Lowered weight gain during pregnancy and risk of neural tube defects among offspring

Maternal nutritional factors have been implicated in the complex aetiology of neural tube defects (NTD). We investigated whether the amount of weight a woman gained during pregnancy was associated with her risk of delivering an infant with an NTD.

We conducted a population-based case-control study within the cohort of 708 129 live births and fetal deaths occurring in selected California counties in 1989-1991. Face-to-face interviews were conducted with mothers of 538 (88% of eligible) NTD cases (including those electively terminated, stillborn, or liveborn) and with mothers of 539 (88%) non-malformed liveborn controls within an average of 5 months from the term delivery date. Respondent-reported weight gain during pregnancy (kg) was analysed. Risks of infants having NTD were estimated among women who gained <10 kg compared to those who gained > or =10 kg during > or =38 week gestations.

Compared to women who gained > or =10 kg, an increased risk for NTD offspring was observed among women who gained <10 kg (odds ratio [OR] = 3.2, 95% CI : 2.3-4.6). The OR was 5.0 (95% CI : 2.6-9.7) among those women who gained <5 kg during pregnancy. The increased risk was not attributable to maternal non-use of a multivitamin containing folic acid, diabetes, NTD-pregnancy history, age, race/ethnicity, education, gravidity, alcohol use, cigarette use, prepregnant obesity, low socioeconomic status, dieting, nausea, nor to lower dietary intakes of folate, zinc, energy, protein, fat, carbohydrates, and methionine. An increased risk was observed even after simultaneous adjustment for most of these factors (OR = 2.2, 95% CI : 1.2-3.8). The risk associated with gaining <10 kg was greater for anencephaly, but still elevated for spina bifida.

We did not have information on weight gain during early pregnancy. Because weight gain during the relevant embryological period for NTD (first month post-conception) is relatively small and often variable, it seems less likely that elevated NTD risks indicate a causal association between lowered weight gain throughout pregnancy and abnormal development of the neural tube. It seems more likely that lowered weight gain is a consequence of carrying an NTD-affected fetus. However, what this consequence is and why risk was substantially larger for anencephaly is unknown.