Feb 13, 2013

More Evidence Prenatal Folic Acid May Lower Autism Risk

More evidence suggests that prenatal folic acid supplementation may lower the risk of developing autism.

A population-based cohort study of almost 85,000 children in Norway showed that those children whose mothers used supplemental folic acid early in pregnancy had 39% lower odds of having autistic disorder than those whose mothers did not use the supplements.

“We were a bit surprised about how large the reduction in risk was and how it was specifically related to folic acid and not to other supplements,” Pål Surén, MD, from the Norwegian Institute of Public Health in Oslo, told Medscape Medical News.

“This was also reassuring, because if we had found [the reduction] was associated with other types of supplements as well, it would have been more likely to be explained by healthy behaviors in general, not the supplements per se,” he added.

Dr. Surén noted that although more research is needed, “the results support the current recommendations of taking folic acid supplements during pregnancy and emphasize the importance of starting early — preferably before conception.”

The study is published in the February issue of JAMA.

Public Health Benefit

Previous research has shown that folic acid supplementation “around the time of conception” can reduce the risk of offspring developing neural tube defects, report the investigators.

“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…starting 1 month before conception,” they write.

“It is not implausible to think that it might also have other beneficial effects, and possibly be protective against other neurodevelopmental disorders, too,” said Dr. Surén. “If folic acid truly has a preventive effect against autism in children, it would have great benefits from a public health perspective, because it would be a preventive measure that is cheap and already in use for other purposes.”

In a study of more than 700 preschoolers published last year in the American Journal of Clinical Nutrition, investigators from California found that those children whose mothers received at least 600 μg per day of folic acid during their first month of pregnancy had a 38% lower chance of having autism or Asperger syndrome.

For the current analysis, the investigators sought to assess the association between maternal use of folic acid, from 4 weeks before the start of pregnancy to 8 weeks afterwards, and subsequent risk for autism spectrum disorders (ASDs), which include autistic disorder, Asperger syndrome, and pervasive developmental disorder–not otherwise specified (PDD-NOS), in offspring.

The investigators evaluated data on 85,176 children born between 2002 and 2008 who participated in the Norwegian Mother and Child Cohort Study. The mean age of the children at the end of follow-up in March 2012 was 6.4 years.

The Autism Birth Cohort substudy was used to identify cases of ASD in these children.

Inverse Association

Results showed that 270 of the children had been diagnosed with an ASD. Of these, 114 had autistic disorder, 100 had PDD-NOS, and 56 had Asperger syndrome.

Of the children whose mothers took folic acid during early pregnancy, 0.10% had autistic disorder vs 0.21% of those whose mothers did not take the supplements (adjusted odds ratio, 0.61; 95% confidence interval, 0.41 – 0.90).

The inverse association found for folic acid use in early pregnancy and subsequent risk for autistic disorder was not found for folic use during midpregnancy.

Although no association was found between prenatal folic acid supplementation and Asperger syndrome or PDD-NOS, “power was limited,” note the investigators.

In addition, further analysis showed no association between risk for an ASD and use of fish oil supplements.

Overall, the main finding does not establish causation between use of folic acid and a lower risk for autistic disorder, write the researchers.

However, it does provide “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.”

“Reassuring Study”

“It is reassuring that the study…found no association between folic acid supplementation and an increased risk for autistic disorder or ASDs,” write Robert J. Berry, MD, and colleagues from the Centers for Disease Control and Prevention in Atlanta, Georgia, in an accompanying editorial.

They note that this has been a hotly debated issue previously. And it is “biologically plausible that folic acid intake might affect numerous conditions positively or negatively depending on timing and dose.”

However, past studies have shown strong benefits from folic acid, including a previous report from the Norwegian Mother and Child Cohort Study that showed that supplementation during early pregnancy was associated with a reduced risk for severe language delay in offspring.

The editorialists point out that more research is now needed, including studies that evaluate timing, dose, and intake of supplements, as well as studies that assess children with autism and comorbid conditions.

Review clinical findings

Nevertheless, “this should ensure that folic acid intake can continue to serve as a tool for the prevention of neural tube birth defects,” they write.

“The potential for a nutritional supplement to reduce the risk of autistic disorder is provocative and should be confirmed in other populations.”

The study was funded by the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research, and the National Institute of Environmental Health Sciences and by grants from the Research Council of Norway/FUGE and the National Institute of Neurological Disorders and Stroke. One study author reports receiving lecture payment. The other study authors, including Dr. Surén, and the editorialists have disclosed no relevant financial relationships.

JAMA. 2013;309:570-577, 611-613. Full articleEditorial


— Deborah Brauser


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