Ambient PM2.5 exposure and gestational diabetes mellitus: Evidence from an instrumental variable analysis in a prospective birth cohort study in China

Evidence on the association between maternal exposure to fine particulate matter (PM 2.5 ) and gestational diabetes mellitus (GDM) remains inconsistent, and more robust evidence is lacking. We investigated the association between maternal PM 2.5 exposure and GDM, identified susceptible exposure windows, and explored potential effect modification. Using data from the China Southwest Birth Cohort, daily PM 2.5 exposure was estimated at residential addresses during the first trimester, the second trimester, and the first two trimesters combined. GDM was diagnosed using a 2-hour 75-g oral glucose tolerance test between 24 and 28 gestational weeks. To strengthen causal inference, we applied a two-stage residual inclusion instrumental variable approach using wind speed as the instrument. Among 15,266 participants, 2487 (16.3%) developed GDM. For each 10 μg/m 3 increase in PM 2.5 , higher exposure during the first trimester (OR: 1.16, 95% CI: 1.04–1.30) and the first two trimesters (OR: 1.15, 95% CI: 1.01–1.31) were associated with increased GDM risk, whereas second-trimester exposure was not (OR: 1.08, 95% CI: 0.95–1.22). Attributable fraction analyses indicated that 7.9% and 30.6% of GDM cases for first-trimester exposure, and 6.9% and 29.8% for exposure during the first two trimesters, were attributable to PM 2.5 above reference levels of 35 and 5 μg/m³ , respectively. For first-trimester exposure, the association appeared weaker among women with normal pre-pregnancy BMI and among those with regular physical activity. This study suggests that higher maternal PM 2.5 exposure is associated with increased GDM risk, with early pregnancy as a susceptible exposure window. Abnormal pre-pregnancy BMI or lack of physical activity may increase susceptibility to PM 2.5 -related GDM.