Congenital heart disease (CHD) is the most common congenital abnormality worldwide, affecting 8 to 12 infants per 1000 births globally and causing >40% of prenatal deaths. However, its causes remain mainly unknown, with only up to 15% of CHD cases having a determined genetic cause. Exploring the complex relationship between genetics and environmental exposures is key in understanding the multifactorial nature of the development of CHD. Multiple population-level association studies have been conducted on maternal environmental exposures and their association with CHD, including evaluating the effect of maternal disease, medication exposure, environmental pollution, and tobacco and alcohol use on the incidence of CHD. However, these studies have been done in a siloed manner, with few examining the interplay between multiple environmental exposures. Here, we broadly and qualitatively review the current literature on maternal and paternal prenatal exposures and their association with CHD. We propose using the framework of the emerging field of the exposome, the environmental complement to the genome, to review all internal and external prenatal environmental exposures and identify potentiating or alleviating synergy between exposures. Finally, we propose mechanistic pathways through which susceptibility to development of CHD may be induced via the totality of prenatal environmental exposures, including the interplay between placental and cardiac development and the internal vasculature and placental morphology in early stages of pregnancy.
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January 2022
State-of-the-Art Review Article|
December 23 2021
Environmental Exposures and Congenital Heart Disease
David Kalfa, MD, PhD
Address correspondence to David Kalfa, MD, PhD, College of Physicians and Surgeons, Columbia University and NewYork-Presbyterian Morgan Stanley Children’s Hospital, 3959 Broadway, CHN-274, New York, NY 10032. E-mail: dk2757@cumc.columbia.edu
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FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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Contributed equally as co-first authors
Address correspondence to David Kalfa, MD, PhD, College of Physicians and Surgeons, Columbia University and NewYork-Presbyterian Morgan Stanley Children’s Hospital, 3959 Broadway, CHN-274, New York, NY 10032. E-mail: dk2757@cumc.columbia.edu
Pediatrics (2022) 149 (1): e2021052151.
Article history
Accepted:
August 19 2021
Citation
Rebekah Boyd, Hannah McMullen, Halil Beqaj, David Kalfa; Environmental Exposures and Congenital Heart Disease. Pediatrics January 2022; 149 (1): e2021052151. 10.1542/peds.2021-052151
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