Associations of prenatal ambient air pollution exposures with asthma in middle childhood

Abstract

We examined associations between prenatal fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), and ozone (O₃) exposures and child respiratory outcomes through age 8-9 years in 1279 ECHO-PATHWAYS Consortium mother-child dyads. We averaged spatiotemporally modeled air pollutant exposures during four fetal lung development phases: pseudoglandular (5-16 weeks), canalicular (16-24 weeks), saccular (24-36 weeks), and alveolar (36+ weeks). We estimated adjusted relative risks (RR) for current asthma at age 8-9 and asthma with recent exacerbation or atopic disease, and odds ratios (OR) for wheezing trajectories using modified Poisson and multinomial logistic regression, respectively. Effect modification by child sex, maternal asthma, and prenatal environmental tobacco smoke was explored. Across all outcomes, 95% confidence intervals (CI) included the null for all estimates of associations between prenatal air pollution exposures and respiratory outcomes. Pseudoglandular PM_2.5 exposure modestly increased risk of current asthma (RR_adj = 1.15, 95% CI: 0.88-1.51); canalicular PM_2.5 exposure modestly increased risk of asthma with recent exacerbation (RR_adj = 1.26, 95% CI: 0.86-1.86) and persistent wheezing (OR_adj = 1.28, 95% CI: 0.86-1.89). Similar findings were observed for O₃, but not NO₂, and associations were strengthened among mothers without asthma. While not statistically distinguishable from the null, trends in effect estimates suggest some adverse associations of early pregnancy air pollution exposures with child respiratory conditions, warranting confirmation in larger samples.

Keywords: Developmental origins of health and disease; Particulate matter; air pollution; asthma.

Fig. 1.

Effect modification of associations between prenatal air pollution and current asthma at age 8–9 by child sex, prenatal environmental tobacco smoke exposure, and maternal history of asthma. Risk ratios for current asthma and corresponding 95% confidence intervals are shown for associations with NO₂ in the first column (panels A, D, and G), O₃ in the second column (panels B, E, and H), and PM_2.5 in the third column (panels C, F, and I). Estimates are reported per 5 ppb NO₂, 5 ppb O₃, and 2 μg/m³ PM_2.5. All models are adjusted for child age, sex, study site, birth year, maternal education, household income*household count, maternal race, maternal smoking during pregnancy, maternal history of asthma, and Neighborhood Deprivation Index, as well as a product term between the air pollutant exposure and effect modifier of interest. P-values for the product interaction term are included at the top of each panel. In the first row (panels A–C), sex-specific effect estimates are shown for models including the full analytic sample (N = 1279). No evidence of effect modification by child sex was observed (all p_interaction >0.05). In the second row (panels D–F), effect estimates are shown among those with maternal history of asthma and those without maternal history of asthma for models including the full analytic sample (N = 1279). For NO₂ and PM_2.5, those without maternal history of asthma tended to have higher risk ratios than among those with a maternal history of asthma (e.g. p-value for interaction of NO₂ in the 24–36 week window and maternal asthma = 0.03), though confidence intervals for strata-specific risk ratios all include the null. In the third row (panels G–I), effect estimates are shown for associations in a post-hoc analysis among those with high versus low environmental tobacco smoke (ETS) exposure, when the sample was restricted to non-smokers (N = 1155). High ETS was defined as participants with a urinary cotinine value in the highest quartile of the sample (>1.43 ng/mL) and low ETS was defined as participants with a urinary cotinine value in the lowest three quartiles (≤1.43 ng/mL). No effect modification by ETS was observed (all p_interaction >0.05).