ORIGINAL RESEARCH article
Front. Public Health
Sec. Environmental Health and Exposome
Joint Effects of Prenatal PM2.5 and Heavy Metals on Preterm Birth: Evidence from a Nest Case–Control Study in China
Provisionally accepted
Jinxiu Feng1
Ziyi He2
Xin Ming2Yunping Yang2Yannan Li2Dong Ting2Xinzhen Chen2
Min Zhang2Yankun Wang2
Li Zhou3*
Wenzheng Zhou2*- 1Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, China
- 2Chongqing Health Center for Women and Children, Chongqing, China
- 3Chongqing Medical University College of Public Health, Chongqing, China
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Background: Preterm birth (PTB) is a global health concern. The combined effects of prenatal PM2.5 and heavy metal exposures on PTB risk remain unclear. Methods: A nested case-control study included 111 PTB cases and 124 controls from Chongqing. Maternal blood concentrations of 18 trace elements were measured in mid-pregnancy. PM2.5 exposure data were obtained from the Tracking Air Pollution in China (TAP). Residential addresses were geocoded and linked to these exposure estimates. Logistic regression, Weighted Quantile Sum (WQS), Grouped WQS (GWQS), and BKMR models were used to evaluate individual, mixture, and interaction effects. Results: Higher PM2.5 exposure during the second trimester and early-to-mid pregnancy was associated with increased PTB risk. Cadmium, selenium, and zinc were positively associated with PTB, whereas lithium and nickel were inversely associated. WQS models indicated the mixture was associated with elevated PTB risk (OR 2.01; 95% CI 1.09–3.71), with PM2.5 contributing the largest weight, lithium and nickel were inversely associated (OR 0.36; 95% CI 0.18–0.74). GWQS models showed that PM2.5 (OR: 2.24; 95% CI: 1.68–3.07) and essential trace elements (ETE) (OR: 2.32; 95% CI: 1.60–3.44) positively associated with PTB, whereas conditionally essential trace elements (CTE) were inversely associated (OR: 0.37; 95% CI: 0.23–0.59). Seven-group GWQS analyses suggested potential interaction between PM2.5 and ETE (OR: 4.44; 95% CI: 2.33–9.10) and inverse associations with CTE. BKMR revealed nonlinear mixture effects and a non-monotonic effect of lithium. Conclusion: Pregnancy exposure to PM2.5 and heavy metal mixtures were associated PTB risk, with evidence of complex and potentially interactive associations. These findings highlight the importance of integrated assessments of multiple environmental exposures and targeted public health strategies to reduce maternal and child health risks.
Keywords: Preterm Birth, heavy metals, Fine Particulate Matter, Maternal Exposure, mixture modeling, environmental epidemiology
Received: 08 Sep 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 Feng, He, Ming, Yang, Li, Ting, Chen, Zhang, Wang, Zhou and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Li Zhou
Wenzheng Zhou
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