Peripheral blood nucleated red blood cells predict short-term mortality and clinical outcomes in critically ill adults: A systematic review and meta-analysis

Peripheral blood nucleated red blood cells (NRBCs) are rarely detected in healthy adults but may appear during severe systemic inflammation, tissue hypoxia, and hematopoietic stress in critical illness. This meta-analysis aimed to evaluate the prognostic value of peripheral blood NRBCs for mortality and clinical outcomes in critically ill adults. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251250833), and included cohort studies identified through PubMed, Embase, the Cochrane Library, and Web of Science from inception to June 2, 2026. Study quality, risk of bias, and certainty of evidence were assessed using the Newcastle-Ottawa Scale (NOS), Quality In Prognosis Studies (QUIPS) tool, and Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Overall, 20 cohort studies including 17,691 critically ill adults were included. NRBC positivity was associated with higher 30-day mortality than NRBC negativity, both by odds ratio (OR = 3.14, 95% confidence interval [CI]: 2.13-4.62) and hazard ratio (HR = 1.55, 95% CI: 1.24-1.93). NRBC-positive patients also had longer total hospital stay (mean difference [MD] = 8.73 days, 95% CI: 2.14-15.33) and intensive care unit (ICU) stay (MD = 7.51 days, 95% CI: 3.29-11.73), whereas 90-day mortality was not significantly different between groups. Dose-response analysis showed a nonlinear positive association between increasing NRBC concentrations and 30-day mortality risk. Peripheral blood NRBCs may serve as an adjunctive marker of short-term prognosis and illness severity in critically ill adults, although substantial heterogeneity and very low certainty for several outcomes warrant cautious interpretation.