Folic Acid Intake and Spina Bifida in the Era of Dietary Folic Acid Fortification

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Background: The US Food and Drug Administration mandated that enriched grain products be fortified with folic acid by 1998. We evaluated whether intake of folic acid from supplements and diet was associated with a reduction in spina bifida in the setting of folic acid fortification. Methods: Data were collected as part of the Slone Birth Defects Study from 1998 to 2008. Mothers of infants with and without birth defects were interviewed within 6 months of delivery about pregnancy exposures, including details of diet and vitamin intake. Dietary natural folate and synthetic folic acid from fortification were combined into a single, weighted measure--dietary folate equivalent. Periconceptional folic acid supplementation and dietary folate consumption were compared between 205 mothers of spina bifida cases and 6357 mothers of nonmalformed controls. Relative risks of a spina bifida-affected birth were estimated with odds ratios (ORs) and 95% confidence intervals (CIs). Results: Spina bifida was not associated with regular folic acid supplementation (≥4 days per week) either around the time of conception (adjusted OR = 1.1 [95% CI = 0.74-1.7]) or initiated in early pregnancy (0.79 [0.54-1.2]). After adjustment for confounders, a 13% reduced odds of spina bifida was estimated for each 100-μg increase in daily dietary folate equivalent consumed. Conclusions: In the setting of folic acid fortification of grains, our data suggest that folic acid supplementation does not appear to offer further benefit for reducing risk of spina bifida. Rather, the folate-associated benefit on spina bifida risk was found with increasing amounts of dietary folic acid consumed, regardless of folic acid supplementation level.


Supported by a grant from the Centers for Disease Control and Prevention, Center on Birth Defects and Developmental Disabilities.