Mothers who had been exposed to agricultural pesticides at any time in the 3 months before and after conceiving, and who took 800 micrograms/ day (ug/d) of folic acid in the first month of pregnancy halved the risk of their child developing ASD, found a multi-disciplinary team of researchers from the University of California, Davis.
Regular exposure to outdoor pesticide sprays and foggers, combined with low folic acid intake (800 ug/d) increased the risk of ASD in offspring by 4 times compared with no exposure and high intake. Increasing intake above the 800 ug/d threshold mitigated this risk to 1.8 times in offspring of frequently exposed mothers.
The study also identified significant ASD risk reductions for high-dose folic acid consumers in mothers exposed to household pesticide products.
"We found that if the mom was taking folic acid during the window around conception, the risk associated with pesticides seemed to be attenuated," said first author Professor Rebecca Schmidt. "Mothers should try to avoid pesticides. But if they live near agriculture, where pesticides can blow in, this might be a way to counter those effects."
"Folic acid intake below the median and exposure to pesticides was associated with higher risk of autism than either low intake or exposure alone," she added. "The mothers who had the highest risk were the ones who were exposed to pesticides regularly."
Although higher folic acid consumption was associated with lower ASD risk, the higher vitamin intake did not eliminate risk.
"It would be better for women to avoid chronic pesticide exposure if they can while pregnant," Schmidt said.
The study is important, the researchers suggest, as it is the first to show evidence for the mitigation of ASD risk from pesticides through maternal folic acid intake. Results are nevertheless consistent with previous research identifying benefits of maternal folic acid intake in protecting against the effects of environmental toxins (including arsenic) on developing offspring.
The case-control study used data from the Childhood Autism Risks from Genetics and the Environment (CHARGE) trial. The cohort of children aged between 2 and 5 included 296 who had developed ASD and 220 healthy controls.
Folic acid consumption and peri-conceptual exposure to household pesticides were evaluated by interview, while exposure to agricultural pesticides was estimated by linking data from California Pesticide Use reports to mothers’ addresses.
The observational design of the study prevents establishment of a causal effect. However, it is widely recognised that pesticides can adversely affect DNA methylation, and that folic acid is a major methyl donor. Therefore, the researchers were able to hypothesise potential causal mechanisms for folic acid’s protective effect.
"Folate plays a critical role in DNA methylation (a process by which genes are turned off or on), as well as in DNA repair and synthesis," said Schmidt. "These are all really important during periods of rapid growth when there are lots of cells dividing, as in a developing foetus. Adding folic acid might be helping out in a number of these genomic functions."
“Larger studies, exposure measurements or markers that are prospectively collected, and research on potential mechanisms would be helpful in moving the field forward,” the researchers proposed regarding possible next steps.
Source: Environmental Health Perspectives
Published online, doi: 10.1289/EHP604
“Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder”
Authors: Rebecca J Schmidt, Vladimir Kogan et al