Pregnant women are uniquely susceptible to adverse effects of air pollution exposure due to vulnerabilities and health consequences during pregnancy (e.g., hypertensive disorders of pregnancy [HDP]) compared to the general population. Because the Clean Air Act (CAA) creates a duty to protect at-risk groups, the regulatory assessment of at-risk populations has both policy and scientific foundations. Previously, pregnant women have not been specially protected in establishing the margin of safety for the ozone and particulate matter (PM) standards. Due to physiological changes, pregnant women can be at greater risk of adverse effects of air pollution and should be considered an at-risk population. Women with preexisting conditions, women experiencing poverty, and groups that suffer systematic discrimination may be particularly susceptible to cardiac effects of air pollutants during pregnancy. We rigorously reviewed 11 studies of over 1.3 million pregnant women in the United States to characterize the relationship between ozone or PM exposure and HDP. Findings were generally mixed, with a few studies reporting a joint association between ozone or PM and social determinants or pre-existing chronic health conditions related to HDP. Adequate evidence associates exposure to PM with an adverse effect of HDP among pregnant women not evident among non-gravid populations.

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 q-value <0.1), near the genes CYP24A1, ASCL2, FAT1, SNX31, NKX6-2, LRC4C, BMP7, HOXC11, PCDH7, ZSCAN18, and VIPR2. Lead-associated sites were enriched (FDR q-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 q-value <0.1), one of which was near the gene ARID2. Manganese-associated sites were enriched for cellular metabolism pathways (FDR q-value<0.1). Effect estimates for DNA methylation sites associated (p < 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.