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More research indicates maternal use of folic acid lowered autism risk
Researchers reported that maternal use of supplemental folic acid around the time of conception was associated with a 39% lower odds of an autism spectrum disorder — specifically, autistic disorder — in children. The study results are consistent with previous research.
“The study provides an additional reason for pregnant women to take folic acid supplements, and the findings underline the importance of starting early, preferably before the start of pregnancy," study researcher Pål Surén, MD, MPH, of the Norwegian Institute of Public Health in Oslo, Norway, told Psychiatric Annals.
Pål Surén
Surén and colleagues examined the association between maternal folic acid use and autism spectrum disorder (ASD) risk in a sample of 85,176 children who were enrolled in the Norwegian Mother and Child Cohort Study. The researchers looked at the effect of folic acid use from 4 weeks before to 8 weeks after the start of pregnancy. The effect of prenatal fish oil supplements was also examined. Logistic regression analyses were used to determine the odds ratios.
At the end of follow-up, 270 children had been diagnosed with an ASD, 114 of whom had autistic disorder. Among children whose mothers used folic acid, 0.1% were diagnosed with autistic disorder vs. 0.21% of children whose mothers’ did not use the supplement. After adjusting for maternal education level, year of birth and parity, the odds ratio for autistic disorder in children whose mothers used folic acid was 0.61 (95% CI, 0.41-0.9). The researchers found no association between folic acid intake and lowered risk for pervasive developmental disorder-not otherwise specified. For Asperger’s syndrome, statistical power was too low.
Prenatal fish oil supplements were not associated with reduced autism risk.
Mothers in the study who used folic acid were more likely of higher socioeconomic status and more health-conscious, according to the researchers, which may have confounded the results. However, fish oil use, which did not lower autism risk, was associated with the same parental characteristics.
Surén and colleagues wrote that the findings do not “establish a causal relation between folic acid use and autistic disorder 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 accompany editorial, Robert J. Berry, MD, MPHTM, of the CDC’s Division of Birth Defects and Developmental Disorders, and colleagues wrote that ASDs have been associated with a combination of heterogeneous genetic and environmental risk factors, presenting a major obstacle to researchers.
“It is reassuring that the study by Surén et al found no association between folic acid supplementation and an increased risk for autistic disorder or ASDs,” they wrote. “This should ensure that folic acid intake can continue to serve as a tool for the prevention of neural tube birth defects. The potential for a nutritional supplement to reduce the risk of autistic disorder is provocative and should be confirmed in other populations.”
For more information:
Berry RJ. JAMA. 2013;309:611-613.
Surén P. JAMA. 2013;309:570-577.
Disclosure: One of the study researchers reported receiving payment for lectures at the University of Oslo and the University Agder.
Perspective
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The recent article by Suren et al in the Feb. 13 edition of JAMA has garnished national attention by showing folic acid was associated with a lower risk for autism. Folic acid has been previously associated with a decreased risk for neural tube defects and language delay; it also has been suggested for treatment of fragile X syndrome, but available evidence is of low quality and can’t support conclusions (Rueda and colleagues). The study also builds on the evidence of a previous case-control study by Schmidt and colleagues, which showed a mean intake of at least 600 mcg during pregnancy was associated with reduced autism spectrum disorder risk (OR=0.62), and the response was associated with certain genotypes.
The data show that among 85,176 children born between 2002 and 2008, 270 children, or 0.32%, received a diagnosis of autism spectrum disorder and the odds ratio for autistic disorder in women who took folic acid was 0.61 compared with those children of non-folic acid users. The study evaluated a possible bias for “health conscious prenatal care” by including analyses for risk of autism in women who also took prescribed doses of fish oil, which showed no association with a risk for autism.
Currently, the CDC recommends all women of childbearing age should consume 400 mcg of folic acid daily to prevent spina bifida and anencephaly, birth defects which occur very early in pregnancy. Similarly, the study found protection from autism came from supplements taken a month before conception through the first 8 weeks of pregnancy.
What’s the pathophysiology suggested by the findings? Current evidence suggests autism is a collection of heterogeneous conditions with multiple genetic and environmental factors. In some cases, the process seems to initiate very early in development. Folic acid supports basic cellular processes and genetic mechanisms and its protective role speaks to general antioxidant effects.
The strengths of the study come from its large population design of children born in a country with a national registry. Such a database allows for prospective identification of possible risk and protective factors for the development of autism. The findings require replication and cannot offer proof that folic acid prevents autism, but clues to possible mechanisms of autism are suggested and further study is warranted.
For more information:
Reuda JR. Cochrane Database Syst Rev. 2011;doi:10.1002/14651858.CD008476.pub2.
Schmidt RJ. Am J Clin Nutr. 2012;96:80-89.