A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Spring, 2016 | Number 2, Volume 30

High maternal folate, B12 linked to increased autism risk—but supplements reduce risk

Very high plasma levels of maternal folate and vitamin B12 are associated with an increased risk for autism in children, a new study suggests. 

Ramkripa Raghavan and colleagues analyzed data from 1,391 mother-child pairs participating in an ongoing study, focusing on the mothers’ maternal plasma biomarkers of folate and vitamin B12 measured 24-72 hours after delivery. (The researchers were not able to determine whether these levels correlated with dietary supplementation.) 

Study coauthor Daniele Fallin says, “When we looked at the vitamin supplementation evidence, we saw what our colleagues see—that indeed, women who took vitamin supplementation during pregnancy had a lower risk of autism in their children and that is very consistent with the literature.” Maternal multivitamin supplementation three to five times per week was associated with significantly lower risk of autism spectrum disorders (ASD) in offspring across all trimesters. 

However, Fallin says, “When we looked at women who had excessively high levels of folate, we saw that very high levels of folate in the mother were responsible for about a twofold increased risk for autism in their child, and when we looked at B12, women who had excessively high levels of B12 had a threefold increased risk for their child to have autism, while women who had extreme levels of both folate and vitamin B12 had a 17.6 times greater risk of having their child diagnosed with an ASD later on.” 

She concludes that for now, “the public health message is, supplementation is good, but there may be a subset of women whose levels are extremely high, and these extreme levels may be harmful.” 

Fallin also notes that blood levels of folate are not just a function of supplement intake. “They are also a function of diet,” she says, “and a genetic makeup that can change dramatically how easily a person retains or clears folate.”

Editor’s note: ARRI asked researcher Richard Deth, Professor of Pharmaceutical Sciences at Nova Southeastern University in Fort Lauderdale, Florida, to comment on these findings. Here is his reply: 

“At first glance, these findings seem contradictory, with consumption of a multivitamin decreasing ASD risk while elevated folate and vitamin B12 increases the risk. However, the study did not establish that the women with very elevated folate and B12 levels were taking multivitamins, so these are two separate issues. 

“Interpretation of the increased ASD rates with very high maternal folate and B12 levels is challenging. High maternal plasma levels do not necessarily mean that the developing fetus was exposed to the high levels since transport across the placenta intervenes. Moreover, high maternal levels might indicate a problem with the folate and B12 transport systems of genetic origin that translates into higher ASD rates in offspring. Dr. Jill James and colleagues previously demonstrated that antioxidant and methylation pathway metabolites are abnormally skewed in mothers of ASD children, so it may not be surprising that folate and B12 levels are abnormal as well. Indeed, the well-recognized genetic influence in ASD may reside within methylation, transsulfuration, and glutathione synthesis pathways. 

“This scientific meeting presentation was only preliminary, and further details may become available when the work is published in a peer-reviewed journal.”


“Maternal plasma folate, vitamin B12 levels and multivitamin supplement during pregnancy and risk of autism spectrum disorders in the Boston Birth Cohort,” R. Raghavan, A. Riley, D. M. Caruso, X. Hong, G. Wang, B. Ajao, J. Zhang, Y. Ji, M. Li, H. He, Z. Chen, M. C. Wang, C. Pearson, L. K. Hironaka, L. Sices, M. D. Fallin, and X. Wang. Dr. Raghavan and colleagues presented their findings at the 2016 International Meeting for Autism Research (IMFAR) in May 2016. 


“Excessive folate, B12 in pregnancy dramatically ups autism risk,” Pam Harrison, Medscape Multispecialty, May 12, 2016.