Risk factor analysis for congenital heart defects in children

  • I. V. Lastivka Bukovinian State Medical University
  • V. P. Pishak National Academy of Pedagogical Sciences
  • М. О. Ryznychuk Bukovinian State Medical University
  • Т. V. Khmara Bukovinian State Medical University
Keywords: environment; heart malformations; newborns; risk factors; infants


Congenital heart defects (CHDs) are the most common malformations, occurring in almost 1.0 in 100 births. We investigated an association between risk factors and CHDs, because epidemiological studies have reported conflicting results regarding risk factors and CHDs recently. The study of CHD frequency was conducted in Chernivtsi region (Northern Bukovina) on the basis of the medical genetic center. A retrospective method of research by studying registration genetic maps was used to analyze risk factors. 91 cards of infants suffering from CHD (47 boys and 44 girls) aged 0–1 living in the territory of Northern Bukovina were selected. In order to identify risk factors, 133 cards of healthy infants (77 boys and 56 girls) were used. The analysis of risk factors revealed that the female gender of a child is a risk factor for CHD development. The analysis of the ordinal number of pregnancy revealed that the second and the third pregnancies are probable risk factors for the development of this pathology. It was found in our study that folic acid intake during the first trimester prevented CHD development (OR 2.33). The study revealed that among stressful risk factors are: unplanned pregnancy (OR 3.13); out-of-wedlock pregnancy and stress during pregnancy. Maternal CHD increased the CHD development in offspring approximately by two times. Some factors, such as a woman doing hard physical work during pregnancy, having sedentary work during pregnancy, the mother being a housewife or having an incomplete secondary education (OR 3.61), the mother’s secondary education, the father’s incomplete secondary education (OR 18.62), the father serving in the army (OR 2.15) or being a student at the time of woman’s pregnancy (OR 2.97) were significant for CHD development in the fetal stage. A young age of the father (up to 43 years) was also considered as one of the risk factors. This article is expected to provide timely information on risk factors for CHD development to a wide range of medical staff, including pediatric and adult cardiologists, pediatricians, thoracic surgeons, obstetricians, gynecologists, medical geneticists, genetic counselors and other relevant clinicians.


Abqari, S., Gupta, A., Shahab, T., Rabbani, M. U., Ali, S. M., & Firdaus, U. (2016). Profile and risk factors for congenital heart defects: A study in a tertiary care hospital. Annals of Pediatric Cardiology, 9(3), 216–221.

Agha, M. M., Glazier, R. H., Moineddin, R., Moore, A. M., & Guttmann, A. (2011). Socioeconomic status and prevalence of congenital heart defects: Does universal access to health care system eliminate the gap? Birth defects research. Part A, Clinical and Molecular Teratology, 91(12), 1011–1018.

Autti-Ramo, I., Fagerlund, A., Ervalahti, N., Loimu, L., Korkman, M., & Hoyme, H. E. (2006). Fetal alcohol spectrum disorders in Finland: Clinical delineation of 77 older children and adolescents. American Journal of Medical Genetics, 140(2), 137–143.

Baardman, M. E., Kerstjens–Frederikse, W. S., Corpeleijn, E., de Walle, H. E., Hofstra, R. M., Berger, R. M., & Bakker, M. K. (2012). Combined adverse effects of maternal smoking and high body mass index on heart development in offspring: Evidence for interaction? Heart, 98(6), 474–479.

Bernier, P. L., Stefanescu, A., Samoukovic, G., & Tchervenkov, C. I. (2010). The challenge of congenital heart disease worldwide: Epidemiologic and demographic facts. Seminars in thoracic and cardiovascular surgery. Pediatric Cardiac Surgery Annual, 13(1), 26–34.

Bhat, N. K., Dhar, M., Kumar, R., Patel, A., Rawat, A., & Kalra, B. P. (2013). Prevalence and pattern of congenital heart disease in Uttakhand, India. Indian Journal of Pediatrics, 80(4), 281–285.

Botto, L. D., Mulinare, J., & Erickson, J. D. (2000). Occurrence of congenital heart defects in relation to maternal multivitamin use. American Journal of Epidemiology, 151(9), 878–884.

Bouma, B. J., & Mulder, B. J. (2017). Changing landscape of congenital heart disease. Circulation Research, 120(6), 908–922.

Brent, L. (2004). Environmental causes of human congenitalmalformations: The pediatrician’s role in dealing with these complex clinical problems caused by a multiplicity of environmental and genetic factors. Pediatrics, 113(4), 957–968.

Carmichael, S. L., Yang, W., Roberts, E., Kegley, S. E., Padula, A. M., English, P. B., Lammer, E. J., & Shaw, G. M. (2014). Residential agricultural pesticide exposures and risk of selected congenital heart defects among offspring in the San Joaquin Valley of California. Environmental Research, 135, 133–138.

Carroll, A. J., Carnethon, M. R., Liu, K., Jacobs, D. R., Colangelo, L. A., Stewart, J. C., Carr, J. J., Widome, R., Auer, R., & Hitsman, B. (2016). Interaction between smoking and depressive symptoms with subclinical heart disease in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Health Psychology, 36(2), 101–111.

Chen, E. K., Zmirou–Navier, D., Padilla, C., & Deguen, S. (2014). Effects of air pollution on the risk of congenital anomalies: A systematic review and meta-analysis. International Journal of Environmental Research and Public Health, 11(8), 7642–7668.

Chou, H. H., Chiou, M. J., Liang, F. W., Chen, L. H., Lu, T. H., & Li, C. Y. (2016). Association of maternal chronic disease with risk of congenital heart disease in offspring. Canadian Medical Association Journal, 188(17–18), E438–E446.

Correa, A., Levis, D. M., Tinker, S. C., & Cragan, J. D. (2015). Maternal cigarette smoking and congenital heart defects. The Journal of Pediatrics, 166(4), 801–804.

Correa-Villaseñor, A., Ferencz, C., Loffredo, C., & Magee, C. (1993). Paternal exposures and cardiovascular malformations. The Baltimore-Washington Infant Study Group. Journal of Exposure Analysis and Environmental Epidemiology, 3(Suppl 1), 173–185.

Cresci, M., Foffa, I., Ait-Ali, L., Pulignani, S., Gianicolo, E. A., Botto, N., Picano, E., & Andreassi, M. G. (2011). Maternal and paternal environmental risk factors, metabolizing GSTM1 and GSTT1 polymorphisms, and congenital heart disease. The American Journal of Cardiology, 108(11), 1625–1631.

Dolk, H., Loane, M., Garne, E., & European Surveillance of Congenital Anomalies (EUROCAT) Working Group (2011). Congenital heart defects in Europe: Prevalence and perinatal mortality, 2000 to 2005. Circulation, 123(8), 841–849.

Donofrio, M. T., Moon-Grady, A. J., Hornberger, L. K., Copel, J. A., Sklansky, M. S., Abuhamad, A., Cuneo, B. F., Huhta, J. C., Jonas, R. A., Krishnan, A., Lacey, S., Lee, W., Michelfelder, E. C. S., Rempel, G. R., Silverman, N. H., Spray, T. L., Strasburger, J. F., Tworetzky, W., Rychik, J., American Heart Association Adults With Congenital Heart Disease Joint Committee of the Council on Cardiovascular Disease in the Young and Council on Clinical Cardiology, & Council on Cardiovascular Surgery and Anesthesia, and Council on Cardiovascular and Stroke Nursing. (2014). Diagnosis and treatment of fetal cardiac disease: A scientific statement from the American Heart Association. Circulation, 129(21), 2183–2242.

Entringer, S., Wüst, S., Kumsta, R., Layes, I. M., Nelson, E. L., Hellhammer, D. H., & Wadhwa, P. D. (2008). Prenatal psychosocial stress exposure is associated with insulin resistance in young adults. American Journal of Obstetrics and Gynecology, 199(5), 498.

Epstein, J. A., Li, J., Lang, D., Chen, F., Brown, C. B., Jin, F., Lu, M. M., Thomas, M., Liu, E., Wessels, A., & Lo, C. W. (2000). Migration of cardiac neural crest cells in Splotch embryos. Development, 127(9), 1869–1878.

Erikssen, G., Liestøl, K., Seem, E., Birkeland, S., Saatvedt, K. J., Hoel, T. N., Døhlen, G., Skulstad, H., Svennevig, J. L., Thaulow, E., & Lindberg, H. L. (2015). Achievements in congenital heart defect surgery: A prospective, 40-year study of 7038 patients. Circulation, 131(4), 337–346.

Fleming, D. A., Woskie, S. R., Jones, J. H., Silver, S. R., Luo, L., & Bertke, S. J. (2014). Retrospective assessment of exposure to chemicals for a microelectronics and business machine manufacturing facility. Journal of Occupational and Environmental Hygiene, 11(5), 292–305.

Fletcher, R., Fletcher, S., & Vagner, J. (1998). Klinicheskaja epidemiologija. Osnovy dokazatel’noj mediciny [Clinical epidemiology. Evidence-based medicine basics]. Media Sfera, Moscow (in Russian).

Gaynes, B. N., Gavin, N., Meltzer-Brody, S., Lohr, K. N., Swinson, T., Gartlehner, G., Brody, S., & Miller, W. C. (2005). Perinatal depression: Prevalence, screening accuracy, and screening outcomes. Evidence Report/Technology Assessment, 119, 1–8.

Hackshaw, A., Rodeck, C., & Boniface, S. (2011). Maternal smoking in pregnancy and birth defects: A systematic review based on 173 687 malformed cases and 11.7 million controls. Human Reproduction Update, 17(5), 589–604.

Hasan, I., Haleem, A. A., & Bhutta, Z. A. (1997). Profile and risk factor for congenital heart disease. Journal of the Pakistan Medical Association, 47(3), 78–81.

Hoffman, J. I. E. (2013). The global burden of congenital heart disease. Cardiovascular Journal of Africa, 24(4), 141–145.

Hornberger, L. K. (2006). Maternal diabetes and the fetal heart. Heart, 92(8), 1019–1021.

Hoyt, A. T., Canfield, M. A., Romitti, P. A., Botto, L. D., Anderka, M. T., Krikov, S. V., Tarpey, M. K., & Feldkamp, M. L. (2016). Associations between maternal periconceptional exposure to secondhand tobacco smoke and major birth defects. American Journal of Obstetrics and Gynecology, 215, e1–e11.

Janssen, I., Powell, L. H., Matthews, K. A., Jasielec, M. S., Hollenberg, S. M., Bromberger, J. T., Sutton-Tyrrell, K., & Everson-Rose, S. A. (2016). Relation of persistent depressive symptoms to coronary artery calcification in women aged 46 to 59 years. The American Journal of Cardiology, 117(12), 1884–1889.

Jenkins, K. J., Correa, A., Feinstein, J. A., Botto, L., Britt, A. E., Daniels, S. R., Elixson, M., Warnes, C. A., Webb, C. L., & American Heart Association Council on Cardiovascular Disease in the Young (2007). Noninherited risk factors and congenital cardiovascular defects: Current knowledge: A scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: Endorsed by the American Academy of Pediatrics. Circulation, 115(23), 2995–3014.

Jortveit, J., Øyen, N., Leirgul, E., Fomina, T., Tell, G. S., Vollset, S. E., Eskedal, L., Døhlen, G., Birkeland, S., & Holmstrøm, H. (2016). Trends in mortality of congenital heart defects. Congenital Heart Disease, 11(2), 160–168.

Kalaĭdzhieva, M., Popivanova, A., Doĭcheva, E., Nikolov, A., & Dimitgrov, A. (2003). Maichin diabet i vrodeni malformatsii na novorodenoto [Maternal insulin-dependent diabetes and congenital malformations in the newborn]. Akusherstvo i Ginekologiia (Sofiia), 42(3), 3–5 (in Bulgarian).

Kazaura, M., Lie, R. T., & Skjaerven, R. (2004). Paternal age and the risk of birth defects in Norway. Annals of Epidemiology, 14(8), 566–570.

Kim, J., Swartz, M. D., Langlois, P. H., Romitti, P. A., Weyer, P., Mitchell, L. E., Luben, T. J., Ramakrishnan, A., Malik, S., Lupo, P. J., Feldkamp, M. L., Meyer, R. E., Winston, J. J., Reefhuis, J., Blossom, S. J., Bell, E., Agopian, A. J., & National Birth Defects Prevention Study (2017). Estimated maternal pesticide exposure from drinking water and heart defects in offspring. International Journal of Environmental Research and Public Health, 14(8), 889.

Kourtis, A. P., Read, J. S., & Jamieson, D. J. (2014). Pregnancy and infection. New England Journal of Medicine, 370(23), 2211–2218.

Lee, L. J., & Lupo, P. J. (2013). Maternal smoking during pregnancy and the risk of congenital heart defects in offspring: A systematic review and metaanalysis. Pediatric Cardiology, 34(2), 398–407.

Li, H., Luo, M., Zheng, J., Luo, J., Zeng, R., Feng, N., Du, Q., & Fang, J. (2017). An artificial neural network prediction model of congenital heart disease based on risk factors: A hospital-based case-control study. Medicine (Baltimore), 96(6), e6090.

Li, M. M., Guo, L. Q., Li, S. S., Zhang, Q., Zhao, D. D., Zhang, B. Y., Dang, S. N., & Yan, H. (2018). [Association between congenital heart disease and medication taken during pregnancy among women of childbearing age]. Zhonghua Liu Xing Bing Xue Za Zhi, 39(10), 1333–1338 (in Chinese).

Li, X., Liu, Z., Deng, Y., Li, S., Mu, D., Tian, X., Lin, Y., Yang, J., Li, J., Li, N., Wang, Y., Chen, X., Deng, K., & Zhu, J. (2015). Modification of the association between maternal smoke exposure and congenital heart defects by polymorphisms in glutathione-S-transferase genes. Scientific Reports, 5, 14915.

Liang, J. J., Huang, C. X., Yang, B., Huang, H., Wan, J., Tang, Y. H., & Zhao, Q. Y. (2009). Depressive symptoms and risk factors in Chinese patients with premature ventricular contractions without structural heart disease. Clinical Cardiology, 32(11), E11–E17.

Liu, S., Joseph, K. S., Lisonkova, S., Rouleau, J., Van den Hof, M., Sauve, R., Kramer, M. S. & Canadian Perinatal Surveillance System (Public Health Agency of Canada) (2013). Association between maternal chronic conditions and congenital heart defects: A population-based cohort study. Circulation, 128(6), 583–589.

Liu, S., Liu, J., Tang, J., Ji, J., Chen, J., & Liu, C. (2009). Environmental risk factors for congenital heart disease in the Shandong Peninsula, China: A hospital-based case-control study. Journal of Epidemiology, 19(3), 122–130.

Liu, Y., Chen, S., Zühlke, L., Black, G. C., Choy, M. K., Li, N., & Keavney, B. D. (2019). Global birth prevalence of congenital heart defects 1970–2017: Updated systematic review and meta-analysis of 260 studies. International Journal of Epidemiology, 48(2), 455–463.

Liu, Y., Zhu, B., Zhuo, L., He, M. Y., Xu, Y., Wang, T. T., Cai, Q. Q., Hu, B., Xu, J. C., & Zhang, W. H. (2017). [Risk factors for congenital heart disease in Chinese neonates: A meta analysis]. Zhongguo Dang Dai Er Ke Za Zhi, 19(7), 754–758 (in Chinese).

Malik, S., Cleves, M. A., Honein, M. A., Romitti, P. A., Botto, L. D., Yang, S., Hobbs, C. A, & National Birth Defects Prevention Study (2008). Maternal smoking and congenital heart defects. Pediatrics, 121(4), e810–e816.

Mandalenakis, Z., Rosengren, A., Skoglund, K., Lappas, G., Eriksson, P., & Dellborg, M. (2016). Survivorship in children and young adults with congenital heart disease in Sweden. JAMA Internal Medicine, 177(2), 224–230.

Martínez-Frías, M. L., Bermejo, E., Rodríguez-Pinilla, E., & Frías, J. L. (2004). Risk for congenital anomalies associated with different sporadic and daily doses of alcohol consumption during pregnancy: A case-control study. Birth Defects Research. Part A, Clinical and Molecular Teratology, 70(4), 194–200.

Mateja, W. A., Nelson, D. B., Kroelinger, C. D., Ruzek, S., & Segal, J. (2012). The association between maternal alcohol use and smoking in early pregnancy and congenital cardiac defects. Journal of Women’s Health, 21(1), 26–34.

Miller, A., Riehle-Colarusso, T., Siffel, C., Frías, J. L., & Correa, A. (2011). Maternal age and prevalence of isolated congenital heart defects in an urban area of the United States. American Journal of Medical Genetics. Part A, 155A(9), 2137–2145.

Moons, P., Bovijn, L., Budts, W., Belmans, A., & Gewillig, M. (2010). Temporal trends in survival to adulthood among patients born with congenital heart disease from 1970 to 1992 in Belgium. Circulation, 122(22), 2264–2272.

Nicoll, R. (2018). Environmental contaminants and congenital heart defects: A re–evaluation of the evidence. International Journal of Environmental Research and Public Health, 15(10), 2096.

Nie, Z. Q., Ou, Y. Q., Chen, J. M., Liu, X. Q., Mai, J. Z., Gao, X. M., Wu, Y., & Zhuang, J. (2013). [Risk factors of congenital heart defects in fetal and infants born from 2004 to 2011 in Guangdong]. Zhonghua Xin Xue Guan Bing Za Zhi, 41(8), 704–708 (in Chinese).

Nielsen, G. L., Nørgard, B., Puho, E., Rothman, K. J., Sørensen, H. T., & Czeizel, A. E. (2005). Risk of specific congenital abnormalities in offspring of women with diabetes. Diabetic Medicine, 22(6), 693–696.

Nold, J. L., & Georgieff, M. K. (2004). Infants of diabetic mothers. Pediatric Clinics of North America, 51(3), 619–637.

Ou, Y., Mai, J., Zhuang, J., Liu, X., Wu, Y., Gao, X., Nie, Z., Qu, Y., Chen, J., Kielb, C., Lauper, U., & Lin, S. (2016). Risk factors of different congenital heart defects in Guangdong, China. Pediatric Research, 79(4), 549–558.

Peng, J., Meng, Z., Zhou, S., Zhou, Y., Wu, Y., Wang, Q., Wang, J., & Sun, K. (2019). The non-genetic paternal factors for congenital heart defects: A systematic review and meta-analysis. Clinical Cardiology, 42(7), 684–691.

Polifka, J. E., & Friedman, J. M. (2002). Medical genetics: 1. Clinical teratology in the age of genomics. Canadian Medical Association Journal, 167(3), 265–273.

Rappazzo, K. M., Warren, J. L., Meyer, R. E., Herring, A. H., Sanders, A. P., Brownstein, N. C., & Luben, T. J. (2016). Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort. Birth Defects Research. Part A, Clinical and Molecular Teratology, 106(4), 240–249.

Roest, P. A., van Iperen, L., Vis, S., Wisse, L. J., Poelmann, R. E., Steegers-Theunissen, R. P., Molin, D. G., Eriksson, U. J., & Gittenberger-De Groot, A. C. (2007). Exposure of neural crest cells to elevated glucose leads to congenital heart defects, an effect that can be prevented by N-acetylcysteine. Birth Defects Research. Part A, Clinical and Molecular Teratology, 79(3), 231–235.

Rosamond, W., Flegal, K., Friday, G., Furie, K., Go, A., Greenlund, K., Haase, N., Ho, M., Howard, V., Kissela, B., Kittner, S., Lloyd-Jones, D., McDermott, M., Meigs, J., Moy, C., Nichol, G., O’Donnell, C. J., Roger, V., Rumsfeld, J., Sorlie, P., Steinberger, J., Thom, T., Wasserthiel-Smoller, S., Hong, Y, & American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2007). Heart disease and stroke statistics – 2007 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation, 115(5), e69–171.

Rufer, E. S., Hacker, T. A., Flentke, G. R., Drake, V. J., Brody, M. J., Lough, J., & Smith, S. M. (2010). Altered cardiac function and ventricular septal defect in avian embryos exposed to low-dose trichloroethylene. Toxicological Sciences, 113(2), 444–452.

Saxena, A. (2018). Congenital heart disease in India: A status report. Indian Pediatrics, 55(12), 1075–1082.

Scanlon, K. S., Ferencz, C., Loffredo, C. A., Wilson, P. D., Correa-Villasenõr, A., Khoury, M. J., & Willett, W. C. (1998). Preconceptional folate intake and malformations of the cardiac outflow tract. Baltimore-Washington Infant Study Group. Epidemiology, 9, 95–98.

Selevan, S. G., Kimmel, C. A., & Mendola, P. (2000). Identifying critical windows of exposure for children’s health. Environmental Health Perspectives, 108(Suppl 3), 451–455.

Shi, Q. Y., Zhang, J. B., Mi, Y. Q., Song, Y., Ma, J., & Zhang, Y. L. (2014). Congenital heart defects and maternal fever: Systematic review and meta-analysis. Journal of Perinatology, 34(9), 677–682.

Shillingford, A. J., & Weiner, S. (2001). Maternal issues affecting the fetus. Clinics in Perinatology, 28(1), 31–70.

Smitha, R., Karat, S. C., Narayanappa, D., Krishnamurthy, B., Prasanth, S. N., & Ramachandra, B. (2006). Prevalence of congenital heart diseases in Mysore. Indian Journal of Human Genetics, 12(1), 11–16.

Steel, Z., Marnane, C., Iranpour, C., Chey, T., Jackson, J. W., Patel, V., & Silove, D. (2014). The global prevalence of common mental disorders: A systematic review and meta-analysis 1980–2013. International Journal of Epidemiology, 43(2), 476–493.

Su, X. J., Yuan, W., Huang, G. Y., Olsen, J., & Li, J. (2015). Paternal age and offspring congenital heart defects: A national cohort study. PLoS One, 10(3), e0121030.

Tanner, J. P., Salemi, J. L., Stuart, A. L., Yu, H., Jordan, M. M., DuClos, C., Cavicchia, P., Correia, J. A., Watkins, S. M., & Kirby, R. S. (2015). Associations between exposure to ambient benzene and PM (2.5) during pregnancy and the risk of selected birth defects in offspring. Environmental Research, 142, 345–353.

Tegethoff, M., Greene, N., Olsen, J., Schaffner, E., & Meinlschmidt, G. (2011). Stress during pregnancy and offspring pediatric disease: A national cohort study. Environmental Health Perspectives, 119(11), 1647–1652.

Van der Lugt, N. M., van de Maat, J. S., van Kamp, I. L., Knoppert-van der Klein, E. A., Hovens, J. G., & Walther, F. J. (2012). Fetal, neonatal and developmental outcomes of lithium-exposed pregnancies. Early Human Development, 88(6), 375–378.

Vrijheid, M., Dolk, H., Stone, D., Abramsky, L., Alberman, E., & Scott, J. E. (2000). Socioeconomic inequalities in risk of congenital anomaly. Archives of Disease in Childhood, 82(5), 349–352.

Wheeler, S. M., Dotters-Katz, S., Heine, R. P., Grotegut, C. A., & Swamy, G. K. (2015). Maternal effects of respiratory syncytial virus infection during pregnancy. Emerging Infectious Diseases, 21(11), 1951–1955.

Wren, C., Irving, C. A., Griffiths, J. A., O’Sullivan, J. J., Chaudhari, M. P., Haynes, S. R., Smith, J. H., Hamilton, J. R., & Hasan, A. (2012). Mortality in infants with cardiovascular malformations. European Journal of Pediatrics, 171(2), 281–287.

Wren, C., Reinhardt, Z., & Khawaja, K. (2008). Twenty-year trends in diagnosis of life-threatening neonatal cardiovascular malformations. Archives of Disease in Childhood. Fetal and Neonatal Edition, 93(1), F33–F35.

Wu, W., He, J., & Shao, X. (2020). Incidence and mortality trend of congenital heart disease at the global, regional, and national level, 1990–2017. Medicine (Baltimore), 99(23), e20593.

How to Cite
Lastivka, I. V., Pishak, V. P., RyznychukМ. О., & KhmaraТ. V. (2020). Risk factor analysis for congenital heart defects in children . Regulatory Mechanisms in Biosystems, 11(4), 524-530. https://doi.org/10.15421/022080

Most read articles by the same author(s)