Maternal and Environmental Risk Factors for Congenital Heart Diseases in Offspring: A Review Article
DOI:
https://doi.org/10.12775/QS.2026.55.70966Keywords
congenital heart disease, maternal risk factors, diabetes, environmental exposureAbstract
Background. Congenital heart diseases (CHDs) are the most common congenital anomalies and a leading cause of infant morbidity and mortality. Although genetic factors play an important role, many cases remain unexplained, highlighting the contribution of maternal and environmental exposures.
Aim. This review aims to provide a comprehensive and up-to-date synthesis of non-genetic maternal risk factors associated with CHDs in offspring.
Material and methods. A literature review was conducted using PubMed, NCBI and Google Scholar, including studies published between 2010 and 2025. Systematic reviews, meta-analyses, cohort and case-control studies evaluating maternal and environmental exposures were analyzed.
Results. Evidence indicates that maternal diabetes and obesity are key risk factors, with clear dose-response relationships. Additional contributors include smoking (active and passive), alcohol consumption, infections, fever, psychological stress and environmental pollutants. Protective effects of folic acid and multivitamin supplementation were also observed. Interaction effects between environmental exposures and parental behaviors further increase CHD risk.
Conclusions. CHD etiology is multifactorial, involving modifiable maternal and environmental factors. Identification and reduction of these exposures, particularly during early pregnancy, are essential for prevention. Further prospective and mechanistic studies are needed to clarify causal pathways and improve risk reduction strategies.
References
Salmeri N, Seidenari A, Cavoretto PI, Papale M, Candiani M, Farina A. Maternal prepregnancy weight as an independent risk factor for congenital heart defect: systematic review and meta-analysis stratified by subtype and severity of defect. Ultrasound Obstet Gynecol. 2024;64(3):294-307. doi:10.1002/uog.27659
Persson M, Razaz N, Edstedt Bonamy AK, Villamor E, Cnattingius S. Maternal Overweight and Obesity and Risk of Congenital Heart Defects. J Am Coll Cardiol. 2019;73(1):44-53. doi:10.1016/j.jacc.2018.10.050
Hedermann G, Hedley PL, Gadsbøll K, et al. Maternal obesity, interpregnancy weight changes and congenital heart defects in the offspring: a nationwide cohort study. Int J Obes (Lond). 2024;48(8):1126-1132. doi:10.1038/s41366-024-01531-5
Liu X, Ding G, Yang W, et al. Maternal Body Mass Index and Risk of Congenital Heart Defects in Infants: A Dose-Response Meta-Analysis. Biomed Res Int. 2019;2019:1315796. Published 2019 Jul 7. doi:10.1155/2019/1315796
Zheng Z, Yang T, Chen L, et al. Increased maternal Body Mass Index is associated with congenital heart defects: An updated meta-analysis of observational studies. Int J Cardiol. 2018;273:112-120. doi:10.1016/j.ijcard.2018.09.116
Mills JL, Troendle J, Conley MR, Carter T, Druschel CM. Maternal obesity and congenital heart defects: a population-based study. Am J Clin Nutr. 2010;91(6):1543-1549. doi:10.3945/ajcn.2009.28865
Turunen R, Pulakka A, Metsälä J, et al. Maternal Diabetes and Overweight and Congenital Heart Defects in Offspring. JAMA Netw Open. 2024;7(1):e2350579. Published 2024 Jan 2. doi:10.1001/jamanetworkopen.2023.50579
McMullan A, Zwierzynski JB, Jain N, et al. Role of Maternal Obesity in Offspring Cardiovascular Development and Congenital Heart Defects. J Am Heart Assoc. 2025;14(9):e039684. doi:10.1161/JAHA.124.039684
Nie X, Liu X, Wang C, et al. Assessment of evidence on reported non-genetic risk factors of congenital heart defects: the updated umbrella review. BMC Pregnancy Childbirth. 2022;22(1):371. Published 2022 Apr 29. doi:10.1186/s12884-022-04600-7
He R, Hornberger LK, Kaur A, et al. Risk of major congenital heart disease in pregestational maternal diabetes is modified by hemoglobin A1c. Ultrasound Obstet Gynecol. 2024;63(3):378-384. doi:10.1002/uog.27456
Nagasawa M, Ikehara S, Aochi Y, et al. Maternal diabetes and risk of offspring congenital heart diseases: the Japan Environment and Children's Study. Environ Health Prev Med. 2024;29:23. doi:10.1265/ehpm.23-00358
Zhao L, Chen L, Yang T, et al. Parental smoking and the risk of congenital heart defects in offspring: An updated meta-analysis of observational studies. Eur J Prev Cardiol. 2020;27(12):1284-1293. doi:10.1177/2047487319831367
Li J, Du YJ, Wang HL, et al. Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(6):884-889. doi:10.3760/cma.j.cn112338-20190710-00509
Taylor K, Elhakeem A, Thorbjørnsrud Nader JL, et al. Effect of Maternal Prepregnancy/Early-Pregnancy Body Mass Index and Pregnancy Smoking and Alcohol on Congenital Heart Diseases: A Parental Negative Control Study. J Am Heart Assoc. 2021;10(11):e020051. doi:10.1161/JAHA.120.020051
Zhang S, Wang L, Yang T, et al. Parental alcohol consumption and the risk of congenital heart diseases in offspring: An updated systematic review and meta-analysis. Eur J Prev Cardiol. 2020;27(4):410-421. doi:10.1177/2047487319874530
Yang G, Deng X, Xiao J, Huang P, Zhang K, Li Y. Maternal fever during preconception and conception is associated with congenital heart diseases in offspring: An updated meta-analysis of observational studies. Medicine (Baltimore). 2021;100(9):e24899. doi:10.1097/MD.0000000000024899
Ye Z, Wang L, Yang T, et al. Maternal Viral Infection and Risk of Fetal Congenital Heart Diseases: A Meta-Analysis of Observational Studies. J Am Heart Assoc. 2019;8(9):e011264. doi:10.1161/JAHA.118.011264
Gu J, Guan HB. Maternal psychological stress during pregnancy and risk of congenital heart disease in offspring: A systematic review and meta-analysis. J Affect Disord. 2021;291:32-38. doi:10.1016/j.jad.2021.05.002
Jing H, Li J, Du YJ, et al. Zhonghua Liu Xing Bing Xue Za Zhi. 2021;42(9):1635-1640. doi:10.3760/cma.j.cn112338-20201103-01301
Li J, Du Y, Liu Y, et al. Maternal exposure to life events during pregnancy and congenital heart disease in offspring: a case-control study in a Chinese population. BMC Pregnancy Childbirth. 2021;21(1):677. Published 2021 Oct 6. doi:10.1186/s12884-021-04154-0
Jin S, Yoon SZ, Choi YJ, Kang G, Choi SU. Prenatal exposure to air pollutants and the risk of congenital heart disease: a Korean national health insurance database-based study. Sci Rep. 2024;14(1):16940. Published 2024 Jul 23. doi:10.1038/s41598-024-63150-4
Ruan X, Shang W, Lu J, et al. Maternal multivitamin supplementation mitigates the risk of fetal congenital heart disease associated with high indoor total volatile organic compounds exposure in east china: a case-control study. Environ Health. 2024;23(1):110. Published 2024 Dec 20. doi:10.1186/s12940-024-01150-7
Wang H, Ruan YP, Ma S, et al. Interaction between ozone and paternal smoking on fetal congenital heart defects among pregnant women at high risk: a multicenter maternal-fetal medicine study. World J Pediatr. 2024;20(6):621-632. doi:10.1007/s12519-023-00755-1
Boyd R, McMullen H, Beqaj H, Kalfa D. Environmental Exposures and Congenital Heart Disease. Pediatrics. 2022;149(1):e2021052151. doi:10.1542/peds.2021-052151
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Agnieszka Zielińska, Zuzanna Zofia Kamińska, Małgorzata Blecharczyk, Martyna Mrozek, Igor Zydlewski, Martyna Pacanowska-Trawnicka, Aleksandra Jakimowicz, Aleksandra Malcher
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 38
Number of citations: 0
