The Global Burden and Diagnostic Challenges of Undiagnosed Congenital Heart Disease in Resource-Limited Settings: A Comprehensive Review from 2019 to 2025

Background: Congenital Heart Disease (CHD) remains the most prevalent congenital anomaly globally, with approximately 90% of affected neonates born in low- and middle-income countries (LMICs). Despite significant advances in paediatric cardiac care over the preceding decade, a substantial proportion of CHD cases in resource-limited settings evade timely detection, resulting in avoidable morbidity and premature mortality. This systematic review synthesizes contemporary evidence published between 2019 and 2025 to delineate the prevalence, determinants, and consequences of undiagnosed CHD in LMICs, whilst critically evaluating emerging strategies for diagnostic optimization. Methods: A systematic literature search was conducted across PubMed/MEDLINE, Emblaze, Scopus, and the Cochrane Library for peer-reviewed studies published between January 2019 and January 2025. The review adhered to PRISMA guidelines. Forty-five primary studies met predefined eligibility criteria, comprising observational cohorts, cross-sectional analyses, and health systems research investigations focusing on pediatric populations (neonates to 18 years) in World Bank-classified LMICs. Data regarding diagnostic timing, barrier categorization, screening implementation, and clinical outcomes were extracted and subjected to qualitative synthesis. Results: Analysis of 45 studies encompassing diverse geographical regions—including sub-Saharan Africa, Southeast Asia, the Middle East, and Latin America—revealed consistently protracted diagnostic delays, with median age at CHD confirmation ranging from 4 days for critically cyanotic lesions to 98 months for acyanotic defects. Pooled prevalence estimates indicated that 47– 63% of CHD cases in LMICs are diagnosed following the onset of irreversible complications. Congestive heart failure was present in 49.4% of patients at initial presentation, whilst Eisenmenger syndrome complicated 15.8% of delayed left-to-right shunt diagnoses. Three principal barrier domains were consistently identified: (i) infrastructural deficiencies, including absent or non-functional echocardiography services in peripheral facilities; (ii) workforce shortages, with pediatric cardiologist-to-population ratios reaching 1:8 million in several regions; and (iii) socioeconomic constraints, including prohibitive out-of-pocket expenditure and geographical maldistribution of specialized centres. Contemporary studies evaluating pulse oximetry screening demonstrated high diagnostic accuracy (sensitivity 76– 93%, specificity 99.4%) for critical CHD; however, implementation fidelity was compromised by absent referral infrastructure and inadequate postnatal follow-up. Conclusion: This systematic review confirms that undiagnosed CHD in resource-limited settings constitutes a persisting public health emergency, characterized by predictable diagnostic delays and preventable clinical deterioration. The evidence synthesis identifies actionable targets for health system strengthening, including mandatory pulse oximetry integration, task-shifting to non-specialist providers, and decentralized tele-echocardiography networks. Without urgent, context-appropriate intervention, the diagnostic gap will continue to exact an unacceptable toll on pediatric populations in LMICs.