Exposure to air pollutant mixture and gestational diabetes mellitus in Southern California: Results from electronic health record data of a large pregnancy cohort

BACKGROUND: Epidemiological findings are inconsistent regarding the associations between air pollution exposure during pregnancy and gestational diabetes mellitus (GDM). Several limitations exist in previous studies, including potential outcome and exposure misclassification, unassessed confounding, and lack of simultaneous consideration of air pollution mixtures and particulate matter (PM) constituents. OBJECTIVES: To assess the association between GDM and maternal residential exposure to air pollution, and the joint effect of the mixture of air pollutants and PM constituents. METHODS: Detailed clinical data were obtained for 395,927 pregnancies in southern California (2008–2018) from Kaiser Permanente Southern California (KPSC) electronic health records. GDM diagnosis was based on KPSC laboratory tests. Monthly average concentrations of fine particulate matter < 2.5 μm (PM(2.5)), <10 μm (PM(10)), nitrogen dioxide (NO(2)), and ozone (O(3)) were estimated using kriging interpolation of Environmental Protection Agency’s routine monitoring station data, while PM(2.5) constituents (i.e., sulfate, nitrate, ammonium, organic matter and black carbon) were estimated using a fine-resolution geoscience-derived model. A multilevel logistic regression was used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of air pollution and PM component mixtures. Main analyses adjusted for maternal age, race/ethnicity, education, median family household income, pre-pregnancy BMI, smoking during pregnancy, insurance type, season of conception and year of delivery. RESULTS: The incidence of GDM was 10.9% in the study population. In single-pollutant models, we observed an increased odds for GDM associated with exposures to PM(2.5), PM(10), NO(2) and PM(2.5) constituents. The association was strongest for NO(2) [adjusted odds ratio (OR) per interquartile range: 1.176, 95% confidence interval (CI): 1.147–1.205)]. In multi-pollutant models, increased ORs for GDM in association with one quartile increase in air pollution mixtures were found for both kriging-based regional air pollutants (NO(2), PM(2.5), and PM(10), OR = 1.095, 95% CI: 1.082–1.108) and PM(2.5) constituents (i.e., sulfate, nitrate, ammonium, organic matter and black carbon, OR = 1.258, 95% CI: 1.206–1.314); NO(2) (78%) and black carbon (48%) contributed the most to the overall mixture effects among all krigged air pollutants and all PM(2.5) constituents, respectively. The risk of GDM associated with air pollution exposure were significantly higher among Hispanic mothers, and overweight/obese mothers. CONCLUSION: This study found that exposure to a mixture of ambient PM(2.5), PM(10), NO(2), and PM(2.5) chemical constituents was associated with an increased risk of GDM. NO(2) and black carbon PM(2.5) contributed most to GDM risk.