Ambient Air Pollution Mixtures During Pregnancy and Evaluation of Intergenerational DNA Methylation Signatures

Abstract Background Ambient air pollutant levels during pregnancy are known to impact the offspring’s health. DNA Methylation (DNAm) may be sensitive to air pollutants throughout pregnancy. This study estimated the effect of ambient air pollution (PM2.5, PM10, NO2, O3) mixture levels in early and late pregnancy on paired maternal prenatal DNAm (N = 116) levels. The impact of average prenatal pollutant mixture on neonatal cord blood DNAm signatures was also evaluated (N = 114). Lastly, the association of pollutant-related maternal DNAm profiles (N = 78 maternal-child dyads) with neonatal DNAm profiles was investigated. Methods Quantile g-computation was applied to maternal and neonatal datasets to test the effect of the pollutant mixture on DNAm signatures. To test the correlation of pollutant associated alteration in maternal DNAm with cord blood DNAm signatures, independent cord blood epigenome wide association studies (EWASs) were applied within the subset of significant maternal CpGs identified in the mixture model. Sex was explored as a modifying variable. Results We identified 18 maternal prenatal CpGs whose methylation levels were associated with ambient air pollution mixtures in pregnancy on average. 1 CpG, cg00723044, displayed significance in models for the neonatal mixtures analysis only among male neonates. Neonatal CpGs were not associated with maternal CpGs identified in the maternal mixtures analysis. Conclusion Ambient air pollution mixtures were associated with maternal methylation levels in 18 CpGs (q 0.1) in pregnancy, and there was some evidence that air pollutant mixture levels in pregnancy affected cord blood DNAm in 1 CpG in male neonates.