ArticleFrontiers in public health2026
Avoidable under-5 mortality from congenital and genetic disorders: a frontier analysis of GBD 2023 identifying intervention targets.
Article in Frontiers in public health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: 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. Methods: 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 (τ = 0.05) with natural cubic splines ( Results: ConGD ASMR fell 29.4% (105.70 [95% UI 72.44-153.23] to 74.64 [49.50-114.00] per 100,000), far slower than the 64.7% decline in communicable, maternal, neonatal, and nutritional (CMNN) diseases. PMR almost doubled (5.59% [3.78-8.20] to 10.28% [6.70-15.98]), 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 (ρ = - 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 201,692-289,940) potentially avoidable deaths in 2023 (52.4% of total), with efficiency gaps at every SDI level. Discussion: 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.
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