Maternal Obesity, Gestational Diabetes, and Central Nervous System Birth Defects

Background: Maternal obesity and diabetes are both associated with increased risk of congenital central nervous system (CNS) malformations in the offspring and may share a common underlying mechanism. Our objective was to evaluate whether gestational diabetes influenced the association of prepregnancy maternal obesity and risks for CNS birth defects. Methods: This Texas population-based case-control study evaluated births occurring January 1997 through June 2001. Data came from structured telephone interviews. Cases (n = 477) were mothers of offspring with anencephaly (n = 120), spina bifida (n = 184), holoprosencephaly (n = 49), or isolated hydrocephaly (n = 124). Controls (n = 497) were mothers of live infants without abnormalities randomly selected from the same hospitals as cases. Response rates were approximately 60% for both cases and controls. We evaluated maternal obesity (body mass index ≥30.0 kg/m2) and risks for CNS birth defects, as well as whether gestational diabetes influenced the risks. Results: After adjusting for maternal ethnicity, age, education, smoking, alcohol use, and periconceptional vitamin use, obese women had substantially increased risks of delivering offspring with anencephaly (odds ratio = 2.3; 95% confidence interval = 1.2-4.3), spina bifida (2.8; 1.7-4.5), or isolated hydrocephaly (2.7; 1.5-5.0), but not holoprosencephaly (1.4; 0.5-3.8). Odds ratios were higher for the joint effects of maternal obesity and gestational diabetes, with evidence for interaction on a multiplicative scale. Conclusions: Maternal obesity and gestational diabetes may increase the risk of CNS birth defects through shared causal mechanisms