BALTIMORE -- While essential B vitamins are important for pregnant women to prevent the risk of birth defects, very high levels of these nutrients may significantly increase the risk of delivering a child with autism, researchers reported here.

In a study of over 1,300 delivering mothers participating in the Boston Birth Cohort study -- 107 of whom had children who developed autism -- those who had very high levels of both plasma folate (>59 nmol/L) and vitamin B12 (>600 pmol/L) were 17.6 times more likely to have a child with an autism spectrum disorder (ASD) (P<0.001) compared with mothers who had normal blood levels of these vitamins, said senior study author M. Daniele Fallin, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Hazard ratios were smaller when looking at each vitamin individually: Women with very high folate levels alone were twice as likely to have a child with ASD as mothers with normal folate levels, and those with very high vitamin B12 levels alone were three times as likely to have a child with ASD as mothers with normal B12 levels, they reported here at the International Meeting for Autism Research.

"We confirm that adequate levels of folate and B12 are essential for child development and that supplementation seems to be protective" against developmental problems like neural tube defects, Fallin said during a press conference at the meeting.

But it's "possible that extreme levels may be harmful," she added.



For the study, researchers analyzed data from 1,391 mother-child pairs participating in a prospective study on early life determinants of autism and other conditions. The study population is predominantly low-income minority women. Mothers were recruited between 1998 and 2013, at the time of their child's birth, and followed for several years, with the mother's blood folate and vitamin B12 levels checked once within the first few days of delivery.

When compared to nonsupplement users, those who had prenatal supplement intake three to five times per week were less likely to have a child with ASD -- suggesting the potential for a U-shaped effect, the researchers said.

While the majority of women reported having taken multivitamins throughout pregnancy, the blood levels of folate and vitamin B12 varied from very high levels to deficiencies (folate <13.5 nmol/L; vitamin B12 <200 pmol/L).

About 10% of women had an excess amount of folate and 6% had an excess of vitamin B12. Between 13.5 and 45.3 nmol/L is an adequate amount of folate for a woman in the first trimester of pregnancy, according to the World Health Organization. There are not well-established thresholds for adequate vitamin B12 levels, Fallin said.

It's unclear why some women had such high levels of the vitamins, she said, because folate levels in the blood could result from supplement intake, how much of a women's diet consists of fortified foods, or genetic makeup that can change how easily someone retains or clears micronutrients.

"These numbers are still relatively small, and this means more work needs to be done before we can say for sure that these increased risks for excessive levels hold, but it's provocative to think of the potential for a sort of U-shape in risk for things like folate and B12," Fallin said. The study underscores the importance of identifying optimum maternal levels of folate and B12 for normal fetal/child neurodevelopment, she said.

A limitation of the study is that blood samples were collected right after birth in the moms and not during pregnancy, Fallin told MedPage Today, so in future studies she would like to check vitamin levels during pregnancy. She also would like to tease out why certain women have such high levels of the vitamins.