Objectives: There has been a dramatic increase in the prevalence of autism worldwide, concurring with growing use of folic acid for the prevention of neural tube defects . Our objective was to examine whether gestational use of folic acid is associated with increased risk of autism. Design: A nested case- control study. Setting: A large health fund ) insuring 2 million citizens. Subjects: All autism spectrum disorder cases diagnosed among 504,028 children born into Maccabi Health Services from 2000 to 2010 (inclusive); singleton children with autistic spectrum disorder (n=2009) were matched with up to 10 non autistic controls (n=19,886). Main outcome measures: Cumulative mean dose of supplemented folic acid dispensed during the 12 months preceding birth was compared between the groups using conditional multivariable logistic regression. Results: Significantly more autistic children were first born, and birth order was independently and significantly associated with folic acid use: Mothers purchased significantly more folic acid during the first pregnancy than during later pregnancies. In multivariate analysis, accounting for birth order and other confounders, folic acid use was not associated with increased autistic risk, and no dose -response trends were observed. Compared with mothers of the lowest average daily folate dose, the odds ratio for autism among mothers of highest daily dose (3mg) was 0.99 (95% confidence interval: 0.59-1.67). The lack of association was further confirmed in sensitivity analysis restricted to first-born children only. Conclusions: The results may be of public health importance given that folic acid is needed to prevent neural tube defects.
