Association between First Trimester Exposure to Ambient [Formula: see text] and [Formula: see text] and Congenital Heart Defects: A Population-Based Cohort Study of 1,342,198 Live Births in Canada

BACKGROUND: The extent to which ambient air pollution contributes to the pathogenesis of congenital heart defects remains uncertain. OBJECTIVE: We investigated whether first trimester exposure to ambient fine particulate matter ([Formula: see text]) and nitrogen dioxide ([Formula: see text]) was associated with the risk of critical and noncritical heart defects in a large population-based cohort of births. METHODS: We carried out a retrospective cohort study of children conceived between 2000 and 2016 in Quebec, Canada. Heart defects were identified via data from the Maintenance and Use of Data for the Study of Hospital Clientele registry. The main exposures were average concentration of [Formula: see text] and [Formula: see text] in a) the first trimester and b) the month of conception. Exposures were estimated at the residential postal code. Associations with critical and noncritical heart defects were assessed using logistic regression models, adjusted for maternal and infant characteristics. We considered single- and two-pollutant models and assessed modifying effects of maternal comorbidity, including preexisting hypertension, preeclampsia, anemia, and diabetes. RESULTS: The cohort comprised 1,342,198 newborns, including 12,715 with heart defects. Exposure in the first trimester and month of conception yielded similar results; both were associated with a greater risk of heart defects. Adjusted odds ratios (OR) for any heart defect per interquartile range increase were 1.02 (95% CI: 1.00, 1.05) for [Formula: see text] and 1.10 (95% CI: 1.07, 1.13) for [Formula: see text]. Associations with atrial septal defects were 1.08 (95% CI: 1.03, 1.14) for [Formula: see text] and 1.19 (95% CI: 1.12, 1.25) for [Formula: see text]. Corresponding ORs for ventricular septal defects and individual critical heart defects were not significant. [Formula: see text] ([Formula: see text]; 95% CI: 1.06, 1.17) and [Formula: see text] ([Formula: see text]; 95% CI: 1.17, 1.31) exposure were associated with a greater risk of heart defects in mothers with comorbidity. DISCUSSION: In this population-based cohort, prenatal exposure to ambient air pollution during the first trimester was associated with an increased risk of heart defects, particularly atrial septal defects. The association with heart defects was greater in mothers with comorbidity. https://doi.org/10.1289/EHP11120