Chapter 46 Diabetes in pregnancy
Diabetes in pregnancy is either preexisting/pregestational diabetes or acquired gestational diabetes.
Physiology and pathophysiology
Maternal glucose homeostasis
• Normally, blood sugar levels are stable in all trimesters. This is achieved by doubling the insulin secretion from the end of the first trimester to the end of the third trimester.
• In early pregnancy, raised oestrogen and progesterone levels cause cell hyperplasia in the pancreas, which results in a rise in insulin secretion and an increase in fat stores.
• In the second and third trimesters, increases in the diabetogenic hormones human placental lactogen, prolactin and free cortisol cause insulin resistance and lipolysis. Therefore, the increased insulin concentration is counterbalanced by increasing insulin resistance, the mechanism of which is not clearly understood.
• Fasting blood glucose level (BGL) decreases, while postprandial BGL increases in pregnancy. The pregestational diabetic is at risk of hypoglycaemia in early pregnancy and ketoacidosis in later pregnancy, as the demand for insulin is increased.
• Fetal glucose homeostasis: maternal glucose crosses the placenta freely by facilitated diffusion. Therefore, the mother is responsible for regulating fetal blood sugar levels. Fetal insulin appears in the circulation at the end of the first trimester, but the exact role of fetal insulin is uncertain and it may act by promoting growth. It normally plays no role in blood glucose homeostasis. In response to fetal hyperglycaemia due to elevated maternal blood sugar, fetal pancreatic cells hypertrophy, leading to inappropriate release of insulin.
Pregestational diabetes
Effects on pregnancy
Fetal effects
• Congenital malformation: pregestational diabetics (both type 1 and type 2) have an increased risk of fetal malformation with increasing levels of hyperglycaemia (see Table 46.1). Literature suggests only small increases in HbA1c are associated with increased risk.
• Type 1 diabetics with an HbA1c of 7.2% (normal range 6%) have double the risk of fetal malformation and type 2 diabetics may have twice the risk of fetal malformation of the non-pregnant population with a normal HbA1c. If their HbA1c rises to 7.3%, their risk of fetal malformation may be as high as 11%.
• Malformations include neural tube defects, cardiovascular and vertebral defects. The risk of malformation is proportional to imperfect metabolic control during organogenesis; improved blood sugar control decreases anomalies. Many malformations can be diagnosed by mid-trimester ultrasound.
• Abortion and perinatal mortality: diabetic women have higher abortion rates. An HbA1c of 6.5% increases the risk of spontaneous abortion by 3%. Perinatal mortality rates also rise in proportion to the rise in mean BGL. The exact mechanisms for the increased risk demise are uncertain.
• Abnormal fetal growth: there is an increase in the incidence of large-for-dates and small-for-dates fetuses, and consequently fetal morbidity. Macrosomia in all organs (except the brain) is due to an increase in cytoplasmic mass. Macrosomic babies are at risk of trauma during delivery, with definite risk of shoulder dystocia in the diabetic mother with a fetus >4000 g. Intrauterine growth restriction (IUGR) may be a complication of placental vasculopathy and may be related to underlying renal disease or the development of pre-eclampsia.
Table 46.1 Maternal diabetes and risk of congenital malformation
| Congenital malformation | Increased risk over non-diabetics |
|---|---|
| Cardiac | 4 times |
| Neural tube defects | 2–10 times |
| Gastrointestinal atresia | 3–10 times |
| Caudal regression | 200 times (though still rare) |
| Urinary tract | 10 times |
Neonatal effects
• Respiratory distress syndrome: carries six times the risk of non-diabetics. Fetal hyperinsulinaemia results in reduced pulmonary phospholipid production and a decrease in surfactant.
• Hypoglycaemia: 50% of babies of insulin-dependent diabetic mothers have blood sugar levels below 2 mmol/L due to fetal hyperinsulinaemia and discontinuation of the maternal glucose supply.
