Women's periconceptional lowered carbohydrate intake and NTD-affected pregnancy risk in the era of prefortification with folic acid.

Abstract

A recent study observed women's restricted carbohydrate diet in the year before conception was associated with increased risk of neural tube defect (NTD)-affected pregnancies. That study corresponded to the era of postfortification of folic acid. Because folic acid and carbohydrate measures would derive from similar foods, investigators of that study could not determine whether the increased risk with restricted carbohydrate intake was a consequence of lower folate intake. We extend their novel observation by examining rigorous NTD data prior to folic acid fortification. Data were derived from a population-based case-control study of fetuses and infants with NTDs among 1989-1991 California births. Interviews were conducted with mothers of 449 NTD cases and with mothers of 458 nonmalformed controls. A standard 100-item food frequency questionnaire was used to assess macro- and micronutrient intakes based on reported intakes 3 months before conception. Case mothers were twice as likely to have consumed a low carbohydrate (≤5th percentile intake among controls) diet with a crude odds ratio of 2.0 (95% confidence interval, 1.2-3.4). Adjustment for race/ethnicity, education, alcohol intake, and folic acid use made very little difference on the odds ratio. Adjustment for total energy intake appeared to be the only factor to slightly attenuate the odds ratio. Our findings indicate that the association between low carbohydrate intake and NTD risk may not be wholly a function of low folic acid in the postfortification era. Such a finding offers new clues to pursue for the seemingly folate-insensitive NTDs that continue to occur.