Air pollutants and adverse pregnancy outcomes: A multi-method integration of Mendelian randomization, meta-analysis, and animal models
Background: Exposure to air pollutants is associated with adverse pregnancy outcomes, but establishing a causal relationship remains challenging. Methods: We integrated Mendelian randomization (MR) and animal experiments to investigate causality. MR analyses leveraged data from FinnGen consortium an...
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Elsevier
2025-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325010449 |
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| author | Wenhan Zhou Jiejie Shao Juanjuan Huang Jianfeng Gan Yinan Wang Jianmin Chen Yunqian Chen Yang Zi Qixin Xu Qiongjie Zhou Huanqiang Zhao Xiaotian Li |
| author_facet | Wenhan Zhou Jiejie Shao Juanjuan Huang Jianfeng Gan Yinan Wang Jianmin Chen Yunqian Chen Yang Zi Qixin Xu Qiongjie Zhou Huanqiang Zhao Xiaotian Li |
| author_sort | Wenhan Zhou |
| collection | DOAJ |
| description | Background: Exposure to air pollutants is associated with adverse pregnancy outcomes, but establishing a causal relationship remains challenging. Methods: We integrated Mendelian randomization (MR) and animal experiments to investigate causality. MR analyses leveraged data from FinnGen consortium and UK Biobank data to assess effects of air pollutants (particulate matter ≤2.5 μm in diameter [PM2.5], particulate matter 2.5–10 μm in diameter [PM2.5–10], and nitrogen oxide [NOx]) on pregnancy complications (preeclampsia, intrauterine fetal growth restriction, gestational hypertension, placental abruption, placenta previa, spontaneous abortion, and preterm birth). Sensitivity analyses employed multiple methods, and two-step MR mediation analyses were performed. In vivo validation utilized C57BL/6 mice exposed to PM2.5. Results: In the FinnGen cohort (423,796 exposed individuals; outcome cases ranging from 691 to 67,323, PM2.5 exposure was significantly associated with an increased risk of preeclampsia (odds ratio [OR]: 1.421; 95 % confidence interval [CI]: 1.066–1.894), corroborated by meta-analysis (OR: 1.281; 95 % CI: 1.045–1.568). No significant associations were found for other outcomes. Sensitivity analyses confirmed robustness. Among 2521 potential mediators, CD27 was identified as significant. PM2.5-exposed mice exhibited preeclampsia-like phenotypes (hypertension, proteinuria) with placental vascularization deficits. Conclusion: Combing MR, meta-analysis, and animal models, this study provides robust causal evidence linking PM2.5 exposure to preeclampsia, mitigating biases inherent in single-database MR. Reducing PM2.5 exposure reduction may be a public health priority for preeclampsia prevention. |
| format | Article |
| id | doaj-art-934835da5ebc4f3b89cfddfb0338c84a |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-934835da5ebc4f3b89cfddfb0338c84a2025-08-20T03:03:53ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211869910.1016/j.ecoenv.2025.118699Air pollutants and adverse pregnancy outcomes: A multi-method integration of Mendelian randomization, meta-analysis, and animal modelsWenhan Zhou0Jiejie Shao1Juanjuan Huang2Jianfeng Gan3Yinan Wang4Jianmin Chen5Yunqian Chen6Yang Zi7Qixin Xu8Qiongjie Zhou9Huanqiang Zhao10Xiaotian Li11Obstetrics and Gynecology Hospital of Fudan University, Shanghai, ChinaObstetrics and Gynecology Hospital of Fudan University, Shanghai, ChinaShenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong, ChinaObstetrics and Gynecology Hospital of Fudan University, Shanghai, ChinaObstetrics and Gynecology Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science & Engineering, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science & Engineering, Fudan University, Shanghai, ChinaShenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong, ChinaShenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong, ChinaObstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Corresponding authors.Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong, China; Corresponding authors.Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong, China; Corresponding author at: Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong, China.Background: Exposure to air pollutants is associated with adverse pregnancy outcomes, but establishing a causal relationship remains challenging. Methods: We integrated Mendelian randomization (MR) and animal experiments to investigate causality. MR analyses leveraged data from FinnGen consortium and UK Biobank data to assess effects of air pollutants (particulate matter ≤2.5 μm in diameter [PM2.5], particulate matter 2.5–10 μm in diameter [PM2.5–10], and nitrogen oxide [NOx]) on pregnancy complications (preeclampsia, intrauterine fetal growth restriction, gestational hypertension, placental abruption, placenta previa, spontaneous abortion, and preterm birth). Sensitivity analyses employed multiple methods, and two-step MR mediation analyses were performed. In vivo validation utilized C57BL/6 mice exposed to PM2.5. Results: In the FinnGen cohort (423,796 exposed individuals; outcome cases ranging from 691 to 67,323, PM2.5 exposure was significantly associated with an increased risk of preeclampsia (odds ratio [OR]: 1.421; 95 % confidence interval [CI]: 1.066–1.894), corroborated by meta-analysis (OR: 1.281; 95 % CI: 1.045–1.568). No significant associations were found for other outcomes. Sensitivity analyses confirmed robustness. Among 2521 potential mediators, CD27 was identified as significant. PM2.5-exposed mice exhibited preeclampsia-like phenotypes (hypertension, proteinuria) with placental vascularization deficits. Conclusion: Combing MR, meta-analysis, and animal models, this study provides robust causal evidence linking PM2.5 exposure to preeclampsia, mitigating biases inherent in single-database MR. Reducing PM2.5 exposure reduction may be a public health priority for preeclampsia prevention.http://www.sciencedirect.com/science/article/pii/S0147651325010449Air pollutantsAdverse pregnancy outcomesImmune cellsMendelian randomizationPM2.5Preeclampsia |
| spellingShingle | Wenhan Zhou Jiejie Shao Juanjuan Huang Jianfeng Gan Yinan Wang Jianmin Chen Yunqian Chen Yang Zi Qixin Xu Qiongjie Zhou Huanqiang Zhao Xiaotian Li Air pollutants and adverse pregnancy outcomes: A multi-method integration of Mendelian randomization, meta-analysis, and animal models Ecotoxicology and Environmental Safety Air pollutants Adverse pregnancy outcomes Immune cells Mendelian randomization PM2.5 Preeclampsia |
| title | Air pollutants and adverse pregnancy outcomes: A multi-method integration of Mendelian randomization, meta-analysis, and animal models |
| title_full | Air pollutants and adverse pregnancy outcomes: A multi-method integration of Mendelian randomization, meta-analysis, and animal models |
| title_fullStr | Air pollutants and adverse pregnancy outcomes: A multi-method integration of Mendelian randomization, meta-analysis, and animal models |
| title_full_unstemmed | Air pollutants and adverse pregnancy outcomes: A multi-method integration of Mendelian randomization, meta-analysis, and animal models |
| title_short | Air pollutants and adverse pregnancy outcomes: A multi-method integration of Mendelian randomization, meta-analysis, and animal models |
| title_sort | air pollutants and adverse pregnancy outcomes a multi method integration of mendelian randomization meta analysis and animal models |
| topic | Air pollutants Adverse pregnancy outcomes Immune cells Mendelian randomization PM2.5 Preeclampsia |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325010449 |
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