Preconception folic acid supplementation use and the occurrence of neural tube defects in Japan: A nationwide birth cohort study of the Japan Environment and Children's Study.

We evaluated the relationship between preconception folic acid supplementation and the occurrence of neural tube defects (NTDs) in offspring, using data from the Japan Environment and Children's Study (a nationwide prospective birth cohort study) database. Of 92 269 participants with single pregnancies, 74 cases (offspring or fetuses) had NTDs, including 32 cases of spina bifida, 24 cases of anencephaly, and 19 cases of encephalocele. A total of 7634 participants (8.27%) used preconception folic acid supplementation, and of these, 621 (0.67%) also took in dietary folic acid at ≥480 μg/day. Multivariate logistic regression analyses demonstrated no association between preconception folic acid supplementation and NTDs in offspring or fetuses (odds ratio [OR] 0.622; 95% confidence interval [CI]: 0.226-1.713). Moreover, the participants who combined preconception folic acid supplement use with dietary folic acid intake ≥480 μg/day demonstrated no incidence of NTDs in offspring or fetuses. Our analysis is limited by the absence of the data on the daily amount of supplementary folic acid intake, requiring careful attention to the interpretation. Additional surveys are required in Japan to resolve those limitations for further comprehensive assessment.