Pathophysiology

• Human placental lactogen (HPL, aka human chorionic somatomammotropin): a hormone synthesized by syncytiotrophoblasts of the placenta, which promotes the production of insulin-like growth factors.
  • Causes insulin resistance to supply growing fetus with glucose and amino acids.
  • Concurrently increases insulin levels; inability to overcome insulin resistance → gestational diabetes.

Treatment

• Glycemic control
  • Dietary modifications and regular exercise (walking)
  • Strict blood glucose monitoring (4x daily)
  • Insulin therapy if glycemic control is insufficient with dietary modifications
    • Fasting blood glucose level > 95 mg/dL or one-hour postprandial blood glucose level > 140 mg/dL or 2-hour postprandial blood glucose level > 120 mg/dL
  • Metformin and glyburide in patients who are unwilling or unable to use insulin
• Regular ultrasound to evaluate fetal development
• Consider inducing delivery at week 39–40, if glycemic control is poor or if complications occur

Complications

Diabetic embryopathy

• Skeletal defects
  • Caudal regression syndrome: a congenital condition characterized by the partial or complete absence of the sacrum and often of the lower lumbar spine
  • Pathophysiology: The cause of caudal regression syndrome is unknown.
  • Maternal diabetes is a known risk factor.
  • Clinical features: based on the level of the spinal lesion and disease severity
    • Lower limb deformities or foot deformities (e.g., club foot)
    • Anorectal malformations
    • Aplasia or hypoplasia of the sacrum and/or lumbosacral spine

Diabetic fetopathy

• Definition: any anomaly in a fetus associated with maternal diabetes, caused by fetal hyperinsulinemia during gestation
• Onset: second and third trimesters
• Pathophysiology: maternal hyperglycemia → fetal hyperglycemia → stimulation of fetal pancreas → fetal hyperinsulinemia → ↑ metabolic rate, oxygen consumption, and fetal hypoxemia → metabolic, respiratory, and cardiovascular complications

Manifestations

• Growth defect: fetal macrosomia
• Polyhydramnios
  • Increased maternal glucose levels increase fetal glucose levels, as well, resulting in polyuria.
• Metabolic defects
  • Neonatal hypoglycemia
    • maternal hyperglycemia → fetal hyperglycemia → beta cell hypertrophy and hyperfunctioning → fetal and neonatal hyperinsulinemia → transient hypoglycemia after birth (when maternal glucose supply stops)
  • Neonatal polycythemia
    • maternal hyperglycemia → chronic fetal hyperglycemia → ↑ metabolic effects and oxygen demand → fetal hypoxemia → ↑ erythropoietin concentrations→ ↑ erythrocyte count
  • Neonatal hypocalcemia and neonatal hypomagnesemia: maternal hyperglycemia → abnormal maternal calcium-phosphorus metabolism → ↑ maternal urinary Mg excretion → maternal hypomagnesemia → fetal hypomagnesemia → impaired PTH synthesis in the fetus → fetal hypocalcemia and hypomagnesemia
• Respiratory defects
  • Acute respiratory distress syndrome
• Cardiovascular defects: transient hypertrophic cardiomyopathy
  • Definition: thickening of one or both of the ventricular walls and the interventricular septum
  • Clinical features: often asymptomatic in infants but may manifest with symptoms of heart failure (e.g., tachypnea, poor feeding, irritability)
  • Pathophysiology: maternal hyperglycemia → fetal hyperglycemia → fetal hyperinsulinemia → ↑ fat and glycogen in fetal myocardial cells → thickening of ventricular walls and the intraventricular septum in utero → ↓ ventricular size → left ventricular outflow obstruction and systolic and diastolic cardiac dysfunction