Physiology
Pregnancy is a “diabetogenic state” with increased insulin resistance and reduced peripheral uptake of glucose (due to placental hormones with anti-insulin activity). In this way, the fetus has a continuous supply of glucose.
Incidence
Three to five percent of pregnancies.
Maternal complications
• Gestational diabetes poses little risk to the mother. Such women are not at risk of diabetic ketoacidosis (DKA), which is a disease resulting from an absolute deficiency of insulin.
• Care should be taken to avoid iatrogenic hypoglycemia due to excessive insulin administration.
• Gestational diabetes is a good screening test for insulin resistance; 50% will develop gestational diabetes in a subsequent pregnancy, and 40–60% will develop diabetes later in life.
Fetal complications
Fetuses of women with poorly controlled gestational diabetes are exposed to high concentrations of glucose and, as a result, grow large. Fetal macrosomia is associated with an increased risk of cesarean section delivery and birth injury.
Screening
• Glucose load test (GLT) is used to screen for gestational diabetes. In the UK, screening is recommended only for high-risk women at approximately 28 weeks. Risk factors include women with a family history of diabetes, sustained glycosuria, obesity, or a history of gestational diabetes, fetus macrosomia, or unexplained fetal demise. US practice favors screening all pregnant women at 24–28 weeks, and high-risk women in the first trimester at 16–20 weeks and again at 24–28 weeks.
• GLT is a non-fasting test, but women should not eat after their 50-g glucose load until a venous blood sample is drawn 1 hour later. A positive test should be followed by a glucose tolerance test (GTT). A GLT cut-off of ≥7.8 mmol/L (≥140 mg/dL) will detect 80% of women with gestational diabetes with a false-positive rate of 14–18%; a cut-off of ≥7.2 mmol/L (≥130 mg/dL) will detect 90% with a falsepositive rate of 20–25%.
• A definitive diagnosis of gestational diabetes requires a GTT; there is no GLT cut-off that is diagnostic. In the UK, a 2-hour 75-g GTT is used. Fasting glucose >5.5 mmol/L (>100 mg/dL) and at 2 hours >7.9 mmol/L (>140 mg/dL) will confirm the diagnosis.
Antepartum Management
• The primary aim is to prevent fetal macrosomia and its complications by maintaining blood glucose at desirable levels (defined as fasting, <95 mg/dL [<5.2 mmol/L] and 1 hour postprandial, <140 mg/ dL [<7.8 mmol/L]).
• A diabetic diet is recommended for all such women.
• Treatment may be required. If fasting glucose levels are >95 mg/dL (>5.2 mmol/L), therapy can be initiated right away because “you cannot diet more than fasting.” Although insulin remains the “gold standard” for the treatment of gestational diabetes in pregnancy, the use of oral hypoglycemic agents is becoming more common.
Intrapartum Management
• Cesarean section delivery may be appropriate if the estimated fetal weight is excessive because of the risk of birth injury.
• As the primary source of anti-insulin hormones is the placenta, no further management is required in the immediate postpartum period.
• All women with gestational diabetes should have a standard (nonpregnant) 75-g GTT 6–8 weeks postpartum, because such women are at increased risk of developing diabetes in later life.
Pregestational Diabetes
Pathophysiology
Results from either an absolute deficiency of insulin (type 1 or insulindependent diabetes mellitus) or increased peripheral resistance to insulin (type 2 or non-insulin-dependent diabetes mellitus).
Incidence
Less than 1% of women of childbearing age.
Classification
• The age of onset and duration of diabetes (White classification) does not correlate with pregnancy outcomes.
• Poor prognostic features include DKA, poor compliance, hypertension, pyelonephritis, and vasculopathy.
Complications
In contrast with gestational diabetes, pregestational diabetes is associated with significant maternal and perinatal mortality and morbidity
MATERNAL COMPLICATIONS OF PREGESTATIONAL DIABETES
• Pre-eclampsia (12%)
• Chronic hypertension (10%)
• Diabetic ketoacidosis (8%)
• Polyhydramnios (18%)
• Preterm labor (8%)
• Cesarean section delivery (20–60%)
• Other obstetric emergencies (hypoglycemia, coma)
• Genetic transmission (infants of mothers with type 1 diabetes have a 4–5% risk of acquiring diabetes; infants of mothers with type 2 diabetes have a 25–50% risk of diabetes)
FETAL COMPLICATIONS OF PREGESTATIONAL DIABETES
Congenital abnormalities of diabetic mothers
• Spontaneous abortion ( 2–3 x)
• Diabetic ketoacidosis (50–90% fetal mortality)
• Intrauterine growth restriction
• Late intrauterine fetal demise
• Fetal macrosomia (with or without birth injury)
• Delayed organ maturation
– respiratory distress syndrome (RDS)
– neonatal hypoglycemia
– neonatal hypocalcemia
– neonatal hypomagnesemia
– polycythemia/hyperviscosity
– neonatal hyperbilirubinemia (40%)
Congenital anomalies in infants of diabetic mothers Cardiac
• Atrial septal defect
• Ventricular septal defect
• Coarctation of aorta
• Transposition of great vessels
Skeletal and central nervous system
• Anencephaly
• Caudal regression syndrome (very rare, but highly specific for diabetes mellitus)
• Microcephaly
• Neural tube defect
Other
• Single umbilical artery
Gastrointestinal
• Anorectal atresia
• Duodenal atresia
• Tracheoesophageal fistula
Renal
• Hydronephrosis
• Renal agenesis
• Ureteral duplication
• Polycystic kidneys
Antepartum management
• Diabetic women should ideally be seen before conception. Pregnancy complications such as fetal congenital anomalies and spontaneous abortion correlate directly with the degree of diabetic control at conception.
• Intense antepartum management can reduce the perinatal mortality rate from 20% to 3–5%.
• Approximately 5% of maternal hemoglobin is glycated (bound to glucose), known as hemoglobin A1 (HbA1). HbA1c refers to the 80–85% of HbA1 that is irreversibly glycated. As red blood cells have a lifespan of 120 days, HbA1c measurements reflect the degree of glycemic control over the previous 3–4 months. HbA1c measurements should be checked before conception, at first prenatal visit, and every 4–6 weeks throughout pregnancy.
Strict glucose control using:
• Diabetic diet (36 kcal/kg or 15 kcal/lb of ideal body weight + 100 kcal per trimester given as 40–50% carbohydrate, 20% protein, 30–40% fat to avoid protein catabolism)
• Insulin (insulin therapy should be individualized, but a common regimen is 0.7–1.0 units/kg/day given 2/3 in AM (2⁄3 NPH, 1⁄3 rapid/short-acting) and 1/3 in PM (50% NPH, 50% rapid/short-acting))
• Goal: fasting blood glucose <95 mg/dL; 1 h postprandial blood glucose <140 mg/dL
• Home monitoring of blood sugar at least 4 x per day Ophthalmological examination every trimester Detailed sonographic fetal structural survey at 18–22 weeks’ gestation (including fetal echocardiogram)
Consider checking thyroid functions (6% have co-existing thyroid disease), baseline preeclampsia blood tests, 24-hour urinary protein and creatinine clearance HbAlc (above) Fetal testing (NST, ultrasound for growth) after 32 weeks given risk of intrauterine growth restriction and fetal demise
Intrapartum and Postpartum Management
• If metabolic control is good, spontaneous labor at term can be awaited. As a result of the risk of unexplained fetal demise, women with pregestational diabetes should be delivered by 39–40 weeks.
• If the estimated fetal weight is excessive (likely ≥4,500 g), the elective cesarean section may be appropriate to avoid birth injury.
• Women may not eat during labor. As such, intravenous glucose should be administered (5% dextrose at 75–100 mL/h) and blood glucose levels checked every 1–2 hours. Regular insulin should be given by subcutaneous injection or intravenous infusion to maintain blood glucose levels at 100–120 mg/dL (5.5–6.6 mmol/L).
• During the first 48 hours postpartum, women may have a “honeymoon period” during which their insulin requirement is decreased. Blood glucose levels of 150–200 mg/dL (8.2–11.0 mmol/L) can be tolerated during this period. Once a woman is able to eat, she can be placed back on her usual regular insulin regimen.