Schmidt et al. published a study in Epidemiology on May 23, 2011, entitled “Prenatal Vitamins, One-carbon Metabolism Gene Variants, and Risk for Autism.” It was a population-based case control study of 566 subjects comparing a group of autistic children to a matched control group of children with normal development. They looked at maternal intake of prenatal vitamins in the 3 months before conception and the first month of pregnancy, and they looked for genotypes associated with autism. They found that mothers who didn’t take prenatal vitamins were at greater risk of having an autistic child, and certain genetic markers markedly increased the risk. There was a dose/response relationship: the more prenatal vitamins a woman took, the less likely she would have an autistic child. There was no association with other types of multivitamins, and no association with prenatal vitamin intake during months 2-9 of pregnancy.
They had a large sample size, and they tried to eliminate confounders. They looked for these potential confounders of the association between prenatal vitamin intake and autism: child’s sex, birth year, parent-reported race/ethnicity, family history of mental health conditions, paternal age at child’s birth, maternal age at child’s birth, education, prepregnancy body mass index (BMI) category, cereal intake from 3 months before through the first month of pregnancy, cigarette smoking, alcohol consumption, and residence with a smoker during the period 3 months before pregnancy to delivery. Only maternal education and the child’s year of birth proved to be confounders. They adjusted for these two factors in their analyses. A weakness of their study is that it depends on patient recall long after the fact. Also, it did not attempt to gather any diet information.
Mothers of children with autism were less likely to report taking prenatal vitamins (odds ratio 0.62). Having certain genotypes increased the odds that a vitamin-omitting woman would have an autistic child. Children with the COMT 472 AA gene were at increased risk of autism. If their mothers took prenatal vitamins, the odds ratio for the risk of autism was 1.8; if their mothers didn’t, the odds ratio jumped to 7.2. This suggests that the maternal-fetal environment can magnify the effects of a child susceptibility gene. There was an association with certain maternal genes as well: those odds ratios went as high as 4.5.
The association was robust. The authors think there are plausible biological explanations. Folate and other B vitamins are critical to neurodevelopment. Iron could be involved. The gene variants were within one-carbon metabolism pathways; methylation mechanisms may be responsible.
The authors speculate as to why multivitamins did not have the same effect. Prenatal vitamins typically contain more iron, vitamins B6 and B12, and twice as much folic acid (800 mcg) as multivitamins (400 mcg).
In their summary, the authors say:
Our data suggest that supplementation with prenatal vitamins before pregnancy and during the first month of pregnancy might protect against autism, particularly in genetically susceptible individuals. Additionally, COMT genotype may contribute to an elevated risk for autism, especially in offspring of unsupplemented mothers. This evidence for gene-by- environment interaction effects in autism etiology could help explain variations in previous findings across genetic studies. Whether similar interactions exist for susceptibility genes in other pathways, particularly those epigenetically regulated through methylation, remains to be explored. More research is warranted to replicate the findings, explicate potential mechanisms, and explore interactions with other autism candidate genes.
This is fascinating stuff. It confirms that certain genotypes are associated with autism and that environmental factors can interact with genetics to increase risk. We still need to pin down what it is about prenatal vitamins that prevents autism better than other multivitamins. Is it the folic acid? Is it a subset of the ingredients, or the whole mixture?
We should never blindly accept the results of a first study. These findings will have to be confirmed by other studies. Meanwhile, should we take action? We already recommend folic acid supplements for women who might become pregnant, and we recommend prenatal vitamins during pregnancy. I can’t see any downside to recommending prenatal vitamins in the pre-conception period for any woman who is likely to become pregnant. Some advisors (for instance the Mayo Clinic) were already recommending this practice even before the new study came out.
How will the anti-vaccine contingent react to this new study? It was convenient and satisfying for parents to be able to blame vaccines and accuse the evil medical establishment of causing their children’s autism. Now will those parents accept that at least part of the responsibility lies with their own genetic contributions and the mother’s actions prior to pregnancy? That’s not as palatable a thought, but it’s more realistic.
This article was originally published in the Science-Based Medicine Blog