Science Selection October 2017 | Volume 125 | Issue 10
Folic Acid and ASDs: A Preventive Measure against Potential Effects of Pesticide Exposures?
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Published: 23 October 2017
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Prenatal exposures to certain household and agricultural pesticides have been associated with increased risk of autism spectrum disorders (ASDs).1 Meanwhile, a separate body of research demonstrates that taking folic acid (FA) early in pregnancy may protect against these disorders.1,2 A new study joins the two bodies of research, suggesting that FA may reduce—but not completely offset—the ASD risk associated with prenatal pesticide exposure.3
ASDs encompass a group of developmental disorders characterized by difficulties in communicating and interacting with other people, repetitive behaviors, and restricted interests and activities.4 Symptoms typically appear by 2 years of age, but the foundations of these disorders may be established well before birth. Genetic factors appear to influence ASD development, and environmental factors have also been identified as contributing to ASD risk.1,4
“Many genes have been identified as risk factors for autism, but none of them are a smoking gun,” says Rebecca J. Schmidt, first author on the new study and an assistant professor in the Department of Public Health Sciences at the University of California, Davis. “I think it is very complex—probably an interaction between genes and environment and different environmental exposures—and, of course, timing plays a big role in all of this.”
With regard to timing, the first months of pregnancy are a critical period for neurodevelopment. Both exposure to certain pesticides and poor maternal nutrition at this time have been associated with increased risk of neurodevelopmental disorders.1,5 A lack of dietary folate (vitamin B9) in early pregnancy is a known cause of central nervous system defects.6,7 Supplementation with FA, a synthetic form of folate, has therefore become a standard preventative approach.8,9
The study used data from the ongoing Childhood Autism Risks from Genetics and the Environment (CHARGE) study, a population-based case–control investigation.10 Children with an ASD and those with typical development were enrolled between ages 2 and 5 years, and their mothers provided information about their household pesticide use, diet, and consumption of vitamin and mineral supplements from 3 months prior to conception onward.
The current study included 296 children with ASDs and 220 with typical development for whom there were data on maternal use of FA supplementation and estimated exposures to household pesticides. The authors also estimated exposure to agricultural pesticides based on reports collected by the California Department of Pesticide Regulation11 cross-referenced against maternal residence during pregnancy.
For each category of pesticide exposure (indoor sprays or foggers, pet flea and tick products, any indoor pesticides, outdoor sprays or foggers, any household pesticides, or any household or agricultural pesticides) the researchers compared two groups of children: those who had some type of pesticide exposure and either high or low maternal FA intake (at least 800 μg/day and below 800 μg/day, respectively), and those without pesticide exposure whose mothers had high FA intake. For each type of pesticide, children with pesticide exposure and low maternal FA intake were at least twice as likely to have an ASD as those with no exposure and high maternal FA intake.3
Among U.S. women of childbearing age, supplements are typically a larger source than diet for FA intake.12 The authors did not examine all sources of dietary folate, although they did include fortified foods including cereals, breakfast shakes, and protein bars.
“I think the positive aspect of this study is that we might, in a way, prevent exposure-related risk by different nutritional intake through supplements,” says Marija Kundakovic, an assistant professor in biological sciences at Fordham University, who was not involved in the study.
Nevertheless, the authors advise avoiding pesticide exposures during pregnancy. “Even though this study supports that folic acid might attenuate the risk associated with pesticides, it did not completely eliminate it,” says Schmidt.
The use of well-confirmed ASD cases is a strength of the study, whereas limitations include self-reported exposure information and potential recall bias, a lack of comprehensive exposure data, and the potential for unmeasured confounding by other factors. The researchers speculated that the potentially protective mechanism may involve the epigenome, a collection of small chemical tags, such as methyl groups, that punctuate the language of the genetic code and influence gene expression and silencing. Because FA is a methyl donor, this mechanism (among others) warrants further exploration in larger studies that include exposure measurements.
Larissa Takser, an associate professor of pediatrics at the Université du Sherbrooke in Quebec, points out that the study was based on existing evidence and that it is already known that many pesticides are neurotoxic in humans. “Now we need more human research, especially prospective studies, to test contaminant–nutritional interactions,” she says. “ASDs are very serious lifetime conditions, and more effort should be invested in promising preventive strategies.”
Julia R. Barrett, MS, ELS, a science writer and editor based in Madison, Wisconsin, is a member of the National Association of Science Writers and the Board of Editors in the Life Sciences.
1. Schmidt RJ, Lyall K, Hertz-Picciotto I. 2014. Environment and autism: current state of the science. Cut Edge Psychiatry Pract 1(4):21–38, PMID: 27453776.
2. Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, et al. 2013. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA 309(6):570–577, PMID: 23403681, 10.1001/jama.2012.155925.
3. Schmidt RJ, Kogan V, Shelton JF, Delwiche L, Hansen RL, Ozonoff S, et al. 2017. Combined prenatal pesticide exposure and folic acid intake in relation to autism spectrum disorder. Environ Health Perspect 125(9):097007, PMID: 28934093, 10.1289/EHP604.
4. National Institute of Mental Health. 2016. Autism Spectrum Disorder [website]. https://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-asd/index.shtml [accessed 21 September 2017].
6. MRC Vitamin Study Research Group. 1991. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338(8760):131–137, PMID: 1677062, 10.1016/0140-6736(91)90133-A.
7. Czeizel AE, Dudás I. 1992. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 327(26):1832–1835, PMID: 1307234, 10.1056/NEJM199212243272602.
8. CDC (Centers for Disease Control and Prevention). 1992. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recomm Rep 41(RR-14):1–7, PMID: 1522835.
9. CDC. 1991. Use of folic acid for prevention of spina bifida and other neural tube defects—1983–1991. MMWR Morb Mortal Wkly Rep 40(30):513–516, PMID: 2072886.
10. Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN, et al. 2006. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect 114(7):1119–1125, PMID: 16835068, 10.1289/ehp.8483.
11. California Department of Pesticide Registration. 2013. Pesticide Use Reporting (PUR) [website]. http://www.cdpr.ca.gov/docs/pur/purmain.htm [accessed 21 September 2017].
12. Yang QH, Carter HK, Mulinare J, Berry RJ, Friedman JM, Erickson JD. 2007. Race-ethnicity differences in folic acid intake in women of childbearing age in the United States after folic acid fortification: findings from the National Health and Nutrition Examination Survey, 2001–2002. Am J Clin Nutr 85(5):1409–1416, PMID: 17490980.