Cardiovascular, respiratory, haematological, neurological and gastrointestinal disorders in pregnancy

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Chapter 15 Cardiovascular, respiratory, haematological, neurological and gastrointestinal disorders in pregnancy

CARDIOVASCULAR COMPLICATIONS IN PREGNANCY

It will be recalled that pregnancy places an increased strain on the heart because of the increased rate and stroke volume. The burden on the heart reaches its maximum at about the 28th week and continues into the puerperium. If a pregnant woman has heart disease, the increased strain may affect her wellbeing.

At present, in the developed countries between 0.2 and 0.5% of pregnant women have heart disease. In 30% of cases a woman has mitral valve disease; in 20% ventricular septal defect; in 15%, atrial septal defect; in 15%, aortic stenosis; and in the remainder, other defects.

Management in pregnancy

The initial assessment of the pregnant woman should be made in conjunction with a cardiologist, after which the medical management of the pregnancy can be carried out by the attending doctor, the patient being reviewed by the cardiologist at intervals. The aims of management are:

Factors that predispose to heart failure include anaemia, infections (particularly urinary tract infections) and the development of hypertension. If any of these are found, treatment should be started.

The woman’s cooperation, and that of her family, should be obtained. Her daily activities should be evaluated and changes suggested if this is appropriate.

The patient should be seen at intervals of no more than 2 weeks up to the 28th week of pregnancy, and thereafter weekly by a doctor (if it causes less stress on the woman, it could be her GP in collaboration with the obstetrician and the cardiologist). At each visit cardiac function is assessed by inquiring about breathlessness on exertion, or if she has a cough or orthopnoea. Her lungs are auscultated to detect rales.

Many cardiologists place pregnant women in categories suggested by the New York Heart Association, and the management is planned according to this. Initially most pregnant women are in class 1 or 2, but during pregnancy in 15–55% some degree of cardiac decompensation occurs.

Management during childbirth

Most women who have heart disease have an easy, spontaneous labour and there is no indication for inducing labour on account of the cardiac condition. During labour the patient should be nursed either on her side or well propped up, as compression of the aorta in the supine position may cause marked hypotension. The woman’s fluid balance and her pulse rate should be checked at intervals. If the woman requires anaesthesia, an epidural blockade is the preferred choice as it decreases sympathetic activity, and reduces both oxygen consumption and variations in cardiac output.

Delay in the second stage of labour should be rectified by the use of forceps or vacuum extractor, but there is no need for prophylactic instrumental delivery. The third stage is conducted in the same way as in non-cardiac patients, and active management using Syntocinon is safe, unless the woman is in heart failure. The accoucheur should always bear in mind that in general, women with cardiac disease tolerate postpartum haemorrhage poorly.

The risks and management of specific cardiac conditions are summarized in Table 15.1.

Table 15.1 Management of specific cardiac conditions

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%

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

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

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).

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).

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.

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.

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:

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.

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.

Non-invasive screening for moderate to severe fetal anaemia is now widely used. Measurement of the peak systolic velocity in the middle cerebral artery and interpretation of the result using gestation-specific charts allows prediction of fetuses at risk of moderate to severe anaemia. In the same way as with amniocentesis, if the middle cerebral artery Doppler is above 1.5 multiples of the median (MoM), either delivery or cordocentesis and intrauterine transfusion can be performed, depending on gestation.

The infant

At birth, the infant is examined to determine the degree of fetal haemolysis, taking particular account of hepatosplenomegaly, ascites, and pleural effusions. The outlook for severely hydropic infants is guarded. A blood sample is collected to determine haemoglobin concentration, the serum bilirubin, ABO and Rh D blood group and direct antiglobulin test (DAT or Coombs’ test).

Careful follow-up of the infant for development of jaundice is essential. In adults and older children development of jaundice is usually first seen in the sclera. The sclera are difficult to see in a newborn infant due to the eyelids which may be swollen or closed. Jaundice may be detected in the skin but is usually not visible until the bilirubin exceeds 100–120 μmol/L and may be difficult to detect in darker-skinned infants.

High levels of unconjugated bilirubin may be toxic to the brain, and can cause the disease called kernicterus. The acute signs of kernicterus include lethargy, poor feeding, temperature instability, hypertonia leading to arching of the head, neck and back (opisthotonus), spasticity and seizures. Death or severe neurological disability may follow. The risk of developing kernicterus increases with increasing unconjugated bilirubin (concentrations greater than 340 μmol/L are considered unsafe), decreasing gestation, asphyxia, acidosis, hypoxia, hypothermia, meningitis, sepsis and decreased albumin binding.

Therapies to manage jaundice include adequate hydration, phototherapy, and exchange transfusion. Exchange transfusion is undertaken to prevent kernicterus. The rate of rise as well as the actual bilirubin level must be taken into account. The red cells used for exchange transfusion must be ABO compatible with the infant and negative for the relevant antigen to which the maternal antibody is directed.

Prevention of Rh D alloimmunization

Since the 1960s there has been considerable success in preventing Rh D immunization in Rh D negative women. Rh D immunization mainly affects Caucasian women where up to 15% of the population are Rh D negative. Lower rates of Rh D negative women are seen in African, Asian and Middle Eastern populations.

The principle of prevention is passive immunization. Rh D negative women are given an injection of anti-D antibody at a time when fetal cells may be present in the circulation. The injected anti-D antibody binds to any fetal Rh D positive red blood cells present in the circulation and allows them to be cleared by the maternal liver and spleen before an immune response can occur. For anti-D antibody to be effective, it must be given at the right time and in the right amount.

Anti-D is given to Rh D negative women in the following circumstances during pregnancy:

The dose of anti-D must be sufficient to remove all fetal cells from the maternal circulation. The Kleihauer–Betke test which identifies fetal cells in maternal blood is used to determine the volume of FMH and should be used to assess whether additional doses of anti-D are required for sensitizing events in the second and third trimesters and postnatally. Anti-D should be administered as close to the sensitizing event as possible and within 72 hours. It may still have an effect if given up to 9–10 days after the event.

NEUROLOGICAL DISORDERS

GASTROINTESTINAL DISORDERS