Abstract
Air pollution has been associated with preterm birth (PTB); however, evidence remains limited about preconception exposure. Additionally, it remains unknown whether air pollution and thyrotropin abnormalities may synergistically contribute to incident PTB. We conducted a nationwide cohort study of 6.1 million singleton births, based on the National Free Prepregnancy Checkups Project across 29 provinces in China, 2014-2020. We observed that interquartile range increases in particulate matter with diameters ≤2.5 and ≤10 μm, nitrogen dioxide, and sulfur dioxide during 12 weeks before conception through pregnancy were associated with increased risks of PTB, with the hazard ratios of 1.25 (95% confidence intervals [CI]: 1.24, 1.25), 1.13 (95% CI: 1.13, 1.14), 1.10 (95% CI: 1.09, 1.10), and 1.24 (95% CI: 1.24, 1.25), respectively. Participants with high air pollution exposure (>75th percentile) and abnormal thyrotropin levels (<0.37 or ≥4.88 mIU/L) showed higher risks of PTB, compared to those with low air pollution exposure (<25th percentile) and normal thyrotropin levels. Additive interactions were also identified between air pollution and thyrotropin abnormalities (relative excess risk due to interaction >0, attributable proportion due to interaction >0, and synergy index >1). Our study showed that exposure to air pollution during preconception through pregnancy was associated with increased risks of PTB and that air pollution and thyrotropin abnormalities may synergistically contribute to incident PTB. These findings highlight the importance of air pollution control and thyroid management.