Israeli researchers caution that 'the effect of confounding was notable'
This article first appeared January 3, 2018 on Medpage Today.
By Molly Walker
Folic acid and multivitamins both before and during pregnancy seemed to reduce the risk of autism spectrum disorder (ASD) in children, a large Israeli study found.
Compared with women with no exposure to folic acid and/or multivitamin supplementation, women who took folic acid and/or these vitamin supplements during pregnancy had a significantly reduced risk of offspring with ASD (adjusted RR 0.27, 95% CI 0.22-0.33, P<0.001), with similar results seen among women who took these supplements before pregnancy (adjusted RR 0.39, 95% CI 0.30-0.50, P<0.001), reported Stephen Z. Levine, PhD, of University of Haifa in Israel, and colleagues.
Similar results were found when the effects of folic acid and multivitamin supplements were examined individually, the authors wrote in JAMA Psychiatry.
But the authors outlined a number of limitations to their findings, namely that "the effect of confounding was notable," and expressed reservations about residual confounding. They also noted the small size of their study, and pointed out potential misclassification of exposure, or unrecorded use of supplements, such as a mother using over-the-counter supplements. Finally, they pointed out that there was no information about the mothers' whole-blood folate levels and that the registry could not distinguish between multivitamins with and without folic acid.
While they noted that vitamin deficiency has inconsistent links with cognitive functioning, previous epidemiological studies found conflicting results when examining multivitamins or folic acid in pregnancy on the risk of ASD in children.
This case-cohort study examined data from certain healthcare registers in Israel on children born from January 2003 to December 2007. A diagnosis of ASD was performed by a physician after evaluation by a team of experts.
Overall, there were 572 children out of 43,500 in the study (1.3%) with a diagnosis of ASD. The study was comprised of 22,090 girls and 23,210 boys, with a mean age of 10 years at the end of follow-up.
In addition to the effects of folic acid and/or multivitamin supplements, Levine's group looked at the individual effects of maternal exposure to folic acid and multivitamin supplements compared to unexposed mothers and found similar results:
- Folic acid during pregnancy: adjusted RR 0.32 (95% CI 0.26-0.41, P<0.001)
- Folic acid before pregnancy: adjusted RR 0.56 (95% CI 0.42-0.74, P=0.001)
- Multi-vitamin supplements during pregnancy: adjusted RR 0.35 (95% CI 0.28-0.44, P<0.001)
- Multi-vitamin supplements before pregnancy: adjusted RR 0.36 (95% CI 0.24-0.52, P<0.001)
Sensitivity analyses that looked at different time periods of exposure or potential additional confounders generally did not lessen these associations, the authors said. They did note that for offspring whose parents had a psychiatric condition, folic acid supplementation did not significantly reduce the risk of ASD.
"This finding may reflect noncompliance, higher rates of vitamin deficiency, or poor dietamong persons with psychiatric conditions," Levine's group wrote.