Prenatal Exposure to Air Pollution and Fetal Cardiac Development: A Population-Based Cohort Study

Abstract Adverse cardiovascular effects of air pollution have been well established, yet its influence on prenatal cardiac development remains unknown. We aimed to investigate whether prenatal exposure to air pollutants is associated with changes in fetal cardiac morphology and function. We used data from 904 pregnant individuals and their fetuses participating in the Barcelona Life Study Cohort (BiSC), who were recruited during their first trimester (∼12 weeks) in Barcelona, Spain, 2018–2021. Prenatal exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) at home and workplace was estimated during pregnancy (from conception to fetal cardiac examination), and for gestational weeks 3–8, using machine-learning hybrid models incorporating individual time-activity patterns. Fetal cardiac morphology and function were assessed by echocardiography in the third trimester (∼32 weeks). We fitted linear mixed-effect models to investigate the associations between exposure to air pollution and fetal cardiac parameters, adjusted for relevant covariates. For cardiac morphology, higher exposure to PM2.5, NO2, and BC was associated with a consistent pattern of fetal cardiac remodeling, characterized by greater biventricular relative wall thickness, higher left ventricular sphericity index, and smaller atrial area. Prenatal exposure to the three pollutants was also associated with altered cardiac function, including lower mitral annular plane systolic excursion and lower mitral E-peak, A-peak, and tricuspid A-peak velocities. We observed a similar pattern of associations for air pollution exposure during gestational weeks 3–8, which is a critical period of cardiac morphogenesis. Overall, prenatal exposure to air pollution was associated with morphological and functional changes in the fetal heart, characterized by concentric remodeling together with altered systolic motion and ventricular filling. These findings suggest cardiovascular vulnerability to air pollution may originate before birth and support incorporating pregnancy into cardiovascular disease prevention strategies.