Spina bifida phenotypes in infants or fetuses of obese mothers

Background: A twofold or greater risk of neural tube defect (NTD)-affected pregnancy has been associated with prepregnant obesity, where obesity was defined as body mass index (BMI) of >29 kg/m(2). Risks have been more elevated for spina bifida than for anencephaly. Methods: We investigated whether finer phenotypic classifications of spina bifida, in combination with other factors, were associated with a BMI of >29 kg/m(2). Data were derived from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. Interviews were conducted with mothers of 277 spina bifida cases and 517 nonmalformed controls. Results: Women with a BMI of >29 kg/m(2) compared with those less than or equal to 29 kg/m(2) revealed an odds ratio (OR) of 2.2 (95% confidence interval [95% CI] = 1.43.3) for spina bifida in their infants and fetuses. Elevated risks were observed for each spina bifida subphenotype, and risks varied by subphenotype: open spina bifida, OR = 2.0 (1.2-3.1); closed (skin-covered), 3.3 (1.4-7.5); isolated, 2.2 (1.4-3.4); nonisolated, 1.9 (0.9-4.2); high, 4.5 (2.1-9.6); low, 1.9 (1.2-2.9); open/isolated/high, 7.1 (2.8-18.1); and open/isolated/low, 1.8 (1.1-3.1). Risks were higher among female infants/fetuses and foreign-born Latinas, and for some phenotypes the risks were quite large, e.g., OR = 8.3 (2.9-23.6) for "closed" spina bifida among female infants/fetuses whose mothers were >29 kg/m(2) compared with males whose mothers were less than or equal to 29 kg/m(2). Maternal periconceptional vitamin use was not observed to influence risk as greatly across phenotypes. Conclusions: The observed pathogenetic heterogeneity of prepregnant obesity and spina bifida risks suggests that there are likely to be several biologic mechanisms underlying the association. (C) 2000 Wiley-Liss, Inc.