Maternal blood metal concentrations and whole blood DNA methylation during pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI).

This study looked at whether metals in pregnant mothers' blood (like lead and manganese) affect how genes work. Researchers studied 97 pregnant women and found that higher levels of lead were linked to changes in gene activity in areas important for brain development and cell connections. Manganese also caused some gene changes. These findings suggest that metal exposure during pregnancy might affect how genes function, though more research is needed.

This study examined associations between maternal blood metal concentrations (cadmium, lead, mercury, manganese, selenium) and DNA methylation patterns during pregnancy in 97 non-smoking women from the EARLI cohort. Researchers found significant associations between lead exposure and hypermethylation at 11 DNA sites, with enrichment in pathways related to cell adhesion, nervous system development, and calcium ion binding. Manganese was associated with hypermethylation at 4 sites, enriched for cellular metabolism pathways. Effect estimates for cadmium, lead, and manganese were highly correlated.

The findings suggest these metals may influence maternal epigenetic patterns during pregnancy, potentially serving as biomarkers of exposure or indicating downstream pathway effects.

Findings suggest prenatal metal exposures may influence maternal epigenetic patterns, particularly in pathways relevant to neurodevelopment. However, clinical significance remains unclear. Results support continued monitoring of environmental metal exposures during pregnancy and may inform future research on epigenetic biomarkers.

Small sample size of 97 women limits generalizability. Study design unclear from abstract. Cross-sectional analysis cannot establish causality. Limited to non-smoking women only. Unclear if findings translate to functional gene expression changes or clinical outcomes.

The maternal epigenome may be responsive to prenatal metals exposures. We tested whether metals are associated with concurrent differential maternal whole blood DNA methylation. In the Early Autism Risk Longitudinal Investigation cohort, we measured first or second trimester maternal blood metals concentrations (cadmium, lead, mercury, manganese, and selenium) using inductively coupled plasma mass spectrometry. DNA methylation in maternal whole blood was measured on the Illumina 450 K array.

A subset sample of 97 women had both measures available for analysis, all of whom did not report smoking during pregnancy. Linear regression was used to test for site-specific associations between individual metals and DNA methylation, adjusting for cell type composition and confounding variables. Discovery gene ontology analysis was conducted on the top 1,000 sites associated with each metal. We observed hypermethylation at 11 DNA methylation sites associated with lead (FDR False Discovery Rate-value <0.1), near the genes, and.

Lead-associated sites were enriched (FDR-value <0.1) for the pathways cell adhesion, nervous system development, and calcium ion binding. Manganese was associated with hypermethylation at four DNA methylation sites (FDR-value <0.1), one of which was near the gene. Manganese-associated sites were enriched for cellular metabolism pathways (FDR-value<0.1). Effect estimates for DNA methylation sites associated ( < 0.05) with cadmium, lead, and manganese were highly correlated (Pearson ρ > 0.86).

DNA methylation sites associated with lead and manganese may be potential biomarkers of exposure or implicate downstream gene pathways.