Several large-scale cohort studies suggest that obese mothers are at increased risk of having infants with neural tube defects and, possibly, other central nervous system (CNS) birth defects. Because obesity and diabetes share similar metabolic abnormalities, a study was planned to determine whether gestational diabetes influences the association between maternal obesity and CNS birth defects. In this population-based case–control study, covering the years 1997 to mid-2000, structured telephone interviews were conducted with mothers of offspring having anencephaly (n = 120), spina bifida (n = 184), holoprosencephaly (n = 49), or isolated hydrocephaly (n = 124). Control women whose infants were neurologically normal were randomly chosen from the same hospitals. Approximately 60% of both cases and control subjects responded. Maternal obesity was defined as a body mass index of 30 kg/m2 or higher.
Pregestational diabetes, both type 1 and type 2, correlated closely with holoprosencephaly (adjusted odds ratio [OR], 47; 95% confidence interval [CI], 9.5–230), and isolated hydrocephaly (OR, 12; 95% CI, 2.9–47). There was no increase in the risk of anencephaly or spina bifida.
Gestational diabetes increased only the risk of holoprosencephaly (OR, 2.9; 95% CI, 1.0–8.4). Mothers of infants with anencephaly were less likely than control mothers to have gestational diabetes. Obese mothers were likelier than control subjects to have infants with any of the 4 CNS birth defects. Underweight women were less likely to have an infant with spina bifida. The association between maternal obesity and an increased risk of neural tube defects and isolated hydrocephaly held for all ethnic groups. Associations between maternal obesity and anencephaly (OR, 2.3; 95% CI, 1.2–4.3), spina bifida (OR, 2.8; 95% CI, 1.7–4.5), and isolated hydrocephaly (OR, 2.7; 95% CI, 1.5–5.0) persisted after adjusting for maternal age, ethnicity, education, smoking, alcohol use, and periconceptional vitamin use. For both spina bifida and holoprosencephaly, the joint effects of maternal obesity and gestational diabetes appeared to be interactive.
These findings suggest that gestational diabetes and maternal obesity may increase the risk of CNS birth defects through common mechanisms, and they strongly support the need for ways of preventing these conditions.