The association between prenatal exposure to mixed air pollutants and birth defects risk: a population-based study in Tangshan, China

Background Birth defects (BDs) are a major health concern worldwide, with air pollution being a key environmental risk factor. Current evidence, especially from industrial regions and regarding multi-pollutant exposure, is limited. This study examined the association between prenatal exposure to mixed air pollutants from preconception to early pregnancy and the risk of BDs in Tangshan, China. Methods We conducted a population-based study using data from a regional maternal and child health surveillance system. Maternal exposure to air pollutants (PM 10 , PM 2.5 , SO 2 , NO 2 , CO, and O 3 ) from 12 weeks before pregnancy to gestational week 13 was assessed using inverse distance weighting interpolation. Multi-pollutant statistical models, including quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR), were employed to analyze the association with offspring BDs while adjusting for covariates. Results This analysis included 19,053 mother–offspring pairs, with 540 cases of BDs identified (28.34 per 1,000, 95%CI: 25.99–30.70). Using QGC, a 19% higher risk of BDs was observed per quartile increase in multi-pollutant mixture (OR = 1.19, 95%CI: 1.01–1.41, P = 0.039). The positive weights for individual pollutants were as follows: PM 2.5 (0.287), SO 2 (0.235), O 3 (0.194), NO 2 (0.149), and PM 10 (0.135). BKMR revealed a nonlinear positive joint effect, with the strength of the association increasing at higher exposure levels. All pollutants except CO contributed positively to the joint effect, and potential interactions were observed between PM 10 -SO 2 , NO 2 -SO 2 , NO 2 -O 3 , and CO-O 3 . No significant effect modification by residential area or offspring sex was found in QGC; however, in subgroup analysis, O 3 was the key pollutant in rural areas and SO 2 in female offspring. Furthermore, BKMR showed a significant positive association in all subgroups when the mixture exposure level exceeded the median. Conclusion The findings suggest that periconceptional exposure to mixed air pollutants is associated with an increased risk of BDs, driven primarily by PM 2.5 , SO 2 , and O 3 . Thus, these results provide a foundation for developing targeted air pollution protection strategies for pregnant women, advancing primary prevention of BDs, and guiding the optimization of healthcare resource allocation.