{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T18:11:45Z","timestamp":1778091105419,"version":"3.51.4"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"publisher","award":["2022D01E71"],"award-info":[{"award-number":["2022D01E71"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Top Young Scientific and Technological Talents of the Tianshan Talent Cultivation Program in Xinjiang","award":["2024TSYCCX0101"],"award-info":[{"award-number":["2024TSYCCX0101"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u20132021). 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 1990 to 2021, the global CHA burden declined. While descriptive analysis showed higher raw point estimates for males, a multivariable mixed-effects analysis\u2014adjusted for SDI (as a proxy for macro-level development and health-system context) and temporal trends\u2014confirmed that male sex was significantly associated with a higher CHA burden (DALYs Adjusted Coefficient: 876.4, P\u2009&lt;\u20090.001; Mortality Adjusted Coefficient: 9.7, P\u2009&lt;\u20090.001). 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0348351","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T17:28:10Z","timestamp":1778088490000},"page":"e0348351","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex differences in global burden of Congenital Heart Anomalies in children under five from 1990 to 2021"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-0384","authenticated-orcid":true,"given":"Huasheng","family":"Lv","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengyu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wentao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"pone.0348351.ref001","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"396","author":"GBD 2019 Diseases and Injuries Collaborators","year":"2020","journal-title":"Lancet"},{"key":"pone.0348351.ref002","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019","volume":"76","author":"GA Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"issue":"10303","key":"pone.0348351.ref003","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/S0140-6736(21)01207-1","article-title":"Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019","volume":"398","author":"GBD 2019 Under-5 Mortality Collaborators","year":"2021","journal-title":"Lancet"},{"issue":"3","key":"pone.0348351.ref004","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S2352-4642(19)30402-X","article-title":"Global, regional, and national burden of congenital heart disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"4","author":"GBD 2017 Congenital Heart Disease Collaborators","year":"2020","journal-title":"Lancet Child Adolesc Health"},{"key":"pone.0348351.ref005","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.cjcpc.2023.10.001","article-title":"Global Access to Comprehensive Care for Paediatric and Congenital Heart Disease","volume":"2","author":"D Vervoort","year":"2023","journal-title":"CJC Pediatr Congenit Heart Dis"},{"issue":"2","key":"pone.0348351.ref006","doi-asserted-by":"crossref","DOI":"10.1161\/CIR.0000000000001245","article-title":"Evaluation and Management of Chronic Heart Failure in Children and Adolescents With Congenital Heart Disease: A Scientific Statement From the American Heart Association","volume":"150","author":"S Amdani","year":"2024","journal-title":"Circulation"},{"issue":"43","key":"pone.0348351.ref007","doi-asserted-by":"crossref","first-page":"4533","DOI":"10.1093\/eurheartj\/ehad570","article-title":"Acquired cardiovascular disease in adults with congenital heart disease","volume":"44","author":"M Brida","year":"2023","journal-title":"Eur Heart J"},{"key":"pone.0348351.ref008","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.7189\/jogh.14.04012","article-title":"The congenital birth defects burden in children younger than 14 years of age, 1990 - 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