Maternal use of folic acid supplements around the time of conception was associated with a lower risk of autistic disorder, the most severe form of autism spectrum disorders, in the children, according to a Norwegian study reported in the Feb. 13 issue of JAMA.
"This finding does 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 biologic mechanisms that may explain the inverse association," said Dr. Pål Surén of the Norwegian Institute of Public Health, Oslo, and his associates.
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Researchers found an inverse association between a mother’s use of folic acid supplements and the risk that her child would develop autistic disorder.
Folic acid supplements during pregnancy reduce the risk of neural tube defects in the offspring, and there is some evidence that they may also reduce the risk of other neurodevelopmental disorders. A recent analysis of data from the Norwegian Mother and Child Cohort Study found that maternal use of folic acid supplements was associated with a lower risk of severe language delay in their children at age 3 years.
Dr. Surén and his colleagues used data from the same cohort study to examine a possible association between the supplements and risk of autism spectrum disorders. The Norwegian Mother and Child Cohort Study is a national registry of 109,020 children born between 1999 and 2009.
For this analysis, the researchers assessed data concerning 85,176 children in the registry. At final follow-up, the subjects ranged in age from 3.3 years to 10.2 years (mean age, 6.4 years).
A total of 270 of these children (0.32%) were diagnosed as having autism spectrum disorders: 0.13% had autistic disorder, 0.07% had Asperger’s syndrome, and 0.12% had pervasive developmental disorder not otherwise specified.
Approximately 33% of the mothers took folic acid supplements during the interval from 4 weeks before conception to 8 weeks afterward. This period was chosen for the analysis because folic acid’s effects on the developing central nervous system of the fetus are most prominent during this time. "The interval covers or precedes events of critical importance to the fetal brain, such as the closure of the neural tube 28 days after conception and the embryonic period that includes development of the basic brain structures 15-56 days after conception," the investigators noted.
They found an inverse association between the mother’s use of folic acid supplements periconceptually and the risk that the child would develop autistic disorder. Of the children whose mothers took the supplements, 0.10% developed autistic disorder, compared with 0.21% in children whose mothers did not.
The adjusted odds ratio of autistic disorder was 0.61 in children of folic acid users. Further adjusting the data to account for comorbid maternal illness and concomitant medication use did not change this OR, Dr. Surén and his associates reported (JAMA 2013;309:570-7).
Women who took folic acid supplements were more likely to have a college-level education, to have planned the pregnancy, to be nonsmokers, and to have a prepregnancy body mass index less than 25 kg/m2, which are all factors that could confound the association with autism. To address this issue, the investigators assessed the use of fish oil supplements in the study sample.
Use of fish oil supplements correlated with the same parental characteristics as did use of folic acid supplements, but it did not correlate with the risk of autistic disorder, they noted.
Similarly, the inverse association for folic acid use in the periconceptual period was not evident in mothers who took the supplements only later in pregnancy.
"Our findings indicate that the inverse association may be largely driven by the children with autistic disorder and severe language delay at 35 months, who were presumably the more severely affected children," the investigators added.
This study was funded in part by the Research Council of Norway. The investigators did not report having any financial conflicts of interest.