Association between particulate air pollution and hypertensive disorders in pregnancy: A retrospective cohort study

Abstract

Background: Epidemiological findings regarding the association of particulate matter ≤2.5 μm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy.

Methods and findings: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 μg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP.

Conclusions: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.

Fig 1. Adjusted HRs and 95% CIs of air pollution during pregnancy associated with GH and PE-E.

HRs and 95% CIs were calculated for per IQR increment for each air pollutant. Model adjusted for maternal age, race/ethnicity, education, block group household income, smoking and passive smoking status during pregnancy, insurance type, season, and year of infant birth. Zip code was fitted as a random effect. CI, confidence interval; GH, gestational hypertension; HR, hazard ratio; IQR, interquartile range; PE-E, preeclampsia-eclampsia.

Fig 2. Monthly associations between maternal exposure to PM_2.5 during pregnancy and hypertensive disorders of pregnancy.

N = 373,905 for GH cohort; N = 386,361 for PE-E cohort. HRs and 95% CIs were calculated for per IQR increment for each air pollutant. Models adjusted for maternal age, race/ethnicity, education, household income, smoking and passive smoking status during pregnancy, parity, insurance type, season, and year of infant birth. CI, confidence interval; GH, gestational hypertension; HR, hazard ratio; IQR, interquartile range; PE-E, preeclampsia-eclampsia.