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).

Overview

Pregestational diabetes represents a greater risk of complications than gestational diabetes. ^[4]

• First trimester
  • Complications more common with pregestational diabetes
  • Associated with a greater risk of major congenital malformations (e.g., neural tube defects, transposition of great arteries, sacral agenesis, small left colon syndrome) and early pregnancy loss
• Second and third trimesters
  • Complications associated equally with pregestational and gestational diabetes
  • Associated with metabolic complications (e.g., acidosis, hypocalcemia), polycythemia, increased weight of organs (e.g., hypertrophic cardiomyopathy), and pregnancy loss

Diabetic embryopathy

• Definition: : any anomaly in an embryo associated with diabetes in the mother. Anomalies typically develop during the main embryonic period (especially during blastogenesis) and include neural tube defects, small left colon syndrome, caudal regression, and renal disorders (e.g., renal agenesis).
• Onset: first trimester
• Pathophysiology: hyperglycemia → inhibition of myoinositol uptake → abnormalities in the arachidonic acid-prostaglandin pathway → birth defects and early pregnancy loss ^[4]
• 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, to a lesser degree, the lower lumbar spine
    • Clinical features: based on the spinal lesion the level and disease severity
      • Lower limb deformities (e.g., inverted champagne bottle appearance due to muscle wasting) or foot deformities (e.g., club feet)
      • Mild to severe motor function impairment and paralysis
      • Anorectal malformations and aplasia or hypoplasia of the sacrum and/or lumbosacral spine
      • Bowel and bladder dysfunction (e.g., neurogenic bladder, bladder incontinence)
      • Flattened buttocks (palpable absent coccyx gives a dimpling appearance to the buttocks) and shallow gluteal clefts
    • May occur as part of other caudal syndromes (e.g., VACTERL, OEIS)
  • Vertebral anomalies (e.g., hemivertebrae)
• Gastrointestinal defects
  • Small left colon syndrome: an abrupt decrease in intestinal diameter characterized by transient intestinal obstruction due to failure to pass meconium
  • Duodenal atresia
  • Anorectal atresia
• Other
  • Early pregnancy loss
  • Cleft palate

Diabetic fetopathy

• Definition: : Any anomaly in a fetus associated with diabetes in the mother. Anomalies typically develop during the second and third trimesters and include macrosomia, postnatal hypoglycemia, and polycythemia due to fetal hyperinsulinemia during gestation.
• Onset: second and third trimesters
• Effects
  • Macrosomia: a significantly larger-than-average fetus, defined as birth weight > 90^th percentile or > 4,000 g (8 lbs 13 oz)
    • Associated with an increased risk of birth injuries (e.g., shoulder dystocia, brachial plexus injury)
    • Maternal hyperglycemia → fetal hyperglycemia → stimulation of fetal pancreas → fetal hyperinsulinemia → ↑ hepatic glucose uptake and glycogen synthesis → ↑ fat and protein synthesis ^[4]
  • Neonatal hypoglycemia: maternal hyperglycemia → chronic fetal hyperglycemia → ↑ metabolic effects and oxygen demand → fetal hypoxemia → ↑ erythropoietin concentrations
  • Neonatal polycythemia
    • Associated with an increased risk of hyperviscosity syndrome, hyperbilirubinemia, and low iron stores
    • ↑ Erythrocyte and iron storage and redistribution of fetal iron → iron deficiency
  • Electrolyte disturbances: neonatal hypocalcemia (serum calcium < 7 mg/dL or serum ionized calcium < 4 mg/dL) and neonatal hypomagnesemia (serum magnesium < 1.5. mg/dL)
    • Typically observed within 72 hours after birth
    • ↑ Maternal urinary Mg excretion → hypomagnesemia in the mother and fetus → impaired PTH synthesis in the fetus → fetal hypocalcemia
    • Clinical features: commonly asymptomatic but may manifest with lethargy, jitteriness, and/or seizures
    • Management: IV calcium and/or magnesium in symptomatic infants
  • Respiratory distress syndrome
  • Transient hypertrophic cardiomyopathy: an often asymptomatic and reversible thickening of one or both of the ventricular walls and the interventricular septum caused by excessive exposure to maternal glucose and insulin.
    • 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/systolic and diastolic dysfunction of the heart
    • Clinical features: often asymptomatic in infants but may manifest with symptoms of heart failure (e.g., tachypnea, poor feeding, irritability)
    • Diagnostics: echocardiography
    • Management: supportive care (e.g., intravenous fluids, beta-blockers) for symptomatic infants
    • Prognosis: Symptoms typically resolve as plasma insulin normalizes.