Ebook Handbook of obstetric medicine (5/E): Part 1

Part 1 book “Handbook of obstetric medicine” has contents: Hypertension and pre-eclampsia, heart disease, thromboembolic disease, respiratory disease, diabetes mellitus, thyroid and parathyroid disease, pituitary and adrenal disease, connective tissue disease.

K23369ISBN: 978-1-4822-4192-1

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Medical professionals are often involved in the management of the pregnant

patient without necessarily being experts on all the complications surrounding

pregnancy The Handbook of Obstetric Medicine addresses the most common

and serious medical conditions encountered in pregnancy, including heart

disease, thromboembolism, diabetes, skin problems, gastrointestinal disease,

neurological problems, hormonal diseases, hypertension and pre-eclampsia,

and more

For each condition, the handbook includes a description of incidence, clinical

features, pathogenesis, diagnosis, the effect of pregnancy, and management of

the condition The book also includes a detailed section focusing on the

differen-tial diagnosis of common symptoms including hypertension, chest pain,

palpita-tions, breathlessness, headaches, dizziness, abdominal pain, and more

The symptoms and differential diagnoses are presented in an easy-to-read

tabular format and include a description of important clinical features and

potential areas of investigation For those clinicians understandably reluctant

to prescribe drugs during pregnancy, a useful appendix includes a list of

contra-indicated drugs In addition, to assist in the interpretation of laboratory tests,

a second appendix lists normal laboratory values in pregnancy, broken down

by trimester

The handbook uses a pragmatic and easy-to-use design by including tables,

bullets, and “Points to remember” boxes for ease of reference It is an essential

on-the-spot guide for obstetricians, physicians, general practitioners, and

midwives in both practice and training

Catherine Nelson-Piercy, MA, FRCP, FRCOG

Past President, International Society of Obstetric Medicine

Professor of Obstetric Medicine, King’s College London

Editor-in-Chief, Obstetric Medicine

Praise for the Previous Edition:

“This is an excellent handbook of obstetric medicine, which deserves to be on the shelves

of all actively practicing obstetricians.”

—British Medical Association Medical Book Awards

The Handbook of Obstetric Medicine

FIFTH EDITION

Obstetric Medicine

Obstetric Medicine

Fifth Edition

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Version Date: 20150226

International Standard Book Number-13: 978-1-4822-4193-8 (eBook - PDF)

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Preface to the fifth edition ��������������������������������������������������������������������������������������������� ixKey terms �������������������������������������������������������������������������������������������������������������������������� xi

Section A: Systems

Index ������������������������������������������������������������������������������������������������������������������������������ 339

Preface to fifth edition

Despite an increasing awareness of the importance of pre-existing or new-onset medical problems in pregnancy as causes of maternal, fetal and neonatal morbid-ity and mortality, care for many women remains sub-optimal� Medical diseases are encountered in every antenatal clinic and in every delivery suite in every country� The prevalence of medical disorders in pregnancy is increasing because women are delaying pregnancy until they are older and more likely to have acquired medical disorders such as hypertension, renal disease and diabetes� In addition, advances in medicine and surgery have resulted in women with complex medical histories now presenting either pregnant or requesting assisted reproductive therapies� Age is no longer a barrier to reproduction� Every clinician caring for pregnant or potentially pregnant women needs to understand the interaction between medical disorders and pregnancy and needs to be able to counsel women about these interactions as well

as about the safety of investigations and drug therapy during pregnancy and while breastfeeding� All obstetricians need to be confident in the diagnosis of new-onset medical problems that may face them with increasing frequency�

This edition of the Handbook of Obstetric Medicine retains the pragmatic, easy-to-use,

ready reference design� For the fifth edition, I have used the same basic format for the first 15 chapters covering different systems� For each condition there is a descrip-tion of incidence, clinical features, pathogenesis, diagnosis, the effect of and on pregnancy and management of each condition� ‘Points to remember’ boxes serve

as summaries and revision� Chapter 16 describes the differential diagnosis of mon symptoms, signs and abnormal investigations encountered in pregnancy and is laid out as tables� All the chapters have been updated and revised to reflect current understanding and evidence to support management strategies for medical disorders

com-in pregnancy� The suggestions for further readcom-ing com-include relevant guidelcom-ines where appropriate� Readers are reminded about other useful resources such as the journal

of the International Society of Obstetric Medicine, Obstetric Medicine: The Medicine of

Pregnancy, available online at obm�sagepub�com�

I am delighted that this Handbook continues to be used by trainees to help them revise for and pass examinations, but more importantly that it fuels an interest and thirst for knowledge in the exciting field of obstetric medicine� I am hugely grateful

to Dr� Oier Ateka, who provided such useful feedback and comments for this edition�

I am also indebted to my many colleagues and patients who have taught and continue

to teach me so much� To practice obstetric medicine remains a huge privilege�

Catherine Nelson-Piercy

Key terms

ECG Electrocardiogram

EEG Electroencephalogram

kDa Kilodalton

blood pressure and S = systolic blood pressure

US Ultrasound

sYsteMs

(see also ‘Cardiovascular adaptation to pregnancy’, in Chapter 2)�

■ Before the increase in cardiac output can adequately compensate for the fall in temic vascular resistance, blood pressure begins to decrease in early pregnancy� It continues to decrease in the second trimester of normal pregnancy until the nadir

sys-in systolic and diastolic blood pressure is reached by about 22–24 weeks’ gestation� From then on, there is a steady rise to pre-pregnancy levels until term�

should be taken as the diastolic reading� Phase V is more reproducible, correlates better with intra-arterial measurements of diastolic blood pressure and is more closely related to outcome�

lower due to decreased venous return to the heart because of pressure from the gravid uterus� Blood pressure should be taken with the woman sitting or lying on her side with a 30° tilt� The upper arm (when using a cuff) should be at the same level as the heart� The cuff should be of the correct size, as failure to use a large cuff with a large upper arm circumference will result in an overestimate of the blood pressure�

■ Blood pressure usually falls immediately after delivery, although tends to rise sequently reaching a peak 3–6 days postpartum�

delivery� This may relate to return of normal vascular tone and a period of tor instability while normal, and non-pregnant vasoregulation is re-established�

scope of the problem

complicating 10%–15% of all pregnancies�

of primiparous women; the incidence of severe pre-eclampsia is about 1%�

and Europe� In some developing countries, the incidence reaches 1%�

and morbidity in the United Kingdom; three to six women die each year in the United Kingdom from pre-eclampsia or eclampsia and severe pre-eclampsia is responsible for about 40% of severe obstetric morbidity�

■ The death rate from eclampsia in the United Kingdom is now less than 1%� A third

of women who die from pre-eclampsia have eclamptic seizures�

■ Antenatal care, especially in the second half of pregnancy, is largely geared towards the detection of hypertension and pre-eclampsia�

■ If hypertension is noted for the first time in the first trimester, it is likely that it is a chronic, pre-existing problem, since pregnancy-induced hypertension (including pre-eclampsia) usually, but not invariably, appears in the second half of pregnancy�

retrospec-tively, i�e�, 3 to 6 months after delivery when the blood pressure has not returned

to normal�

(idio-pathic) hypertension before secondary causes such as renal or cardiac disease, and rarely hyperparathyroidism, Cushing’s syndrome, Conn’s syndrome or phaeo-chromocytoma have been excluded�

be examined for clues to a possible secondary cause� This should include the following:

– Examination of the femoral pulses (looking for radiofemoral delay suggesting coarctation of the aorta)

– Listening for renal bruits (possible renal artery stenosis)

– Urinalysis (looking for proteinuria or haematuria suggesting renal disease)

■ Screening investigations for secondary causes of hypertension include the following:– Serum creatinine (to exclude renal impairment)�

– Electrolytes (to exclude hypokalaemia, which may suggest hyperaldosteronism/Conn’s syndrome)�

– Serum calcium (to exclude hyperparathyroidism)�

– Urinary catecholamines should be measured in cases suggestive of mocytoma (see Chapter 7)�

phaeochro-■ Women with pre-existing hypertension from whatever cause are at increased risk of superimposed pre-eclampsia (25%), preterm delivery (28%), birth weight <2500 g (17%), small for gestational age infants, placental abruption and perinatal death (4%)�

■ For those with severe hypertension (diastolic blood pressure >110 before 20 weeks’ gestation), the risk of pre-eclampsia in one study was over 46%� These women are also at particular risk of early-onset pre-eclampsia�

Pregnancy-induced hypertension

half of pregnancy and resolve within 6 weeks of delivery, although blood pressure may remain elevated up to 3 months postpartum�

second half of pregnancy but in the absence of proteinuria or any other features

of pre-eclampsia (Table 1�1)�

important when considering if, how and when to institute treatment because the drugs suitable for the treatment of hypertension in pregnancy are the same for both conditions (Table 1�2)�

however important since pre-eclampsia is associated with a worse pregnancy come and warrants admission to hospital�

pre-eclampsia is about 15%� This risk is related to the gestation at presentation

of pregnancy-induced hypertension� Thus, for hypertension presenting before

30 weeks, the risk is about 40%, but if it presents after 38 weeks, the risk is only 7%�

women remain hypertensive following a pregnancy complicated by induced hypertension�

pregnancy-Pre-eclampsia

variable and widespread manifestations�

manifest�

■ Diffuse vascular endothelial dysfunction may cause widespread circulatory bances, involving the renal, hepatic, cardiovascular, central nervous and coagula-tion systems�

distur-■ The ‘classic’ signs of pre-eclampsia are hypertension, proteinuria and oedema, but their absence does not exclude the diagnosis�

pre-eclampsia, they may be late or mild features and the wider spectrum of the disorder should always be considered�

quadrant pain, nausea, vomiting or rapidly progressive oedema�

sever-ity, timing, progression and order of onset of different clinical features�

table 1.1 – Clinical features of pre-eclampsia

Symptoms (may be absent)

Proteinuria (new onset)

Rapidly progressive oedema

epigastric/right upper quadrant tenderness

Convulsions, mental disorientation

FGR/intrauterine death

Placental abruption

Investigations (Interpret with reference to normal values in pregnancy, Appendix A.2)

24-hour urinary protein excretion >0.3 g

Protein creatinine ratio (PCR) >30 mg/mmol

thrombocytopenia

Prolonged clotting times (if concommittent DiC in HeLLP syndrome)

Raised serum creatinine

increased haematocrit and haemoglobin levels

Anaemia if haemolysis; associated with raised lactate dehydrogenase and bilirubinAbnormal liver function tests, particularly raised transaminases

Reduced fetal growth, oligohydramnios

Abnormal uterine artery Doppler (bilateral notches and increased resistance/pulsatility index at 24 weeks predict pre-eclampsia)

Abnormal umbilical artery Doppler (reduced, absent or reversed end diastolic flow indicating fetal compromise)

Low placental growth factor (PlGF) (reduced in pre-eclampsia and predictive of delivery for pre-eclampsia within 2 weeks)

Labetalola First-line therapy 100 mg b.d 500 mg q.d.s Asthma Yes

Methyldopa First-line therapy 250 mg b.d 1 g t.d.s Depression Yes

nifedipine First-line therapy 10 mg slow-release

b.d 40 mg slow-release b.d YesHydralazine second-line therapy 25 mg t.d.s 75 mg q.d.s Yes

α-blockers e.g.,

doxazosin

second-line therapy 1 mg o.d 8 mg b.d nob

ACe inhibitors e.g.,

enalapril not in pregnancy only postpartum Yes

b.d., twice daily; o.d., once daily; q.d.s., four times daily; t.d.s., thrice daily.

or postpartum� Postpartum pre-eclampsia is more likely to be associated with symptoms�

■ Effects on the kidney result in decreased glomerular filtration rate, proteinuria, a rise in serum creatinine and/or serum uric acid levels and oliguria�

turnover and the production of purines (substrate for xanthine oxidase)�

haemoconcen-tration, abnormal liver function, hypoalbuminemia and thrombocytopenia�

elevated liver enzymes and low platelets, and may be associated with severe seminated intravascular coagulation (DIC) (see ‘HELLP syndrome’ in Chapter 11)�

dis-■ Several possible crises (Table 1�3) may develop�

■ Hyponatraemia is usually due to fluid overload with an element of SIADH (syndrome

of inappropriate antidiuretic hormone)� If severe (Na < 130 mmol/L) it may cause bral oedema leading to confusion and convulsions� Treatment is with fluid restriction�

(sec-ondary to inadequately controlled hypertension), multi-organ failure and adult respiratory distress syndrome�

abruption and, in severe cases, intrauterine death�

eclampsia and other neurological manifestations

■ Eclampsia may be defined as a tonic–clonic (grand mal) seizure occurring in ciation with features of pre-eclampsia (although the diagnosis may only be pos-sible in retrospect) (Table 1�1)�

eclamp-tic seizure have established hypertension and proteinuria in the week before� fifth has their first seizure prior to admission�

One-table 1.3 – Crises in pre-eclampsia

■ Three-quarters of women with eclampsia in the United Kingdom have at least one premonitary symptom (commonly headache or visual disturbance) or sign before their first seizure�

(36%)�

18% of women with eclampsia in one UK study were multiparous without a ous history of pre-eclampsia�

vasospasm and oedema�

■ Cortical blindness (usually reversible) is a well-described, although rare, ciation of pre-eclampsia/eclampsia� Cerebral imaging with magnetic resonance imaging will usually reveal findings typical of posterior reversible encephalopathy syndrome (PRES)� The typical clinical features of PRES syndrome are thought to

asso-be due to vasogenic oedema in the central nervous system leading to headache, seizure, confusion and frequent visual loss�

Pathogenesis

threefold in women with a family history (sister or mother) of pre-eclampsia�

spec-trum and both relate to a problem of placentation (occurring in the first half of pregnancy) and consequent placental ischaemia� They differ with regard to the extent of the maternal response (developing in the second half of pregnancy)� Pre-eclampsia can be thought of as a two-stage disorder� The first stage is abnor-mal perfusion of the placenta� The second is the maternal syndrome� Both pla-cental and maternal factors can predispose to the development of pre-eclampsia�

Stage 1—Abnormal placentation

– The spiral arteries in the placental bed do not undergo normal vascular remodelling as trophoblast invasion is abnormal� The invading placenta

is unable to optimize its blood supply from maternal uterine vessels� The spiral arteries fail to adapt to become high-capacitance, low-resistance vessels�

– It is uteroplacental ischaemia, whether due to poor implantation in underlying microvascular disease or underperfusion of a relatively large placenta (e�g�, in a pregnancy complicated by diabetes, a multiple preg-nancy or a hydropic fetus) that is the common feature in pre-eclamptic pregnancies�

Stage 2—Maternal response

– Normal pregnancy is associated with a systemic inflammatory response, and this is exacerbated in pre-eclampsia� The maternal features of pre-eclampsia include metabolic disturbance including high levels of tri-glycerides, an exaggerated inflammatory response with higher levels of pro-inflammatory cytokines associated with endothelial dysfunction�

– Endothelial cell activation leads to increased capillary permeability, increased endothelial expression of cell adhesion molecules and pro-thrombotic factors, platelet activation and increased vascular tone� There

is a decrease in prostacyclin synthesis and an increase in thromboxane

A2 (TXA2) synthesis� It is thought that this reversal in prostanoid balance contributes to the platelet activation and vasoconstriction�

– These factors cause widespread microvascular damage and dysfunction, which lead to the clinical manifestations of the maternal syndrome such as hypertension, proteinuria and hepatic disturbance�

– Women who already have a degree of metabolic derangement (e�g�, because

of obesity, dyslipidaemia or insulin resistance) causing chronic systemic inflammation are more susceptible to pre-eclampsia, thus explaining the risk factors described below�

Role of anti-angiogenic factors

growth factor (VEGF) and transforming growth factor (TGF-β1) maintain thelial health by interacting with their endogenous endothelial receptors�

endo-■ Soluble Flt1 (sFlt1) and soluble endoglin (sEng), secreted by the placenta in excess

in pre-eclampsia, are anti-angiogenic factors producing systemic endothelial function by antagonizing VEGF and TGF-β1 signalling� sFlt1 is secreted into the circulation where it binds and antagonizes VEGF and placental growth factor PlGF�

weeks before the onset of pre-eclampsia�

Risk factors

The risk factors include general, genetic, obstetric and medical, each of which will be discussed below�

General factors

increased risk exists for primiparous and multiparous women�

increases the risk of pre-eclampsia and obesity (BMI ≥30) is associated with an approximate doubling of the risk�

■ Primiparity (two- to threefold risk)

■ Multiple pregnancy (twofold risk for twins)

■ Previous pre-eclampsia (sevenfold risk)

■ Long birth interval (two- to threefold if 10 years)

■ Hydrops with a large placenta

multipa-Medical factors

■ Diabetes (pre-existing or gestational)

■ Sickle cell disease (see Chapter 14)

Diagnosis

directed towards screening for this condition�

the urine for protein�

■ There is no diagnostic test for pre-eclampsia, but there are ‘pointers’ to the nosis (Table 1�1)�

occasions or a blood pressure of >160/110 mm Hg on a single occasion�

■ Since it is the rise in blood pressure that may be important, rather than the lute value, some definitions include a systolic blood pressure of 30 mm Hg above the earliest recorded pregnancy reading or a diastolic increase of 15–25 mm Hg�

pro-teinuria either >0�3 g/24 hr or a PCR of >30 mg/mmol�

■ These definitions of pre-eclampsia are very simplistic, since pre-eclampsia is a drome that may affect any system in the mother and indeed the fetus� In practice, the diagnosis is made when there is a constellation of recognized features (Table 1�1)�

syn-■ It is the association of new-onset hypertension with these features that allows tinction of pre-eclampsia from pre-existing hypertension without superimposed pre-eclampsia and from pregnancy-induced hypertension�

pre-existing hypertension and/or proteinuria� In these situations, the clinician is ant on other clinical features as well as the degree and rate of increase in blood pressure and proteinuria (see Chapter 10)�

reli-Management

Management of women with hypertension in pregnancy can be considered as

■ Screening for secondary causes of hypertension (if hypertension is present before

20 weeks gestation) (see ‘Clinical features’)

Mild cases, especially where there is no evidence of pre-eclampsia, may be aged as outpatients�

man-If there is new-onset hypertension and proteinuria, the woman should be ted for assessment and will usually need to remain in hospital if pre-eclampsia is confirmed�

admit-Monitoring for pre-eclampsia

thrombo-cytopenia is present and platelet count <100 × 109/L, a coagulation screen) and liver function�

24-hour protein excretion�

particularly for the presence of a prediastolic ‘notch’ or a persistent high-resistance waveform is predictive of subsequent pre-eclampsia, FGR and placental abruption� The negative predictive value is high and such screening is useful in high-risk women; for example, those with antiphospholipid syndrome or previous severe pre-eclampsia�

com-mercial tests are now available�

treatment of hypertension

under-lying pathology (pre-eclampsia, pre-existing hypertension, pregnancy-induced hypertension)� This is because above a mean arterial (blood) pressure (MAP) of

150, there is loss of cerebral autoregulation and the mother is at risk of cerebral

cases had a systolic blood pressure >160 mm Hg�

jeopardizing the uteroplacental circulation� The CHIPS study (control of tension in pregnancy study) demonstrated that for women with pre-existing or pregnancy-induced hypertension neonatal outcomes were no different when the target diastolic blood pressure was 85 compared with 100 mm Hg� Conversely, maternal outcome of severe hypertension was increased when the target diastolic blood pressure was 100 mm Hg�

hypertension (and therefore such severe complications as maternal cerebral

haemorrhage), but there is no good evidence to suggest that good control of blood pressure (although desirable) decreases the risk of superimposed proteinuric pre-eclampsia�

■ In the late second trimester or early third trimester, treatment of severe sion associated with pre-eclampsia that would otherwise be an indication for deliv-ery may allow prolongation of pregnancy (and therefore indirectly improve fetal outcome), but this does not actually modify the disease process�

signs of pre-eclampsia� By treating the hypertension, clinicians are not treating but only palliating pre-eclampsia�

■ Good control of blood pressure is important, but it should not preclude the tive treatment of delivery if this is indicated for maternal (e�g�, in HELLP syn-drome or another crisis) or fetal (e�g�, with severe growth restriction) reasons�

defini-Fetal surveillance

management should, therefore, include regular ultrasound examination of the fetus to assess growth, liquor volume and umbilical artery blood flow�

gestation should receive betamethasone to induce fetal lung maturation� However, there is accumulating evidence that repeated antenatal steroid injections might be harmful to fetal growth and lung and neurodevelopment and these are no longer recommended�

Decision regarding timing of delivery

■ The only cure for pre-eclampsia is delivery�

coagu-lopathy, eclamptic seizures and haemodynamic stability are achieved�

cus-tomary to try and prolong the pregnancy with ‘expectant’ management� This is often not possible for more than a few weeks, and in severe cases, only hours or days may be gained�

the time of diagnosis�

■ Indications for delivery are shown in Table 1�4� These are not necessarily absolute and depend upon the gestational age and the speed of deterioration�

Drug treatment

Drugs used to treat hypertension in pregnancy are shown in Table 1�2�

First-line drugs

Labetalol

drug� It is well tolerated with few side effects, but needs to be given two to four times daily and should be avoided in women with asthma� Parenteral labetalol has an impor-tant role in the intrapartum management of acute severe hypertension (see later)�

Methyldopa

Methyldopa has been used for many years without any reports of serious adverse effects on the fetus or on children up to the age of 7 years� Methyldopa does have side effects, including depression, sedation and postural hypotension� Patients become tolerant to the sedative effect and this is less of a problem beyond 1 week after start-ing or increasing therapy� Depression or other side effects such as liver function test abnormalities, which persist or are severe, and haemolytic anaemia necessitate a change to an alternative drug�

Nifedipine

Calcium antagonists (e�g�, slow-release nifedipine or amlodipine) can be used alone

or in conjunction with labetalol or methyldopa in women who fail to respond to monotherapy or to replace methyldopa in the minority of women who are unable to tolerate it� Side effects include headache, facial flushing and oedema, and may neces-sitate withdrawal in some patients�

second-line drugs

Second-line drugs used for the treatment of hypertension in pregnancy include α-adrenergic blockers, (e�g�, doxazosin) which are safe and well tolerated and other vasodilators such as oral hydralazine�

third-line drugs

β-blockers

β-blockers have fewer maternal side effects than methyldopa, but their safety in the fetus is not so well established� There is concern that these drugs may inhibit fetal growth when used in large doses, long term (and started in the first trimester) throughout pregnancy, but claims of neonatal hypotension and hypoglycaemia have not been substantiated in the randomized, controlled trials performed� There is no evidence for the superiority of any one β-blocker over the others� β-blockers should not be given to women with a history of asthma�

table 1.4 – indications for delivery

inability to control blood pressure, e.g., maximal dose of three antihypertensive drugs

Rapidly worsening maternal biochemistry/haematology, e.g., falling platelet levels (<100 × 109/L), coagulopathy, deteriorating liver or renal function, falling albumin levels (<20 g/L)

eclampsia or other crisis (see table 1.3)

Maternal symptoms, e.g., severe headache, epigastric pain

Fetal distress/severe FGR/reversed umbilical artery diastolic flow

in hyperaldosteronism-associated hypokalaemia�

Angiotensin-converting enzyme inhibitors

The angiotensin-converting enzyme (ACE) inhibitors (e�g�, ramipril, enalapril) should not be used in pregnancy because they are teratogenic, increasing the risk

of cardiovascular and neurological malformations, when used in the first trimester� Use later in pregnancy may cause oligohydramnios, renal failure and hypotension

in the fetus� Their use has been associated with decreased skull ossification, calvaria and renal tubular dysgenesis, and there is also a risk of intrauterine death� Any woman on maintenance antihypertensive therapy with an ACE inhibitor should discontinue this prior to pregnancy (and if necessary switch to an alternative suitable for pregnancy such as amlodipine)�

hypo-Angiotensin ii receptor blockers

There are little data concerning these agents (e�g�, losartan, candesartan) in nancy, but they are similar to the ACE inhibitors and, therefore, should be avoided�

preg-treatment of acute severe hypertension/pre-eclampsia

■ A protocol for the management of severe pre-eclampsia (blood pressure >160/110

mm Hg or a crisis) should be available in every obstetric unit and agreed by tricians, anaesthetists, neonatologists and physicians�

environment (on the delivery suite if undelivered)�

mercury sphygmomanometers�

clinical situation but is between hydralazine (intermittent intravenous [i�v�] bolus), labetalol (bolus followed by continuous i�v� infusion) or slow-release nifedipine (orally)� Sublingual nifedipine causes too rapid a fall in blood pressure and utero-placental perfusion and, therefore, should not be used� All are effective but labet-alol is associated with fewer side effects�

there-fore pretreatment with crystalloid (no more than 500 mL) is appropriate bethere-fore/when parenteral hydralazine is started�

uteroplacen-tal blood flow� Volume loading is usually omitted if the pre-eclampsia protocol is commenced after delivery�

fluid losses (e�g�, haemorrhage) to avoid fluid overload and pulmonary oedema�

many patients and are easier to use if the sympathetic nervous system is already inhibited with methyldopa or labetalol�

hypotension� In general, diuretic therapy should be avoided unless there is volume overload or pulmonary oedema�

■ Continuous fetal heart rate monitoring is appropriate since fetal distress may be precipitated by antihypertensive therapy�

■ Renal function and fluid balance must be monitored carefully� There is usually guria and poor tolerance to volume loading� Continuous oxygen saturation (SaO2) monitoring is vital as aspiration of gastric contents and pulmonary oedema are potential risks�

monitored�

monitoring with central venous pressure and intra-arterial lines�

Management of eclampsia

magne-sium sulphate� This probably acts as a cerebral vasodilator�

infu-sion (for 24–48 hours after delivery or after the last seizure) to prevent further seizures�

who have continued signs of cerebral irritation, such as headache, agitation and clonus, or drowsiness despite good blood pressure control) as primary prophylaxis for eclampsia, but the case for routine prophylaxis in the developed world in all cases of severe pre-eclampsia is more controversial�

5–10 minutes, followed by a maintenance infusion of 1 g/hr�

■ Recurrent seizures should be treated by a further bolus of 2 g�

and loss of tendon reflexes, double vision and slurred speech, respiratory sion and cardiac arrest� Its use necessitates close monitoring of the respiratory rate, SaO2 and tendon reflexes�

depres-■ If the woman is oliguric, has liver impairment or acute kidney injury (AKI) or has

a further convulsion, serum magnesium levels should be monitored (therapeutic range 2–4 mmol/L)� In AKI, the same loading dose of magnesium is used, but the maintenance dose is halved�

Management of delivery

in labour or for caesarean section�

■ This helps control of hypertension by reduction of pre- and afterload and by viding adequate analgesia� It also avoids the fluctuations in blood pressure associ-ated with general anaesthesia and intubation�

pro-■ In the presence of thrombocytopenia, regional blockade may not be deemed safe, and general anaesthesia becomes necessary for caesarean section� Most obstetric anaesthetists use a cut-off for the platelet count of 60–80 × 109/L� If the count is low, an immunoplatelet count may be requested that may be normal (see Chapter 14)�

Postpartum management

par-ticularly hypertension, may take many weeks to resolve� There is often transient deterioration in the clinical state following delivery�

to blood pressure control, fluid balance, haematology and biochemistry�

■ Diuresis usually occurs spontaneously, but is often preceded by a period of oliguria�

pre-eclampsia because of the risk of AKI especially in volume deplete patients and fluid retention that may cause pulmonary oedema�

oliguria

delivery or after induction of labour with Syntocinon�

safer to err on the side of volume depletion and mild AKI than to treat immediate postpartum oliguria with aggressive volume replacement� This is an example of the need for a different strategy from that used in other causes of oliguria present-ing to intensive care units�

more concentrated form (e�g�, through a syringe driver) to avoid excess fluid�

unless there are obvious signs of fluid overload or pulmonary oedema�

setting�

pathology, but may take several weeks or months to do so�

Hypertension

pregnancy, often not reaching a peak until 3 to 6 days postpartum� Consequently, although normotensive immediately following delivery, women with hyperten-sion during pregnancy may become hypertensive again within the first week postpartum� This is often apparent prior to planned discharge and may prolong the stay in hospital until the hypertension is brought under control�

stop antihypertensive medication within 6 weeks postpartum�

■ All the drugs discussed earlier, including the ACE inhibitors, are safe to use in a woman who is breastfeeding�

associated side effect of increased maternal thirst�

■ For women with existing hypertension, it is usual to switch to the patient’s vious antihypertensive regime after delivery (but replacing the ACE or angio tensin

pre-II receptor blocker with enalapril as there are more safety data in breast feeding) and avoiding diuretics�

■ For women requiring an α-blocker, prazosin is preferred to doxazosin as the latter accumulates in breast milk�

Prophylaxis

Low-dose aspirin

■ The rationale for the use of low-dose aspirin is that it inhibits platelet ase and therefore TXA2 synthesis�

eclampsia shows a 15% reduction in the incidence of pre-eclampsia in women taking antiplatelet therapy� However, 90 women need to be treated with low-dose aspirin to prevent one case of pre-eclampsia�

Low-dose Aspirin Study in Pregnancy (CLASP) trial suggest that aspirin may be effective in reducing the risk of early-onset pre-eclampsia (i�e�, that necessitating delivery before 32 weeks’ gestation)�

pregnancy�

gestation and be continued throughout pregnancy� There is some evidence that the reduction in risk of pre-eclampsia is greater if the aspirin is taken later in the day�

Calcium and vitamin D

■ Meta-analysis of 13 randomized trials comparing at least 1 g daily of calcium

pre-eclampsia� The effect was greatest for high-risk women where the reduction was 80% and for those with low baseline calcium intake�

preg-nant women with low dietary calcium intake�

pre-eclampsia risk, and vitamin D supplementation lowers this risk�

Recurrence/pre-pregnancy counselling

(or sevenfold increased risk compared to women who have not had previous eclampsia) of developing pre-eclampsia in their second pregnancy�

pre-■ This risk is increased if they have an underlying medical risk factor such as existing hypertension, CKD or antiphospholipid syndrome�

(see Table 1�6) or HELLP syndrome�

■ Pre-eclampsia increases the risk of subsequent hypertension (three- to fourfold), ischaemic heart disease (twofold) and cerebrovascular disease�

factors and pathological changes including widespread endothelial damage and dysfunction and an increased systemic inflammatory response� Thus, women who have suffered pre-eclampsia are candidates for CVD risk screening and possible intervention�

table 1.6 – Risk of recurrent pre-eclampsia

Delivery due to pre-eclampsia

in preceding pregnancy (wk) Recurrence risk ( %)

table 1.5 – indications for prophylaxis with low-dose aspirin

Women with the following medical conditions should be commenced on aspirin

75 mg daily from 12 weeks gestation until the birth of the baby:

Pre-eclampsia in a previous pregnancy

Chronic hypertension

Chronic kidney disease (CKD)

Autoimmune disease, e.g., systemic lupus erythematosis or antiphospholipid

syndrome

type 1 or type 2 diabetes

Women with more than one moderate risk factor for pre-eclampsia should be

commenced on aspirin 75 mg daily from 12 weeks gestation until birth of the baby Moderate risk factors include:

First pregnancy

Age 40 years or older

Pregnancy interval of more than 10 years

BMi of 35 kg/m2 or more at first visit

Family history of pre-eclampsia

Multiple pregnancy

Further reading

Ayala, D�E�, Ucieda, R�, Hermida, R�C� (2013) Chronotherapy with low-dose aspirin for

prevention of complications in pregnancy� Chronobiol Int, 30(1–2), 260–279�

Bellamy, L�, Casas, J�P�, Hingorani, A�D�, Williams, D�J� (2007) Pre-eclampsia and risk of cardiovascular disease and cancer in later life: Systematic review and meta-analysis�

sia: A prospective multicenter study� Circulation, 128, 2121–2131�

Critchley, H�, MacLean, A�, Poston, L�, Walker, J� (eds) (2003) Pre-eclampsia� London,

United Kingdom: RCOG Press�

Duckitt, K�, Harrington, D� (2005) Risk factors for pre-eclampsia at antenatal booking:

Systematic review of controlled studies� BMJ, 330, 565–567�

Hypertensive disorders in pregnancy—points to remember

signifi-cant cause of maternal morbidity in the United Kingdom�

causes widespread effects, more than just hypertension and proteinuria�

■ Labetalol, nifedipine and methyldopa are the drugs of choice for treatment of hypertension in pregnancy�

par-ticular regard to symptoms, blood pressure control, renal and liver function, platelet count and fetal well-being�

■ Delivery is the only cure for pre-eclampsia and this may be indicated for fetal

or maternal reasons�

postpar-tum antihypertensives, but methyldopa should be avoided because of the risk

of depression�

not be treated with large volumes of i�v� fluids, except if there is objective dence of volume depletion�

hypertension can replace labetalol and methyldopa therapy after delivery, and these drugs are safe to use when breastfeeding�

■ The recurrence risk of pre-eclampsia is increased with early-onset disease�

signifi-cantly more likely to develop hypertension, ischaemic heart disease, vascular disease and CKD in later life�

cerebro-Duley, L�, Henderson-Smart, D�J�, Meher, S�, King, J�F� (2007) Antiplatelet agents

for preventing pre-eclampsia and its complications� Cochrane Database Syst Rev, 2,

CD004659�

Hofmeyr, G�J�, Lawrie, T�A�, Atallah, A�N�, Duley, L�, Torloni, M�R� (2014) Calcium plementation during pregnancy for preventing hypertensive disorders and related

sup-problems� Cochrane Database Syst Rev 24, 6, CD001059�

Hyppönen, E�, Cavadino, A�, Williams, D�, Fraser, A�, Vereczkey, A�, Fraser, W�D�, Bánhidy, F�, Lawlor, D�, Czeizel, A�E� (2013) Vitamin D and pre-eclampsia: Original

data, systematic review and meta-analysis� Ann Nutr Metab 63(4), 331–340�

Knight, M�, on behalf of UKOSS (2007) Eclampsia in the United Kingdom 2005� BJOG,

114, 1072–1078�

Magee, L�A�, von Dadelszen, P�, Rey E, Ross, S�, Asztalos, E�, Murphy, K�E�, Menzies, J�, Sanchez, J�, Singer, J�, Gafni, A�, Gruslin, A�, Helewa, M�, Hutton, E�, Lee, S�K�, Lee, T�, Logan, A�G�, Ganzevoort, W�, Welch, R�, Thornton, J�G�, Moutquin, J�M�

(2015) Less-tight versus tight control of hypertension in pregnancy� N Engl J Med

Saudan, P�, Brown, M�A�, Buddle, M�L�, Jones, M� (1998) Does gestational

hyperten-sion become pre-eclampsia� Br J Obstet Gynaecol, 105, 1177–1184�

The Magpie Trial Collaborating Group (2002) Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie trial: A randomized

placebo-controlled trial� Lancet, 359, 1877–1890�

Heart disease

Cardiovascular adaptation to pregnancy (table 2.1)

endothelium-dependent factors, including nitric oxide synthesis upregulated by oestradiol and possibly vasodilatory prostaglandins�

■ Peripheral vasodilation leads to a fall in systemic vascular resistance (SVR) and to compensate for this, the cardiac output increases by around 40% during pregnancy� This is achieved predominantly by an increase in stroke volume but also by a lesser increase in heart rate�

output has already increased by 20%�

a minimal fall at term� An increase in stroke volume is possible due to the early increase in ventricular wall muscle mass and end-diastolic volume (but not end-diastolic pressure) seen in pregnancy� The heart is physiologically dilated and myocardial contractility is increased�

■ Although stroke volume declines towards term, the increase in maternal heart rate (10–20 beats per minute [b�p�m�]) is maintained, thus preserving the increased cardiac output�

haemo-dynamic profile of both the mother and fetus� In the supine position, pressure

of the gravid uterus on the inferior vena cava (IVC) causes a reduction in venous return to the heart and a consequent fall in stroke volume and cardiac output� Turning from the lateral to the supine position may result in a 25% reduction in cardiac output� Pregnant women should, therefore, be nursed in the left or right lateral position wherever possible� If the woman has to be kept on her back, the

Congenital heart disease

Acquired heart disease

Cardiomyopathies

Artificial heart valves Antibiotic prophylaxis Myocardial infarction/acute coronary syndromes Dissection of thoracic aorta Arrhythmias

Planning for delivery Anticoagulation

pelvis should be rotated so that the uterus drops to the side and off the IVC and cardiac output and uteroplacental blood flow are optimized�

therefore in placental perfusion; this can compromise the fetus�

capillary wedge pressure (PCWP) and central venous pressure do not increase significantly�

pregnancy�

■ Although there is no increase in PCWP, serum colloid osmotic pressure is reduced� The colloid osmotic pressure/PCWP gradient is reduced by about 30%, making preg-nant women particularly susceptible to pulmonary oedema�

preload (such as infusion of fluids) or increased pulmonary capillary permeability (such as in pre-eclampsia), or both�

intrapartum and postpartum haemodynamic changes

stage and 50% in the second stage)� Uterine contractions lead to autotransfusion

of 300–500 mL of blood back into the circulation and the sympathetic response to pain and anxiety further elevate heart rate and blood pressure� Cardiac output is increased more during contractions but also between contractions�

■ Following delivery, there is an immediate rise in cardiac output due to the relief of IVC obstruction and contraction of the uterus that empties blood into the systemic circulation� Cardiac output increases by 60%–80% followed by a rapid decline to prelabour values within about 1 hour of delivery� Transfer of fluid from the extra-vascular space increases venous return and stroke volume further�

table 2.1 – Cardiovascular adaptation to pregnancy

Physiological variable Direction of change Degree/timing of change

serum colloid osmotic

■ Those women with cardiovascular compromise are, therefore, most at risk of

pulmonary oedema during the second stage of labour and the immediate

post-partum period�

■ Cardiac output has nearly returned to normal (pre-pregnancy values) 2 weeks after delivery, although some pathological changes (e�g�, hypertension in pre-eclampsia) may take much longer (see Chapter 1)�

normal findings on examination of cardiovascular

system in pregnancy

These may include:

loud and audible all over the precordium)

■ Relative sinus tachycardia

normal findings on electrocardiogram (eCG) in pregnancy

These are partly related to changes in the position of the heart and may include:

■ Atrial and ventricular ectopics

■ ST segment depression and T-wave inversion inferior and lateral leads

General considerations

Ideally, pre-pregnancy counselling of women with heart disease will allow detailed assessment of cardiac status, and any potential risk to be explained before conception� But although most women with heart defects are aware of the diagnosis, many preg-nancies are not planned, and increasingly, migrant women who may never have had

a medical check-up present with previously undiagnosed heart disease in pregnancy�The heart has relatively less reserve than the lungs (see Chapter 4)� Whatever the underlying cause of cardiac insufficiency, the ability to tolerate pregnancy is related

to the following:

■ Presence of cyanosis (arterial oxygen saturation <80%)

Other predictors of cardiac events in pregnant women with heart disease include:

■ History of transient ischaemic attacks or arrhythmias

■ History of heart failure

■ Left heart obstruction (mitral valve area <2cm2, aortic valve area <1�5 cm2, aortic valve gradient [mean non-pregnant] >30 mm Hg)

■ Myocardial dysfunction (left ventricular ejection fraction [LVEF] <40%)

Cyanosis alone may not be as important in predicting poor outcome as the tion of cyanosis with pulmonary hypertension typically in Eisenmenger’s syndrome, poor functional class, or both�

associa-Poor pregnancy outcome is more likely if the woman has a poor functional status (NYHA class III or IV) regardless of the specific lesion� Conversely, those in func-tional classes I or II are likely to do well in pregnancy� Each case must be assessed individually but those who require special consideration (even if asymptomatic) are women with the following conditions:

■ Marfan’s syndrome (risk of aortic dissection or rupture)

■ Mechanical heart valves (risk of valve thrombosis)

Detailed assessment by a cardiologist, obstetrician and obstetric anaesthetist with

an agreed and documented plan for delivery (see below) is crucial� Any woman with any of the above features should be referred to a specialist unit for counselling and management during pregnancy�

The levels of risk associated with pregnancy for individual conditions are rized in Table 2�3, based on the European Society of Cardiology Guidelines�

summa-Women advised against pregnancy should be given appropriate contraceptive advice and guidelines are available�

Pulmonary hypertension

Women with pulmonary hypertension from whatever cause are at increased risk

sug-gest this may have fallen to about 10%–25%� Pulmonary hypertension in the pregnant woman may be due to the following:

septal defect (ASD)/ventricular septal defect (VSD) with PAH� This includes

table 2.2 – nYHA functional classification

Class i no breathlessness/uncompromised

Class ii Breathlessness on severe exertion/slightly compromised

Class iii Breathlessness on mild exertion/moderately compromisedClass iV Breathlessness at rest/severely compromised