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

Abstract

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 ${\log }_2$-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 [${\beta }_{adj}=3.3$; 95% confidence interval (CI): 1.1, 5.5] among participants with low ($<10\text{th}$ percentile), third-trimester, plasma total folate concentrations, but BLL-SRS-2 associations were null (${\beta }_{adj}=-0.3$; 95% CI: $-1.2$, 0.5) among those in the middle category ($\ge 10\text{th}$ and $<80\text{th}$ 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 (${\beta }_{adj}=0.9$; 95% CI: $-1.2$, 3.1) than those without the T allele (${\beta }_{adj}=-0.3$; 95% CI: $-1.3$, 0.7), but the difference was not statistically significant ($p\text{-interaction}=0.28$).

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.