Preview

Complex Issues of Cardiovascular Diseases

Advanced search

ANALYSIS OF FACTORS AFFECTING THE FORMATION OF CONGENITAL HEART DEFECTS IN CHILDREN (LITERARY REVIEW)

https://doi.org/10.17802/2306-1278-2025-14-3-112-120

Abstract

Highlights

  • Specific associations between specific risk factors and types of CHD have been identified, which allows differentiating high-risk groups.
  • Pathogenetic mechanisms of the influence of maternal factors on the formation of congenital heart defects, including placental dysfunction, have been established.
  • The need for comprehensive prevention, including pregravid correction of modifiable factors and optimization of prenatal screening in the formed risk groups, has been substantiated.

 

Abstract

The article presents a comprehensive analysis of risk factors for the development of congenital heart defects (CHD) in children associated with the health status of the mother and environmental exposure. The main attention is paid to the mechanisms of influence of somatic pathology of the mother, including metabolic disorders (diabetes mellitus, obesity), pregnancy complications (preeclampsia) and environmental factors on the processes of cardiogenesis. The key pathogenetic pathways are considered, including placental function disorders, epigenetic changes and oxidative stress. Particular importance is attached to the analysis of the relationship between specific risk factors and types of developing heart defects. Modern approaches to the prevention of CHD are presented, including pregravid preparation, correction of modifiable risk factors and improvement of prenatal diagnostic methods. The importance of an interdisciplinary approach to reducing the incidence of congenital cardiac pathology is emphasized.

About the Authors

Yuliana V. Serezhkina
Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation
Russian Federation

Senior Laboratory Assistant, Department of Faculty Pediatrics, Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation, Samara, Russian Federation



Galina V. Santalova
Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation
Russian Federation

Phd, Professor, Professor, Department of Faculty Pediatrics, Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation, Samara, Russian Federation



Galina Yu. Poretskova
Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation
Russian Federation

PhD, Associate Professor, Head of the Department of Faculty Pediatrics, Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation, Samara, Russian Federation



Victoria G. Tarasova
Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation
Russian Federation

Student, Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation, Samara, Russian Federation



Elena V. Barinova
Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation
Russian Federation

Student, Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation, Samara, Russian Federation



References

1. Sharipova Z.U., Ahrarova N.A., Umarova M.S. Osobennosti techeniya posleoperatsionnogo perioda u detey s vrozhdennymi porokami serdtsa. Science and innovation. 2024; 3 (Special Issue 54): 408-413. doi: 10.5281/zenodo.14185925. (In Russian)

2. Saperova E.V., Vahlova I.V. Vrozhdennye poroki serdtsa u detey: rasprostranennost', faktory riska, smertnost'. Voprosy sovremennoy pediatrii. 2017; 16(2): 126-133. (In Russian)

3. Santalova G.V., Shorokhov S.E., Stadler E.R., Avramenko A.A., Gorbunova A.V., Nurullina A.V. Kriticheskie vrozhdennye poroki serdtsa novorozhdennykh. Voprosy prakticheskoy pediatrii. 2019; 14(5): 78-86. doi: 10.20953/1817-7646-2019-5-76-86. (In Russian)

4. Zubrzycki M., Schramm R., Costard-Jäckle A., Grohmann J., Gummert J.F., Zubrzycka M. Cardiac Development and Factors Influencing the Development of Congenital Heart Defects (CHDs): Part I. Int J Mol Sci. 2024;25(13):7117. doi:10.3390/ijms25137117.

5. Villavicencio-Guzmán L., Sánchez-Gómez C., Jaime-Cruz R., Ramírez-Fuentes T.C., Patiño-Morales C.C., Salazar-García M. Human Heart Morphogenesis: A New Vision Based on In Vivo Labeling and Cell Tracking. Life. 2023;13:165. doi:10.3390/life13010165.

6. Courtney J.A., Cnota J.F., Jones H.N. The Role of Abnormal Placentation in Congenital Heart Disease; Cause, Correlate, or Consequence? Front Physiol. 2018;9:1045. doi: 10.3389/fphys.2018.01045.

7. Cole C.R., Yutzey K.E., Brar A.K., Goessling L.S., Van Vickle-Chavez S.J., Cunningham M.W., Eghtesady P. Congenital Heart Disease Linked to Maternal Autoimmunity against Cardiac Myosin. J Immunol. 2014;192:4074-4082. doi:10.4049/jimmunol.1301264.

8. Salmeri N., Seidenari A., Cavoretto P.I., 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.

9. Ponasenko A.V., Tsepokina A.V. Posttranscriptional regulation in congenital heart disease: the role of miRNA. Complex Issues of Cardiovascular Diseases. 2019;8(3):85-95. doi:10.17802/2306-1278-2019-8-3-85-95. (In Russian)

10. Kelly A.C., Powell T.L., Jansson T. Placental function in maternal obesity. Clin Sci (Lond). 2020;134(8):961-984. doi:10.1042/CS20190266.

11. Artymuk N.V., Tachkova O.A., Shurygin S.N. "Porochchnyy reproduktivnyy krug" ozhireniya: obzor literatury. Doctor.Ru. 2018; (10)154: 22-26. doi: 10.31550/1727-2378-2018-154-10-22-26. (In Russian)

12. Xiao-Xia Wu, Ru-Xiu Ge, Le Huang, Fu-Ying Tian, Yi-Xuan Chen, Lin-Lin Wu, Jian-Min Niu. Maternal Obesity and the Risk of Congenital Heart Defects: the Mediation Effect of Pregestational Diabetes. Preprint 20 April 2021. doi:10.21203/rs.3.rs-430110/v1

13. Liang J. Progress of pregestational diabetes mellitus and congenital heart defects. Int J Pediatr. 2010;37:484-486. doi:10.3760/CMA.J.ISSN.1673-4408.2010.05.014.

14. Chen Z., Mao S., Guo L., Qin J., Yang L.X., Liu Y. Effect of maternal pregestational diabetes mellitus on congenital heart diseases. World J Pediatr. 2022;19:303-314. doi:10.1007/s12519-022-00582-w.

15. Sharifi A., Ekram K., Wali W. The spectrum of congenital heart defects in neonates of diabetic mothers. Pediomaternal Nurs J. 2023;9(2). doi:10.20473/pmnj.v9i2.39020.

16. Chen L., Yang T., Chen L., Wang L., Wang T., Zhao L., Ye Z., Zhang S., Luo L., Zheng Z., Qin J. Risk of congenital heart defects in offspring exposed to maternal diabetes mellitus: An updated systematic review and meta-analysis. Arch Gynecol Obstet. 2019;300:1491-1506. doi:10.1007/s00404-019-05289-4.

17. Ibrahim S., Gaborit B., Lenoir M., Collod-Beroud G., Stefanovic S. Maternal Pre-Existing Diabetes: A Non-Inherited Risk Factor for Congenital Cardiopathies. Int J Mol Sci. 2023;24:16258. doi:10.3390/ijms242316258.

18. Köse S., Sözlü S., Bölükbaşi H., Ünsal N., Gezmen-Karadağ M. Obesity is associated with folate metabolism. Int J Vitam Nutr Res. 2020;90(3-4):353-364. doi:10.1024/0300-9831/a000602.

19. Gu Q., Li Y., Cui Z.L., Luo X.P. Homocysteine, folate, vitamin B12 and B6 in mothers of children with neural tube defects in Xinjiang, China. Acta Paediatr. 2012;101:e486-e490. doi:10.1111/j.1651-2227.2012.02781.x.

20. Mitchell L.E., Long J., Garbarini J., Paluru P., Goldmuntz E. Variants of folate metabolism genes and risk of left-sided cardiac defects. Birth Defects Res A Clin Mol Teratol. 2010;88:48-53. doi:10.1002/bdra.20635.

21. Li F. Folic acid and birth defects. Int J Pediatr. 2019;46:640-643. doi:10.3760/CMA.J.ISSN.1673-4408.2019.09.006.

22. Liu H., Ou J., Chen Y., Chen Q., Luo M., Wang T., Qin J. Association of Maternal Folate Intake and Offspring MTHFD1 and MTHFD2 Genes with Congenital Heart Disease. Nutrients. 2023;15:3502. doi:10.3390/nu15163502.

23. Yelbuz T.M, Waldo K.L, Kumiski D.H, Stadt H.A., Wolfe R.R., Leatherbury L., Kirby M.L. Shortened outflow tract leads to altered cardiac looping after neural crest ablation. Circulation. 2002;106:504-510. doi:10.1161/01.CIR.0000023044.44974.8A.

24. Szymanski P., Klisiewicz A., Lubiszewska B., Lipczyńska M., Konka M., Kuśmierczyk M., Hoffman P. Functional anatomy of tricuspid regurgitation in patients with systemic right ventricles. J Am Soc Echocardiogr. 2010;23:504-510. doi:10.1016/j.echo.2010.02.006.

25. Liu S., Joseph K., Lisonkova S., Rouleau J., Van Den Hof M., Sauve R., Kramer M. Association Between Maternal Chronic Conditions and Congenital Heart Defects: A Population-Based Cohort Study. Circulation. 2013; 128: 583–589. doi:10.1161/CIRCULATIONAHA.112.001054.

26. Kilkenny K., Frishman W. Preeclampsia's Cardiovascular Aftermath: A Comprehensive Review of Consequences for Mother and Offspring. Cardiology in review. 2024. doi:10.1097/CRD.0000000000000639.

27. Tezikov Yu.V., Lipatov I.S., Gogel' L.Yu., Azamatov A.R., Ermetov V.K. Perinatal'nyj podhod k klinicheskoj klassifikacii khronicheskoj placentarnoj nedostatochnosti: standartizaciya diagnostiki i akusherskoj taktiki. Nauka i innovacii v medicine. 2019; 4 (1): 8–15. doi: 10.35693/2500-1388-2019-4-1-8-15. (In Russian)

28. Brodwall K., Leirgul E., Greve G., Vollset S., Holmstrøm H., Tell G., Øyen N. Possible Common Aetiology behind Maternal Preeclampsia and Congenital Heart Defects in the Child: a Cardiovascular Diseases in Norway Project Study. Paediatric and perinatal epidemiology. 2016; 30 (1): 76–85. doi:10.1111/ppe.12252.

29. Liu J., Zhao G., Xie J., Wu S., Li B., Yao J. There is a Strong Association between Early Preeclampsia and Congenital Heart Defects: A Large Population-Based, Retrospective Study. Gynecologic and Obstetric Investigation. 2020; 86: 40–47. doi:10.1159/000506804.

30. Emanuel J., Iannuzzelli A., Venkataraman V. Investigating the Link Between Preeclampsia/Eclampsia in Mothers and Cardiovascular Risk Among Their Neurodivergent Children. Research Posters. 2024. doi:10.31986/issn.2689-0690_rdw.stratford_research_day.141_2024.

31. Lin S., Herdt-Losavio M., Gensburg L., Marshall E., Druschel C. Maternal asthma, asthma medication use, and the risk of congenital heart defects. Birth Defects Res A Clin Mol Teratol. 2009;85:161-168. doi:10.1002/bdra.20523.

32. Szabó A, Mayor R. Mechanisms of neural crest migration. Annu Rev Genet. 2018;52:43-63. doi:10.1146/annurev-genet-120417-031559.

33. Chernova T.M., Timchenko V.N., Pavlova E.B., Barakina E.V. Vrozhdennye krasnukha i kor' v periode global'noy likvidatsii. Pediatria. 2019;98(3):172-179. (In Russin)

34. George S., Viswanathan R., Sapkal G. Molecular aspects of the teratogenesis of rubella virus. Biol Res. 2019;52:47. doi:10.1186/s40659-019-0254-3.

35. Bilz N., Willscher E., Binder H., Böhnke J., Stanifer M.L., Hübner D., Boulant S., Liebert U.G., Claus C. Teratogenic Rubella Virus Alters the Endodermal Differentiation Capacity of Human Induced Pluripotent Stem Cells. Cells. 2019;8:870. doi:10.3390/cells8080870.

36. Priyanka P., Vyas V., Deora S., Nag V.L., Singh K. Epidemiology, etiology and clinical associations of congenital heart disease identified during congenital rubella syndrome surveillance. J Trop Pediatr. 2022;68(6). doi:10.1093/tropej/fmac089.

37. Yazigi A., De Pecoulas A., Vauloup-Fellous C., Grangeot-Keros L., Ayoubi J.M., Picone O. Fetal and neonatal abnormalities due to congenital rubella syndrome: a review of literature. J Matern Fetal Neonatal Med. 2017;30(3):274-278. doi:10.3109/14767058.2016.1169526.

38. Osman M., Zakaria M., Alnofal M., Hamdoun S.A., Alissa M.S. Congenital rubella syndrome: a case report. Int J Contemp Pediatr. 2020;7(4):1-3. doi:10.18203/2349-3291.ijcp20204052.

39. Kuciene .R, Dulskienė V. Selected environmental risk factors and congenital heart defects. Medicina (Kaunas). 2008;44(11):827-832. doi:10.3390/medicina44110104.

40. Shalen E.F, McGrath L.B, Bhamidipati C.M, Garcia I.C., Ramsey K., Broberg C.S., Khan A.M. Substance Use Disorders Are Prevalent in Adults With Congenital Heart Disease and Are Associated With Increased Healthcare Use. Am J Cardiol. 2023;192:24-30. doi:10.1016/j.amjcard.2023.01.012.

41. Cipollone D., Amati F., Carsetti R., Placidi S., Biancolella M., D'Amati G., Novelli G., Siracusa G., Marino B. A multiple retinoic acid antagonist induces conotruncal anomalies, including transposition of the great arteries, in mice. Cardiovasc Pathol. 2006;15:194-202. doi:10.1016/j.carpath.2006.04.001.

42. Liu Y., Xiao A. Epigenetic regulation in neural crest development. Birth Defects Res A Clin Mol Teratol. 2011;91:788-796. doi:10.1002/bdra.20783.

43. Taylor I.M, Wiley M.J, Agur A. Retinoic acid-induced heart malformations in the hamster. Teratology. 1980;21:193-197. doi:10.1002/tera.1420210208.

44. Kuehl K.S, Loffredo C.A. Genetic and environmental influences on malformations of the cardiac outflow tract. Expert Rev Cardiovasc Ther. 2005;3:1125-1130. doi:10.1586/14779072.3.6.1125.

45. Loffredo C.A, Silbergeld E.K, Ferencz C., Zhang J. Association of transposition of the great arteries in infants with maternal exposures to herbicides and rodenticides. Am J Epidemiol. 2001;153:529-536. doi:10.1093/aje/153.6.529.

46. Shabaldin A.V., Tsepokina A.V., Shmulevich S.A., Tabakaev M.V., Shabaldina E.V. Vliyanie sotsial'nykh, meditsinskikh i ekologicheskikh faktorov na formirovanie sporadicheskikh vrozhdennykh porokov serdtsa. Rossiyskiy vestnik perinatologii i pediatrii. 2018; 63(1): 14–21. doi: 10.21508/1027-4065-2018-63-1-14-21 (In Russian)

47. Yang B., Qu Y., Guo Y., Markevych I., Heinrich J., Bloom M.S., Bai Z., Knibbs L.C., Li S., Chen G. et al. Maternal exposure to ambient air pollution and congenital heart defects in China. Environ Int. 2021;153:106548. doi:10.1016/j.envint.2021.106548

48. Michel S., Atmakuri A., Von Ehrenstein O. Prenatal exposure to ambient air pollutants and congenital heart defects: An umbrella review. Environ Int. 2023;178:108076. doi:10.1016/j.envint.2023.108076.

49. Gorini F., Chiappa E., Gargani L., Picano E. Potential Effects of Environmental Chemical Contamination in Congenital Heart Disease. Pediatr Cardiol. 2014;35:559-568. doi:10.1007/s00246-014-0870-1.

50. Carmichael S., Yang W., Roberts E., Kegley S.E., Padula A.M., English P.B., Lammer E.J., Shaw G.M. Residential agricultural pesticide exposures and risk of selected congenital heart defects among offspring in the San Joaquin Valley of California. Environ Res. 2014;135:133-138. doi:10.1016/j.envres.2014.08.030.

51. Hu C., Huang K., Fang Y., Yang X.J., Ding K., Jiang W., Hua X.G., Huang D.Y., Jiang Z.X., Zhang X.J. Maternal air pollution exposure and congenital heart defects in offspring: A systematic review and meta-analysis. Chemosphere. 2020;253:126668. doi:10.1016/j.chemosphere.2020.126668.


Supplementary files

Review

For citations:


Serezhkina Yu.V., Santalova G.V., Poretskova G.Yu., Tarasova V.G., Barinova E.V. ANALYSIS OF FACTORS AFFECTING THE FORMATION OF CONGENITAL HEART DEFECTS IN CHILDREN (LITERARY REVIEW). Complex Issues of Cardiovascular Diseases. 2025;14(3):112-120. (In Russ.) https://doi.org/10.17802/2306-1278-2025-14-3-112-120

Views: 101


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2306-1278 (Print)
ISSN 2587-9537 (Online)