Excessive Folate, B12 in Pregnancy Dramatically Ups Autism Risk

Pam Harrison

May 12, 2016

BALTIMORE ― Excessive levels of plasma folate and vitamin B12 during pregnancy have been linked to a dramatic increase in autism risk in offspring, new research shows.

Investigators at Johns Hopkins University, Baltimore, found that when maternal plasma folate levels and vitamin B12 levels are >59 nmol/L and >600 pmol/L, respectively, autism risk is increased more than 17-fold.

The findings were presented at the International Meeting for Autism Research (IMFAR) 2016.

"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," principal investigator Daniele Fallin, PhD, director, Wendy Klag Center for Autism and Developmental Disabilities, John Hopkins Bloomberg School of Public Health, said during a press briefing.

"But 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 [P = .007], 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 [P = .001], 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 [autism spectrum disorder] later on [P < .001]," she added.

"So 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."

Led by Ramkripa Raghavan, MPH, investigators analyzed data from 1391 mother-child pairs enrolled in the Boston Birth Cohort, an ongoing, longitudinal study that includes a predominantly low- income, minority population.

The study included children born between 1998 and 2013 who were followed from birth through childhood. At the time of delivery, maternal serum folate and vitamin B12 levels were analyzed. Mothers were asked whether they took a multivitamin supplement during pregnancy and, if so, how often.

A total of 107 infants were diagnosed with autism, Asperger syndrome, and/or pervasive developmental disorder not otherwise specified and were categorized as having ASD.

Investigators noted that levels of both nutrients varied from deficiency levels of plasma folate (<13.5 nmol/L) and vitamin B12 (<200 pmol/L) to excessive levels of plasma folate (>59 nmol/L) and vitamin B12 (>600 pmol/L).

Dr Fallin said that the team was not able to determine whether excessive plasma folate and vitamin B12 levels corresponded to a certain level of intake of both supplements during pregnancy.

"In our study, we were not able to connect precise vitamin use and later folate and B12 levels in these mothers. But, generally speaking, it's important to appreciate that levels of folate in blood are not just a function of supplement intake. They are also a function of diet and a genetic makeup that can change dramatically how easily a person retains or clears folate," she said.

She acknowledged that it is important to establish what constitutes a safe and effective intake of supplements for women during pregnancy.

A Balanced Approach

Geraldine Dawson, MD, president of the International Society for Autism Research and professor of psychiatry and behavioral science at Duke University School of Medicine, Durham, North Carolina, told Medscape Medical News that it has long been known that diet and vitamin supplementation are very important for fetal brain development.

"Now we're also seeing that it's also important for lowering the risk that your child will have autism," she added.

Future research will help to identify exactly what levels of vitamins pregnant women need to take, she said.

"But I think the new finding here is that we've been focusing on the need for supplementation of vitamin B and also folate, but now we're also seeing that we don't want to take too much ― that if you have very high levels of these nutrients, that this is not optimal," Dr Dawson said.

"So the next step is to define what the right level is, but I think the message so far is to take moderate levels of supplements and not to overdo it, but certainly don't 'under-do' it, either."

Dr Fallin has disclosed no relevant financial relationships.

International Meeting for Autism Research (IMFAR) 2016: Abstract 149.004, to be presented May 13, 2016.


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