Koren F, et al. - An inquiry was set up with regard to the link between the cumulative dose of folic acid purchased by the mother from 3 months prior to and throughout pregnancy, and the risk of autism. The findings did not reveal any association between the amount of folic acid purchased and the occurrence of autistic spectrum disorders (ASD). The higher folic acid exposure in autistic children was possibly attributed to the colinearity between the order of birth (first born) and the trend of mothers to consume considerably more folic acid in their first pregnancy.

Methods

• The enrollment comprised of 1650 children with ASD diagnosed from a cohort of 504028 children, born in a large health organisation in Israel from 2000 through 2013.
• ASD patients were individually matched in a ratio of 1:5 to ASD-free children (n=7591) from the cohort on age and maternal age, sex, residential area and level of socio-economic status.
• An estimation was performed of the odds ratios and 95% confidence intervals by a mean daily dose of supplemented folic acid during the 12 month period via unconditional multivariable logistic regression.
• Adjustment was done for potential confounders including age of mother, place of the child in the family, having a fertility problem and being enrolled in the fertility register, suffering from epilepsy, maternal BMI, and serum concentrations of vitamin B12.

Results

• A markedly higher mean daily dose of folic acid purchases among ASD cases (177.84 μg, SD=250.7) during the 12 month study period was noted when compared to controls (145.87 μg, SD=214.2) (p<0.001).
• Prominently more ASD children were first born, and mothers purchased considerably more folic acid during the first pregnancy than in the second pregnancy, and even less in the third pregnancy.
• The ages of ASD mothers were notably older, more subfertility was displayed, visited more frequently at their physicians’ offices.
• In multivariable analysis, accounting for these confounders, no noticeable variations were found in the amount of folic acid purchased between the groups.
• There was no dose-response effect of folic acid on the occurrence of autism.
• The folic acid purchases between healthy and ASD first-born children underwent comparative study while regarding all other variables, in a sensitivity analysis.
• It did not exhibit any association between higher folic acid purchases and ASD occurrence.