Association between First Trimester Exposure to Ambient PM2.5 and NO2 and Congenital Heart Defects: A Population-Based Cohort Study of 1,342,198 Live Births in Canada

Abstract

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 ( ) and nitrogen dioxide ( ) 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 and 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 and 1.10 (95% CI: 1.07, 1.13) for . Associations with atrial septal defects were 1.08 (95% CI: 1.03, 1.14) for and 1.19 (95% CI: 1.12, 1.25) for . Corresponding ORs for ventricular septal defects and individual critical heart defects were not significant. ( ; 95% CI: 1.06, 1.17) and ( ; 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

An Overview of Adverse Outcome Pathway Links between PM2.5 Exposure and Cardiac Developmental Toxicity

“…The first trimester of the pregnancy was identified as a critical period for fetal heart development. Case-control and time-series studies from China and a cohort study from America have observed a higher risk of CHDs in infants was associated with higher concentrations of PM 2.5 exposure during the first trimester. ,− However, time-series studies and case-control studies in China confirmed a correlation between increased morbidity of CHD and exposure to PM 2.5 during the second and third trimester. − Another case-control study from China found a higher risk of CHD in offspring associated with higher concentrations of PM 2.5 exposure during preconception . On the contrary, case-control studies from America and China reported a reduced risk of ventricular septal defect (VSD) and atrial septal defect (ASD) associated with PM 2.5 exposure during pregnancy. ,− A study conducted in Israel demonstrated that PM 2.5 exposure decreased the risk of patent ductus arteriosus (PDA) .…”

Invited Perspective: Air Pollution and Congenital Heart Defects (CHDs)—a Summary of Two Decades and Future Direction in Research

“…In their study published in this issue, Buteau et al. 8 used a retrospective registry-based cohort to analyze data for 1,342,198 live births, including 12,715 with CHDs, from Quebec, Canada. They found that maternal exposure to fine particulate matter and nitrogen dioxide in the first trimester was associated with an increased risk of noncritical CHDs (particularly atrial septal defects) in mothers with comorbidities (particularly anemia, preeclampsia, and preexisting hypertension).…”