The effects of exposure to ambient PM_2.5 during pregnancy on septal defects in offspring: A retrospective population-based case-control study

Recent epidemiological studies conducted over the past ten years have increasingly investigated the association between ambient air pollution exposure and the risk of congenital heart defects, yet the findings have shown considerable inconsistency across different research populations and methodological approaches. This study sought to examine the association between maternal exposure to fine particulate matter (PM_2.5) during the critical first eight weeks of gestation and the risk of septal defects in offspring. A population-based case-control study in Beijing, China (2008–2012) was conducted to assess the association between maternal exposure to PM_2.5 during the first eight weeks of pregnancy and the risk of septal defects in offspring. Multi-variable logistic regression regression models were used to estimated adjusted odds ratio (aOR) and corresponding 95% confidence intervals (CIs) for exposure-risk association, and the exposure-response association was investigated using restricted cubic spline analysis. Maternal exposure to PM_2.5 were positively associated with the risk of overall septal defects in the 10^th-50^th percentile (aOR = 2.415; 95%CI: 1.424 to 4.359), 51^th-90^th percentile (aOR = 2.539; 95%CI: 1.472 to 4.643), and &gt;90^th percentile (aOR = 2.991; 95%CI: 1.601 to 5.832) groups during the fourth week, and in the 10^th-50^th percentile (aOR = 1.432; 95%CI: 0.899 to 2.362), 51^th-90^th percentile (aOR = 1.874; 95%CI: 1.162 to 3.128), and &gt; 90^th percentile (aOR = 2.468; 95%CI: 1.398 to 4.453) groups during the fifth week, all compared with the &lt; 10^th percentile group. Non-isolated atrial septal defect demonstrated the strongest association with PM_2.5 exposure during these weeks (aOR range: 1.882 to 4.382). Individual characteristics showed no meaningful effect modification. Furthermore, PM_2.5 exposure exhibited a linear dose-response association with overall septal defects. This study identified a significant positive association between maternal exposure to ambient PM_2.5 during the first eight gestational weeks and fetal septal defects. <i>Implications</i>: This study demonstrates that maternal PM2.5 exposure, especially in the first trimester, increases congenital septal defect risk. The findings support stricter air quality policies for vulnerable populations and highlight a critical susceptibility window. Clinically, prenatal care should incorporate PM_2.5 exposure reduction strategies, such as real-time air quality monitoring for pregnant individuals. Further research should explore PM_2.5’s mechanistic pathways (e.g., oxidative stress, placental inflammation) in cardiac malformations. These results align with A&amp;WMA’s focus on air pollution management and its health impacts.