Condition	Pregnancy Risks	Management
Atrial septal defect	Rarely causes problems	Nil specific after exclusion of other secondary complications
Ventricular septal defect	Small defects rarely cause problems	Avoid hypertension, endocarditis prophylaxis
Patent ductus arteriosus	Small shunts rarely problematic	Exclude pulmonary hypertension
Coarctation of aorta	Corrected, few problems; uncorrected, maternal mortality (15%)	Prevent hypertension, use epidural in labour
Primary pulmonary hypertension	Maternal mortality of 50%	Offer termination Anticoagulation, O₂ therapy, epidural in labour Assisted vaginal delivery

Eisenmenger’s syndrome Maternal mortality 30%, termination mortality 10% As for pulmonary hypertension Fallot’s tetralogy

Good outcome if corrected

Uncorrected – increased, risk miscarriage, IUGR, prematurity

Avoid hypotension which can cause shunt reversal, assisted vaginal delivery Mitral stenosis Uncorrected – IUGR and prematurity, maternal mortality 5–15% Control heart rate with β-blockers, use epidural, assisted delivery not mandatory, endocarditis prophylaxis Aortic stenosis Endocarditis. Severe – IUGR, maternal mortality 5–15% Avoid hypo- and hypervolaemia, endocarditis prophylaxis Prosthetic heart valves Pregnancy accelerates need for replacement, thromboembolism Careful anticoagulation throughout pregnancy Marfan syndrome

Aortic root involvement – maternal mortality up to 50%

Autosomal dominant so 50% fetuses affected

β-Blockers, serial echocardiography, avoid hypertension, epidural and assisted vaginal delivery

The puerperium

The burden on the heart continues into the puerperium. For the first 24–48 hours the patient must be constantly observed for signs of decompensation. She should then be closely monitored for the first few days, and additional support should be made available when she returns home.

Prognosis for mother and baby and for future pregnancies

The prognosis for the mother is dependent on the underlying aetiology. With good antenatal care the risk to the mother or fetus if the disease is mild is not usually increased during the current pregnancy. Women with significant impairment of cardiac function should be dissuaded from further pregnancies until the condition of the heart has been assessed and further treatment, including surgery, discussed.

VENOUS THROMBOEMBOLISM IN PREGNANCY

Venous thromboembolism (VTE) affects between 50 and 60 pregnant or postpartum women per 100 000, with a mortality rate of 1 per 100 000 maternities. It is highest in women aged over 39, the mortality rate being 1 per 3300. The prevalence of VTE is equally distributed throughout pregnancy, but the day-by-day risk is greatest in the immediate puerperium. The major risk factors include caesarean section, obesity, prolonged immobility, pre-eclampsia, current infection, previous VTE and familial thrombophilia.

Treatment of a pulmonary embolus during pregnancy consists of unfractionated heparin (UH), initially intravenously (40 000 U/day by continuous infusion in normal saline) to obtain a concentration of 0.6–1.0 U/mL. Once full heparinization has been obtained for 3–7 days, the infusion may be replaced by calcium heparin given subcutaneously. A deep vein thrombosis (DVT) is treated either with UH if delivery or surgery is imminent, or low molecular weight heparin (LWMH) given subcutaneously. UH is substituted for LMWH 24–36 hours prior to delivery. UH is suspended once labour is established or 6 hours before surgery, and recommenced 2–6 hours after vaginal or caesarean delivery. If the woman has a high risk of VTE antenatally (includes recurrent VTE, previous idiopathic VTE or previous VTE and a strong family history of VTE) she may be given LMWH prophylaxis throughout pregnancy and for 6 weeks postpartum (see also postpartum thromboembolism, p. 186).

ANTIPHOSPHOLIPID SYNDROME

Antiphospholipid syndrome (APS) is associated with early-onset pre-eclampsia, intrauterine fetal growth restriction, preterm birth, miscarriage, fetal death and venous thromboembolism. Diagnosis requires at least one of the clinical criteria and one of the laboratory criteria (see Box 15.1). Women who have suffered from clinical complications should be screened and referred for specialist evaluation.

Box 15.1 Criteria for diagnosis of antiphospholipid syndrome

Clinical	Laboratory*
Recurrent early pregnancy loss Fetal death Preterm birth <34 weeks for pre-eclampsia or fetal growth restriction Thrombosis Venous Arterial including stroke Autoimmune thrombocytopenia

Lupus anticoagulant

Anticardiolipin antibodies

Anti-β₂ glycoprotein IgG or IgM

* moderate to high levels

Because of the high-risk nature of the pregnancy, women with APS should be managed by a specialist team and require close surveillance during pregnancy. Low-dose aspirin and heparin has been shown to reduce the risk of pregnancy loss (RR 0.48; 95% CI 0.33–0.68).

RESPIRATORY CONDITIONS

Asthma

The effect of pregnancy on asthma is variable, but most asthmatic women experience fewer attacks. Well-controlled asthma has no effect on the course of pregnancy, labour or the birthweight of the infant; suboptimal treatment is associated with growth restriction, premature birth and increased perinatal mortality. Treatment is no different from that of a non-pregnant asthmatic woman. Regional anaesthesia is preferable to general anaesthesia if the woman requires an operative delivery.

Pulmonary tuberculosis

Although the prevalence of pulmonary tuberculosis in most developed countries is low, it appears to be increasing with increased movement of populations. Over 8 million new cases are being reported per annum.

A patient diagnosed with active tuberculosis in the first half of pregnancy should be treated with isoniazid and ethambutol. After the 20th week rifampicin may be used.

The management of labour does not differ from that for a non-infected woman. If the mother’s sputum shows acid-fast bacilli, after the birth the baby should be separated from her, vaccinated with bacille Calmette–Guérin (BCG) and remain separate for about 6 weeks. If the mother’s sputum has no acid-fast bacilli the baby should be vaccinated with BCG and may remain with her and be breastfed if the mother wishes it.

ANAEMIA IN PREGNANCY

Anaemia, the most common haematological abnormality encountered during pregnancy, remains an important cause of adverse maternal–fetal outcome worldwide. Iron deficiency and acute blood loss are the leading causes of maternal anaemia. All pregnant women should have a blood sample tested for the presence of anaemia at the first antenatal visit.

During pregnancy, the plasma volume begins to increase by the sixth week of gestation, peaking at around 30 weeks, with a total extra volume of 1.2–1.3 litres by term. The red cell mass also slowly increases, but proportionately less than the plasma volume. This results in reference values for haemoglobin in pregnancy being lower than in age-matched non-pregnant females and is sometimes referred to as the ‘physiologic anaemia of pregnancy’. A haemoglobin less than 110 g/L in first trimester and less than 100 g/L in late second or third trimester should be considered as anaemia and investigated further.

Iron requirements during pregnancy increase in response to fetal growth and development and the increase in maternal red cell mass. Total iron requirements in normal pregnancy have been estimated as approximately 1300 mg/day. Iron is absorbed predominantly through the proximal small intestine and is highly regulated. Iron absorption is increased in iron deficiency and in pregnancy.

Iron deficiency

Worldwide, iron deficiency remains a significant cause of maternal anaemia. A serum ferritin less than 15 μg/L indicates body iron depletion and values <12 μg/L are associated with iron deficiency. In iron deficiency the mean red cell volume (MCV) and mean red cell haemoglobin (MCH) are usually reduced. Inadequate dietary iron intake and gastrointestinal blood loss (hookworm infestation) are the commonest causes of iron deficiency. Prevalence rates for iron deficiency are increased amongst women from lower socioeconomic groups, teenage mothers, those eating predominantly vegetarian or vegan diets, and women with closely spaced pregnancies.

Treatment of iron deficiency and routine iron supplementation

Pregnant women with iron deficiency anaemia should be treated with oral iron. Oral iron replacement containing 30–60 mg elemental iron is usually used. Women who are unable to take oral iron or in those with malabsorption (coeliac disease), intravenous iron can be considered. Blood transfusion for the treatment of iron deficiency anaemia should be avoided unless there is active bleeding or cardiovascular compromise.

Routine iron supplementation is known to decrease the prevalence of maternal anaemia at delivery. However, it is unclear whether routine iron supplementation provided to well-nourished women who are not anaemic affects perinatal outcome. Among fertile women including those from higher socioeconomic groups, a significant proportion have depleted iron stores or iron stores which are inadequate to meet the needs of pregnancy. When available, decisions regarding an individual woman’s iron supplementation during pregnancy should take into account her baseline haemoglobin and ferritin results.

Folate and vitamin B₁₂

Folate (also called folic acid) is a B-group vitamin. Folate requirements are increased in pregnancy. Body stores of folate may be rapidly exhausted and generally last less than 3 weeks. Red cell folate (RCF) is a more accurate measure of folate status than serum folate. Routine measurement of RCF is not required but should be considered if there is an increased MCV, prolonged hyperemesis/poor oral intake in pregnancy or gastrointestinal pathology (coeliac disease, Crohn’s disease, gastric bypass).

Routine supplementation with folate (0.4–0.5 mg) is recommended for all women prior to conception and for the first trimester to reduce the incidence of neural tube defect. Higher doses of folate (4 mg/day) throughout pregnancy are required in folate deficiency and in women with increased folate requirements (for example those with chronic haemolysis or beta thalassaemia minor).

Vitamin B₁₂ is essential for infant neurodevelopment. Undiagnosed maternal vitamin B₁₂ deficiency may result in irreversible neurological damage to the breastfed infant. Although maternal vitamin B₁₂ deficiency is uncommon, the majority of women with deficient B₁₂ levels are asymptomatic. Routine measurement of vitamin B₁₂ is not required; however, serum vitamin B₁₂ levels should be checked in the following circumstances: the complete blood count is suggestive of megaloblastic anaemia (increased MCV, hypersegmented neutrophils); vegetarian or vegan diet; gastrointestinal pathology (coeliac disease, Crohn’s disease, gastric banding/bypass); family history of vitamin B₁₂ deficiency or pernicious anaemia.

Acute blood loss

Haemorrhage remains a leading preventable cause of maternal mortality particularly in the developing world. Deaths from haemorrhage would be dramatically reduced if all pregnant women could access a skilled birth attendant at the time of childbirth, and have access to quality emergency obstetric care including a safe blood supply.

THALASSAEMIA AND HAEMOGLOBINOPATHIES

The haemoglobinopathies (thalassaemia and sickle cell disease) (Box 15.2) are inherited disorders of haemoglobin. They are autosomal recessive defects, and characterized by reduced production of one or more of the chains of globin that make up haemoglobin. Carriers (who have only one affected globin locus) remain healthy throughout life. People who are homozygous or doubly heterozygous have haemoglobin disorders of varying clinical severity.

Ethnic populations at increased risk for thalassaemia or sickle cell disorders include those from Africa, the Mediterranean region, the Middle East, South East Asia including the subcontinent, Western Pacific region, Caribbean and South American countries.

In α-thalassaemias the α chains accumulate and eventually precipitate, causing severe anaemia (thalassaemia major, or Cooley’s anaemia). The β-thalassaemias may be either heterozygous, when they are symptomless, or homozygous, when they produce severe anaemia.

Thalassaemia in a woman who is anaemic in pregnancy can generally be excluded if the MCV is greater than 80 fL. An MCV of less than 80 fL indicates that haemoglobin electrophoresis should be performed. An HbA₂ greater than 3.5 indicates a β-thalassaemia trait. Because a significant number of women with α-thalassaemia and other rarer haemoglobinopathies have normal red cell indices, routine haemoglobin electrophoresis should be offered to all previously unscreened pregnant women from communities at greater risk because of ethnicity.

A pregnant woman carrying the thalassaemia trait has a 30% chance of becoming anaemic and a similar chance of developing urinary tract infection. Thalassaemia major in the fetus can be detected in the first quarter of pregnancy by chorionic villus sampling. If the test is positive, termination of the pregnancy is an option for the parents.

In sickle cell anaemia a defective gene on the chromosome responsible for haemoglobin synthesis leads to the production of abnormal haemoglobin and an erythrocyte life of less than 15 days. The episodes of erythrocyte destruction may cause severe haemolytic anaemia and bone pains, because of infarction of the vessels supplying the bones.

All pregnant women suspected of carrying an abnormal haemoglobin should be given folate (15 mg daily) routinely, and have frequent haemoglobin estimations. If the haemoglobin level falls below 60 g/L a direct or an exchange transfusion should be made. Infections, especially of the urinary tract, should be treated and prophylactic antibiotics given during childbirth and the puerperium. If a bone pain crisis occurs heparin should be given and the haemoglobin measured every 2 hours; a fall of more than 2 g indicates the need for an exchange transfusion.

Issues for antenatal care include:

• Accurate diagnosis of women with thalassaemia minor in order to avoid confusion with iron deficiency since the MCV and MCH are reduced in both conditions

• Antenatal screening to identify carriers and offer them partner screening to facilitate informed choices about reproduction

• Neonatal screening programmes aim to identify infants with sickle cell disease (SCD) in order to commence early prophylactic penicillin and comprehensive care.

Antenatal or preconceptual screening

Carrier screening should be offered to a woman if she and/or her partner are identified as belonging to an ethnic population whose members are at higher risk of being carriers.

Screening consists of a complete blood count, as well as haemoglobin electrophoresis or high performance liquid chromatography (HPLC). This investigation should include measurement of HbA₂ and HbF and a serum ferritin (to exclude iron deficiency) should be performed simultaneously.

If a woman’s screening is abnormal, then screening of her partner should be performed.

If both partners are found to be carriers of thalassaemia or an Hb variant, they should be referred for genetic counselling. Prenatal diagnosis may be offered to couples at risk for having a fetus with a clinically significant thalassaemia or haemoglobinopathy. Screening programmes should aim to identify couples at risk for having a child with Bart’s hydrops fetalis (four-gene deletion alpha thalassaemia), beta thalassaemia major (homozygous β-thalassaemia, β/E-thalassaemia) and sickle cell disease (HbSS, HbSC, S/β-thalassaemia).

Pregnancy care in women with serious haemoglobin disorders

Women with homozygous or doubly heterozygous haemoglobin disorders require special attention during pregnancy. Women with SCD have higher rates of spontaneous miscarriage, preterm birth, fetal growth restriction and perinatal morbidity and mortality. Infections and sickling crises are more common during pregnancy. Reproductive failure is common in women with beta thalassaemia major because of endocrine damage resulting from iron overload. In well-chelated patients, pregnancies occur. Cardiac complications may occur during pregnancy from iron-related cardiac damage.

RED CELL ALLOIMMUNIZATION

Pathophysiology

During pregnancy, fetal cells may cross the placenta and enter the maternal circulation, exposing the mother to ‘foreign’ paternally acquired red cell antigens. This fetomaternal haemorrhage (FMH) is most likely to occur at delivery (60% of pregnancies) but may also occur spontaneously during pregnancy and in association with threatened or complete miscarriage, after trauma or placental abruption, with termination of pregnancy and after invasive procedures such as amniocentesis, chorionic villous sampling (CVS), external cephalic version (ECV) and curettage. Exposure to ‘foreign’ red cell antigens may also occur through blood transfusion.

Exposure to foreign red cell antigens may result in the development of alloantibody. Development of antibody depends on a number of factors including the potency or antigenicity of the antigen, the dose of antigen to which the mother is exposed, the responsiveness of her immune system and ABO compatibility between the mother and fetus. Rh D is the most immunogenic of the red cell antigens. A single pregnancy with an Rh D positive, ABO compatible fetus initiates immunization in about 1 in 6 Rh D negative women.

Antibodies of the immunoglobulin G (IgG) class are actively transported from mother to fetus, commencing in the second trimester and increasing exponentially towards term. Haemolytic disease (HDN) occurs when the fetal red cell life-span is shortened by the action of a specific antibody derived from the mother and transferred across the placenta. Antibody-coated red cells are removed from the circulation by the fetal liver and spleen resulting in anaemia. This increased breakdown of haemoglobin results in increased pigment in the amniotic fluid.

In mild cases of HDN, the fetus may be born with minimal or no clinical affects and postnatal observation may be all that is required. The direct antiglobulin test (DAT) on cord blood is positive reflecting the presence of maternally-derived IgG on the infant’s red cells. In some cases hyperbilirubinaemia may develop requiring phototherapy or sometimes exchange transfusion for the prevention of bilirubin encephalopathy.

In severe cases, there may be early onset of fetal anaemia. The fetal response to anaemia results in increased haemopoiesis in the liver and spleen resulting in enlargement of these organs. As anaemia progresses, decompensation occurs with development or cardiac compromise, ascites, pleural effusions and polyhydramnios (immune hydrops fetalis). Without treatment this condition may result in fetal death.

Investigations

The presence of red cell antibodies in maternal blood may be detected by an indirect antiglobulin test (IAT). A routine ABO and Rh D blood group and antibody screen (IAT) should be performed at the first antenatal visit. If a clinically significant red cell antibody is detected, levels should be monitored periodically through pregnancy by either titration or measurement.

Antigens that stimulate antibodies known to cause clinically significant haemolytic disease are shown in Box 15.3.

Box 15.3 Antigens that stimulate antibodies that can cause significant haemolytic disease of the newborn (HDN)

The aim of surveillance during pregnancy is to ensure that the fetus does not develop life-threatening anaemia. Antibody titration or quantitation give an indirect measure of the likelihood of fetal anaemia, as severe fetal disease is unlikely at low antibody levels such as a titre below 1 in 16. At antibody titres above these levels, fetal monitoring through ultrasound is usually performed. Fetal haemoglobin concentration may be measured from a sample collected at cordocentesis (fetal blood sampling). As this is an invasive procedure associated with significant risk to the fetus (1–2% chance of fetal loss), it is usually only performed when there is a high likelihood of moderate to severe anaemia requiring fetal transfusion.

Indirect methods of screening for moderate to severe fetal anaemia are available. Spectrophotometric examination of amniotic fluid is performed to identify the presence of bilirubin. A sample is collected at amniocentesis and bilirubin is measured as a change in optical density at 450 nanometres (OD 450) (Fig. 15.1). The OD 450 level is then interpreted using a curve (Liley, Queenan or Robertson) that predicts the degree of anaemia based on the amount of haemolysis at a given gestation (Fig. 15.2). Depending on the gestational age at which the OD 450 reaches a critical level, either delivery or cordocentesis (fetal blood sampling) with intrauterine transfusion can be arranged. The OD 450 is most widely used in Rh D alloimmunized pregnancies and may underestimate the degree of anaemia in Kell immunization. In Kell immunization both haemolysis and suppression of red cell production contribute to anaemia.