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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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325010449 |
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| Summary: | 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. |
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| ISSN: | 0147-6513 |