Globally, congenital heart anomalies (CHA) represent a significant burden of disease, contributing to substantial morbidity and mortality, particularly among pediatric populations (1–3). In 2019, there were 8.52 million cases and 0.55 million fatalities attributed to congenital birth defects, with CHAs constituting the predominant group globally (4). The impact of CHA extends beyond individual health, affecting families, healthcare systems, and society at large (5–7). The burden of CHA is not uniformly distributed, it exhibits sex disparities, age variations, and significant regional and national differences (8). Understanding the uneven distribution of CHA across different Socio-demographic Index (SDI) regions, sex, and age groups is crucial for developing targeted interventions to address these disparities (9).

CHAs are the most common type of birth defect, and their management is a critical component of global child health initiatives (10). International policies, such as the Sustainable Development Goals (SDG) set by the World Health Organization (WHO), aim to reduce neonatal and under-five mortality rates (11), which are directly influenced by the prevalence and outcomes of CHA. Efforts to improve prenatal care, screening, and access to pediatric cardiac care are essential in mitigating the disease burden (12, 13). The prevention of congenital birth defects necessitates a multifaceted approach that encompasses prenatal screening, nutritional support, vaccination programs, and the avoidance of detrimental exposures (14). Prenatal screening, which includes ultrasound and blood testing, is instrumental in identifying potential fetal abnormalities early in gestation, allowing for early decision-making and possible corrective measures. Low-resource settings often lack access to advanced diagnostics (e.g., fetal echocardiography, genetic screening), leading to underreporting of mild/asymptomatic cases and delayed interventions. In high-SDI regions, improved diagnostics increase detected prevalence but reduce mortality through early management (15).

Nutritional supplementation is also paramount, with a particular emphasis on folic acid and iodine (16). The study suggests that maternal folic acid supplementation before pregnancy is associated with a reduced risk of congenital heart defects, and lower dietary folate intake during pregnancy is linked to an increased risk of CHDs (17). Preconception folic acid supplementation and adequate dietary folate intake are crucial for the prevention of congenital heart defects (18).

Pregnant women should abstain from alcohol, tobacco, and illicit drugs, as these substances can elevate the risk of birth defects (19). Maintaining a healthy lifestyle, replete with a balanced diet and regular physical activity, is supportive of maternal health and avoiding CHA (20).

The significance of our study lies in its ability to provide insights into the changing landscape of CHA and its impact on global health. Our findings reveal that incidence and years lived with disability (YLDs) increase with higher SDI, indicating a complex relationship between economic development and health outcomes. Additionally, the higher disability-adjusted life years (DALYs) and years of life lost (YLLs) among males compared to females underscore the need for sex-specific health policies. By examining these trends, we can better allocate resources and develop strategies to reduce the global burden of CHA.

The study builds on this foundation by examining long-term trends and the impact of policy changes on the incidence and mortality of CHA. Additionally, the study provides insights into the potential future trends of disease burdens attributable to CHA, emphasizing the need for continued vigilance and intervention strategies to mitigate the impact of these conditions. Through this comprehensive analysis, we aim to contribute to the body of knowledge on CHA and inform future policy and research directions.

The GBD 2021 analysis provides critical insights into the evolving burden of congenital heart anomalies. Global trends from 1990 to 2021 show that congenital heart anomalies had stable global prevalence and incidence but declining mortality, DALYs, and YLLs. Males had higher fatality rates, especially in low - SDI regions. YLDs increased significantly in non - high - SDI areas, indicating a shift to a disability - driven burden. Regionally, South Asia had the most cases in 2021 (1.75M females/1.58M males). Western Sub - Saharan Africa had the fastest incidence growth and rising DALYs/YLLs. Sex disparities grew in Latin America. Mortality fell in 97% of 204 countries, but disability (YLDs) worsened in 50%. SDI correlations: Higher SDI quintiles were associated with rising prevalence/YLDs (r > 0.64) but falling incidence/mortality (r < −0.6). Children aged 0–4 were the most vulnerable across all SDI levels. Projections to 2050 suggest a 500% increase in global cases among 0–4 - year - olds (to 25.2M), with slowly declining mortality and sharply rising YLDs. This shows an epidemiological transition from a lethal to a disabling disease. Low - SDI regions face high incidence, while middle/high - SDI regions deal with increasing disability. Targeted child - focused interventions are needed in poor areas, and disability management in developed economies.

Previous research on CHA has not consistently examined the disease burden from 1990 to 2021 through the lens of sex, age, and SDI (1, 8, 9). Our study addresses this omission, offering a comprehensive overview of CHA's global impact during this period, with detailed analysis across sex, age groups, SDI regions, and countries. It also projects prevalence, mortality, DALYs, YLDs, and YLLs for different age groups from 2022 to 2050, including specific predicted numerical values. This in-depth analysis offers fresh insights into CHA's global public health and informs future health policy and resource allocation.

The findings indicate that CHA prevalence and incidence remained largely stable from 1990 to 2021, with a minor increase. The ASPR rose slightly from 209.53 (186.4–231.49) to 210.7 (187.92–232.48), and the ASIR increased marginally from 36.88 (29.06–47.82) to 37.18 (29.31–47.96). In low SDI areas, age-standardized incidence rates slightly dipped from 45 (35.47–58.74) to 44.28 (34.88–57.33), but remained elevated, indicating a need for targeted interventions to reduce CHA incidence (25, 26). Age-standardized mortality and DALY rates saw a significant drop, from 8.51 (5.01–10.9) to 3.86 (3.19–4.7) and from 750.3 (440.94–960.11) to 345.24 (288.34–422.16), respectively. High SDI areas showed a more pronounced decline in death rates and age-standardized DALY rates, reflecting improved CHA treatment worldwide (5, 27, 28). In 2021, global female CHA prevalence rates were higher at 217.2 (193.26–240.16) compared to males at 204.17 (181.75–225.77), yet female death rates were lower at 3.51 (2.74–4.29) compared to males at 4.18 (3.31–5.42). This could suggest higher susceptibility in male, a protective role for estrogen (29, 30), or superior treatment adherence in female (31). From 1990 to 2021, CHA deaths in South Asia fell significantly, from 115.43 (72.64–154.22) thousand to 57.26 (41.72–78.5) thousand. East Asia is projected to experience the steepest decline in future mortality, with an EAPC of −5.02 (−5.28 to −4.76). The downward death rate trend across all SDI regions points to advancements in CHA treatment, improved public health policies, and better socioeconomic conditions (32, 33). Globally, the disease burden is highest in CHA patients aged 0–4, decreasing with age, except in high SDI regions where advanced medical facilities and treatments have led to improved survival rates, allowing patients to live longer and thus not showing a significant age-related prevalence decline (34). CHA prevalence and YLDs rise with SDI, while incidence, mortality, DALYs, and YLLs fall. Improved diagnostics have led to earlier detection of mild or asymptomatic cases, increasing prevalence (35). The increased survival rate of CHA patients has reduced mortality and DALYs, as many now survive to adulthood or old age.

Looking ahead to 2050, our predictions suggest a rise in the occurrence of CHA, particularly among younger individuals. The death rate is projected to decrease gradually, yet the DALYs are expected to see a substantial increase, maintaining an upward trajectory (Figure 7). While global pediatric populations are declining (UNPD 2022), CHA prevalence is rising disproportionately in low/middle-SDI regions due to: higher fertility rates and improving survival (reducing mortality but increasing lifelong disability burden) (36). With the anticipated growth in the global population, especially in regions with low and medium SDI, an increase in the number of CHA cases is likely, potentially raising prevalence rates. This necessitates targeted interventions. Despite the slow decline in mortality, individuals with CHA may still experience disabilities and a diminished quality of life, resulting in a rise in YLDs. Furthermore, as CHA patients age, they are likely to confront health issues associated with aging, further elevating DALYs (37).

Based on our GBD 2021 analysis, we acknowledge that adult congenital heart disease (ACHD) represents a growing clinical challenge as survival into adulthood has dramatically improved. While the GBD framework classifies congenital heart anomalies as a unified entity without explicit ACHD stratification, our findings likely capture this evolving burden. The sustained high DALYs and YLDs observed across older age groups probably reflect ACHD sequelae—including heart failure, arrhythmias, and complications from previous interventions that characterize this population. Geographic variations in burden may mirror disparities in pediatric cardiac surgical access and lifelong ACHD care infrastructure, which significantly influence outcomes. Recent registry data confirm the ACHD population is expanding and aging, with substantial numbers now surviving beyond 60 years. We agree that future studies should incorporate specific ACHD classifications and age-stratified analyses to better characterize this population's unique burden, as current global health metrics may underestimate the true impact of lifelong complications in ACHD patients who now routinely survive into their sixth and seventh decades.

This study utilizes the most recent GBD 2021 data, providing a more accurate reflection of CHA's current disease burden and enabling more reliable predictions of its future trajectory. We systematically analyzed how sex, age groups, and SDI levels impact CHA across various countries and regions. The EAPC was employed to forecast disease burden trends in different nations, while the BAPC model was used to project CHA disease burden from 2022 to 2050.

There are some limitations in our study: (1) a limitation of this study is its reliance on the BAPC model alone; it did not incorporate ARMIA or Nordped for a broader comparison of future CHA disease burden predictions (38–40). (2) Global diagnostic coverage disparities, (3) birth registration gaps, and (4) interconnected health conditions. As referenced (https://www.OurWorldinData.org), accurate neonatal diagnostics (ultrasound, genomic screening) remain highly inequitable—widely available in high-income countries but critically limited in LMICs, contributing to delayed diagnoses and higher mortality. Significant birth under-registration, particularly in sub-Saharan Africa and South Asia, compromises data accuracy and obscures true disease burden. Additionally, neonatal mortality is intrinsically linked to infections, congenital disorders, and maternal complications, with premature birth being the leading cause of child mortality globally. These diagnostic and registration gaps in LMICs hinder early detection of interconnected risks, preventing timely interventions and perpetuating preventable deaths.

To encapsulate, this study offers a thorough analysis of the global disease burden of CHA and its anticipated trends over the coming decades. The findings underscore the importance of devising health strategies tailored to different SDI regions, particularly those with low SDI, to alleviate the disease burden of CHA. With continued research and intervention, we anticipate a reduction in CHA's impact on global child health and an enhancement in the quality of life for patients in the future.