underlying liver disease, such as

chronic hepatitis or cirrhosis.

Clearly, the last category was not considered as a differential diagno-

sis in this case because there was no previous history of liver disease.

As a symptom of liver disease, jaundice occurs in 1:1500 pregnan-

cies:

40% of cases result from viral hepatitis,

20% of cases are

secondary to intrahepatic cholestasis, and

6% of cases result from

common biliary duct obstruction and gallstones. A normal gall bladder

scan excluded the latter in this patient.

Pruritus can occur in a broad spectrum of liver disease and its pres-

ence does not necessarily help in reaching the correct diagnosis.

Although pruritus classically occurs in conditions associated with

intrahepatic cholestasis, such as primary biliary cirrhosis and obstetric

cholestasis, drug hepatotoxicity, viral hepatitis, AFLP and even pre-

eclampsia are sometimes associated with itching. The absence of

antimitochondrial antibodies and lack of a positive history of drug

ingestion excluded primary biliary cirrhosis (PBC) and drug-induced

causes in Mrs J.

The length of gestation at presentation is important in consider-

ing possible diagnoses because, unlike viral hepatitis, which can occur

at anytime, liver disease specifically associated with pregnancy occurs

at characteristic times. In the third trimester, HELLP syndrome,

AFLP, obstetric cholestasis and pre-eclampsia

(PET) should be

considered.

The pattern of serum liver enzyme abnormalities cannot be relied

on to make a diagnosis. Classically, in intrahepatic liver disease,

transaminases tend to be high, with only a small increase in alkaline

phosphatase; in extrahepatic obstruction, alkaline phosphatase is

high and transaminases are relatively lower. In Mrs J, the pattern was

consistent with the picture in viral hepatitis, drug-induced hepato-

toxicity, obstetric cholestasis, AFLP, HELLP syndrome and PET.

The absence of thrombocytopenia, which is one of the hallmarks of

HELLP syndrome, and impaired liver function (coagulation and glu-

cose were both normal), which is a prominent feature of AFLP, made

these two conditions unlikely. There is a tendency in pregnancy to

assume that pruritus is always due to obstetric cholestasis: it was vital

in this case that the viral titres were obtained quickly, because this

enabled the correct diagnosis to be made.

Viral hepatitis is mostly due to hepatitis A, B, C, D or E, Epstein-

Barr virus, or cytomegalovirus. Pregnant women are not more

susceptible to hepatitis, and the incidence in epidemics is usually

5. CASE STUDIES

123

the same in pregnant and nonpregnant women. However, hepatitis

E is more aggressive in pregnancy, with a maternal mortality rate of

up to 50% [31].

Acute hepatitis A in pregnancy is a systemic, short-term viral

illness, with general symptoms of malaise and jaundice. It is the most

common cause of jaundice in pregnancy [32]. The virus belongs to

the picornaviridae RNA family. Transmission is through the faeco-

oral route, and it is endemic in countries with poor sanitation. The

incubation period is generally 15-50 days. It multiplies in the intes-

tine and invades the blood, liver and saliva before any clinical mani-

festation of the disease appears. It is highly contagious, with maximal

viral shedding occurring in the 1-2 week period before the onset of

symptoms and lasting 3 weeks. The virus disappears soon after the

peak of serum transaminases is reached, at which time the immune

response and hepatocellular repair start. The risk of transmission

diminishes following the onset of symptoms and is minimal in the

week after the onset of jaundice.

Hepatitis A is not debilitating, even in the presence of jaundice.

Jaundice lasts 7-10 days and the whole illness lasts about 4 weeks.

Typically, all clinical forms, with the exception of the rare, lethal,

fulminant type, resolve with complete liver regeneration, and with-

out chronicity or long-term carrier state. Serum IgM antibodies

are present during the acute phase and disappear within 3 months.

Serum IgG antibodies develop after the acute illness and persist

for life, representing immunity. Serum transaminases rise with

acute illness and return to normal with recovery; they seldom are

higher than 1000 iu/l. There is no correlation between their level

and prognosis.

Maternal-fetal transmission is rare but could result if the mother

has hepatitis at or around the time of delivery. In such cases, the baby

should be given Ig at birth. It is recommended that pregnant women

who are exposed to hepatitis A are given Ig prophylaxis, because it

reduces the risk of infection. Ig must be given within 2 weeks of

exposure but should be given as soon as possible.

Hepatitis A vaccination

(inactivated noninfectious hepatitis A

virus) is not contraindicated in pregnancy. It is recommended for

some individuals working in high-risk professions, people travelling

to at-risk countries and individuals with medical conditions that

place them at a high risk of complications from hepatitis A. It offers

good protection and is thought to be effective for 20 years.

Breastfeeding can continue without interruption if a mother

has hepatitis A. If the mother becomes acutely ill or jaundiced,

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

breastfeeding might be interrupted. The mother should practise

good handwashing and other appropriate hygiene.

Acute hepatitis A is the commonest cause of viral hepatitis in preg-

nancy; it is usually self-limiting and nondebilitating and is associated

with transient abnormal liver function, mostly with no significant

implications to the pregnancy. It is vital that abnormal liver function in

pregnancy is investigated fully so that the correct diagnosis is reached.

5.10 RENAL ARTERY STENOSIS

Mrs K was a 25 year old Asian woman who presented in her third

pregnancy at 22 weeks’ gestation with severe secondary hyperten-

sion. She was diagnosed with bilateral renal artery stenosis follow-

ing a limited angiogram during her second pregnancy, when she was

found to be severely hypertensive. She unfortunately miscarried her

second pregnancy at 20 weeks’ gestation. Her first pregnancy was a

termination at 9 weeks’ gestation. Following her miscarriage, she

had a left renal artery angioplasty, and the right angioplasty was

planned as an interval procedure. Before having the right renal

artery angioplasty, she was found to be pregnant. It was felt that

angioplasty during pregnancy would, on one hand, be an unwar-

ranted radiation dose but, in contrast, would reduce the risk of

severe hypertension.

She booked-in late in her third pregnancy at 22 weeks’ gestation

with a blood pressure of 199/125 mmHg, despite therapy with two

agents, atenolol (50 mg once daily) and doxazosin (4 mg twice daily).

Methyldopa (500 mg three times daily) and aspirin (75 mg once

daily) were added. Booking bloods were normal, in addition to base-

line renal function: urea,

3.5 mmol/l; creatinine, 65

mol/l; uric

acid, 0.31 mmol/l. Urinalysis was normal and 24-hour urine protein

leak was

0.24 g/save. An obstetric scan at

22 weeks’ gestation

revealed bilateral uterine artery Doppler notching, with a raised

resistance index.

Mrs K was closely monitored and her blood pressure remained

well controlled on the above three antihypertensive agents. At 26

weeks’ gestation, a growth scan revealed evidence of IUGR with

reduced liquor volume and AC below the fifth centile. An umbilical

artery Doppler scan showed absent end diastolic flow. Estimated fetal

weight (EFW) was 669 g. She was admitted because of the scan find-

ing and also to exclude a possible diagnosis of pre-eclampsia.

Investigations for pre-eclampsia were normal and the protein leak

remained nonsignificant. The risk of a poor outcome, including a

high risk of intrauterine death, reduced chance of neonatal survival

5. CASE STUDIES

125

and significant risk of neurological impairment, was discussed. It was

decided to avoid delivery at this gestation and wait for the fetus to

gain more maturity. Mrs K was discharged home with a plan for

weekly umbilical Doppler scans and 2-weekly growth scans.

Her blood pressure remained stable and well controlled, with no

signs of superimposed pre-eclampsia. At 30 weeks’ gestation, her scan

revealed no fetal growth in 4 weeks, brain sparing and anhydramnios.

It was felt that delivery was now necessary because the additional

weeks gained had improved the fetal prognosis. She had a course of

steroids and was delivered 24 hours later, at 30 weeks

6 days, by

Caesarean section with an inverted T-incision on the uterus; Apgar

scores at delivery were 9 and 10 at 1 minute and 5 minutes, respec-

tively, and the infant had a birth weight of 815 g. Postoperatively, she

was converted to her prepregnancy antihypertensive medication, with

good blood pressure control. The neonatal course was complicated by

necrotizing enterocolitis, which required surgical intervention, with

subsequent full recovery. She was referred to the renal physician for

renal angioplasty.

Discussion

Renovascular hypertension is one of the potentially curable second-

ary causes of hypertension. It is the cause of hypertension in

5% of

all patients. In women of child-bearing age, fibromuscular hyperpla-

sia is more often the aetiology. Patients with renal artery stenosis usu-

ally present with hypertension and varying degrees of renal impair-

ment. Narrowing of the renal artery, because of fibromuscular dys-

plasia, leads to reduced renal perfusion. The consequent activation of

renin-angiotensin system causes hypertension

(mediated by

angiotensin II), hypokalaemia and hypernatraemia (which are fea-

tures of secondary hyperaldosteronism). Correcting the stenosis

might reverse these features and improve hypertension control.

Before her first angioplasty, Mrs K required three antihyperten-

sive agents, which was reduced to two agents after the angioplasty. It

would be expected that following angioplasty of the other renal

artery a cure might be achieved, without the need for medication.

Secondary, potentially curable causes of hypertension should be

sought whenever hypertension is present in young women, whether

pregnant or not. This is especially true for pre-existing hypertension in

pregnancy that has not been previously diagnosed. Clinical features

and pointers to a diagnosis of renal artery stenosis are as follows: young

hypertensive patients with no family history, resistant hypertension,

1.5 cm difference in kidney size on ultrasonography, and secondary

hyperaldosteronism (low plasma potassium concentration). Clinical

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

examination might reveal bruits over major vessels, including the

abdominal aorta.

Angiography remains the standard test for diagnosis, but it is not

without risks and could worsen renal function. Noninvasive tech-

niques are beginning to replace conventional angiography. These

include Doppler ultrasonography, captopril renography, spiral CT

scanning and magnetic resonance angiography. The significance of

lesions found by renal arteriography should be confirmed by differ-

ential renal function studies and renal venous renin activity before

surgical management is undertaken. The severity of stenosis determines

treatment. Hypertension caused by slight or moderate stenosis

commonly responds favourably to medical management.

The concern in pregnancy, and especially in the case discussed,

was the risk of the radiation dose involved with angiography. Mrs K

had had a renal angiogram in her second pregnancy, which resulted

in the diagnosis of renal artery stenosis, but subsequently miscarried.

Although one can argue that the radiation dose involved with an

angiogram would not be greater than the maximum allowed in preg-

nancy (˜5 rad), it was felt wise to avoid angioplasty in the subsequent

pregnancy because the patient perceived the angiogram as a possible

causal factor for the miscarriage. It is more likely that this late mis-

carriage related to severe hypertension rather than radiation. By con-

trast, performing the second angioplasty in the third pregnancy

might have led to a better outcome for the patient and her fetus.

Although Mrs K’s blood pressure was well controlled by antihyper-

tensive therapy, poor fetal growth resulted from the effects of hyper-

tension on placental perfusion, which might have been avoided if an

angioplasty had been carried out in the pregnancy.

Angioplasty is the traditional revascularization procedure, and this

often leads to cure in patients with fibromuscular dysplasia. Resistant

hypertension secondary to fibromuscular dysplasia has been the

primary indication cited for dilatation of the renal artery. Although a

modest improvement in blood pressure or reduction in antihyperten-

sive drug requirement might be the goal of revascularization, renal

protection could emerge as the more important factor.

Drugs alone can control hypertension in almost 90% of patients

with renal artery stenosis. Antihypertensive therapy during pregnancy

might need to be adjusted. Methyldopa, labetalol, hydralazine and nife-

dipine are safe. Angiotensin receptor blockers and ACE inhibitors are

contraindicated in pregnant women and in renal artery stenosis. It is

important to note that lowering blood pressure might decrease utero-

placental perfusion and impair fetal growth.

Renal artery stenosis is an uncommon secondary cause of hyper-

tension in pregnancy, which can be associated with poorly controlled

5. CASE STUDIES

127

hypertension and poor fetal outcome. It can usually be managed with

antihypertensive medication, but definitive treatment is revascular-

ization with angioplasty, which should be considered in pregnancy, in

the face of resistant hypertension.

5.11 THYROID CANCER

Ms L was a 34 year old nulliparous caucasian woman who presented

to her GP at 11 weeks’ gestation complaining of a thyroid lump,

which she had noticed during the preceeding year. On examination,

she was clinically euthyroid. An irregular mass was palpable in the

right lobe of the thyroid, measuring 5 cm

3 cm. There was no

bruit or palpable lymphadenopathy. An ultrasound scan confirmed a

solid thyroid mass, with a 9 mm lymph node at its inferio-lateral

aspect. Fine-needle aspiration (FNA) of the thyroid mass was sugges-

tive of papillary thyroid carcinoma. Biochemically she was euthyroid.

She was commenced on a suppressive dose of thyroxine, 300

g/day.

Mrs L was reviewed at a tertiary oncology centre at 12 weeks’

gestation. A repeat FNA confirmed the diagnosis of papillary thyroid

carcinoma, and an MRI confirmed nodal involvement. She had a

total thyroidectomy with selective right-neck dissection and conser-

vation of two parathyroid glands at 16 weeks’ gestation. Histology

reported complete excision of a 4 cm papillary carcinoma with follic-

ular pattern, with extranodal extension but no extension to the capsule.

Because of the constellation of adverse pathological features (i.e. the

site, nodal involvement and extranodal spread), radio- iodine ablation

was planned after delivery. Her pregnancy progressed well, with a

satisfactory growth scan at 32 weeks’ gestation. Her thyroid function

was regularly monitored, with TSH level moderately suppressed to a

low-to-middle range of normal (0.5-2.8 mu/1). Her free T₄ level was

14 pmol/l on a dose of 200

g of thyroxine. Her corrected calcium

level was initially low and required calcium supplementation, which

was discontinued after the calcium level normalized.

Mrs L went into spontaneous labour at 39 weeks’ gestation and

was delivered by vacuum extraction of a live infant in good condition

and with birth weight of 3.41 kg. At 6 weeks postpartum, her TSH

level was significantly suppressed, at

0.1 mu/1, with a free T₄ level

21.5 pmol/l on a dose of 200

g of thyroxine. This dose was

reduced to 150

g. She was clinically euthyroid and was supplement-

ing breastfeeding with bottle feeding. At 3 months postdelivery, when

her T₄ had been suspended for several weeks, she had radio-iodine

ablation treatment. She was advised not to conceive within the next

6-12 months and to avoid close contact with her baby for 3-4 weeks.

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Discussion

Half of all thyroid cancers occur in women of child-bearing age, but

presentation in pregnancy is rare, occurring in approximately 1 in

10,000 pregnancies. The most common complaint is that of a thyroid

nodule, but these occur in up to 5% of women of child-bearing age,

and only a small proportion are malignant. Overall, most authorities

believe that pregnancy neither stimulates the growth of thyroid

cancer nor worsens the prognosis [33].

If thyroid cancer is diagnosed before the mid-trimester, surgical

intervention can be performed with normal surgical management, as

in the case described above. Recent data suggest that the risk of fetal

loss related to surgery is minimal. When the diagnosis is reached dur-

ing late pregnancy, resection after delivery is the option of choice,

with surgery being performed once the pregnancy-associated vascu-

larity is judged to have resolved. In women whose FNA suggests a

well-differentiated tumour, some studies have shown no difference in

the outcome between those patients that had early surgery and those

patients who had surgery delayed. There is no indication for termi-

nation of pregnancy, although if the tumour is felt to be aggressive or

disseminated, early delivery might be appropriate, in which case the

balance of risks of fetal and maternal well-being must be carefully

assessed [34].

In this case, radio-iodine ablation was indicated postdelivery. T₄

must be stopped 4 weeks before treatment to enable the TSH level

to rise, which facilitates uptake of iodine into the residual thyroid

tissue. Pregnancy should be delayed usually for at least 12 months

after radio-iodine treatment, because it has a long half-life and is

associated with an increased risk of miscarriage and congenital

abnormality if conception occurs sooner. In addition, this time period

enables appropriate suppression of TSH to be achieved; if there is

an early recurrence, management is easier. Clearly, radio-iodine

should not be given in pregnancy: inadvertent use in the early

second trimester causes fetal thyroid destruction and subsequent

hypothyroidism [35].

The mammary gland binds iodide avidly, especially during lacta-

tion, so if radio-iodine treatment is required, breastfeeding should

be stopped and contact with the baby reduced to limit the radiation

to the child to the lowest levels: the length of time is determined

by the dose of radioactive iodine required, but is often around

3 weeks [36].

The prognosis of most thyroid cancers is excellent. Many women

are maintained on a suppressive dose of thyroxine, aiming for an

undetectable TSH level, and so minimizing the risk of stimulation of

5. CASE STUDIES

129

any residual thyroid tumour. Subsequent pregnancies do not alter the

risk of disease recurrence, but for women on a suppressive dose of

T₄, thyroid function should be monitored and the dose adjusted as

indicated.

5.12 ABDOMINAL PAIN

Ms M was a 24 year old para 1

1 who presented to the antenatal

day unit at 30

2 weeks’ gestation with a history of a fall on a wet

surface that caused some bruising on the left leg and left side of the

abdomen. Her examination was normal and no uterine contractions,

vaginal discharge or bleeding were noted. A CTG was normal, and

after being given anti-D for a rhesus-negative blood type, she was

discharged.

Her past obstetric history was of one miscarriage at 9 weeks’ ges-

tation and one Caesarean section at 41 weeks’ gestation (delivering a

2.5 kg baby) because of suspected fetal distress after prostaglandin

administration for induction of labour. Her past medical history

included mild asthma, for which she was using regular salbutamol

and beclomethasone inhalers.

At 31

1 weeks’ gestation, Ms M was admitted with continuing

abdominal pain and decreased fetal movements. The abdominal pain

was in the left iliac fossa, constant in nature and made worse by move-

ment. No cause for the abdominal pain could be found and fetal

assessment, with both CTG and umbilical artery Doppler scanning,

was normal. Fetal movements returned to normal the day after admis-

sion. Ms M was reviewed at 31

6 weeks’ gestation and had contin-

uing left iliac fossa pain, which radiated to her back and was constant

in nature, but worse on movement. While in the day unit waiting for

the results of repeat blood tests, she noticed sudden-onset epigastric

pain, which was associated with shortness of breath, a

nonproductive cough and inspiratory chest pain. On examination, her

heart rate was 100 bpm, her respiratory rate was 28 per minute, her

temperature was normal and her blood pressure was 117/65 mmHg.

The jugular venous pressure (JVP) was not raised, the chest was clear

on auscultation and heart sounds were normal. Neither calf was ten-

der. Her oxygen saturation on air was 94%. After 1 hour, she started

complaining of dizziness at rest.

Further urgent investigations included a 12-lead ECG, which

showed a sinus tachycardia, a full blood count, which showed poly-

morphonuclear leukocytosis, liver function tests, which were normal,

and measurement of serum amylase and C-reactive protein. Arterial

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

blood gases showed a pH of 7.431, pCO₂ of 3.59 kPa and a pO₂ of

9.1 kPa (hypoxaemia). A chest X-ray was normal.

Pulmonary thromboembolism was felt to be the most likely diag-

nosis and therapy was commenced with a therapeutic dose of enoxa-

parin (1 mg/kg body weight/twice daily). The following day, a (V/Q)

lung scan confirmed bilateral ventilation perfusion mismatches con-

sistent with pulmonary emboli. Her leg vein Doppler scans showed

extensive thrombus in the left iliac vein.

Anticoagulation was continued until

2 weeks’ gestation,

when Ms M went into spontaneous labour. Because a dose of 80 mg

of enoxaparin had been given 6 hours before the request for epidural

analgesia, this was declined. Pain relief was achieved with patient-

controlled intravenous opiate analgesia and Ms M had a spontaneous

vaginal delivery of a 2.9 kg baby boy. The estimated blood loss was

300 ml. Following delivery and 26 hours after her last dose of enoxa-

parin, anticoagulation was restarted with enoxaparin, 120 mg once

daily (1.5 mg/kg body weight once daily). Warfarin was commenced at a

dose of 7 mg on day 3, and by day 6, the international normalized

ration (INR) was 2.3 and the enoxaparin was discontinued. Warfarin

was continued for a further 3 months postpartum. A thrombophilia

screen after the discontinuation of warfarin showed that Ms M was

heterozygous for factor V Leiden.

Discussion

Ms M had several risk factors for venous thromboembolism. She was

pregnant and had recently sustained a minor injury that had left her

relatively immobile. Her mother had suffered a deep vein thrombosis

(DVT) aged 42 years.

Included in the differential diagnosis of the epigastric and pleuritic

pain should be an atypical acute asthmatic episode, pneumonia,

pneumothorax, ischaemic/cardiac causes, aortic dissection, cholecys-

titis, pancreatitis and gastro-oesophageal reflux. The presence of

hypoxia made pulmonary embolism a likely diagnosis.

Arterial blood gases in pulmonary embolism might show hypox-

aemia, as in Ms M, with or without hypocapnia caused by hyperven-

tilation to compensate for the loss of pulmonary function. In a small

pulmonary embolism hyperventilation causing respiratory alkalosis

might be the first change in arterial blood gases. Using pulse oxime-

try, a drop in oxygen saturation after exercise (such as walking up

and down a flight of stairs) is a useful screening test if the oxygen

saturation at rest is normal. In normal pregnancy, there is relative

hypocapnia because of the increased respiratory work of pregnancy,

5. CASE STUDIES

131

such that the normal pCO₂ is 3.5-4.5 kPa, approximately 1 kPa lower

than outside pregnancy.

D-dimer measurement in pregnancy is not useful. In nonpregnant

women they are thought to be fairly sensitive, but nonspecific, for

thrombosis and therefore are helpful, if negative, to exclude diagno-

sis of thrombosis. In the pregnant woman, there is a physiological

rise in D-dimers, but normal ranges for pregnancy have not been

fully established, such that the false-positive rate is high [37].

In retrospect, it is likely that the left iliac fossa pain was due to iliac

vein thrombosis, which then dislodged to cause the pulmonary

embolism. Iliac vein thrombosis is more common on the left-hand

side in pregnancy because the inferior vena cava runs on the right-

hand side of the aorta and therefore the left iliac vein is more likely

to be compressed by the right iliac artery. DVT in pregnancy is eight

to nine times more common on the left than the right [38,39].

Alternative to awaiting spontaneous labour would have been

induction of labour or elective repeat Caesarean section. Both these

strategies would have allowed planned temporary interruption of

LMWH to permit regional analgesia or anaesthesia, but the latter

would have increased the risk of thrombosis compared with vaginal

delivery. However, Ms M was keen for a vaginal birth after

Caesarean section (VBAC) and induction of labour was not felt to

be desirable because of the previous Caesarean section, and because

it might have introduced extended bed rest and dehydration. It is

important that women receiving therapeutic LMWH are seen and

counselled by an obstetric anaesthetist before delivery so that the

issues surrounding options for analgesia and anaesthesia can be

discussed before delivery.

5.13 MITRAL STENOSIS

Ms N was a 26 year old primiparous woman from East Africa who

booked-in at her local hospital in the sixth week of her pregnancy.

She was known to have “mild mitral stenosis” from an echocardio-

gram she had following an earlier miscarriage. She had previously

been investigated, but the results of those investigations were not

known. She had mild asthma and used a salbutamol inhaler for this

on an “as required” basis. She was also a smoker.

Ms N presented locally at 24 weeks’ gestation with possible haemop-

tysis. The differential diagnosis was haematemesis and gastroscopy was

carried out, in addition to a V/Q scan and sputum microscopy and cul-

ture, to exclude tuberculosis. The gastroscopy, under antibiotic cover,

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

revealed a Mallory-Weiss tear and she was therefore prescribed raniti-

dine. An echocardiogram repeated at this time confirmed “mild mitral

stenosis” and at this time Ms N was asymptomatic. At 26 weeks’gesta-

tion, she was becoming breathless on climbing stairs, but could still walk

well on the flat. There was no orthopnoea. An anaesthetic opinion was

arranged.

At 35 weeks’ gestation, Ms N was admitted through the accident

and emergency department to a tertiary obstetric unit. She gave a

history of 4 hours of cough, pink frothy sputum and no response to

her inhaler. There was also associated pleuritic chest pain. A malar

flush, typical of mitral stenosis, was also evident [40].

On examination, she had a pulse rate of 130 bpm, her blood pres-

sure was 84/51 mmHg, her respiratory rate was 18 breaths per

minute and she had a PEFR of 300 l/min. The JVP was elevated, and

she had a mid-diastolic murmur and bibasal lung crepitations.

Oxygen saturation was 97% in room air. An ECG revealed a sinus

tachycardia and the chest X-ray showed consolidation at the right

base. Obstetrically, all was well. She was given frusemide, 40 mg

intravenously and diamorphine, 5 mg intravenously, with oxygen, by

mask, at 5 l/min. The transthoracic echocardiogram showed rheu-

matic mitral stenosis of moderate severity, with a dilated left atrium

(5.6 cm), mitral valve area of

1.1 cm²

and mean gradient of

8.5 mmHg (normal, 0-2), and good biventricular function. The diag-

nosis was pulmonary oedema, related to mitral stenosis.

A history of 7 years of dyspnoea was then obtained through the

husband; dyspnoea was worse in pregnancy, with orthopnoea and

paroxysmal nocturnal dyspnoea. He also reported recent onset of

haemoptysis and a much reduced exercise tolerance, i.e. five steps up

a flight of stairs.

Treatment commenced with regular frusemide and diltiazem.

Diltiazem was used to control the heart rate instead of a beta-blocker,

because of the history of asthma. She was also commenced on

LMWH prophylaxis and required potassium supplementation.

Amiloride was added to frusemide for potassium conservation.

Despite this therapy, she remained tachycardic. Diltiazem was, there-

fore, increased and the option of balloon valvotomy was discussed,

should medical therapy fail to prevent further episodes of pulmonary

oedema. Ms N was placed on a 1500 ml/24 hours fluid restriction

regimen as an adjunct to drug therapy.

By day 3 after admission, her heart rate had dropped below

100 bpm and she was less dyspnoeic. By day 4, there was still signif-

icant difficulty maintaining the serum potassium; therefore, the

amiloride dose was doubled. She was also given an infusion of 8 mM

of magnesium in 100 ml of physiological saline, to help maintain her

5. CASE STUDIES

133

potassium level and prevent atrial fibrillation. After a few more days

of diuretics in combination with fluid restriction (1500 ml/24 hours),

she became asymptomatic. Induction of labour was scheduled for

38 weeks’ gestation. An obstetric anaesthetic opinion was obtained

and a plan was made for an elective epidural.

At 38 weeks’ gestation, Ms N went into spontaneous labour.

During labour, fluids were restricted to 85 ml/hour. Antibiotics were

given for endocarditis prophylaxis and care was taken to avoid the

lithotomy and supine positions. Labour progressed well until aug-

mentation was necessary, with a low-volume Syntocinon infusion,

at 9 cm. The morning diuretic dose was administered as usual. After

pushing for 35 minutes she was delivered, with the ventouse and a

right medio-lateral episiotomy. The estimated blood loss was 200 ml.

Ms N had routine postnatal care, with an appointment scheduled

for valvotomy. She was advised not to conceive again before treatment

of the valve. Warfarin was commenced on the third postnatal day and

Ms N was discharged with sustained-release diltiazem and

co-amilofruse. She was also given contraceptive advice, choosing

Depo-Provera as her preferred method. She underwent balloon

mitral valvuloplasty 2 months later; her postprocedure echocardio-

gram showed a mitral valve area of 2.2 cm².

Discussion

Globally, rheumatic heart disease is the most common cardiac disease

presenting in pregnancy, with mitral stenosis the commonest lesion

[41]. The most likely time for complications to present is during the

late second and third trimesters, as occurred in this case and can be

expected in up to 60% of all cases. Complications are usually pul-

monary oedema, arrhythmias or deterioration in New York Heart

Association (NYHA) functional class [41].

Ms N presented during the third trimester with pulmonary

oedema, which took a long time to bring under control. The deteri-

oration seemed to be associated with pneumonia (basal consolida-

tion on chest X-ray) [42] and a tachycardia of

130 bpm, which

resulted in elevation of left atrial pressure (as evidenced by a dilated

left atrium on echocardiography) and pulmonary oedema. If the

medical measures had been unsuccessful in treating her pulmonary

oedema, a mitral valvotomy would have been undertaken, which

would have improved cardiac function significantly for labour and

delivery [41].

Therapeutic strategies include off-loading the heart by reducing

both preload (volume) and afterload (peripheral resistance). Ms N

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

immediately received emergency treatment for pulmonary oedema

with diamorphine, frusemide and oxygen. With the history of

haemoptysis, one of the most obvious diagnoses to exclude would be

pulmonary embolus, which might have explained the tachycardia and

basal consolidation. However, an urgent echocardiogram showed no

evidence of acute pulmonary embolus and suggested mitral stenosis

as the cause of the pulmonary oedema.

Diagnosis and management were further complicated in this case by

the history of asthma. The PEFR, carried out at the bedside, did not

suggest significant reversible airway obstruction as a cause for the

breathlessness. Before the cardiac diagnosis is made, many pregnant

women with heart disease causing pulmonary oedema are initially

labelled as having asthma. It is possible that this was also the case with

Ms N. The possibility of asthma also dictated the medication used to

slow her heart rate and therefore improve left-ventricular filling time

(thus reducing left atrial pressure). Beta-blockers were avoided, but

would have been more effective than diltiazem, a calcium-channel

antagonist. Other possibilities would have been cardioselective beta-

blockers, such as bisoprolol or carvedilol.

LMWH was given as recommended by Lupton et al. [43], because

there was a risk of atrial fibrillation and mural thrombus.

Vaginal delivery in controlled circumstances is advocated in mitral

stenosis, with careful attention to the length and normal progress of

labour. A very careful epidural was given by a senior anaesthetist.

Regional analgesia given slowly minimizes the risk of abrupt vasodi-

lation that would be poorly tolerated in mitral stenosis. Adequate

analagesia is important to limit the increased cardiac output from

pain and thus reduce the risk of pulmonary oedema during the intra-

partum period. LMWH administration was withheld once labour

had started to ensure time for safe epidural administration. The strat-

egy of fluid restriction was continued. The second stage of labour

was curtailed, as recommended, by ventouse.

A further pregnancy without mitral valvotomy or valve replace-

ment in this woman would be high risk, and for that reason, a plan

for contraception was made, in addition to a plan for definitive

treatment of the underlying cardiac disease.

5.14

SPONTANEOUS PNEUMOTHORAX

Ms P was a 29 year old nonsmoker in the 33rd week of her first preg-

nancy. She attended the accident and emergency department with a

2-day history of breathlessness and chest pain. On examination,

there was reduced air entry on the right and reduced chest expansion.

At the time, she looked well and could talk in sentences.

5. CASE STUDIES

135

A chest X-ray with abdominal shielding confirmed a large right-

sided pneumothorax, with no mediastinal shift. Air (100 ml) was

aspirated and she was transferred to the delivery suite. A repeat X-ray

confirmed 70% expansion; a further 60 ml of air was aspirated and a

chest drain was inserted. She continued to be well overnight, with

oxygen saturation

97% and a respiratory rate of 31 breaths/min.

She was given inspired oxygen by mask. The drain fell out, with con-

sequent recurrence of the pneumothorax; a second drain was placed

and had an underwater seal.

After 4 days, because there was a persistent air leak, pleurodesis

was discussed due to the high possibility of a recurrent pneumothorax

at delivery. High-volume, low-pressure suction was set up and she was

transferred to the cardiothoracic ward 1 week after admission.

On day 10 after her original admission, she was taken to theatre for

video-assisted thoracoscopic surgery (VATS). She was anaesthetized

with a left lateral tilt. A pulmonary bleb was excised and abrasion

pleurodesis was carried out. The following chest X-ray showed a small

apical pneumothorax, but the drain still “bubbled” on coughing. This

continued and she was transferred to the maternity unit with a

Heimlich (flutter) valve rather than an underwater seal. By this time,

she was at 35 weeks’ gestation and all investigations on the fetus

remained normal.

However, 10 days after VATS, the persistent air leak continued

and a plan was made to remove the drain if the bubbling ceased for

24 hours. Furthermore, 3 weeks after the original admission, the pos-

sibility of performing talc pleurodesis was discussed because of the

persistent air leak. The chest drain was, therefore, clamped and

adjusted, with a reduction in the volume of the pneumothorax to

5%. Because this manoeuvre had been successful, the decision was

then made to leave the chest drain in until delivery, with a plan for a

further surgical procedure postpartum.

At 39 weeks’ gestation, Ms P spontaneously ruptured her mem-

branes, draining meconium-stained liquor. Following a failed stimu-

lation of labour, she was delivered of a live male infant by emergency

Caesarean section under epidural anaesthesia. The chest drain was

clamped for some hours on the day after delivery, with no deteriora-

tion in symptoms. The following day, the drain was clamped for 24

hours. The drain was finally removed on day 11 postcaesarean

section. A further 4 days later, she remained asymptomatic and

there was no radiological evidence of pneumothorax, only pleural

thickening at the apex of the right lung where the original pleurode-

sis was attempted.

Follow-up was planned with the chest physicians 2 weeks after

discharge.

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Discussion

Primary spontaneous pneumothorax is a rare complication of preg-

nancy, mostly occurring in the late third trimester, although some-

times at other times in pregnancy or the early postpartum period.

There is a high risk of recurrence following initial resolution.

In this case, there were no obvious predisposing factors, such as

smoking, either before or during pregnancy, or asthma. Ms P was of

slim build, but not particularly tall. Management was in keeping with

the recommendations made by the British Thoracic Society’s

(BTS’s) latest guideline for management of primary spontaneous

pneumothorax [44].

Ms P presented 2 days after onset of her symptoms, which seems

to be the median time for presentation. The significance of the time

lag between lung collapse and re-expansion is the risk of pulmonary

oedema that can occur with re-expansion and when early suction is

applied to a chest drain [44]. Here, the BTS recommendations differ

from the consensus statement of the American College of Chest

Physicians [45].

Because the pneumothorax was large and the patient was clinically

stable, the first management measure was aspiration, followed by a

repeat chest X-ray. This should be standard practice, as discussed in

the BTS guideline. The pneumothorax was too large for observation

alone. Again, when the lung was found not to have fully re-expanded,

aspiration without recourse to a chest drain with an underwater seal

was in keeping with the BTS guideline. During this time, oxygen was

given by mask because this has been found to increase the

reabsorption rate and improve hypoxaemia resulting from the

pneumothorax [46].

Ms P needed a drain with an underwater seal once the small-bore

drain had fallen out. She could equally have had a small-bore drain

with a Heimlich valve inserted, giving the opportunity for out-

patient management or mobilization, which was important in the

prevention of thromboembolic disease, because she was in the third

trimester of her pregnancy. A high-resolution CT scan could have

been used at this point to image the chest and establish an underly-

ing cause for spontaneous pneumothorax, but this would have

exposed the fetus to more radiation than a plain X-ray, and several

chest X-rays are likely to be requested for someone with a pneu-

mothorax checking for resolution. The CT scan might have demon-

strated underlying abnormalities and suggested the need for early

surgical intervention. However, there is currently insufficient evi-

dence to support routine use of CT, except in very specific situations

[44,47].

5. CASE STUDIES

137

Because of the continued air leak despite the use of an effective

chest drain, the BTS guideline was followed, with two considerations

in mind:

1. Definitive treatment for a protracted air leak, which was not

responding to drainage with the chest drain.

2. Prevention of recurrence at the time of labour and delivery, when

she was most at risk of recurrent spontaneous pneumothorax.

VATS was the treatment of choice because it enabled a good view of

the lung surface, with the facility to carry out bullectomy or bleb

resection, in addition to mechanical pleurodesis, an additional measure

to prevent recurrence. VATS was chosen instead of talc pleurodesis

because the evidence shows that VATS has a greater efficacy in pre-

venting recurrence than talc or other forms of chemical pleurodesis

because the primary cause can be located and removed [48].

Unfortunately, the VATS procedure was unsuccessful, possibly

because they were unable to gain full lung re-expansion postoperatively,

despite applying suction, and possibly because there was an inadequate

inflammatory response to the pleurodesis procedure, perhaps due to the

pregnancy. It has been suggested that VATS procedures have a higher

failure rate because of a less intense pleural reaction compared with tho-

racotomy procedures. It is also possible that the anatomical defect

responsible for the pneumothorax was not identified and removed. At

this point, the small-bore chest drain with the Heimlich valve was used.

Unfortunately, despite the possibility of being treated as an out-patient,

Ms P no longer had the confidence to go home with the chest drain in

situ, having been in hospital for 2 weeks by this time.

The decision was finally made to allow her to labour with the chest

drain in situ because this was the safest option and the concern about

curtailing the second stage of labour due to the risk of recurrence

would be avoided. This was followed by spontaneous resolution in

the immediate postpartum period.

By its very nature, management of this condition requires that

several chest X-rays be carried out to demonstrate resolution. In this

woman, some of these X-rays were performed in the delivery suite

using portable equipment that produced antero posterior (AP) films.

Because of the potential risks to the fetus of ionizing radiation (i.e.

an increased risk of malignancy in later life) [47], it might have been

wiser to try as far as possible to have all films taken in the X-ray

department because this ensures that the lowest dose of radiation

possible is given to the mother and fetus. By definition, the portable

film increases exposure because of the position of the patient, the

equipment itself, the difficulty in the patient holding her breath in

expiration and the need for extended exposure time [47]. This

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

should encourage departmental X-rays, where possible. However,

the risk from chest X-rays is very low, whether portable or within the

department, because the radiation dose is small, being equivalent to

only a few days of background irradiation. Chest X-rays that are

clinically indicated should never be withheld because of pregnancy.

Although CT has been suggested to have a limited role in the man-

agement of pneumothorax, the type of CT has not been elucidated.

Spiral CT, as used in the diagnosis of pulmonary embolus, will afford

reduced radiation doses, but it could be that high-resolution CT is

more appropriate for the investigation of pneumothorax, particularly

secondary pneumothorax.

It is difficult to know whether chemical pleurodesis would have

given success in this case, when mechanical pleurodesis did not. The

only other procedure that could have been considered to prevent a

recurrence of pneumothorax is pleurectomy, either at the time of the

VATS procedure or through open thoracotomy. Chemical

pleurodesis is known to have reduced efficacy, compared with VATS,

for prevention of recurrence and is also associated with particular

dangers. Doxycycline, a tetracycline, could not have been used in this

patient because she was pregnant and there is a potential risk of dis-

colouration of fetal teeth and bones. With talc pleurodesis, there is a

potential risk of empyema and acute adult respiratory distress syn-

drome (ARDS), especially with doses above 5 g [44].

Finally, the question of whether an adequate sterile inflamma-

tion would develop in a pregnant patient remains unaddressed in

the literature.

5.15 SEVERE PRE-ECLAMPSIA AND HAEMOLYTIC

URAEMIC SYNDROME

Mrs Q was a 26 year old, black African nurse booked-in during her

first ongoing pregnancy. She had a normal booking blood pressure of

100/60 mmHg and normal booking investigations, including a full

infection screen that was negative. She remained well until 25 weeks’

gestation, when she was admitted from the antenatal clinic with a blood

pressure of 190/108 mmHg, 4

proteinuria and 2

blood in her urine.

She also said she had passed less urine during the preceding 3 days and

was complaining of headache, nausea and vomiting.

Mrs Q was admitted and therapy with methyldopa, 500 mg three

times daily was commenced. A 24-hour urinary protein collection of

528 ml was analysed and found to have a protein excretion rate of

15.75 g/24 hours. Her MSU, which was sent that day, was negative.

Other results of note were as follows: platelet count,

275

10⁹

5. CASE STUDIES

139

platelets/l; creatinine, 63

mol/l; albumin, 27 g/l; and urate, 0.32 mmol/l.

With the diagnosis of pre-eclampsia confirmed, the plan was for con-

tinued in-patient management and delivery for the usual fetal or

maternal indications.

After 5 days, Mrs Q awoke with a severe frontal headache and

blood pressure of

198/110 mmHg; she was also complaining of

severe blurring of vision and epigastric pain. There was no vaginal

bleeding. The CTG trace at this point was also suspicious, with

recurrent, unprovoked, shallow decelerations. She was transferred to

the obstetric high-dependency unit, for stabilization before delivery,

and the pre-eclampsia protocol was commenced. She was given a pre-

load of 500 ml of colloid and then bolus doses of hydralazine and

MgSO₄ (4 g), followed by a MgSO₄ infusion of 1 g/hour. Within 30

minutes, she was found to be coughing up pink frothy sputum. On

examination, she had a raised JVP and bilateral basal inspiratory

crepitations, suggesting pulmonary oedema. She was treated with a

40 mg intravenous bolus of frusemide. Blood results, from serum

taken that morning, were then obtained. These showed creatinine of

126

m/l, albumin of 18 g/l (the previous day’s result was 24 g/l),

bilirubin of 30

m/l and urate of 0.4 mmol/l. Her platelet count had

dropped to 108

10⁹ platelets/l. The serum potassium value was

unavailable because the sample was thought to be haemolysed. The

MgSO₄ infusion was stopped because of anuria. Fetal demise was

also confirmed at this time by ultrasound scan, once the heart trace

was lost on the CTG.

An urgent ultrasound of the renal tract excluded renal vein

thrombosis and showed normal-size kidneys, but suggested dif-

fuse parenchymal renal disease. She was given misoprostol per

vagina, followed by oral misoprostol 3 hours later. By this time,

her serum urea level was 7.5 mmol/l and her creatinine level was

189

mol/l.

By the following morning, her creatinine level had risen to

273

mol/l and her urea level had risen to 10.3 mmol/l. The Hb

concentration was

8.5 g/dl and the platelet count was

10⁹

platelets/l. A blood film showed burr cells, fragmented red cells,

spherocytes and normal platelets, suggesting a microangiopathic

coagulopathy. At that point, a reticulocyte count, direct Coombs’

antibody test (DAT) and serum antibodies were requested.

Despite the rising creatinine level and oliguria, her serum potas-

sium level was not raised. Her liver function remained normal, but

her serum albumin level dropped to 16 g/l. The expectation was that

once the fetus was delivered, which occurred 3 hours later, renal

function would improve. This was also the opinion of the renal

physician that morning.

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Unfortunately, despite vaginal delivery of a 960 g male fetus, her

renal function continued to deteriorate over the next

36 hours:

her creatinine level was 791

m/l, her urea level was 23.5 mmol/l

and her serum potassium level was 6.0 mmol/l. The anaemia and

thrombocytopenia had also worsened: her Hb concentration was

6.7 g/dl, her haematocrit was

0.197 and her platelet count was

10⁹ platelets/l. Treatment for hyperkalaemia was instituted with

actrapid insulin, glucose and calcium resonium (15 g orally). Once

the serum potassium level had fallen to 5.1 mmol/l, 2 days after deliv-

ery, Mrs Q was transferred to the renal unit.

On the renal unit, she was treated with plasmapheresis on five

occasions and had two episodes of dialysis. With the last four treat-

ments of plasmapheresis, she was given chlorpheniramine and hydro-

cortisone because she had a severe allergic reaction to the first treat-

ment.

She was discharged 10 days later with a creatinine level of

191

mmol/l and on the following medication:

Doxazocin, 8 mg twice daily

Nifedipine modified release, 20 mg twice daily

Bisoprolol, 10 mg once daily

Sandocal, 1 tablet twice daily

Her blood pressure was well controlled on these drugs and she

remained under the care of the renal physicians for follow-up.

Discussion

Haemolytic uraemic syndrome (HUS) is a constellation of three clin-

ical features, as follows:

Microangiopathic haemolytic anaemia ( DAT negative)

Thrombocytopenia

Renal failure [49]

HUS can be further divided into diarrhoeal and nondiarrhoeal sub-

types; the diarrhoeal form is seen most commonly in children and

adults in association with bacterial gastrointestinal infection, notably

with Escherichia coli 0157. HUS is thought to develop because of

the verocytotoxin produced by the interaction of E. coli with a

lipopolysaccharide co-factor [49]. It is a very rare condition, related

to thrombotic thrombocytopenic purpura (TTP), with an incidence

of 3.7 cases per million (in adults) [50]. In pregnancy, it is thought to

occur 3-10 weeks postpartum [51].

Nondiarrhoeal HUS can be familial or sporadic. In the familial

form, there are autosomal dominant and autosomal recessive patterns

of inheritance [49].

5. CASE STUDIES

141

Sporadic HUS can be associated with a number of factors, such as

the following:

Pregnancy

SLE

Antiphospholipid syndrome

HIV

The combined oral contraceptive pill (COCP)

Ciclosporin

In Mrs Q, pregnancy was obviously an issue, but SLE or other

autoantibody condition could have been contributory

[52].

Interestingly, Mrs Q subsequently tested positive for both anticardi-

olipin antibodies and lupus anticoagulant and had a high (1/1280)

antinuclear antibody (ANA) titre.

HUS in this case declared itself at the time of delivery but it has also

been described in the first trimester. If, as in this case, HUS occurs imme-

diately postpartum or in the third trimester of pregnancy, the following

differential diagnoses, or associated conditions, must be excluded:

HELLP syndrome

AFLP

TTP

In both AFLP and HELLP syndrome, liver function tests are abnor-

mal; however, abnormal liver function tests are unusual in HUS and

TTP. TTP can be more difficult to differentiate clinically, although

it causes a more widespread thrombotic angiopathy, often with

neurological symptoms.

Nondiarrhoeal HUS is thought to be due to a deficiency or muta-

tion in the gene coding for factor H, a complement regulator. As a

result, low complement C3 levels might be a feature, although they are

not always. Because of the absence or deficiency of this factor, it could

be that the alternative complement pathway cannot be activated to

interrupt the clotting cascade once endothelial damage has occurred.

The following treatments have been described as effective in the

literature:

Plasmapheresis

Antithrombin infusions

Prostacyclin infusions

Immunoglobulin (Ig) after failed plasmapheresis and plasma replace-

ment [51].

The mainstay of therapy is now plasmapheresis, and platelet transfu-

sion is contraindicated, because it can exacerbate rather than amelio-

rate the condition. Currently, it is unclear why plasmapheresis

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

works in HUS. It might help to remove large platelet aggregates

and might, in some way, help to control or reduce further platelet

agglutination.

Although the differential diagnosis, especially between HELLP

syndrome and HUS, is often difficult, this case was relatively clear-cut

because there was little liver dysfunction, thereby excluding AFLP

and HELLP syndrome. There were no focal neurological symptoms,

making TTP unlikely, and renal dysfunction seemed to be out of pro-

portion to the pre-eclampsia. Until relatively recently, HUS had a

high mortality rate (of

60%). Thankfully, the advent of plasma-

pheresis has reduced this considerably. However, for Mrs Q, careful

counselling is required concerning the next pregnancy.

5.16 HYPERSPLENISM

Mrs R was a 28 year old black, African woman, who booked in her first

pregnancy at 9 weeks’ gestation. She was fit and well, apart from

splenomegaly, for which she had undergone extensive investigation dur-

ing the previous year. She was known to have sickle cell trait and

received appropriate counselling from the haemaglobinopathy specialist

nurse counsellor. Her partner was sickle cell negative. Her other book-

ing results confirmed that she was negative for HIV 1 and 2, and that

she was a low infectivity carrier of hepatitis B. After a consultation with

the consultant virologist, her partner was vaccinated and arrangements

were set in place for the baby to be treated after birth. Results of the

booking full blood count showed a platelet count of 38

10⁹ platelets/l,

a Hb concentration of 11.9 g/dl and that there was relative leucopenia.

Splenomegaly was first detected by her GP, before this pregnancy,

when she attended the surgery complaining of constipation. During

the examination, the spleen was palpable five fingerbreadths below

the left costal margin. She was referred to a gastroenterologist and

investigated over a 12-month period (Table 5.4).

It was felt that splenomegaly was secondary to a previous malarial

infection and no further action was taken, apart from regular follow-up.

After the finding of thrombocytopenia in pregnancy, a trial of pred-

nisolone (20 mg for 2 weeks) was given in the hope that the platelet count

might rise. However, the platelet count remained between 31

10⁹

platelets/l and 53

10⁹ platelets/l, and thus prednisolone was stopped.

The clinical haematologists became involved in her care and suggested

that splenectomy should be considered following delivery, to allow the

platelet level to rise. The pregnancy continued uneventfully, with Hb

levels within the normal range for pregnancy and no evidence of

haemolysis. There were no episodes of bruising, vaginal bleeding or

epistaxis during the pregnancy.

5. CASE STUDIES

143

TABLE 5.4. Results of investigations for splenomegaly

Upper abdominal

Normal liver, no ascites. Spleen 19 cm

ultrasound

with normal uniform texture

Brucella serology

Negative

Malaria

Negative

Abdominal CT scan

Confirmed normal liver, with normal portal

circulation, and normal kidneys. Massively

enlarged spleen with no focal abnormality

G6PD assay

Negative

Reticulocyte count

Normal, with normal ferritin levels

FBC

Hb, 13.2 g/dl; WBC, 7.6

10⁹/l; platelet count,

10⁹ platelets/l

Clotting

INR, 1.18; APTT, 1.07 (both with 50/50

correction)

Fibrinogen, 1.48 g/l

Bone marrow

Normal

APTT - activated partial thromboplastin time; CT - computed tomography; FBC - full

blood count; G6PD - glucose 6 phosphate dehydrogenase; Hb - haemoglobin; INR -

international normalized ratio; WBC - white blood cells.

The plan for labour included taking samples for a full blood count

and crossmatching two units of blood on admission, and establishing

intravenous access. A consultant obstetric anaesthetist counselled

that regional anaesthesia was contraindicated if the platelet count was

below 80

10⁹ platelets/l and suggested that Entonox and intra-

venous opioids could be used for analgesia in labour. General anaes-

thesia was recommended in the event of an emergency Caesarean

section. It was also noted that NSAIDs should not be used for anal-

gesia and that intramuscular injections should be avoided.

At 41 weeks’ gestation, a membrane sweep was carried out. She

was admitted at 41

3 weeks’ gestation for induction of labour. The

Hb concentration was 11.9 g/dl and the platelet count was 54

10⁹

platelets/l when induction was commenced. She laboured after

receiving 5 mg of intravaginal prostin in divided doses. Unfortunately,

an emergency Caesarean section was necessary at 8 cm dilatation, for

suspected fetal distress. Free fluid was noted at the time of the

Caesarean. A live female infant was delivered, weighing 3.13 kg. The

estimated blood loss was 750 ml and an infusion of Syntocinon

(40 iu) was commenced at a rate of 10 iu/hour. A negative pressure

drain was placed at the time of surgery, which drained 370 ml in the

first 24 hours and, subsequently, a further 870 ml of serosanguinous

fluid. Postpartum ultrasound confirmed the presence of ascites and

revealed that the splenic size had reduced from a maximum of 21 cm

to 12 cm. On the first day postcaesarean section, she was found to

be anaemic with a Hb concentration of 8.8 g/dl and a platelet count

144

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

of 38

10⁹ platelets/l; iron was prescribed. The drain was removed

and she was discharged on the fifth postoperative day, with arrange-

ments for haematology and gastroenterology follow-up appointments.

Discussion

“Hypersplenism” is a term used to describe splenomegaly, from any

cause, and its consequences.

The causes of splenomegaly include the following:

Infection

Inflammation

Haematological

Miscellaneous

A greatly enlarged spleen is more common in the presence of myelofi-

brosis, chronic leukaemia, chronic malaria, kala-azar or Gaucher’s dis-

ease (lysosomal storage disease). Chronic malaria was felt to be the

cause of splenomegaly in this case, although no evidence of malarial

parasites had ever been found. Other infectious causes had been

excluded, including hepatitis. Although Mrs R was known to be hep-

atitis B positive, she was shown to be of low infectivity and did not

have evidence of chronic hepatitis [53]. There was no evidence of

investigation for sarcoidosis, another recognised cause for hyper-

splenism [54].

Hypersplenism can result in pancytopenia, haemolysis and an

increased plasma volume, but the only features present during preg-

nancy in Mrs R were thrombocytopenia and intermittent leucopenia,

which had been evident before pregnancy.

When she was first seen by the obstetrician, her previous medical

notes were unavailable. The first thought was that the thrombocy-

topenia was caused by immune thrombocytopenic pupura (ITP),

because the count was lower than expected for gestational thrombocy-

topenia at 20 weeks’ gestation. It was known that Mrs R was HIV 1

and 2 negative and that she did not have lupus anticoagulant or anti-

cardiolipin anibodies. Antiplatelet antibodies were not assayed,

because they were considered unlikely to change management. There

was no evidence of SLE. The platelet count was checked using a cit-

rate sample, which confirmed that it was a true thrombocytopenia,

rather than a spurious result due to in-vitro platelet clumping.

A trial of prednisolone was given to promote a rise in the platelet

count, assuming the low count was related to an immunological cause.

The platelet count did not rise and prednisolone was stopped. It could

5. CASE STUDIES

145

be argued that immune thrombocytopenia was not adequately excluded

because the steroid trial was not at a dose high enough to bring about a

response. The usual treatment for suspected refractory ITP is pred-

nisolone at a dose of 1 mg/kg body weight, but this is often associated

with relapse. A dose equivalent to 250 mg of prednisolone over 4 days

has been recommended [55] and found to produce a sustained rise in the

platelet count; however, this runs the significant risk of side effects, such

as mood swings, steroid psychosis, hypertension and deranged glucose

metabolism, all of which would be best avoided in pregnancy.

It was appropriate to make appointments for a predelivery anaes-

thetic opinion, both to give the obstetric anaesthetic staff warning of

this high-risk patient and to allow the patient to be fully informed of

her choices and the potential difficulties surrounding delivery and

analgesia. It meant that when an emergency caesarean was carried out,

she was emotionally and mentally prepared, and the unit was prepared

with crossmatched blood and intravenous access. The haematologists

should have been informed when she went into labour, because of the

possibility of needing platelet cover during delivery, if her platelets

had dropped low enough (

10⁹ platelets/l) [56]. In fact, at the

time of induction (which was carried out because she was approaching

42 weeks of completed gestation), her platelet level was

10⁹

platelets/l, a level at which she was not expected to be at higher risk of

bleeding, although it still precluded regional anaesthesia.

Fetal blood sampling was avoided because Mrs R was known to be

hepatitis B positive and fetal thrombocytopenia remained a possibil-

ity. Her blood pressure during labour was around 140/80 mmHg,

compared with a booking blood pressure of 94/60 mmHg, and it is

noteworthy that there was a degree of renal impairment, with the cre-

atinine level rising from

mol/l in the mid-trimester to

138

mol/l peripartum. This was associated with a rise in bilirubin

mol/l and ALT 180 iu/l, which together with an additional fall in

the platelet count and a drop in the Hb concentration greater than

expected for the estimated blood loss, suggested HELLP syndrome;

there was no record of proteinuria or urinalysis during labour, but

this does not preclude the diagnosis. Alternatively, the rise in creati-

nine might have been related to postpartum haemorrhage and the rise

in ALT might have been related to the usual physiological postpar-

tum effect, although both changes were more marked than is usually

seen in those circumstances.

The cause of the splenomegaly remains unresolved in this case,

although the new finding of ascites might help future investigations.

The platelet count is one of the factors that will determine management,

including the need for splenectomy.

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

5.17 SPINA BIFIDA WITH SEVERE KYPHOSCOLIOSIS

Mrs S was a 31 year old para 1

0 who attended the medical obstet-

ric clinic at 10 weeks’ gestation with an unplanned pregnancy.

She had spina bifida diagnosed at birth and underwent repair of

two large thoraco-lumbar lesions, with subsequent surgery on several

occasions as an infant. She had very severe kyphoscoliosis, but did

not report any bladder or bowel problems nor suffer from recurrent

urinary tract infections.

Mrs S had had one previous pregnancy and reported that an elec-

tive Caesarean section had been performed at 34 weeks’ gestation

because “the baby ran out of room”. That pregnancy had been

planned and she had attended for prepregnancy counselling and had

pulmonary function tests performed before conception. These indi-

cated that the forced vital capacity (FVC) was 1.21 l, resting blood

gases were normal and overnight oximetry showed no desaturation.

There was no evidence of incipient respiratory failure, but the respi-

ratory reserve was very limited. She was strongly encouraged to stop

smoking, which she succeeded in doing. An echocardiogram showed

no evidence of secondary pulmonary hypertension.

During that previous pregnancy, she had presented for booking at

14 weeks’ gestation and was taking folic acid (5 mg) at conception.

She had early dating and nuchal translucency scans, which were nor-

mal, in addition to a fetal anomaly scan at 20 weeks’ gestation, which

was also normal. The respiratory physicians, obstetrician and the

medical obstetric team saw her regularly. The respiratory team

arranged a trial of nasal intermittent positive airways ventilation

(NIPPV) on an in-patient basis at 30 weeks’ gestation and she toler-

ated this very well. Overnight oximetry was performed at home at 31

weeks’ gestation, with no evidence of desaturation.

She had become increasingly breathless at 32 weeks’ gestation and

could only walk 20 m without stopping because of severe breathless-

ness. She was admitted to the antenatal ward for rest. Further sleep

testing showed deterioration in her oxygen saturation and it was

decided to deliver her by elective Caesarean section at

34 weeks’ gestation. A female infant was delivered without complica-

tions. Mrs S was initially admitted to the intensive care unit (ICU)

postoperatively and NIPPV was required for several days postdeliv-

ery. The baby remained in SCBU for a few days, and at the time of

presentation in the second pregnancy, she was a fit and healthy 4 year

old. Mrs S returned to her prepregnancy function level within a

few days.

On this occasion, Mrs S had been using condoms for contraception,

and because this was an unplanned pregnancy, she had commenced

5. CASE STUDIES

147

5 mg of folic acid only on confirmation of a positive pregnancy test,

at approximately 8 weeks’ gestation. She was keen to proceed with

the pregnancy and thus an early dating scan and first trimester

screening tests were organized. Pulmonary function tests and an

echocardiogram were arranged. Mrs S was warned that there might

have been some deterioration in her pulmonary capacity since her

previous pregnancy and that the likelihood was of a similar preg-

nancy course, with admission necessary during the third trimester

and early delivery by Caesarean section. She was concerned by this

possibility and the necessary frequent visits to hospital, because this

would have an impact on her daughter.

Discussion

Mrs S was born with diastematomyelia, also termed “split cord mal-

formation”, which is a form of occult spinal dysraphism character-

ized by a cleft in the spinal column. It can be isolated or associated

with other dysraphisms, segmental anomalies of the vertebral bodies

or visceral malformations - horseshoe or ectopic kidney, utero-ovarian

malformation and anorectal malformation. It is rare, but the neonatal

outcome of isolated diastematomyelia is generally good, even if sur-

gical repair is required.

The issues relating to pregnancy in these patients include the

following:

Genetic counselling - any female patient with spina bifida is

strongly recommended to have preconceptual genetic counselling.

For parents with spina bifida, the risk of having affected offspring is

approximately 4%, which is considerably increased compared with

the general population (in which the risk is 0.1-0.3% [57]). This risk

can be lowered if periconceptual folic acid is given.

Potential urological complications include neurogenic bladder,

incontinence, chronic infection, an increased risk of developing blad-

der carcinoma and impaired renal function, and are common in spina

bifida. In cases of urinary diversion, obstruction could complicate

the pregnancy. The risk of recurrent urinary tract infection is

increased, especially if there is a history of recurrent urinary tract

infection outside pregnancy - a careful and detailed history must be

taken at the initial booking appointment.

The incidence of preterm labour is increased, in addition to

cephalo-pelvic disproportion because of a possibly contracted pelvis -

this can be assessed to a limited extent using CT or MRI scanning.

Transverse lie is common, but if the head engages normally, vaginal

delivery should be allowed, if possible.

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Cerebrospinal fluid shunts could produce neurological prob-

lems during pregnancy. In most reported cases, symptoms

improved spontaneously after delivery. In a woman with a shunt,

vaginal delivery is preferable, pushing during the second stage of

labour is not contraindicated and, for a Caesarean section, prophy-

lactic antibiotics and thorough irrigation of the peritoneal cavity

are indicated.

A large case series describes 29 pregnancies in 17 women, with

23 pregnancies progressing to births [58]. Of the 17 women, 14

women had antenatal admissions, with wheelchair-dependent

women requiring more frequent and longer admissions. Recurrent

urinary tract infection occurred in women with a prior history of

urinary infection. Mobility was reduced for two women during

pregnancy, with a full recovery afterwards. Pre-existing pressure

sores worsened during pregnancy. Vaginal deliveries occurred in

20% of wheelchair-dependent women and in 55% of independently

mobile women. Caesarean sections had a high postoperative com-

plication rate.

The problem of kyphoscoliosis in pregnancy is uncommon: the

literature since 1996 describes only 36 cases [59].

Women with severe lung disease are less likely to deteriorate in

pregnancy than those with severe cardiac disease. Figures, such as

1 l or 50% of predicted FVC, have been suggested for successful

pregnancy outcome. However, women with much lower FVC have

had successful pregnancies. Further deterioration in lung function

as a result of the pregnancy can be expected, and in women with

a FVC of 1-1.5 l, severe limitations in exercise capacity, fatigue

and hypersomnolence are expected. Pulmonary hypertension

should be excluded with a prepregnancy echocardiogram. There

are case reports in the literature of NIPPV with bilevel positive

airway pressure used to correct exercise tolerance, fatigue and noc-

turnal oxygen desaturation

[60]. This was trialled in Mrs S,

although it was not required until the immediate postpartum

period.

Anaesthetic review is essential as part of delivery planning.

5.18 PEMPHIGOID GESTATIONIS

Ms T was a 24 year old primigravid patient from the Middle East

who booked at 13 weeks’ gestation. Her booking bloods were normal,

with no evidence of a haemoglobinopathy. Her Hb concentration was

5. CASE STUDIES

149

11.2 g/dl and her booking blood pressure was recorded as

110/75 mmHg.

There was no contributory past medical history. She had been well

throughout the pregnancy, until presenting at 29 weeks’ gestation with

a rash. On examination, she had pruritic erythematous, urticarial

plaques and vesicles on her hands, extremities, trunk, face and scalp.

There was no history of any drug ingestion, hormonal therapy or any

systemic symptoms.

A skin biopsy was performed under local anaesthetic, which showed

positive complement C3 linear basement-membrane staining with

direct immunofluorescence and positive staining to IgG and comple-

ment C3 under indirect immunofluorescence. Therefore, a diagnosis of

pemphigoid gestationis was made. Therapy was commenced with pred-

nisolone, 60 mg/day, topical betamethasone cream and antihistamines.

Over the next month, her condition improved. A preterm, healthy baby

boy was delivered vaginally at 34 weeks’ gestation. However, during his

first week of life, he developed multiple erythematous urticarial plaques

and bullae, which responded well to a low-potency steroid cream.

In the puerperium, Ms T developed a flare, for which she was

treated with prednisolone, 80 mg/day, chlorpheniramine, 4 mg three

times daily, and fucidin and betnovate creams. Additional treatment

included ciclosporin,

300 mg/day, intravenous Ig

(two courses),

pulsed intravenous methylprednisolone, mycophenolate mofetil,

3 g/day, and azathioprine, 200 mg daily.

At 10 months postpartum, she again developed widespread

blisters on erythrematous itchy plaques, which showed positive IgG

linear basement-membrane staining. Investigations performed at this

stage showed the following:

C-reactive protein:

55 g/l

Albumin:

29 g/l

Hb:

10.3 g/dl

Eosinophils:

1.6

10⁹/l

Autoantibody screen: negative

A hormone profile and glucose test were both normal. A chest X-ray

was normal and a dual X ray absorpitometry (DEXA) bone-density

scan revealed osteopenia. The following treatment was commenced:

methylprednisolone, 1 g/day intravenously for 3 days; Ig, 2 g/kg

body weight intravenously over 3 days; prednisolone, 50 mg/day;

mycophenolate mofetil,

3.5 g/day; Atarax,

25 mg/day; ranitidine,

150 mg/day; alendronate,

70 mg once weekly; Calcichew,

tablets/day; antiseptic soaks; and emollients. Over the ensuing

months she made a full recovery.

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Discussion

Pemphigoid gestationis is a rare condition that can complicate 1 out of

40,000-60,000 pregnancies. It was initially named “herpes gestationis”

by Milton in 1872, which comes from the Greek “to creep”. This is,

however, a misnomer because the disease is not related to any active

or prior herpes infection. Jenkins et al. have argued for the term

“pemphigoid gestationis” [61].

Pemphigoid gestationis is a pregnancy-associated autoimmune

disease. Most patients develop antibodies to the basement-membrane

protein bullous pemphigoid antigen 2 (BPAG2; collagen XVII),

which has a crucial role in epidermal-dermal adhesion. Binding of

IgG to the basement membrane is believed to trigger an immune

response that leads to the formation of subepidermal vesicles and

blisters. The same antibodies occur in patients with bullous pem-

phigoid (BP) [62].

The trigger for development of autoantibodies remains elusive.

Crossreactivity between placental tissue and skin has been proposed to

have a role. Pemphigoid gestationis has a strong association with HLA-

DR3 and HLA-DR4, and virtually all patients with a history of pem-

phigoid gestationis have demonstrable anti-HLA antibodies. The pla-

centa is known to be the main source of disparate (paternal) antibodies

and thus can present an immunological target during gestation.

Pemphigoid gestationis typically occurs in the second to third

trimester, with 50-75% of affected women experiencing a postpartum

flare within 24-48 hours of delivery [63]. Classically, it presents as

pruritic erythematous, urticated papules and plaques (which might

appear target-like, annular or polycyclic) and could develop into vesi-

cles/tense blisters within days or a few weeks. The rash usually starts

in the periumbilical area (90%).

Pemphigoid gestationis is a dermatosis specific to pregnancy, in

addition to polymorphic eruption of pregnancy (PEP), prurigo of

pregnancy and pruritic folliculitis, from which it can usually be easily

differentiated [64]. The differential diagnoses include other autoim-

mune bullous diseases, drug eruptions and erythema multiforme.

Diagnosis is made by direct immunofluorescence, which shows

positive complement C3 deposition at the basement membrane. IgG

titres do not correlate to disease activity.

Prognosis for the initial presentation is good, but recurrences are

common (as demonstrated by this case), especially postpartum, and

can occur with oral contraceptive use, the menstrual cycle and,

less commonly, ovulation. The disease could persist for anything

from a couple of weeks to several years postpartum. There is a

reported case of active disease 12 years postpartum [63].

5. CASE STUDIES

151

There is a high risk of recurrence in subsequent pregnancies,

unless the partner is changed. Recurrences tend to occur at an earlier

gestational age and with increased severity.

Because there are immunological factors implicated in the patho-

genesis, fetal and/or neonatal disease is a logical possibility. There is

debate in the literature about overall fetal outcome, but generally it is

accepted that 5-10% of babies present with transient urticarial or

vesicular lesions, which resolve spontaneously in 2-3 weeks (as in this

case). Some studies have shown an increased incidence of prematurity

and small-for-date babies; therefore, regular ultrasound surveillance

is suggested [63]. There is no apparent increase in the long-term risk

of other autoimmune diseases.

Pemphigoid gestationis is associated with HLA-DR3 and HLA-

DR4, in addition to trophoblastic tumours (choriocarcinoma and

hydatidiform mole), Graves’ disease, Hashimoto’s thyroiditis, perni-

cious anaemia, Crohn’s disease, alopecia areata, and antithyroid and

antiplatelet antibodies.

This case is unusual, because there was a recurrence of symptoms

10 months after the postpartum recurrence. Because there is an over-

lap between these bullous diseases, it is conceivable that this actually

represented a conversion from pemphigus gestationis to bullous pem-

phigoid, which has been previously reported [61].

5.19 TAKAYASU’S ARTERITIS

Mrs V was a 29 year old nulliparous Asian woman who presented to

the obstetric medicine clinic for prepregnancy counselling. She had

been diagnosed with Takayasu’s arteritis 8 years previously but was

told her disease was now quiescent. She was asymptomatic and tak-

ing prednisolone, 5 mg/day. Both radial and brachial pulses were

absent on the left, but using auscultation over the right brachial

artery, her blood pressure was 132/76 mmHg.

Discussion

Takayasu’s arteritis is a disease of heterogeneous manifestation, pro-

gression and response to treatment. It is characterized by acute

attacks of pulseless large-vessel arteritis, followed by stenosis, most

commonly of the aorta and its branches above and below the

diaphragm. Following clinical assessment, the diagnosis is made using

angiography, duplex ultrasound scanning and/or MRI. There are no

reliable biochemical markers of disease activity, and C-reactive

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

protein and ESR are not helpful in initial diagnosis or assessment of

relapse. Fulfilment of three of the six diagnostic criteria is necessary

for the diagnosis of Takayasu’s arteritis, as proposed by the

American College of Rheumatology (ACR) in 1990 (Table 5.5).

Table

5.6 describes the anatomical angiographic classification

adapted from the Takayasu Conference of 1994.

Asian people are more commonly affected than other ethnic

groups, regardless of their country of residence. It is a rare condition,

with a prevalence of 2 in 1 million individuals in the UK. The mean

age of diagnosis is 25 years, and 70% of patients are female. Hence,

the commonest patient group is women of reproductive age.

However, it also occurs in children. A monophasic attack with resid-

ual stenotic sequelae is exhibited by 20% of patients. Half of these

patients go into remission with immunosuppressive therapy, but 50%

of these treated patients relapse within 5 years. A further 30% of

these patients have progressive disease that is unresponsive to ther-

apy. Although the 10-year survival rate is

90%, 75% of patients

suffer significant morbidity, affecting their daily life. Cardiac failure

is the most common cause of death.

Clinical symptoms depend on the site, and extent, of pathology and

are attributed to end-organ ischaemia. Feeble or absent peripheral

TABLE 5.5. Modified American College of Rheumatology diagnostic

criteria, 1990 for Takayasu’s arteritis

1. Development of symptoms or signs before 40 years of age.

2. Claudication of extremeties, fatigue or discomfort on use of limbs.

3. Decreased brachial artery pulse, either unilateral or bilateral.

4. Blood pressure difference of at least 10 mmHg between arms.

5. Audible bruit over subclavian artery or abdominal aorta.

6. Angiogram abnormalities: stenosis or occlusion of aorta, its main branches

or large vessels in proximal upper and lower extremities, which is not

caused by atherosclerosis.

Table 5.6. Angiographic classification for

Takayasu’s arteritis

Type

Site of disease

Type I

Only branches of aortic arch

Type IIa

Ascending aorta and above

Type IIb

Descending thoracic aorta and above

Type III

Thoracic, abdominal and/or renal

Type IV

Abdominal and/or renal

Type V

Mix of types IIb and IV

5. CASE STUDIES

153

pulses, with resultant claudication, with or without bruits are hall-

marks of the disease. Bruits are the most common clinical sign, pres-

ent in 80% of patients. These are most commonly heard over the

carotid arteries, which are involved in 60% of patients, of which 60%

have bilateral disease. Carotidynia is present in up to 30% of patients.

Cardiovascular pathology is present in 40% of patients, most com-

monly aortic regurgitation. Pulmonary hypertension is present in 5%

of patients. Systemic and renovascular hypertension develops in 75%

of patients. Other complications include cardiac insufficiency and

stroke. Systemic symptoms of lethargy and fatigue are present in 40%

of patients, and about 25% of patients have significant pyrexia during

acute episodes. Ophthalmological and neurological symptoms warrant

aggressive assessment and urgent treatment [65,66,67].

Ishikawa suggested a clinical classification, grouping 54 patients

into

4 categories according to the site and severity of disease

(Table 5.7). Ishikawa gave importance to four main complications,

namely retinopathy, secondary hypertension, aortic regurgitation and

aneurysm formation. Most of the fatalities occurred in groups II and

III. All patients with aortic regurgitation were classified as group

IIB. However, this system of classification is not applicable to preg-

nant women, because pulmonary hypertension carries a 30-50% mor-

tality in pregnancy.

There have been various series reporting an association between

Takayasu’s arteritis and tuberculosis. These series are mainly from

Asia, where the prevalence of tuberculosis is high and it is difficult to

prove causality.

NSAIDs are used during acute attacks to alleviate symptoms, but

the main treatment option is corticosteroids. In 50% of cases, steroids

alone fail to achieve remission and adjuvant immunosuppressive

agents are added to the regimen; the most commonly used immuno-

supressive agents are methotrexate, cyclophosphamide and azathio-

prine. No one agent is superior to another in achieving disease remis-

sion. Surgical grafting of critically stenosed vessels is indicated in the

following situations:

Severe renovascular hypertension.

Table 5.7. Ishikawa classification 1978 for Takayasu’s arteritis

Group I

Uncomplicated disease, with or without

pulmonary involvement

Group IIA

Mild/moderate single complication with

uncomplicated disease

Group IIB

Single severe complication

Group III

Two or more complications

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Significant (symptomatic) cerebral ischaemia, with a minimum of

three-vessel involvement.

Grade II aortic regurgitation.

Coronary insufficiency.

Claudication of extremities.

Almost one-third of surgical procedures have significant complica-

tions, including restenosis in 25% of these [68].

It is not uncommon for Takayasu’s arteritis to present for the first

time in pregnancy. Indeed, this was the main route of patient recruit-

ment in some series. Because pregnancy is rare among women with

severe disease, favourable pregnancy outcomes have been reported in

many series. One study observed that pregnancy seems to confer a

prognostic advantage, but this is likely to be due to the fact that

women with milder forms of the disease conceive.

Pregnancy itself does not seem to affect the course or prognosis of

the disease, and the risk of relapse does not seem to be increased,

even in the postpartum period. Pregnancy, however, might mask and

delay the diagnosis of Takayasu’s arteritis. Fatigue, lethargy,

headaches, light-headedness, calf cramps and cardiac murmurs are all

inherent to pregnancy. Furthermore, there might be temptation to

delay diagnostic testing in pregnancy for fear of fetal radiation expo-

sure. Duplex ultrasound scanning and MRI are safe alternatives to

angiography, with negligible fetal risks. Steroid therapy must be con-

tinued in pregnancy if clinically indicated.

Monitoring of disease could pose a clinical challenge.

Angiography is relatively contraindicated. The ESR is raised in preg-

nancy, and both the ESR and the C-reactive protein level are non-

specific disease markers. The hyperdynamic circulation of pregnancy

can make bruits louder, giving a false sense of disease progression.

Blood pressure measurement should ideally be performed on an

unaffected limb. However, this might be difficult and even impossi-

ble if all four limbs are involved.

There might be deterioration of cardiac and renal function during

pregnancy. The risks are proportional to the degree of prepregnancy

insufficiency.

The worst outcomes are usually in women with cardiac insuffi-

ciency, severe hypertension and significant aortic regurgitation, for

which the risks of miscarriage, IUGR, prematurity, intrauterine

death (IUD) and Caesarean section are increased. The risk of pre-

eclampsia is increased with renovascular hypertension. Fetal or

neonatal arteritis has not been described.

Outcomes are favourable if pregnancy is conceived during a

quiescent phase or if the maintenance immunosuppressive regimen

5 mg of prednisolone on alternate days.

5. CASE STUDIES

155

Complications that must be addressed before embarking on preg-

nancy include cardiac insufficiency, severe renovascular hypertension,

aortic regurgitation and renal insufficiency. Pregnancy is contraindi-

cated in the presence of pulmonary hypertension and significant

cardiac insufficiency.

Steroid therapy is safe in pregnancy. However, the commonly used

immunosuppressive agents methotrexate and cyclophosphamide are

contraindicated because they cause pregnancy loss and are terato-

genic. Azathioprine seems to be safe in pregnancy and breastfeeding.

Acute inflammation can pose a therapeutic challenge because long-

term use of NSAIDs beyond 24 weeks’ gestation has been associated

with oligohydramnios and premature closure of the ductus arterio-

sus. Short-term use before 32 weeks’ gestation is permissible with

monitoring of liquor volume and, if feasible, Doppler assessment of

ductus arteriosus flow. Oligohydramnios is an indication to stop

treatment, following which there is usually spontaneous restoration

of liquor volume.

The patient with Takayasu’s arteritis who wishes to embark on

pregnancy should ideally be seen in the prepregnancy clinic setting.

A planned pregnancy is vital because the outcome is determined by

the lack of active disease at conception. Disease-suppressive or dis-

ease-modifying drugs must be reviewed, and if necessary, changed to

an alternative therapy that is less damaging to the fetus. Hypertension

must be controlled with agents that are not teratogenic. Severe

stenoses should be surgically corrected before pregnancy. Aneurysms,

especially cerebral, should be sought and treatment considered before

pregnancy. Severe uncorrected aortic regurgitation is also a relative

contraindication to pregnancy. Steroid-induced diabetes should be

controlled. Women with hypertension should be counselled concern-

ing the increased risk of pre-eclampsia. Women with mild quiescent

disease should not be discouraged from pregnancy because outcomes

are favourable.

Pregnancy should be managed by a multidisciplinary team who

are familiar with high-risk pregnancies, including a physician, obste-

trician and neonatologist. The woman should be seen more

frequently in pregnancy, to be screened for pre-eclampsia and IUGR.

She should be screened for gestational diabetes if she is receiving

steroid therapy. There should always be a high index of suspicion of

relapse, even if symptoms seem compatible with normal pregnancy.

She should receive the appropriate thromboprophylaxis treatment

throughout pregnancy and the puerperium. Low-dose aspirin can be

useful for the inhibition of inflammation, prevention of pre-eclampsia

and thromboprophylaxis throughout pregnancy.

Postpartum haemorrhage has not been reported in association with

Takayasu’s arteritis. Intrapartum intravenous steroid support should

156

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

be considered if the woman has been taking a dose of prednisolone

equivalent to or greater than 7.5 mg/day in the 14 days preceding

delivery.

Presence of untreated aneurysms might be an indication for oper-

ative delivery, especially if there has been a recent haemorrhage or for

fetal salvage in the moribund mother.

5.20 PNEUMONIA

Mrs W was a 45 year old nonsmoking woman in her second preg-

nancy. Her first baby was delivered by Caesarean section at 37 weeks’

gestation following a failed induction of labour for suspected fetal

growth restriction.

She booked in the first trimester and had uncomplicated care with

regular antenatal checks. Serial growth scans showed normal growth

of the fetus on the 50th centile. Mrs W developed some shortness of

breath at about 22 weeks’ gestation, which subsequently resolved. At

32 weeks’ gestation, it was noted that she had a productive cough.

At 34 weeks’ gestation, Mrs W presented to the antenatal day unit

with severe shortness of breath and a cough productive of green spu-

tum. She had been unwell for more than 2 weeks and her cough had

worsened over the past few days. The night before she had been

unable to sleep because she was so dyspnoeic and she also had

pleuritic chest pain radiating to the interscapular region. She was

generally tired and exhausted. Mrs W was initially transferred to the

delivery suite and then to the obstetric high-dependency unit when

her clinical condition continued to deteriorate.

On examination, she was pyrexial, tachypnoeic, with a respiratory

rate of 30/min, and using the accessory muscles of respiration. She

could only talk in short sentences. Her blood pressure was

90/55 mmHg, her pulse was bounding at 130 bpm, the JVP was nor-

mal and auscultation of the heart revealed a soft ejection systolic

murmur. There was decreased air entry and dullness to percussion at

the left base, with coarse inspiratory and expiratory crackles. There

was minimal ankle oedema. Blood gases that were performed while

she was breathing air showed a pH of 7.469, a pCO₂ of 3.6 kPa, a pO₂

of 7.9 kPa and a base excess of

2.9. The differential diagnosis was

of probable pneumonia and possible pulmonary embolism.

She was given facial oxygen at 3 l/min and clarithromycin, 500 mg

intravenously twice daily and cefuroxime, 1.5 mg three times daily.

A therapeutic dose of enoxaparin was also given to treat a possible

pulmonary embolism. An urgent chest X-ray, echocardiogram and

ECG were requested, the former confirming left lower lobe pneumonia.

She was also given betamethasone for fetal lung maturation.

5. CASE STUDIES

157

While Mrs W was being stabilized, the CTG showed recurrent

variable decelerations. Repeat abdominal examination remained nor-

mal and there were no signs of an abruption. Blood gases were

repeated 40 minutes later after she had received 10 l of oxygen, and

the hypoxia had improved: pH, 7.459; pCO₂, 3.3 kPa; pO₂, 14 kPa;

and base excess,

4.4. Mrs W remained unwell, and in the light of

concerns for fetal well-being too, it was decided to stabilize and

deliver her by urgent (grade 2) Caesarean section under a general

anaesthetic. General anaesthesia was chosen because the recent ther-

apeutic dose of enoxaparin precluded regional anaesthesia and,

because of worsening maternal exhaustion, mechanical ventilation

might become necessary.

The Caesarean section was uncomplicated, and a healthy nonaci-

dotic, normally grown baby was delivered. Postpartum haemorrhage

prophylaxis, in the form of a Syntocinon infusion, was started,

because anaemia would potentially worsen Mrs W’s oxygenation.

Perioperatively Mrs X required noradrenaline (norepinephrine) and

was transferred to the ICU for continued ventilation. Inotropic sup-

port was required for only a few hours.

The next day she was extubated without difficulty and transferred

back to the obstetric high-dependency unit. Oxygen saturation was

between 93% and 95% with air. Mrs W continued to improve over the

next few days and her antibiotics were changed to oral preparations.

On the fourth postoperative day, the oxygen saturation with room air

was consistently

97%. The chest X-ray was repeated on day 9 and

showed some bronchial thickening, but no residual consolidation.

She went home the following day.

Discussion

Mrs W was unwell for some time and presented only once she

became extremely sick; in hospital, she continued to deteriorate. She

was resuscitated and stabilized, and delivered by Caesarean section

for fetal distress.

Mrs W had two of the four BTS criteria for severe pneumonia and

postoperatively required admission to ICU. Fortunately, she made a

quick recovery, with minimal morbidity.

Pregnant women do not get pneumonia more often than nonpreg-

nant women, but it can result in greater morbidity and mortality

because of the physiological adaptations of pregnancy [69]. The

hormonal effects of progesterone and beta-human chorionic

gonadotrophins, changes in chest dimension and elevation of the

diaphragm all result in a state of relative dyspnoea, which worsens in

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

the third trimester. Changes in maternal oxygen consumption and

tidal volume result in a decreased capacity to compensate for respira-

tory disease.

Additionally, pregnancy results in a compensated respiratory alka-

losis. Minute ventilation increases, in addition to the increase in pO₂

to 13-14 kPa (104-108 mmHg), whereas pCO₂ decreases to 4.0 kPa

(30; 27-32 mmHg). The arterial pH is maintained through increased

renal excretion of bicarbonate. Small changes in these compensated

values can indicate more severe respiratory dysfunction than outside

pregnancy and can alter fetal oxygenation. Co-existing maternal dis-

ease, such as asthma and anaemia, increase the risk of pneumonia in

pregnancy. Neonatal consequences include low birth weight and

premature delivery in 44% of patients.

The estimated prevalence of antepartum pneumonia ranges from

0.78 in 1000 to 2.7 in 1000 deliveries. Pregnancy increases the risk of

maternal complications from community-acquired pneumonia, such

as mechanical ventilation (10-20%), bacteraemia (16%) and empyema

(8%). The advent of antibiotics has reduced maternal mortality from

23% to

4%.

The most common organisms implicated in community-acquired

pneumonia are Streptococcus pneumonia, Haemophilus influenza and

Mycoplasma pneumonia [70]. Viral pneumonia contributes 5% of the

pathogens, the commonest being influenza and varicella. Clinical

symptoms include fever, cough (59%), pleuritic chest pain (27%),

rigors and dyspnoea (32%) [71]. On examination, there is usually

tachypnoea, dullness to percussion, vocal fremitus and use of the

accessory muscles. Auscultation could reveal a pleural friction rub,

inspiratory rales or absent breath sounds. Because physical examina-

tion is only 47-69% sensitive and 58-75% specific, all cases must

be confirmed by chest X-ray [72]. Of patients with pneumonia,

98% have abnormal chest X-rays. The differential diagnosis should

include pulmonary embolism, cholecystitis, appendicitis and

pyelonephritis.

The optimal location for treatment (e.g. as an out-patient or

in-patient, or in the ICU) can be decided by using the BTS guide-

lines [73]: consider that the presence of two or more of the following

four criteria indicates severe disease:

Respiratory rate of

30 breaths/min

Diastolic blood pressure of

60 mmHg

Blood urea nitrogen of

19.1 mg/dl

Confusion

The pregnancy-associated fall in blood pressure means that the sec-

ond criterion might not necessarily indicate circulatory compromise.

5. CASE STUDIES

159

Patients with two or more of the above criteria are considered to have

severe disease, and have a 36-fold increase in mortality: they are

candidates for elective admission to the ICU. Management of pneu-

monia in pregnancy includes admission, initiation of antimicrobial

therapy, evaluation of fetal well-being and maintenance of normal

maternal respiratory function. Supplemental oxygen is required in

the majority of patients to treat the increased alveolar-arterial oxy-

genation gradient. Any reversible airway obstruction should be

treated and physiotherapy is advisable.

ICU admission and intubation are indicated if there is inadequate

ventilation, a need for airway protection or persistent metabolic aci-

dosis. Although elective delivery has been advocated to improve

maternal respiratory status, there is little evidence to support this.

Several authors have concluded that delivery should be performed

only for obstetric indications.

In the case of Mrs W, delivery was indicated for fetal indications

but was delayed until the maternal condition had stabilized enough to

proceed with anaesthesia and surgery.

5.21 TYPE IV EHLERS-DANLOS SYNDROME: TWO

MANAGEMENT DILEMMAS

Ms Y, a 28 year old nulliparous woman, attended for prepregnancy

counselling. She gave a history of type IV (vascular) Ehlers-Danlos

syndrome (EDS). She was in a long-term relationship and had been

considering a pregnancy for some time. She was using condoms for

contraception and had never previously been pregnant.

In her personal history, she had had recurrent shoulder disloca-

tions and had frequently attended the accident and emergency

department. The possibility of a stabilizing operation on the shoul-

der joint had been discussed by the orthopaedic surgeons.

She reported easy bleeding from her gums. An echocardiogram,

performed because of a heart murmur, showed mild mitral regurgita-

tion only. She had deliberately not investigated the significance of

EDS either in pregnancy or outside pregnancy because she “did not

want to be frightened” by the information.

In her family history, her mother, who has EDS, had a history of a

DVT in her 30 s and had had two pregnancies ending in two normal

deliveries. She had one younger sister, with a history of easy bruising

and bleeding, who had died suddenly 3 years previously at the age of

25 years. A postmortem gave “natural causes” as the cause of death.

Mrs X, a 30 year old Caucasian woman was referred to the obstet-

ric medicine clinic at 16 weeks’ gestation for discussion regarding her

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

possible diagnosis of type IV EDS. She was first suspected to have

this condition 1 year previously when she presented with a sponta-

neous pneumothorax. Following recovery from this, a tissue biopsy

was planned, but she conceived and it was therefore deferred. In her

family history, her sister, who was known to have type IV EDS, died

at the age of 21 years from an aortic rupture, having previously had an

aortic-root replacement.

She had had four successful pregnancies in the past, before the

pneumothorax. The first ended with an uncomplicated Caesarean

section after failed induction of labour for prolonged pregnancy;

postoperative convalescence was normal. She then had three suc-

cessful VBACs, the last two births taking

4 hours. There were no

associated traumatic or haemorrhagic complications in any of the

deliveries. There was no history of prolonged bleeding or easy bruising

at any time.

On examination, she did not exhibit skin hyperelasticity or joint

hypermobility. However, she did have the characteristic circinate rash

on the medial aspect of one foot. Examination of the respiratory and

cardiovascular systems was normal. Her prepregnancy echocardio-

gram was normal.

On balance, it was felt that there was a high chance that she had

type IV EDS, and termination of pregnancy was discussed with her.

She decided to continue with the pregnancy, acknowledging the 25%

mortality risk, because she felt reassured by her previously successful

confinements. She was kept under close surveillance by an obstetrician

and an obstetric physician.

An echocardiogram performed in pregnancy revealed normal

chambers and large vessels. There were trivial mitral, tricuspid

and aortic valve prolapses. A fetal anomaly scan was normal. The

following care plan was made:

Await spontaneous labour.

Aim for spontaneous vaginal delivery.

Elective admission at 38 weeks’ gestation (because she lived far from

the tertiary centre).

Planned early epidural anaesthesia in labour.

Normal intrapartum and postpartum monitoring and management.

Intravenous access in labour.

Active management of the third stage of labour.

Shortened second stage of labour.

If Caesarean section is required, the following steps will be necessary:

(a) A senior obstetrician must be present for the operation.

(b) A polydioxanone surgical (non-absorbable) (PDS) suture must

be used to close the rectus sheath.

5. CASE STUDIES

161

Nonabsorbable material must be used for skin closure.

Antibiotic cover for 48 hours.

Subsequent obstetric events were uneventful. She had a normal

anomaly scan at 20 weeks’ gestation, with a normal uterine artery

Doppler study. She was admitted at 38 weeks’ gestation, as planned.

After 1 week, she was increasingly distressed by being separated from

her family. Her cervix was favourable, and so an amniotomy was per-

formed to induce labour. She delivered a healthy infant, exhibiting no

signs of EDS.

Discussion

EDS is a spectrum of conditions characterized by defect either in the

synthesis or in the structure of connective tissue. There are 10 vari-

ants of EDS, types I-X. It is often difficult to assign patients to a

specific classification because the biochemical and clinical criteria are

difficult to define. Furthermore, people with the milder form of the

disease have no need to seek medical advice. Thus, it is difficult to

ascertain the true incidence and definition of the spectrum of EDS.

It is estimated that EDS occurs in approximately 1 in 5000 individ-

uals. It is more common in black people.

From a clinical and obstetric point of view, type I and type IV

EDS are the most relevant and carry the most morbidity. Type I

EDS is the classic form of the disease, characterized by hypermobil-

ity of the joints and hyperelasticity of the skin, which is prone to

“cigarette paper burns”.

Type IV EDS, also known as the “ecchymotic” or “vascular” form,

is generally inherited as an autosomal dominant condition. Type IV

EDS causes severe fragility of connective tissues and is associated

with sudden death from arterial and visceral rupture and complica-

tions of surgical and radiological interventions. Vessels commonly

affected include the iliac, splenic and renal arteries and the aorta. This

results in either massive haematoma or death. Repeated rupture of

viscera and diverticulae could be the presenting symptoms.

Hypermobility of large joints, characteristic of other types of EDS,

is an uncommon finding in patients with vascular EDS, but recurrent

shoulder dislocations occur (as in Ms Y). In contrast to type I EDS,

skin changes are more prominent in type IV EDS. The basic defect

lies in the synthesis or structure of type III procollagen, which is

found abundantly in viscera, vessels and the uterus. Delay in diagno-

sis is common, and in adulthood, four main clinical findings - a strik-

ing facial appearance, easy bruising, translucent skin with visible veins

and rupture of vessels and gravid uterus or intestines - contribute to

the diagnosis. Arterial rupture and intestinal perforation develop in

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OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

25% of patients before the age of 20 years and 80% of patients before

the age of 40 years. In a recent series, the median survival was 48

years.

A search of the literature relating to pregnancy was performed, in

order to advise Ms Y and Mrs X. The world literature reports fewer

than 200 cases of type IV EDS in pregnancy. Complications of EDS

are more common in pregnancy. Obstetric complications include

prelabour rupture of membranes, preterm labour, precipitate labour,

abnormal lie of an affected fetus, antepartum haemorrhage, postpartum

haemorrhage from perineal trauma and uterine rupture. The risk of

mortality is highest, from vascular rupture, during the antenatal period

and the initial 2 weeks postpartum. Although mortality rates as high as

25% have been quoted, a more recent review quotes 6% [74,75].

The largest series reports 183 pregnancies in 81 cases [76]. There

were 167 deliveries of live born infants at term, three stillbirths, 10

spontaneous abortions and three voluntary terminations. There were

12 deaths in the peripartum period: five deaths from uterine rupture

during labour, two deaths from vessel rupture at delivery, and

five deaths in the postpartum period after vessel rupture. The

incidence of preterm delivery was reported as 12.4%.

Before this series, the largest case series was published in 1983

[77]. This paper describes 10 women who had had 20 pregnancies;

five women had died as a result of pregnancy-related complications.

The overall risk of death in each pregnancy within this group was

25%. In this paper, two cases are described in detail, one case in which

the woman was admitted at 28 weeks’ gestation in preterm labour

(with EDS undiagnosed). As labour progressed, she suddenly col-

lapsed and was unable to be resuscitated. At postmortem, she was

found to have a ruptured thoracic aorta in two places between which

a dissection had occurred. There was also a tear in the uterus. In the

second case, the woman presented in her third pregnancy in labour at

term. During the second stage of labour, the contractions stopped

and the fetal heart could not be heard. An emergency Caesarean

section was performed and she was found to have a ruptured uterus.

Surgical repair was attempted but haemostasis could not be achieved

and the patient died. The baby also died.

The morbidity rate could be as high as 25%. Surgical complica-

tions include arterial bleeding, easy tissue shearing, trauma resulting

in further haemorrhage, infection and delayed healing. The two most

common forms of congenital abnormality among infants born to

mothers with EDS are talipes and congenital dislocation of the hip.

Ms Y was counselled that pregnancy would be associated with a

significant risk of maternal death (10-15%). The main risk seems to

be peripartum, but there is no evidence that elective delivery by

5. CASE STUDIES

163

Caesarean section reduces the risk of arterial rupture, in particular.

She specifically asked about the risks of termination of pregnancy if

she became pregnant and the child was found to be affected. This

would be a lesser risk than a pregnancy going to full term. However,

because she would be pregnant for at least 12 weeks to enable prena-

tal diagnosis and termination, this would be an increased risk com-

pared with not becoming pregnant. (One published case reports an

intestinal rupture at 8 weeks’ gestation [77].)

Because it was very important that Ms Y did not have an

unplanned pregnancy, contraception was discussed. The proges-

terone-only pill, Implanon or the Mirena IUS, would be suitable and

effective methods to use. Ms Y was made aware of the need to con-

tact the obstetric medicine clinic should she become pregnant and

was informed that she would be fully supported if she decided to go

ahead with a pregnancy.

The dilemma in managing Mrs X included the lack of a precise diag-

nosis in a potentially lethal condition, causing anxiety to the clinicians

caring for her. Although there were some features of the history and

signs suggestive of the disease, there were negative factors as well. She

had had an uncomplicated Caesarean section in the past, with no evi-

dence of haemorrhage, postoperative infection or bleeding. This was

followed by three successful VBACs, when one might have expected

scar and even spontaneous uterine rupture to complicate delivery.

These vaginal births were not associated with bleeding or trauma. All

her children seem well, although none had yet been tested. In addition,

it is known that the risk of complications from type IV EDS increases

with age. Hence, Mrs X might have been “relatively” protected in

her past pregnancies and birthing experiences and more at risk in her

current pregnancy. The possibility was significant and the consequences

potentially lethal, hence the option of termination of pregnancy when

she presented at 16 weeks’ gestation. It has been suggested that EDS is

associated with IUGR, but these claims have originated from case

reports. Serial growth ultrasound scans were not performed for this lady

because her uterine artery Doppler study was normal and her past

obstetric history did not suggest increased risk of IUGR.

5.22 SUPRAVENTRICULAR TACHYCARDIA

Mrs Z, a fit and healthy 40 year old lady of African origin whose two

previous pregnancies were uncomplicated, experienced episodes of

palpitations from the 16th week of her current pregnancy. These

episodes lasted 4-5 hours and occurred approximately three times

weekly. At 21 weeks’ gestation, during an episode of palpitations, she

164

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

had a syncopal attack. At 23 weeks’ gestation, she had a second synco-

pal episode, and presented to the emergency unit. On both occasions,

her 12-lead ECG was normal, simply showing sinus tachycardia.

She was a nonsmoker, with no personal or family history of

cardiac disease. There was no history of rheumatic fever.

On examination, her blood pressure was normal and her pulse was

90 bpm and regular. Examination of the cardiovascular system was

normal. The

12-lead ECG was normal, with no evidence of

ischaemia or arrhythmia; there were no delta waves in the precordial

leads. Echocardiography was normal.

A 24-hour ambulatory ECG (Holter monitoring) showed paroxys-

mal supraventricular tachycardia

(SVT) with runs as high as

200 bpm, which co-incided with her feeling faint. There were also

runs of bradycardia suggestive of type I heart block.

Oral flecainide therapy, 50 mg twice daily was commenced, with a

dramatic resolution of symptoms. Therapy was continued throughout

pregnancy and postpartum. Fetal echocardiography was normal.

The pregnancy progressed normally to 36 weeks’ gestation, when

she developed severe pre-eclampsia that required urgent delivery by

Caesarean section, which was complicated by massive postpartum

haemorrhage of 2000 ml of blood.

She underwent slow pathway ablation for atrioventricular (AV)

nodal re-entry tachycardia 3 months postpartum, which proved suc-

cessful. Flecainide was discontinued.

Discussion

Cardiac arrhythmias can occur in a heart that appears structurally

normal or originate from scar tissue due to structural disease, includ-

ing, for example, abnormal heart valves, scarring secondary to surgi-

cal correction of congenital heart disease and coronary artery disease.

In some cases, there might be a genetic predisposition. Pregnancy can

increase the incidence of palpitations, possibly because of the normal

tachycardia of pregnancy, increased re-entry phenomena, the ante-

rior rotation of the heart and hyperdynamic circulation of pregnancy

increasing the sensation of an abnormal heart beat or a lower thresh-

old and greater opportunity for presenting with palpitations to health

carers; the evidence for this comes from small case series and

anecdote. In a large survey conducted over 2 years and involving

107 subjects, it was noted that the risk of having a first episode of

tachyarrhythmia was 3.9%, which was thought to be similar to the

background rate. However, if the subjects were pregnant at diagno-

sis, they were at a 22% increased risk of having more severe or

frequent attacks [78].

5. CASE STUDIES

165

The most common arrhythmias encountered in pregnancy are

SVTs, atrial premature contractions

(APCs) and ventricular

premature contractions

(VPCs)

[79]. These are usually not

sustained, and resolve spontaneously. Of pregnant women aged

over 40 years who had “routine” Holter monitoring, 60% had some

form of arrhythmia [80], the majority of which were asymptomatic.

Sustained arrhythmia is rare, occurring in

2-3 out of

1000

pregnancies [81].

The predominant symptoms of arrhythmia are palpitations, dizzi-

ness, syncope and sudden death. Palpitations are a relatively common

symptom of pregnancy, and it can be very difficult to differentiate

physiology from pathology in the pregnant setting. In one study, only

10% of symptomatic patients were diagnosed with arrhythmia [82].

Ultimately, the decision to investigate further depends on the severity

of symptoms, presence of risk factors and physical signs. A 12-lead

ECG is usually only diagnostic if performed during a palpitation.

However, it could indicate other relevant information, such as the

presence of a structural abnormality, coronary artery disease or delta

waves (suggesting Wolff-Parkinson-White syndrome). The definitive

tests for paroxysmal arrhythmias are 24-hour Holter monitoring or

event monitoring.

The primary treatment for acute SVT remains vagal stimulation,

including self-administered carotid massage, Valsalva manoeuvre,

bulbar pressure or ice-cold water wipes over the face. Primary treat-

ment is only effective in 50% of cases, and medical therapy should be

considered in those who do not respond, especially if symptoms are

sustained or severe. Adenosine, an endogenous nucleoside, is ultra-

short-acting, with a plasma half-life of

2 seconds. It is safe and effec-

tive in pregnancy, but should be avoided in women with asthma

because it could precipitate bronchospasm. Propranolol and verapamil

are also used for terminating SVTs. There are no data that directly

compare these agents, but verapamil has had adverse effects reported,

including fetal death, and should not be the agent of first choice.

There is increasing experience of flecainide use in the treatment of

arrhythmias, especially in Wolff-Parkinson-White syndrome. This is

largely because it is the drug of choice for the in-utero treatment of

fetal SVTs, for which it has been shown to be superior to digoxin [83].

It is considered to be safe in pregnancy, although it is still classified as

a category C drug by the FDA. In Mrs Z, flecainide was preferred to

beta-blockers such as sotalol because there was a concern that the lat-

ter might worsen the episodes of bradycardia. In resistant cases DC,

cardioversion is an option, which is considered to be safe in pregnancy

[84] with no known adverse effects on the mother or fetus. If sympto-

matic attacks are frequent, prophylaxis should be considered.

166

OBSTETRIC MEDICINE: A PROBLEM-BASED APPROACH

Ultimately, the definitive treatment is to eliminate the cause of the

attacks. Electrophysiological conduction studies can be performed in

pregnancy to detect and treat aberrant conducting pathways, and this

should be considered if medical therapy fails.

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Glossary

ACE: angiotensin converting enzyme

ACTH: adrenocorticotrophic hormone

ADH: antidiuretic hormone

AFLP: acute fatty liver of pregnancy

AIHA: autoimmune haemolytic anaemia

AlkP: alkaline phosphatase

ALT: alanine transaminase

ARM: artificial rupture of membranes

AST: aspartate transaminase

AP: anteroposterior

APS: antiphospholipid syndrome

AV: atrioventricular

CEMACH: Confidential Enquiry into Maternal and Child Health

Cl : chloride

Cr: creatinine

CRP: C reactive protein

CT: computerised tomography

CTG: cardiotocograph

CVS: chorionic villus sampling

DAU: Day Assessment Unit

DC: direct current

DEXA: dual energy X ray absorptiometry

DI: diabetes insipidus

DIC: disseminated intravascular coagulopathy

DVT: deep vein thrombosis

ECG: electrocardiogram

EFW: estimated fetal weight

ESR: erythrocyte sedimentation rate

FBC: full blood count

FEV₁: forced expiratory volume in one second

fT₄: free thyroxine

FSH: follicle stimulating hormone

FVC: forced vital capacity

174

GLOSSARY

Gamma GT: gamma glutamyl transpeptidase

GH: growth hormone

HbA_1c: glycosylated haemoglobin

Hb: haemoglobin

HCO₃ : bicarbonate

HCG: human chorionic gonadotrophin

HELLP: haemolysis, elevated liver enzymes and low platelets

HG: hyperemesis gravidarum

HIT: heparin induced thrombocytopenia

HIV: human immunodeficiency virus

HUS: haemolytic uraemic syndrome

INR: international normalised ratio

ITP: idiopathic thrombocytopenic purpura

IUGR: intrauterine growth restriction

JVP: jugular venous pressure

K⁺: potassium

LFT: liver function tests

LH: luteinising hormone

LMWH: low molecular weight heparin

LSCS: lower segment Caesarean section

MCHC: mean cell haemoglobin concentration

MCV: mean cell volume

MgSO₄: magnesium sulphate

MRI: magnetic resonance imaging

MSU: mid stream urine

Na⁺: sodium

NASH: non-alcoholic steatohepatitis

NSAIDS: non steroidal anti-inflammatory drugs

NTD: neural tube defect

OC: obstetric cholestasis

OCP: combined oral contraceptive pill

PA: posterior: anterior

pCO₂: partial pressure of carbon dioxide

PET: pre-eclampsia

PHT: pulmonary hypertension

PKU: phenyl ketonuria

pO₂: partial pressure of oxygen

POP: progestogen only pill

PSC: primary sclerosing cholangitis

PTU: propylthiouracil

PV: per vaginam

RBG: random blood glucose

RCOG: Royal College of Obstetricians and Gynaecologists

RCP: Royal College of Physicians

Index

Amniotic fluid embolus, 45, 46

Abdominal pain, 44, 50, 65-66,

Amoxicillin, 6, 65

68-70, 111, 129-131

Anaemia, 15, 44-45, 50, 60, 62,

Accelerated starvation, 13

65-66, 78, 140, 157, 158

Aciclovir, 73, 87, 94, 95-96

haemolytic, 16, 44, 45, 56, 65,

Acute adult respiratory distress

66, 77, 78

syndrome (ARDS), 138

iron-deficiency, 26

Acute cholecystitis, 52, 54, 91, 92

macrocytic normochromic, 45

Acute fatty liver of pregnancy

megaloblastic, 44, 45

(AFLP), 30-31, 52, 54, 56,

microcytic hypochromic, 45

69, 70, 84, 85, 91, 111, 120,

normocytic, 27, 45, 50, 65

121, 141, 142

pernicious, 44, 45, 151

Addisonian collapse, 28

Anatomical angiographic

Addison’s disease, 47, 49, 111

classification, 152

Adenosine, 4, 5, 165

Aneuploidy risk, 10, 11, 83

Adrenal carcinoma, 47

Aneurysms, 155, 156

Adrenal cortex, 112

Angiography, 19, 116, 126,

Adrenal dysfunction causes,

151, 154

47-49

Angiotensin-converting enzyme

Adrenocorticotropic hormone

(ACE) inhibitor, 2, 3, 4, 9,

(ACTH), 22, 23, 48, 49

14, 39, 50, 51, 62, 102, 103,

Alanine transaminase (ALT),

104, 126

108, 110, 112, 114, 145

Angiotensin receptor blockers,

Alendronate, 149

126

Alkaline phosphatase (AlkP),

Anion gap, 67

29, 30, 32, 33, 53, 54, 55,

Ankylosing spondylitis, 28, 52

56, 92, 120, 121

Antibiotic prophylaxis, 6,

Alloimmune thrombocytopenia,

99, 148

15, 16

Antibody see individual entries

Alopecia areata, 151

Anticoagulation, 75, 76, 88, 89,

Alpha thalassaemia trait, 44, 45

90, 99, 130

Alveolar-arterial oxygenation

Antidiuretic hormone (ADH),

gradient, 159

22, 23, 84, 85, 100, 101

Amiloride, 132

Antiemetics, 110, 113

Aminosalicyclates, 27

Antihistamines, 120, 149

Amiodarone, 4, 5

Antihypertensive agents, 2, 3, 4,

Ammonium load test, 119

124, 125, 126

178

INDEX

Anti-La antibodies, 51, 86, 116

Antimalarial prophylaxis, 66

Backache, 27, 28

Antimicrobial therapy, 159

Ball-and-cage valves, 76

Antiphospholipid syndrome

Balloon mitral valvuloplasty, 133

(APS), 3, 4, 16, 25, 50, 116

Basal bolus insulin regime,

anticardiolipin antibodies, 86,

9, 10

102, 104, 141, 144

Bell’s palsy, 17, 72, 73

antiphospholipid antibodies,

Betamethasone, 58, 59, 60,

2, 51, 86, 104

149, 157

antiphospholipid screening, 71

Beta-sympathomimetics,

Antiplatelet antibodies,

64, 119

144, 151

Bicarbonate supplementation,

Anti-Ro antibodies, 51, 86, 116

119

Antithyroid antibodies, 81, 151

Bicuspid aortic valve, 6

Antithyroid medication, 65, 79,

Bilateral adrenal hyperplasia, 2

80, 81

Bi-leadlet values, 75

Aortic regurgitation, 43, 105,

Biliary colic, 33, 91

153, 154, 155

Bilirubin, 12, 54, 55, 56, 57, 65,

Aplasia cutis, 21, 80

68, 92, 139, 145

Arrhythmia, 6, 117, 118, 133,

Biochemical hyperthyroidism, 80

164, 165

Bipolar disease, 38, 39

Arterial blood gases, 51, 62,

Bisoprolol, 134, 140

130-131

Bjork-Shiley valves, 76

Artificial rupture of membranes

Blood glucose, 10, 31, 48, 49,

(ARM), 90

66, 92, 113, 120

Ascending cholangitis, 26

Blood pressure, 1, 3, 41, 42,

Aspartate aminotransferase

48, 52, 54, 58, 59, 60,

(AST), 112

61, 65, 66, 68, 71, 83,

Aspirin, 3, 4, 7, 68, 76, 83, 85,

85, 87, 97, 99, 102, 105,

86, 91, 102, 104, 105, 106,

107, 108, 109, 112, 114,

114, 124, 155

115, 120, 124, 125, 126,

Asthma, 48, 49, 102, 104, 129,

129, 132, 138, 139, 140,

130, 131, 132, 134, 136,

145, 149, 151, 152, 154,

158, 165

156, 164

Atarax, 149

diastolic, 2, 57, 62, 158

Atenolol, 21, 108, 109, 114, 124

Bradycardia, 164, 165

Atorvastatin, 105

fetal, 51, 87

Atrial premature contractions

Breastfeeding, 3, 8, 13, 14, 18,

(APC), 165

23, 32, 36, 37, 61, 62, 77,

Atrial septal defect, 6

103, 104, 123, 124, 127,

Atrioventricular (AV) node, 5, 164

128, 155

Autoantibodies, 45, 80, 150

British Thoracic Society (BTS),

Autonomic neuropathy, 11, 12

136, 137, 157, 158

Azathioprine, 105, 149, 153, 155

Bromocriptine, 24

INDEX

179

Bronchospasm, 165

Chest X-ray, 34, 35, 50, 51, 62,

Bullous pemphigoid, 150, 151

130, 132, 133, 135, 136,

137, 138, 149, 156, 157,

158; see also X-ray

Caesarean section, 28, 31, 32,

Chiasm, 24

43, 48, 54, 58, 60, 69, 70,

Chicken pox, 93-96

78, 82, 88, 89, 90, 98, 103,

Chlamydial infection, 24

105, 107, 108, 109, 117,

Chlorpheniramine, 140, 149

119, 125, 129, 131, 135,

Chlorpromazine, 113

143, 146, 147, 148, 154,

Chorionic villus sampling

156, 157, 160, 162, 163, 164

(CVS), 78

Ciclophosphamide, 153, 155

Calcium supplementation,

Ciclosporin, 26, 105, 106,

119, 127, 149

141, 149

Cancer, in childhood, 34, 35

Cirrhosis, 32, 33, 55, 91, 93, 121

Captopril renography, 126

Clarithromycin, 97, 98, 156

Carbamezepine, 16, 17, 18

Clotting, 15, 54, 69, 70, 92, 141

Carbimazole, 20, 21, 64, 80

Codeine phosphate, 102

Cardiac arrhythmias, 118, 164

Coeliac disease, 44, 45

Cardiac transplant, 62, 104-106

Combined oral contraceptive

Cardioselective betablockers, 134

pill (COCP), 13, 14, 25,

Cardiotocograph (CTG), 48, 58,

116, 141

63, 64, 88-89, 119, 120,

Computed tomography (CT)

129, 134, 139, 157

scan, 19, 34, 35, 36, 107,

Cardiovascular pathology, 153

114, 116, 126, 136, 138,

Carotid sinus massage, 4, 5

143, 147

Carpal tunnel syndrome, 82

Confidential Enquiry into

Carvedilol, 134

Maternal and Child Health

Cefadroxil, 98

(CEMACH), 10, 12, 38, 84

Cefuroxime, 97, 156

Connective tissue disease,

Central pontine myelinolysis

50-52

(CPM), 29

Conn’s syndrome, 2, 41, 47

Cerazette, 15

Coombs’ test, 44, 45, 56, 66

Cerebral angiography, 116

Corneal dryness, 73

Cerebral ischaemia, 154; see also

Costochondritis, see Tietze’s

Ischaemia

syndrome

Cerebral malaria, 66

Craniosynostosis, 63

Cerebral vein thrombosis,

C-reactive protein (CRP), 25,

18-19

129, 149, 154

Cerebrospinal fluid shunts, 148

Crohn’s disease, 26, 151

Cerebrovascular disorders, 115

CT pulmonary angiogram,

Chest drain, 135, 136, 137

126, 138

Chest pain, 5, 45-47, 61, 78,

Cushing’s syndrome, 2, 41,

95, 97, 98, 129, 132, 134,

47, 49

156, 158

180

INDEX

Cyclizine, 110, 113

Disseminated intravascular

Cytomegalovirus, 69, 93, 121

coagulopathy (DIC), 3, 4,

15, 47, 69

Diuretic therapy, 2, 3, 62, 83,

D-dimer measurement, 7, 131

117, 133

Deep vein thrombosis (DVT),

Domperidone, 110, 113

8-9, 88, 130, 131, 159

Dopamine receptor antagonists,

Demyelination, 73

113

Depot-Provera, 14, 133

Doppler scan, 58, 86, 98, 103,

Desmethylamiodarone, 5

124, 125, 129, 130

DEXA bone-density scan, 149

Doxazosin, 124, 140

Dextrose solution, 28, 49,

Drug reaction, 55

70, 101

Drug therapy, 26, 132

Diabetes, 10-12, 14, 15, 23,

Duplex ultrasound scanning,

69-72, 82-83

151, 154

gestational diabetes, 12-13,

Dyspnoea, 5, 50, 51, 62, 67, 95,

87, 118, 155

132, 157, 158

treatment options, 9-10

type 1 diabetes, 11, 12, 13, 48

type 2 diabetes, 11, 12, 52

Electrocardiogram (ECG), 46,

Diabetes control and complica-

62, 103

tion trial (DCCT), 10

Echocardiogram, transthoracic,

Diabetes insipidus (DI), 23, 85

132

Diabetic eye disease, 82

Echocardiography, 36, 77,

Diabetic ketoacidosis, 67, 82, 118

133, 164

Diabetic management

Eclampsia, 19-20, 60; see also

principles, 82-83

Pre-eclampsia

Diabetic pregnancy, 9, 10, 12,

Ehlers-Danlos syndrome

82-83

(EDS), 159-163

Diamorphine, 132, 134

Electrophoresis, 77

Diarrhoea, 50, 53, 117, 118,

Electrophysiological conduction

119, 120, 140

studies, 166

Diastematomyelia, 147

Empyema risk, 138, 158

Diastolic blood pressure, 2, 57,

Enalapril, 13, 14, 71

62, 158

Endocarditis prophylaxis, 6-7,

Diazepam, 102

76, 133

Digoxin, 4, 5, 165

Endometritis, 15

Dilated fundoscopy, 71

Endothelial damage, 8, 141

Diltiazem, 132, 133, 134

Enoxaparin, 58, 76, 88, 91, 97, 98,

Direct Coombs’ antibody test

102, 103, 110, 130, 156, 157

(DAT), 45, 139

Entonox, 143

Disease-modifying

Epigastric pain, 58, 109, 129,

antirheumatic drugs

130, 139

(DMARDS), 26

Epilepsy, 17-18

INDEX

181

Epstein-Barr virus, 69, 93, 121

Frusemide, 132, 134, 139

Erythema multiforme, 26,

Fucidin, 149

27, 150

Full blood count (FBC), 62,

Erythema nodosum, 24-25,

65, 69

26, 27

Erythrematous itchy plaques, 149

Erythrocyte sedimentation rate

Gamma-globulin, 55

(ESR), 25, 152, 154

Gamma glutamyl transpeptidase,

Escherichia coli 0157, 140

120, 122

Euthyroidism, 22, 80, 81

Genetic counselling, 147

Gestational diabetes, 12-13, 87,

118, 155

Facial nerve, 17

Gestational thrombocytopenia,

Facial weakness, 72-73

16, 144

Facilitated anabolism, 13

Gilbert syndrome, 52, 55, 92

Ferrous sulphate (FeSO₄), 108

Ginger, 111, 113

Fetal anomaly scan, 103, 146, 160

Gliclazide, 9

Fetal bradycardia, 51, 86

Glycaemic control, 9, 10,

Fetal renal artery

11, 82

vasoconstriction, 14, 26, 87

Glyceryl trinitrate (GTN)

Fetal tachyarrythmia, 64

spray, 102, 103

Fetal tachycardia, 5, 63-65

Glycosylated haemoglobin

Fetal thrombocytopenia, 145

(HbA1c), 11, 71, 82

Fetal thyroid, 63, 64, 80, 128

Graves disease, 64, 79, 151

Fetal ultrasound scan, 71

Growth hormone, 22, 23

Fetus, 11, 12, 21, 31, 58, 59, 60,

75, 77, 78, 87, 89, 93, 94,

95, 103, 104, 106, 113, 125,

Haematuria, 42, 50

126, 135, 136, 137, 139,

Haemoconcentration, 58, 59

140, 155, 156, 162, 165

Haemodilution, 30, 117

Fine-needle aspiration (FNA),

Haemoglobin SC disease,

79, 80, 127, 128

77, 78

Flecanide, 4, 5, 164, 165

Haemolysis, 4, 52, 55, 56, 65,

Flucloxacillin, 97, 98

69, 91, 92, 98, 142, 144

Folic acid, 9, 10, 16, 17, 18, 26,

Haemolytic anaemia, 16, 44, 45,

27, 45, 78, 83, 85, 87, 97,

56, 65, 66, 77, 78

102, 105, 110, 146, 147

Haemolytic uraemic syndrome

Follicle stimulating hormone

(HUS), 16, 138-142

(FSH), 23

diarrhoeal, 140

Forced vital capacity (FVC), 52,

nondiarrhoeal, 140, 141

146, 148

sporadic, 141

Free thyroxine (fT₄) level, 21,

treatments, 141-142

49, 81, 110

Haemophilus influenza, 158

Fresh frozen plasma (FFP), 76

Haemoptysis, 95, 131, 132, 134

182

INDEX

Haemorrhage, 4, 8, 15, 19, 49,

Human immunodeficiency

62, 75, 76, 87, 88, 89, 90,

virus (HIV), 15, 31, 32, 33,

100, 163

34, 55, 69, 93, 94, 120, 141,

Hartmann’s solution, 28, 101, 113

142, 144

Hashimoto’s thyroiditis, 151

Hydralazine, 126, 139

Headache, 19, 20, 23, 58, 60,

Hydrocortisone, 49, 87, 110,

107, 109, 114, 138, 139, 154

113, 140

Heaf test, 33, 34

Hydronephrosis, 65, 66

Heartburn, 11, 54, 82

Hydrops fetalis, 51, 86, 95

Heart disease

Hyperaldosteronism, 1, 2, 42,

congenital, 7, 37, 51, 76-77,

117, 125

86, 164

Hypercalcaemia, 83, 111

ischaemic, 102-104

Hypercholesterolaemia, 102,

Heart sounds and murmurs,

104

42-43

Hyperemesis gravidarum

Heimlich valve, 136, 137

(HG), 28-29, 54, 79, 80,

Helicobacter pylori, 112

81, 91, 109-113, 116,

HELLP syndrome, 4, 44, 52,

118, 120

54, 56, 60, 66, 68, 69, 84,

aetiology, 112

91, 111, 121, 141, 142, 145

management, 28, 113

Hemiparesis, 19

Hyperglycaemia, 10, 28, 83,

Heparin, 7, 19, 58, 62, 75, 76,

84, 110

77, 86, 89, 90

Hyperpyrexia, 66

Heparin-induced

Hypersplenism, 144, 142-145;

thrombocytopenia (HIT),