Sex differences in global burden of Congenital Heart Anomalies in children under five from 1990 to 2021

Abstract

Background Congenital heart anomalies (CHA) significantly contribute to childhood morbidity and mortality worldwide. Understanding sex-specific differences and their association with societal development levels is crucial for formulating effective health strategies. Methods We extracted sex-stratified incidence, mortality, and disability-adjusted life years (DALYs) for CHA among children under five from the Global Burden of Disease Study 2021 for 204 countries and territories (1990–2021). Sex differences were quantified using male-to-female rate ratios with 95% uncertainty intervals. Temporal trends were evaluated using the estimated annual percentage change (EAPC) derived from log-linear regressions. We assessed the association between disease burden and development status using the Sociodemographic Index (SDI). To address confounding variables and geographic clustering, we fitted linear mixed-effects models with sex, SDI, and calendar year as fixed effects and GBD region as a random intercept, reporting adjusted coefficients with 95% confidence intervals. Results From 1990 to 2021, the global CHA burden declined. While descriptive analysis showed higher raw point estimates for males, a multivariable mixed-effects analysis—adjusted for SDI (as a proxy for macro-level development and health-system context) and temporal trends—confirmed that male sex was significantly associated with a higher CHA burden (DALYs Adjusted Coefficient: 876.4, P < 0.001; Mortality Adjusted Coefficient: 9.7, P < 0.001). This suggests a robust male disadvantage independent of socioeconomic status. The highest CHA burdens were observed in Sub-Saharan Africa, Southeast Asia, and South Asia, while improvements in SDI were significantly associated with overall reductions in burden. Conclusion Despite overall reductions in CHA burden, profound regional disparities and observable sex differences persist, especially in resource-limited areas. Policy interventions focusing on gender-sensitive resource allocation, enhanced neonatal screening, and improved surgical access are critical to mitigating these disparities and advancing global pediatric health equity.