Abstract
Background and Objectives: Early recognition of life-threatening organ dysfunction is central to modern sepsis frameworks. We systematically reviewed the prognostic performance and clinical utility of the Neonatal Sequential Organ Failure Assessment (nSOFA) for mortality and major morbidity in NICU populations. The search identified 939 records across databases; after screening and full-text assessment, 16 studies met the inclusion criteria. Methods: Following PRISMA guidance, we searched major databases (2019-2025) for observational or interventional studies reporting discrimination or risk stratification using nSOFA in neonates. Populations included suspected/proven infection and condition-specific cohorts. Heterogeneity in timing, thresholds, and outcomes precluded meta-analysis. Results: A cumulative sample exceeding 25,000 neonates was identified across late- and early-onset infection, all-NICU admissions, necrotizing enterocolitis, respiratory distress, and very preterm screening cohorts. Across settings and timepoints, nSOFA demonstrated consistent, good-to-excellent mortality discrimination, with reported AUROCs ≥ 0.80 and upper ranges near 0.90-0.92; serial scoring within the first 6-12 h generally improved risk classification. Disease-specific applications (NEC, early-onset infection) showed similar discrimination for death or composite adverse outcomes. Conclusions: Evidence from diverse NICU contexts indicates that nSOFA is a pragmatic, EHR-ready organ dysfunction score with robust discrimination for mortality and serious morbidity, supporting routine, serial use for risk stratification and standardized endpoints in neonatal sepsis pathways, aligned with contemporary organ dysfunction-based pediatric criteria.