{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T21:14:27Z","timestamp":1788815667369,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Global under-5 mortality has fallen sharply since 1990, yet congenital and genetic disorders (ConGDs), spanning structural birth defects and inherited red-cell disorders (hemoglobinopathies and hemolytic anemias), have not previously been assessed as a composite burden. Effective interventions exist, but an implementation gap persists between availability and population-level delivery. We aimed to (1) quantify the temporal shift in the relative importance of ConGDs within under-5 mortality across 204 countries, and (2) apply frontier analysis to estimate avoidable ConGD mortality and identify intervention targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using GBD 2023, we aggregated 13 congenital and genetic causes (9 structural anomalies, 4 hemoglobinopathies and hemolytic anemias) for children under 5 from 1990 to 2023. We calculated age-standardized mortality rates (ASMR), proportional mortality ratios (PMR), and 95% uncertainty intervals (UI). Frontier analysis used log-transformed quantile regression (\u03c4 = 0.05) with natural cubic splines (\n                      <jats:italic>df<\/jats:italic>\n                      = 3) to estimate best-achievable mortality at each Socio-demographic Index (SDI) level.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ConGD ASMR fell 29.4% (105.70 [95% UI 72.44\u2013153.23] to 74.64 [49.50\u2013114.00] per 100,000), far slower than the 64.7% decline in communicable, maternal, neonatal, and nutritional (CMNN) diseases. PMR almost doubled (5.59% [3.78\u20138.20] to 10.28% [6.70\u201315.98]), reflecting differential decline rather than rising incidence. ConGDs moved from the 4th to the 2nd leading cause of under-5 death. ASMR correlated negatively with SDI (\u03c1 = \u2212 0.78); the PMR-SDI relationship was positive but is a compositional artifact of faster all-cause mortality decline at higher SDI. Mortality concentrated neonatally (0-6 days) for structural defects but peaked in early childhood for hemoglobinopathies. Frontier analysis estimated up to 251,423 (95% CI 201,692\u2013289,940) potentially avoidable deaths in 2023 (52.4% of total), with efficiency gaps at every SDI level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Nearly half of ConGD deaths in children under 5 are potentially avoidable. Three priority intervention targets emerge: (1) point-of-care newborn screening scale-up; (2) pediatric surgical capacity building for congenital heart defects; and (3) sickle cell chronic care programs that use proven therapies. A fourth, emerging opportunity lies in molecular diagnostics. Closing these gaps offers a high-impact route toward SDG 3.2.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2026.1886383","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:35:10Z","timestamp":1785216910000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Avoidable under-5 mortality from congenital and genetic disorders: a frontier analysis of GBD 2023 identifying intervention targets"],"prefix":"10.3389","volume":"14","author":[{"given":"Jingjing","family":"Ruan","sequence":"first","affiliation":[{"name":"Liangzhu Laboratory, Department of Genetics and Metabolism, National Clinical Research Center for Children and Adolescents' Health and Diseases, Children's Hospital, Zhejiang University School of Medicine","place":["Hangzhou, 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