Exposure to multiple air pollutant mixtures and the subtypes of hypertensive disorders in pregnancy: A multicenter study

Background: Hypertensive disorders in pregnancy (HDP) have heterogeneous etiologies. Previous studies have linked individual air pollutants to overall HDP with inconsistent results. Moreover, it has not been explored how exposure to a mixture of multiple air pollutants may affect the risks of the subtypes of the disorders. Objectives: To investigate the associations of exposure to air pollutant mixture in the 1st and 2nd trimesters of pregnancy with the risks of HDP and its subtypes.Methods: Pregnancy data were obtained from the China Labor and Delivery Survey, a nationwide cross-sectional survey in 2015 and 2016. Levels of air pollutants [including fine particulate matter (PM2.5), carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2)] in the 1st and 2nd trimesters were estimated based on the model developed by the Institution of Atmospheric Physics, Chinese Academy of Science. Generalized linear mixed models were built to assess the single-exposure effects of air pollutants in early gestation on HDP. The restricted cubic spline function was further applied to assess the potential non-linearity. The weighted quantile sum (WQS) regression was used to investigate the effects of co-exposure to multiple air pollutants. Results: A total of 67,512 pregnancies were included, and 2,834 were HDP cases. The single-effect analysis showed that CO, PM2.5, and SO2 exposure in the 2nd trimester was positively associated with the risks of gestational hypertension (GH), with adjusted odds ratios (aORs) and 95% confidence intervals (CI) of 1.16 (1.04, 1.28), 1.19 (1.04, 1.37), and 1.13 (1.04, 1.22), respectively. The first-trimester O3 exposure was also associated with an increased preeclampsia/eclampsia (PE) risk (aOR = 1.17; 95%CI: 1.02, 1.33). WQS regression confirmed positive associations of air pollutant mixture with HDP subtypes, with PM2.5 as the main contributing pollutant to GH, and CO and O3 as the main pollutants to PE. Conclusions: Exposure to multiple air pollutant mixtures in early pregnancy was associated with increased risks of hypertensive disorders in pregnancy.