Maternal exposure to fine particulate matter and the risk of congenital heart diseases: a meta-analysis of 14 million infants

Background Congenital heart disease (CHD) is among the most prevalent congenital malformations in humans. Existing studies have reported inconsistent findings regarding the relationship between air pollution with fine particulate matter (PM2.5) and CHD. Purpose This study aims to assess the association between gestational exposure to air pollutants and the development of congenital heart disease, while also identifying critical exposure windows that may influence this condition. Methods We systematically searched PubMed, Embase, and Cochrane databases for studies assessing the influence of PM2.5 maternal exposure and the development of CHD. Using a random-effects model, we pooled odds ratios (OR) for binary outcomes, accompanied by 95% confidence intervals (CI). Additionally, we performed subgroup analyses based on the continent of the study (Asia, America, or Europe), the timing of maternal exposure (preconception, first, second, and third trimesters), and the specific types of CHD (including atrial, ventricular, tetralogy of Fallot, aortic coarctation, and ductus arteriosus). Whenever available, we utilized the most adjusted data to mitigate potential cofounders in our analyses. All statistical analyses were conducted using R version 4.4.2. Results Our meta-analysis included 33 studies, encompassing a pooled population of 14,223,903 mother-infant pairs, among which 166,822 (1.17%) infants were diagnosed with CHD. An increase in PM2.5 exposure throughout the entire pregnancy was significantly associated with a heightened risk of cardiac congenital anomalies (OR 1.1138; 95% CI: 1.0318 to 1.2023; p<0.01; Figure 1). A similar association was noted when analyzing exposure specifically during the first trimester of gestation (OR 1.0391; 95% CI: 1.0128 to 1.0661; p<0.01). In subgroup analyses based on the continent of the trial, a significant correlation was found in Asia and America, whereas no such association was observed in Europe. Regarding the timing of exposure, only those exposed during the first trimester demonstrated an association. However, no specific type of CHD was found to be correlated solely with PM2.5 exposure (Figure 2). Conclusion Our findings suggest that elevated levels of PM2.5 are associated with an increased risk of CHD, particularly when exposure occurs during the first trimester. However, further research is needed to investigate maternal exposure at different stages of pregnancy and across various ethnic groups.Primary Analysis Subgroup Analyses