A Comprehensive Investigation into the Correlation between Atmospheric Pollutants and Genetic Alterations in Products of Conception

Objective This study aims to unravel the intricate correlation between atmospheric pollutants and genetic alterations in products of conception, with the ultimate goal of identifying hazardous airborne agents and laying a scientific foundation for targeted air quality interventions to safeguard maternal and infant health. Methods A multicenter retrospective analysis was conducted on clinical data from women who experienced missed abortions and underwent genetic screening across seven hospitals in China between December 2020 and December 2024. Genetic testing results of abortive tissues were categorized into two groups: those exhibiting genetic material alterations—encompassing chromosomal numerical abnormalities, structural aberrations, and gene-level mutations—and those with normal genetic profiles. Concurrently, longitudinal environmental data on ambient concentrations of key air pollutants—PM10, PM2.5, and O3—were collected from Hefei City, Anhui Province, spanning December 2018 to December 2024. Daily exposure levels for each participant were reconstructed, covering the two-year period preceding pregnancy through to the time of fetal arrest. Three critical exposure windows were defined around gestation: W1 (two years prior to conception), W2 (three months before conception), and W3 (from conception to embryonic demise). Using advanced statistical models, the associations between PM10, PM2.5, and O3 exposures during these windows and the three types of genetic anomalies were systematically evaluated. Results In correlation analyses, elevated O3 exposure emerged as a significant risk factor for both chromosomal numerical and structural abnormalities during the W1 window, and continued to pose a risk for structural aberrations in the W2 window. Notably, no such association was observed during the W3 window. In contrast, neither PM2.5 nor PM10 demonstrated an increased risk for genetic alterations across any of the three exposure periods. Restricted cubic spline (RCS) analyses revealed no linear dose-response relationships between the three pollutants and genetic changes throughout the defined windows. Subgroup analyses by age stratification unveiled compelling insights: among women aged ≥35 years, exposure to PM2.5 and PM10 during W1 significantly heightened the risk of chromosomal structural abnormalities compared to their younger counterparts (<35 years). Similarly, during W2, O3 exposure conferred an elevated risk of structural defects specifically in the older age group. However, no significant interactions were found between BMI categories (≥24 vs. <24) and pollutant exposure. Sensitivity analyses excluding individuals with autoimmune conditions confirmed the robustness of findings: O3 remained a persistent risk factor for chromosomal structural abnormalities during W1. Furthermore, even after adjusting for comorbidities such as hypertension and diabetes, O3 continued to exhibit a significant association with structural chromosomal defects in both W1 and W2 windows. Conclusion Ozone (O3) stands out as a critical preconceptional environmental hazard, significantly linked to chromosomal abnormalities in women of reproductive age, particularly during the extended pre-pregnancy period. While PM2.5 and PM10 do not universally elevate genetic risks, they may disproportionately impact high-risk subpopulations—especially older women—during early preparatory phases of pregnancy. These findings underscore the imperative for precision public health strategies in air pollution control, offering vital evidence for identifying vulnerable cohorts and guiding clinical practices in prenatal screening and genetic counseling.