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
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