Ambient PM_2.5 exposure and gestational diabetes mellitus: Evidence from an instrumental variable analysis in a...

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/m³ 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.