Medical disorders are relatively common in pregnancy and often have no implications for the mother or her baby. However, the alteration in maternal physiology, which occurs during pregnancy may affect the medical condition, or the medical condition itself may affect the pregnancy and the baby. Treatment options for the mother may be limited by concerns for fetal welfare and there is therefore the potential for difficult clinical decision-making.

The following conditions will be considered, but see also hypertension (p. 293) and infection in pregnancy (p. 273):

diabetes mellitus

venous thromboembolic disease

cardiac disease

connective tissue disease

epilepsy

hepatic disorders

renal disorders

respiratory disorders

thrombocytopenia

thyroid disorders.

Diabetes mellitus

Diabetes mellitus may be diagnosed before pregnancy (pre-existing) or may be discovered for the first time during pregnancy (gestational). Discovery during pregnancy is rare for type 1 (insulin-dependent) diabetes but not uncommon for type 2 (non-insulin-dependent) diabetes. In addition to these, a transient self-limiting state of hyperglycaemia may occur in pregnancy as a result of maternal endocrine changes.

Glucose homeostasis is maintained by the balance between insulin, which reduces glucose levels by increasing cellular uptake, and other hormones such as glucagon and cortisol, which increase glucose production. In pregnancy, the placenta produces additional cortisol as well as other insulin antagonists, such as human placental lactogen, progesterone and human chorionic gonadotrophin, all of which tend to increase the maternal glucose level. If the pancreatic β islet cells are unable to produce sufficient insulin to balance this increase, or if there is maternal insulin resistance, the mother may develop a state of hyperglycaemia referred to as ‘gestational diabetes’.

Women with pre-existing diabetes mellitus may have high glucose levels in the first trimester at the time of organogenesis, and there is a consequent increase in the rate of congenital abnormalities. The abnormalities are principally cardiac defects, neural tube defects and renal anomalies and are more likely to occur when diabetic control has been poor. Although the mechanism of this teratogenesis is unclear, there is evidence that improved pre-pregnancy and early pregnancy blood glucose control reduces the risk of congenital abnormality.

Fetal glucose levels closely reflect those of the mother, with glucose crossing the placenta through facilitated diffusion. Maternal insulin does not cross the placenta and the fetus produces its own insulin from around 10 weeks’ gestation. This insulin is recognized to have a significant role in promoting fetal growth. As maternal levels of glucose are higher in mothers with diabetes, fetal levels are also increased and, in turn, there is increased fetal insulin production. This fetal hyperinsulinaemia often results in macrosomia (large babies) and organomegaly as well as increased erythropoiesis and neonatal polycythaemia.

In addition to the risk of congenital abnormality, there is also a risk of unexplained intrauterine fetal death, possibly because fetal hyperinsulinaemia leads to chronic hypoxia and acidaemia. A macrosomic fetus may be more at risk of these complications because of its increased oxygen demands.

Because babies of women with diabetes are often macrosomic, labour and delivery may be complicated by dystocia and in particular, shoulder dystocia. Neonates may have hypoglycaemia, hypocalcaemia, hypomagnesaemia and polycythaemia. There is also an increased incidence of hyaline membrane disease.

Effects of pregnancy on diabetes

Insulin requirements may be static or decrease during the first trimester. They typically increase during the second and third trimesters and may reduce slightly towards term. Pregnancy may exacerbate diabetic retinopathy, and the fundi should be assessed for signs of proliferative retinopathy, with laser treatment advised as necessary.

Effects of diabetes on pregnancy

The incidence of pre-eclampsia is increased. There is also an increased incidence of maternal infection, particularly of the urinary tract. Polyhydramnios, which probably results from fetal polyuria, may result in unstable lie, malpresentation and pre-term labour.

Screening for gestational diabetes

This is a controversial subject. National (UK) guidelines recommend offering a 75 g glucose tolerance test (GTT) at 24–28 weeks to women with risk factors, including a family history of diabetes; a raised BMI (> 30); a previous macrosomic baby (> 4.5 kg); or those with previous gestational diabetes (GDM). For those with previous GDM, early self-monitoring or a GTT should be offered at 16–18 weeks and, if normal, repeated at 28 weeks.

The normal fasting plasma glucose is < 5.5 mmol/L. For an oral GTT, patients should fast overnight. Venous blood is taken for fasting blood glucose and a 75 g glucose drink is given. Further venous blood samples are taken after 1 h and 2 h. The International Association of Diabetes and Pregnancy Study Groups’ diagnostic criteria are:

GDM

fasting glucose ≥ 5.1 mmol/L and/or 2-h level > 8.5 mmol/L

Overt diabetes

fasting glucose > 7.0 mmol/L or

HbA_1c > 6.5% or

Random plasma glucose > 11.1 mmol/L.

Management of gestational diabetes

Treatment with dietary advice and adjustment should be the first step, and metformin and then insulin therapy instituted if the target levels are not achieved. Insulin treatment should aim to keep the preprandial glucose < 5.5 mmol/L and postprandial < 7.5/8 mmol/L.

Women with GDM have an increased risk of developing diabetes mellitus in the subsequent 25 years. Recurrence of GDM in subsequent pregnancies is up to 75% (especially if treatment with insulin was required).

Antenatal management of established diabetes

At pre-pregnancy counselling, advice should be given about good diabetic control, diet, smoking and high-dose (5 mg) folate supplements. Pregnancy management should be in a combined obstetric/diabetic clinic, with frequent visits planned as required. Blood glucose should be measured several times a day at home, aiming for tight control (e.g. with preprandial levels 3.5–5.9 mmol/L and 1-h postprandial levels of < 7.8 mmol/L). Glycosylated haemoglobin (HbA_1c) should be checked monthly when planning a pregnancy and in early pregnancy, aiming for levels towards 6.0%.

Insulin is commonly given as a short-acting analogue three times a day (with meals), with an intermediate- or long-acting insulin once or twice a day as background. Ketoacidosis should be avoided, as it is associated with an increased risk of perinatal mortality.

Maternal kidney function and optic fundi should be examined in early pregnancy, and a detailed anomaly scan offered at 18–22 weeks. The maternal abdomen should be examined for polyhydramnios, macrosomia or fetal growth restriction (measurement of symphysis–fundal height), and serial ultrasound fetal biometry is recommended.

Delivery at 38 weeks is recommended but there is no indication for elective caesarean section on the basis of diabetes alone. If pre-term labour occurs, steroids may be given as for the non-diabetic patient, but will lead to marked deterioration in diabetic control, unless insulin doses are increased appropriately or a sliding scale employed.

Delivery

Concern regarding fetal macrosomia and the potential for shoulder dystocia in particular, may necessitate a planned caesarean section.

There are numerous different regimens of intravenous dextrose and insulin, but the aim of them all is to maintain tight intrapartum control, whether during labour or for caesarean section. In the immediate postpartum period, insulin requirements rapidly return to pre-pregnancy levels and the previous subcutaneous regimen can be re-established. For women with GDM, insulin should be discontinued following delivery.

Venous thromboembolic disease

Antenatal

In pregnancy, the balance of the coagulation system is altered towards thrombus formation. There are increased levels of fibrinogen, prothrombin and other clotting factors, together with reduced levels of endogenous anticoagulants. This tendency to clot formation is only in part offset by an increase in fibrinolysis. In addition to the clotting system changes, the gravid uterus causes a degree of mechanical obstruction to the venous system and leads to peripheral venous stasis in the lower limbs.

Venous thromboembolic disease appears to be very rare in Africa and the Far East but is a common direct cause of maternal mortality in the UK. The reason for such wide racial differences may be that the factor V Leiden mutation and prothrombin gene variants are rare in African and Asian populations. In the UK, over 50% of maternal deaths from thromboembolism occur antenatally.

Over 80% of deep venous thromboses (DVTs) in pregnancy are left-sided, in contrast to only 55% in the non-pregnant woman. This difference may reflect compression of the left common iliac vein by the right common iliac artery and the ovarian artery, which cross the vein on the left side only. The gravid uterus lies over the right common iliac artery. Furthermore, over 70% of DVTs in pregnancy are iliofemoral rather than femoral popliteal compared with the non-pregnant rate of around 9%, and are therefore more likely, than lower calf vein thromboses, to give rise to pulmonary embolism.

Thromboembolism may be asymptomatic but usually presents with the traditional symptoms and signs, such as calf tenderness, breathlessness and chest pain. It may also present with lower abdominal or groin pain. It is essential to make a definitive diagnosis, not just for management of the current pregnancy but because there are major implications with regard to the need for thromboprophylaxis in subsequent pregnancies.

Haematological testing for D-dimers is not helpful in pregnancy. Radiological investigations are required if there is clinical suspicion. Duplex Doppler ultrasound is particularly useful for identifying femoral vein thromboses, although iliac veins are less easily seen (Fig. 32.1). It is safe and should be the first-line investigation. X-ray venography is more specific, but has the disadvantage of radiation exposure. Venography or magnetic resonance venography (MRV) is appropriate if Doppler studies give equivocal results, or negative results, despite strong clinical suspicion. Pregnancy is not a contraindication to carrying out a chest X-ray and/or a ventilation-perfusion () scan – any radiation risks are outweighed by the benefits of accurate diagnosis (Fig. 32.2). A normal scan virtually excludes the diagnosis of pulmonary embolism. A computerized tomography pulmonary arteriogram (CTPA) may also be appropriate, especially if the chest X-ray is abnormal or an alternative diagnosis is suspected. CTPA, despite involving less radiation to the fetus than () scanning is associated with significant radiation to the maternal breasts.