Diabetes mellitus in pregnancy

Diabetes in pregnancy refers to the presence of diabetes mellitus in a pregnant individual. Depending on whether the condition develops during pregnancy or was already present prior to the pregnancy, it is referred to as gestational diabetes and pregestational diabetes respectively.

Gestational diabetes mellitus is a condition of impaired glucose tolerance during pregnancy that most commonly develops during the second and third trimesters. Patients are usually asymptomatic but may develop polyhydramnios. The fetus is often large for gestational age. All pregnant women should be screened for gestational diabetes with an oral glucose challenge test. Diagnosis is confirmed with an oral glucose tolerance test (OGTT). Treatment involves glycemic control, e.g., dietary modifications and regular exercise. If glycemic control is insufficient, insulin therapy should be initiated. In most cases, gestational diabetes resolves after pregnancy, but complications may occur, including maternal type 2 diabetes mellitus, gestational hypertension, (pre)eclampsia, and diabetic fetopathy.

Pregestational diabetes refers to the presence of type 1 or type 2 diabetes mellitus prior to pregnancy. It is associated with a significantly increased risk for maternal and fetal complications during pregnancy and delivery. Management includes stringent glycemic control and close monitoring of fetal development (e.g., regular ultrasounds to screen for congenital abnormalities).

Pregestational diabetes poses a greater risk of complications than gestational diabetes. Complications during the first trimester are more common in pregestational diabetes, while complications during the second and third trimesters are equally associated with pregestational and gestational diabetes. ^[4]

Diabetic embryopathy

• Definition: any anomaly in an embryo associated with maternal diabetes, typically developing during the main embryonic period
• Onset: first trimester
• Pathophysiology: hyperglycemia → inhibition of myo-inositoluptake → abnormalities in the arachidonic acid-prostaglandin pathway → congenital anomalies and early pregnancy loss ^[4]

Manifestations of diabetic embryopathy ^[4]

• Early pregnancy loss and perinatal death
• Cardiovascular defects: congenital heart disease
  • Transposition of the great vessels
  • Ventricular septal defect
  • Truncus arteriosus
  • Coarctation of the aorta
  • Patent ductus arteriosus
• Central nervous system defects: neural tube defects
  • Anencephaly
  • Spina bifida
  • Myelomeningocele
• Genitourinary defects
  • Renal agenesis
  • Ureteral duplication
  • Hydronephrosis
• 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
      • Mild to severe motor function impairment and paralysis
      • Flat buttocks and shallow gluteal clefts
      • Bowel and bladder dysfunction (e.g., neurogenic bladder, bladder incontinence)
    • May occur as part of other caudal syndromes (e.g., VACTERL, OEIS syndrome)
  • Vertebral anomalies (e.g., hemivertebrae)
• Gastrointestinal defects
  • Small left colon syndrome: an abrupt decrease in intestinal diameter characterized by transient intestinal obstruction due to inability to pass meconium
  • Duodenal atresia
  • Anorectal malformation
• Other: cleft palate

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 of diabetic fetopathy ^[4]

• Growth defect: fetal macrosomia
• 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
  • Transient tachypnea of the newborn
  • Perinatal asphyxia
• 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
  • Diagnostics: echocardiography showing thickened ventricular walls and interventricular septum
  • Management: supportive care(e.g., intravenous fluids, beta blockers) for symptomatic infants
  • Prognosis: Symptoms typically resolve as plasma insulin normalizes.