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Folic acid use may reduce offspring’s autism risk

Tuesday February 12, 2013
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In a study that included approximately 85,000 Norwegian children, maternal use of supplemental folic acid from four weeks before to eight weeks after the start of pregnancy was associated with a lower risk of autistic disorder in children.

"Supplementation with folic acid around the time of conception reduces the risk of neural tube defects in children," researchers wrote in background information for the study, which appears in the Feb. 13 issue of the Journal of the American Medical Association. "This protective effect has led to mandatory fortification of flour with folic acid in several countries, and it is generally recommended that women planning to become pregnant take a daily supplement of folic acid starting one month before conception."

Whether prenatal folic acid supplements protect against other neurodevelopmental disorders has not been determined. To investigate, Pal Surén, MD, MPH, of the Norwegian Institute of Public Health, and colleagues examined the association between the use of maternal folic acid supplements before and in early pregnancy and the subsequent risk of autism spectrum disorders in children.

The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study. The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (with an average age of 6.4). The exposure of primary interest was use of folic acid from four weeks before to eight weeks after the start of pregnancy. Analyses were adjusted for maternal education level, year of birth and parity.

A total of 270 children (0.32%) in the study sample had been diagnosed with ASDs: 114 (0.13%) with autistic disorder, 56 (0.07%) with Asperger syndrome and 100 (0.12%) with pervasive developmental disorder-not otherwise specified. The researchers found an inverse association between folic acid use and subsequent risk of autistic disorder, which was present in 0.1% (64 out of 61,042) of children whose mothers took folic acid, compared with 0.21% (50 out of 24,134) in children whose mothers did not take folic acid, representing 39% lower odds of autistic disorder in children of folic acid users.

Characteristics of women who used folic acid within the exposure interval included being more likely to have college- or university-level education, to have planned the pregnancy, to be nonsmokers, to have a pre-pregnancy body mass index below 25 and to be first-time mothers.

The researchers reported no association with Asperger syndrome or unspecified autism disorder, although in the case of AS, the sample size was too small to establish a meaningful odds ratio.

Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use, the researchers wrote. The inverse association found for folic acid use in early pregnancy was absent for folic acid use in mid pregnancy.

"Our main finding was that maternal use of folic acid supplements around the time of conception was associated with a lower risk of autistic disorder," the researchers wrote. "This finding does not establish a causal relation … but provides a rationale for replicating the analyses in other study samples and further investigating genetic factors and other biological mechanisms that may explain the inverse association."

In an accompanying editorial, Robert J. Berry, MD, MPHTM, and colleagues with the Centers for Disease Control and Prevention, said the study was "reassuring" for what it did not find: any association between folic acid supplementation and an increased risk of autistic disorder or ASDs.

"This should ensure that folic acid intake can continue to serve as a tool for the prevention of neural tube birth defects," they wrote. Meanwhile, the "potential for a nutritional supplement to reduce the risk of autistic disorder is provocative and should be confirmed in other populations."

The study is available at http://jama.jamanetwork.com/article.aspx?articleid=1570279.


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