Unveiling the Burden of Prevalence of Congenital Heart Defects in Down Syndrome Patients in Indonesia: A Systematic Review and Meta-analysis
Keywords:
paediatrics, meta-analysis, Indonesia, Down syndrome, congenital heart defects
Abstract
Down syndrome or trisomy 21 is frequently accompanied by Congenital Heart Disease (CHD), which is a major cause of mortality and morbidity within the first two years of life in children with Down Syndrome (DS). This systematic review and meta-analysis aimed to analyze the literature to assess the pooled prevalence of overall CHDs among children with DS in Indonesia. The search was conducted across major databases, including PubMed, Google Scholar, ScienceDirect, Cochrane, and Garuda (an Indonesian database), using Boolean operators and a range of keywords. Citation management was performed using the Rayyan Intelligent Systematic Reviews website (https://www.rayyan.ai/). Quantitative data synthesis was conducted using Comprehensive Meta-Analysis version 4.0 (Biostat, Englewood, NJ, USA). Initially, 1,915 citations were retrieved from the primary search; after screening titles and assessing full texts, a total of 11 articles were included in this study. A total of 1,122 subjects from 11 different studies were analyzed. The overall pooled prevalence of CHDs among children with DS was 44.6% (95% CI: 34.9% to 54.8%). We also found a high degree of heterogeneity between the studies (I² = 88.8%), and inspection of the forest plot revealed that the distribution of the plotted data was asymmetrical. Approximately one in two children with DS in Indonesia has at least one type of CHD. These findings highlight the need for early routine cardiac screening to reduce morbidity and mortality. We recommend further research to provide more data to assess the prevalence of CHD
Downloads
Download data is not yet available.
References
1. Versacci P, Di Carlo D, Digilio MC, Marino B. Cardiovascular disease in Down syndrome. Curr Opin Pediatr [Internet]. 2018 [cited 2024 Oct 11];30(5):616–22. Available from: https://journals.lww.com/co-pediatrics/fulltext/2018/10000/cardiovascular_disease_in_Down_syndrome.5.aspx
2. Sabatini SE, Rahardjo TA, Ulvyana V, Cayami FK, Winarni TI, Utari A, et al. Status antropometri pada anak dengan Sindrom Down di Indonesia: Kurva Sindrom Down versus kurva internasional. Sari Pediatri [Internet]. 2022 Jun 29 [cited 2024 Oct 11];24(1):44–50. Available from: https://saripediatri.org/index.php/sari-pediatri/article/view/2127
3. Benhaourech S, Drighil A, El Hammiri A. Congenital heart disease and Down syndrome: various aspects of a confirmed association. Cardiovasc J Afr [Internet]. 2016 [cited 2024 Oct 11];27(5):287–90. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370349/
4. Jain S. Congenital heart disease: saving lives and securing liveliness with early primary care and expert family care. J Fam Med Prim Care. 2021;10(9):3178–84.
5. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ [Internet]. 2021 [cited 2024 Oct 14];372:n71. Available from: https://www.bmj.com/content/372/bmj.n71
6. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan: a web and mobile app for systematic reviews. Syst Rev [Internet]. 2016 [cited 2024 Oct 14];5(1):210. Available from: https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-016-0384-4
7. Moola S, Munn Z, Tufanaru C, Aromataris E, Sears K, Sfetcu R, et al. Systematic reviews of etiology and risk. In: Aromataris E, Munn Z, editors. JBI Reviewer’s Manual. The Joanna Briggs Institute; 2017. Available from: https://reviewersmanual.joannabriggs.org/
8. Borenstein M, Hedges L, Higgins J, Rothstein H. Comprehensive Meta-Analysis Version 4. Englewood (NJ): Biostat; 2022.
9. Arifiyah AP. Hubungan antara Insulin-like Growth Factor-1 dengan pertumbuhan dan perkembangan anak Sindrom Down. 2017.
10. Santoso R, Hardaningsih G, Rahmadi FA. Hubungan kadar hormon tiroid dengan perkembangan anak Sindrom Down. Media Medika Muda. 2015;4.
11. Patria SY, Triono A. Health comorbidities in children with Down syndrome at Dr. Sardjito General Hospital, Yogyakarta. Indones J Biomed Clin Sci. 2024;56(3).
12. Gartika MA, et al. Karyotype analyses of Down syndrome children in East Priangan Indonesia. J Int Dent Med Res. 2018.
13. Windiani IGAT, Aryati NMD, Adnyana IGANS, Murti NLSP, Soetjiningsih S. Association of comorbidity with developmental quotient in Down syndrome children. Open Access Maced J Med Sci. 2021;9(B):1484–8.
14. Simamora TR, Patria SY, Wandita S. Congenital heart disease, gastrointestinal defect, and low birth weight as contributing factors for three-year survival among Down syndrome children in Indonesia. Indones J Biomed Sci. 2022;16(2):65–9.
15. Zevanya E, Indrarto W, Lestari D, Widagdo TMM. Maternal age increases the risk of Down syndrome: a case-control study in Yogyakarta. Berk Ilm Kedokteran Duta Wacana. 2024;9(1).
16. Azzahra SR, Utari A, Soetadji A, et al. Clinical characteristics of Down syndrome with congenital heart disease. eJKI [Internet]. 2022 [cited 2024 Oct 14];10(1). Available from: https://doi.org/10.23886/ejki.10.108.33
17. Rajamany T, Kuswiyanto RB, Lubis L. Congenital heart disease among Down syndrome children at Dr. Hasan Sadikin General Hospital. Althea Med J. 2018;5(1):6–11.
18. Hisbiyah Y, Endaryanto A, Setyoboedi B, Rochmah N, Faizi M. Correlation between vitamin D and IFN-γ, NF-κB, thyroid antibodies in Down syndrome. Acta Biomed. 2022;93(6).
19. Hariyanti LR, Widjaja SL, Hidayah D. TNF-α as a predictive factor of pulmonary hypertension in Down syndrome children. Paediatr Indones. 2022;62(1):61–5.
20. Benhaourech S, Drighil A, El Hammiri A. Congenital heart disease and Down syndrome: various aspects of a confirmed association. Cardiovasc J Afr. 2016;27(5):287–90.
21. Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital heart defects in metropolitan Atlanta, 1998–2005. J Pediatr. 2008;153(6):807–13.
22. Santoro SL, Steffensen EH. Congenital heart disease in Down syndrome: temporal changes. J Congenit Cardiol. 2021;5(1).
23. Sharaf R, Garout W, Sharaf R. Prevalence of congenital heart defects in Down syndrome in Saudi Arabia: a systematic review and meta-analysis. Cureus. 2022.
24. Lakhani B, Karkera S, Manahan KJ, Geisler J. Clinical features and cardiac anomalies of children with Down syndrome. Eur J Med Health Res. 2024;2(2):206–19.
25. Bermudez BEBV, Medeiros SL, Bermudez MB, Novadzki IM, Magdalena NIR. Síndrome de Down: Prevalência e distribuição de cardiopatia congênita no Brasil. Sao Paulo Med J. 2015;133(6):521–4.
26. El-Shazali O. The spectrum of congenital heart defects in infants with Down’s syndrome in Khartoum. J Pediatr Neonatal Care. 2015;2(5).
27. Liu Y, Chen S, Zühlke L, et al. Global prevalence of congenital heart disease in school-aged children: a meta-analysis. BMC Cardiovasc Disord. 2020;20(1).
28. Yuyun MF, Sliwa K, Kengne AP, Mocumbi AO, Bukhman G. Cardiovascular diseases in Sub-Saharan Africa. Glob Heart. 2020;15(1).
29. Sterne JAC, Sutton AJ, Ioannidis JPA, et al. Recommendations for examining and interpreting funnel plot asymmetry. BMJ. 2011;343:d4002.
30. Borenstein M. Software for publication bias. In: Rothstein HR, Sutton AJ, Borenstein M, editors. Publication Bias in Meta-analysis. John Wiley & Sons; 2005. p. 193–220.
31. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Performance of the trim-and-fill method. Stat Med. 2007;26(25):4544–62.
32. Freeman SB, Taft LF, Dooley KJ, et al. Population-based study of congenital heart defects in Down syndrome. J Med Genet. 1998;80.
33. Kim MA, Lee YS, Yee NH, et al. Prevalence of congenital heart defects in Down syndrome in Korea. J Korean Med Sci. 2014;29(11):1544–9.
34. Knowles RL, Ridout D, Crowe S, et al. Ethnic and socioeconomic variation in congenital heart defect incidence. Arch Dis Child. 2017;102(6):496–502.
35. Backes CH, Hill KD, Shelton EL, et al. Patent ductus arteriosus: a contemporary perspective. J Am Heart Assoc. 2022;11(17):e025784.
36. Hill GD, Block JR, Tanem JB, Frommelt MA. Disparities in prenatal detection of critical congenital heart disease. Prenat Diagn. 2015;35(9):859–63.
2. Sabatini SE, Rahardjo TA, Ulvyana V, Cayami FK, Winarni TI, Utari A, et al. Status antropometri pada anak dengan Sindrom Down di Indonesia: Kurva Sindrom Down versus kurva internasional. Sari Pediatri [Internet]. 2022 Jun 29 [cited 2024 Oct 11];24(1):44–50. Available from: https://saripediatri.org/index.php/sari-pediatri/article/view/2127
3. Benhaourech S, Drighil A, El Hammiri A. Congenital heart disease and Down syndrome: various aspects of a confirmed association. Cardiovasc J Afr [Internet]. 2016 [cited 2024 Oct 11];27(5):287–90. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370349/
4. Jain S. Congenital heart disease: saving lives and securing liveliness with early primary care and expert family care. J Fam Med Prim Care. 2021;10(9):3178–84.
5. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ [Internet]. 2021 [cited 2024 Oct 14];372:n71. Available from: https://www.bmj.com/content/372/bmj.n71
6. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan: a web and mobile app for systematic reviews. Syst Rev [Internet]. 2016 [cited 2024 Oct 14];5(1):210. Available from: https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-016-0384-4
7. Moola S, Munn Z, Tufanaru C, Aromataris E, Sears K, Sfetcu R, et al. Systematic reviews of etiology and risk. In: Aromataris E, Munn Z, editors. JBI Reviewer’s Manual. The Joanna Briggs Institute; 2017. Available from: https://reviewersmanual.joannabriggs.org/
8. Borenstein M, Hedges L, Higgins J, Rothstein H. Comprehensive Meta-Analysis Version 4. Englewood (NJ): Biostat; 2022.
9. Arifiyah AP. Hubungan antara Insulin-like Growth Factor-1 dengan pertumbuhan dan perkembangan anak Sindrom Down. 2017.
10. Santoso R, Hardaningsih G, Rahmadi FA. Hubungan kadar hormon tiroid dengan perkembangan anak Sindrom Down. Media Medika Muda. 2015;4.
11. Patria SY, Triono A. Health comorbidities in children with Down syndrome at Dr. Sardjito General Hospital, Yogyakarta. Indones J Biomed Clin Sci. 2024;56(3).
12. Gartika MA, et al. Karyotype analyses of Down syndrome children in East Priangan Indonesia. J Int Dent Med Res. 2018.
13. Windiani IGAT, Aryati NMD, Adnyana IGANS, Murti NLSP, Soetjiningsih S. Association of comorbidity with developmental quotient in Down syndrome children. Open Access Maced J Med Sci. 2021;9(B):1484–8.
14. Simamora TR, Patria SY, Wandita S. Congenital heart disease, gastrointestinal defect, and low birth weight as contributing factors for three-year survival among Down syndrome children in Indonesia. Indones J Biomed Sci. 2022;16(2):65–9.
15. Zevanya E, Indrarto W, Lestari D, Widagdo TMM. Maternal age increases the risk of Down syndrome: a case-control study in Yogyakarta. Berk Ilm Kedokteran Duta Wacana. 2024;9(1).
16. Azzahra SR, Utari A, Soetadji A, et al. Clinical characteristics of Down syndrome with congenital heart disease. eJKI [Internet]. 2022 [cited 2024 Oct 14];10(1). Available from: https://doi.org/10.23886/ejki.10.108.33
17. Rajamany T, Kuswiyanto RB, Lubis L. Congenital heart disease among Down syndrome children at Dr. Hasan Sadikin General Hospital. Althea Med J. 2018;5(1):6–11.
18. Hisbiyah Y, Endaryanto A, Setyoboedi B, Rochmah N, Faizi M. Correlation between vitamin D and IFN-γ, NF-κB, thyroid antibodies in Down syndrome. Acta Biomed. 2022;93(6).
19. Hariyanti LR, Widjaja SL, Hidayah D. TNF-α as a predictive factor of pulmonary hypertension in Down syndrome children. Paediatr Indones. 2022;62(1):61–5.
20. Benhaourech S, Drighil A, El Hammiri A. Congenital heart disease and Down syndrome: various aspects of a confirmed association. Cardiovasc J Afr. 2016;27(5):287–90.
21. Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital heart defects in metropolitan Atlanta, 1998–2005. J Pediatr. 2008;153(6):807–13.
22. Santoro SL, Steffensen EH. Congenital heart disease in Down syndrome: temporal changes. J Congenit Cardiol. 2021;5(1).
23. Sharaf R, Garout W, Sharaf R. Prevalence of congenital heart defects in Down syndrome in Saudi Arabia: a systematic review and meta-analysis. Cureus. 2022.
24. Lakhani B, Karkera S, Manahan KJ, Geisler J. Clinical features and cardiac anomalies of children with Down syndrome. Eur J Med Health Res. 2024;2(2):206–19.
25. Bermudez BEBV, Medeiros SL, Bermudez MB, Novadzki IM, Magdalena NIR. Síndrome de Down: Prevalência e distribuição de cardiopatia congênita no Brasil. Sao Paulo Med J. 2015;133(6):521–4.
26. El-Shazali O. The spectrum of congenital heart defects in infants with Down’s syndrome in Khartoum. J Pediatr Neonatal Care. 2015;2(5).
27. Liu Y, Chen S, Zühlke L, et al. Global prevalence of congenital heart disease in school-aged children: a meta-analysis. BMC Cardiovasc Disord. 2020;20(1).
28. Yuyun MF, Sliwa K, Kengne AP, Mocumbi AO, Bukhman G. Cardiovascular diseases in Sub-Saharan Africa. Glob Heart. 2020;15(1).
29. Sterne JAC, Sutton AJ, Ioannidis JPA, et al. Recommendations for examining and interpreting funnel plot asymmetry. BMJ. 2011;343:d4002.
30. Borenstein M. Software for publication bias. In: Rothstein HR, Sutton AJ, Borenstein M, editors. Publication Bias in Meta-analysis. John Wiley & Sons; 2005. p. 193–220.
31. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Performance of the trim-and-fill method. Stat Med. 2007;26(25):4544–62.
32. Freeman SB, Taft LF, Dooley KJ, et al. Population-based study of congenital heart defects in Down syndrome. J Med Genet. 1998;80.
33. Kim MA, Lee YS, Yee NH, et al. Prevalence of congenital heart defects in Down syndrome in Korea. J Korean Med Sci. 2014;29(11):1544–9.
34. Knowles RL, Ridout D, Crowe S, et al. Ethnic and socioeconomic variation in congenital heart defect incidence. Arch Dis Child. 2017;102(6):496–502.
35. Backes CH, Hill KD, Shelton EL, et al. Patent ductus arteriosus: a contemporary perspective. J Am Heart Assoc. 2022;11(17):e025784.
36. Hill GD, Block JR, Tanem JB, Frommelt MA. Disparities in prenatal detection of critical congenital heart disease. Prenat Diagn. 2015;35(9):859–63.
Published
2026-03-31
Views & Downloads
Abstract views: 109
PDF downloads: 10
PDF downloads: 10
How to Cite
Saini, P., Yunita, L., & Fernandez, S. (2026). Unveiling the Burden of Prevalence of Congenital Heart Defects in Down Syndrome Patients in Indonesia: A Systematic Review and Meta-analysis. Indonesian Journal of Cardiology, 47(1). https://doi.org/10.30701/ijc.1836
Section
Review Article
Copyright (c) 2026 Indonesian Journal of Cardiology
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
