Combined Exposure to Folate and Lead during Pregnancy and Autistic-Like Behaviors among Canadian Children from the MIREC Pregnancy and Birth Cohort.

BACKGROUND Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead. OBJECTIVES We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. METHODS We used data from the Maternal-Infant Research on Environmental Chemicals study (2008-2011), a Canadian pregnancy and birth cohort study. Childhood autistic-like behaviors were documented in 601 children 3-4 y of age with the Social Responsiveness Scale-2 (SRS-2), where higher scores denote more autistic-like behaviors. We measured BLLs and plasma total folate concentrations during the first and third trimesters of pregnancy. We also estimated gestational FA supplementation via surveys and genotyped the maternal MTHFR 677C>T single nucleotide polymorphism (SNP). We estimated the confounder-adjusted associations between log2-transformed BLLs and SRS-2 scores by two indicators of folate exposure and maternal MTHFR 677C>T genotype using linear regression. RESULTS Third-trimester BLLs were associated with increased SRS-2 scores [βadj=3.3; 95% confidence interval (CI): 1.1, 5.5] among participants with low (<10th percentile), third-trimester, plasma total folate concentrations, but BLL-SRS-2 associations were null (βadj=-0.3; 95% CI: -1.2, 0.5) among those in the middle category (≥10th and <80th percentiles) (p-interaction <0.001). FA supplementation also attenuated these associations. Both folate indicators modified first-trimester BLL-SRS-2 associations, but to a lesser extent. Third-trimester BLL-SRS-2 associations were slightly stronger among participants who were homozygous for the T (minor) allele of the MTHFR 677C>T SNP (βadj=0.9; 95% CI: -1.2, 3.1) than those without the T allele (βadj=-0.3; 95% CI: -1.3, 0.7), but the difference was not statistically significant (p-interaction=0.28). DISCUSSION Folate may modify the associations between gestational lead exposure and childhood autistic-like behaviors, suggesting that it mitigates the neurotoxic effects of prenatal lead exposure. https://doi.org/10.1289/EHP14479.