The association between maternal folic acid and multivitamin supplementation and risk of autism spectrum disorder (ASD) has been evaluated in several epidemiologic studies
The California Childhood Autism Risks from Genetics and Environment (CHARGE) study identified a reduced risk of ASD with folic acid supplementation beginning 12 weeks prior to pregnancy and into the first 4 weeks into pregnancy.
Studies in Norway have reported similar findings, but studies in Denmark have not.
Results from the Stockholm Youth Cohort reported an association between multivitamin use during pregnancy and a reduced risk of ASD with intellectual disability.
The current study aimed to further explore the association between maternal folic acid or multivitamin supplementation and ASD in the offspring.
This case-control study involved 45,300 children born in Israel between 2003 and 2007.
During a mean follow-up of 10 years, 572 (1.3%) were diagnosed with ASD (as defined by the ICD-9 codes 299.0, 299.1, or 299.8).
These children were compared with a control sample of children not diagnosed with ASD. The exposure variables of interest were maternal supplementation with folic acid or multivitamin before or during pregnancy.
Maternal use of folic acid and/or multivitamin before pregnancy was associated with a significantly lower risk of ASD compared with no exposure (70% lower risk; RR=0.30; 95% CI, 0.30-0.50; p<.001).
Maternal use of folic acid and/or multivitamin during pregnancy was also associated with a significantly lower risk of ASD compared with no exposure (73% lower risk; RR=0.27; 95% CI, 0.22-0.33; p<.001).
Risk reductions were similar when folic acid use and multivitamin use were evaluated independently.
Sensitivity analyses showed that folic acid or multivitamin use from 4 weeks before to 8 weeks into pregnancy significantly reduced the risk of ASD, as did maternal exposure during the 2 years before pregnancy.
The results of this study are consistent with the earlier results of the CHARGE study and the studies in Norway. A unique finding in this study was that vitamin use for 2 years before pregnancy reduced the risk of ASD in the offspring.
Although causality cannot be determined by an observational study, these results support the current recommendations for prenatal vitamin supplementation.