Prenatal fine particulate exposure associated with reduced childhood lung function and nasal epithelia GSTP1 hypermethylation: Sex-specific effects

BACKGROUND: In utero exposure to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM(2.5)) has been linked to child lung function. Overlapping evidence suggests that child sex and exposure timing may modify effects and associations may be mediated through glutathione S-transferase P1 (GSTP1) methylation. METHODS: We prospectively examined associations among prenatal PM(2.5) exposure and child lung function and GSTP1 methylation in an urban pregnancy cohort study. We employed a validated satellite-based spatiotemporally resolved prediction model to estimate daily prenatal PM(2.5) exposure over gestation. We used Baysian distributed lag interaction models (BDLIMs) to identify sensitive windows for prenatal PM(2.5) exposure on child lung function and nasal epithelia GSTP1 methylation at age 7 years, and to examine effect modification by child sex. RESULTS: BDLIMs identified a sensitive window for prenatal PM(2.5) exposure at 35–40 weeks gestation [cumulative effect estimate (CEE) = − 0.10, 95%CI = − 0.19 to − 0.01, per μg/m(3) increase in PM(2.5)] and at 36–40 weeks (CEE = − 0.12, 95%CI = − 0.20 to − 0.01) on FEV(1) and FVC, respectively, in boys. BDLIMs also identified a sensitive window of exposure at 37–40 weeks gestation between higher prenatal PM(2.5) exposure and increased GSTP1 percent methylation. The association between higher GSTP1 percent methylation and decreased FEV1 was borderline significant in the sample as a whole (β = − 0.37, SE = 0.20, p = 0.06) and in boys in stratified analyses (β = − 0.56, SE = 0.29, p = 0.05). CONCLUSIONS: Prenatal PM(2.5) exposure in late pregnancy was associated with impaired early childhood lung function and hypermethylation of GSTPI in DNA isolated from nasal epithelial cells. There was a trend towards higher GSTP1 percent methylation being associated with reduced FEV1. All findings were most evident among boys.