High dose folic acid during pregnancy and the risk of autism; The birth order bias: A nested case-control study.

OBJECTIVE

To examine whether there is an association between the cumulative dose of folic acid (FA) purchased by mothers, and risk of autistic spectrum disorders (ASD) in their progeny.

METHODS

We identified 2009 singletons who received an ASD diagnosis from a cohort of 480,526 children born in a large health organization in Israel from 2000 through 2013. ASD patients were individually matched to ASD-free children (n = 19,886). Median cumulative daily doses of supplemented FA during the 12-month period prior to the end of pregnancy (from dispensing records) were compared using conditional logistic regression models.

RESULTS

Children with ASD were more likely to be first-born, and birth-order was significantly associated with FA use. In multivariable analysis, there were no statistically significant differences in the cumulative dose of FA between the groups.

CONCLUSION

Birth order effects need to be accounted for in analyses aiming to decipher the associations between gestational FA use and developmental outcomes.