Prenatal Exposure to Arsenic, Umbilical Cord Blood DNA Methylation, and Child Neurodevelopment: A Prospective Birth Cohort Study.

Prenatal Exposure to Arsenic (As) is associated with child neurodevelopment disorders. However, the specific mechanisms involved remain unclear. This work intends to investigate the associations between prenatal As exposure and epigenome-wide Deoxyribo Nucleic Acid methylation (DNAm) and evaluate the role of DNAm in moderating the association between prenatal As exposure and child neurodevelopment. An As-related epigenome-wide DNAm association analysis was performed using robust linear models, and mediation analysis was further applied to explore potential DNAm mediators. Robust linear models were applied to perform an epigenome-wide association study (EWAS) for DNAm related to As exposure. Mediation analysis was subsequently conducted to explore potential DNAm mediators. The mental development index (MDI) score was found to be inversely associated with urinary As levels during the third trimester [β = -3.52, 95% CI: -6.34, -0.71]. A total of 48 differential DNAm locations and 13 differentially methylated regions were found to be associated with urinary As concentration. Three cytidylyl phosphate guanosine positions (annotated to ARMC5, KIAA1217, and intergenic region, mediated proportion is around 30%) mediated the association between urinary As and a reduction of MDI score (P < 0.05). Our findings indicated adverse effects of prenatal As exposure on child neurodevelopment, and specific DNAm played the role of partial mediator.