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

Abstract

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/m³ increase in PM_2.5] and at 36-40 weeks (CEE = - 0.12, 95%CI = - 0.20 to - 0.01) on FEV₁ 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.

Fig. 1

Associations between weekly PM_2.5 levels over gestation and FEV₁ z-score. This figure demonstrates the association between PM_2.5 exposure over pregnancy and FEV₁ z-scores using a BDLIM assuming week-specific effects, for (a) overall sample, and (b) interaction by sex. Models were adjusted for maternal age and education, and z-scores were adjusted for child’s age at spirometry test, sex, race/ethnicity, and height. The y-axis represents the change in FEV₁ z-scores corresponding to a 1 μg/m³ increase in PM_2.5; the x-axis is gestational age in weeks. Solid lines show the predicted change in FEV₁ z-score. Gray areas indicate 95% confidence intervals (CIs). A sensitive window is identified for the weeks where the estimated pointwise 95% CI (shaded area) does not include zero

Fig. 2

Associations between weekly PM_2.5 levels over gestation and FVC z-score. This figure demonstrates the association between PM_2.5 exposure over pregnancy and FVC z-scores using a BDLIM assuming week-specific effects, for (a) overall sample, and (b) interaction by sex. Models were adjusted for maternal age and education, and z-scores were adjusted for child’s age at spirometry test, sex, race/ethnicity, and height. The y-axis represents the change in FVC z-scores corresponding to a 1 μg/m³ increase in PM_2.5; the x-axis is gestational age in weeks. Solid lines show the predicted change in FVC z-score. Gray areas indicate 95% confidence intervals (CIs). A sensitive window is identified for the weeks where the estimated pointwise 95% CI (shaded area) does not include zero

Fig. 3

Associations between weekly PM_2.5 levels over gestation and GSTP1 percent methylation. This figure demonstrates the association between PM_2.5 exposure over pregnancy and GSTP1 DNA methylation using a BDLIM assuming week-specific effects. The model was adjusted for maternal age, education, child’s age at spirometry test, sex, and race/ethnicity. The y-axis represents the change in GSTP1 percent methylation corresponding to a 1 μg/m³ increase in PM_2.5; the x-axis is gestational age in weeks. Solid lines show the predicted change in GSTP1 percent methylation. Gray areas indicate 95% confidence intervals (CIs). A sensitive window is identified for the weeks where the estimated pointwise 95% CI (shaded area) does not include zero