A Canadian study reported an association between gestational blood lead levels and autistic-like behaviors in preschool-age children, with the relationship appearing stronger when maternal folate levels were lower.

In the study, published in Environmental Health Perspectives, researchers examined 601 mother-child pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC) prospective cohort study. They measured maternal blood lead levels and plasma folate concentrations during both the first and third trimesters of pregnancy as well as folic acid supplementation. At ages 3 to 4 years, children's autistic-like behaviors were assessed using the Social Responsiveness Scale-2 (SRS-2). 

The researchers found that third-trimester blood lead levels were associated with increased SRS-2 scores among participants with low (< 10th percentile) plasma total folate concentrations but not among those with higher folate levels. Specifically, for each doubling of third-trimester blood lead levels, there was a 3.3-point increase in SRS-2 scores among those with low folate compared with essentially no association (–0.3 points) among those with adequate folate. Similar patterns were observed for folic acid supplementation, with stronger associations between lead exposure and autistic-like behaviors among women with lower supplementation.

The researchers also reported evidence that the MTHFR 677C>T genotype, affecting folate metabolism, may have influenced these associations. Exploratory analyses using continuous plasma folate concentrations and three-way interactions with MTHFR genotype supported the main findings.

The researchers noted several limitations, including that the study population was generally folate-replete and had relatively low lead exposure compared with the general population. Additionally, the participants were generally more educated and affluent compared with the general Canadian population, potentially limiting generalizability. The researchers were unable to rule out residual confounding.

Despite these limitations, the study suggested that folic acid supplementation during pregnancy may have additional benefits in mitigating the effects of lead exposure beyond its known benefits for reducing neural tube defects. The researchers recommended further research in populations with higher lead exposure and lower folate consumption to explore these relationships more fully.

Conflict of interest disclosures can be found in the study.