Diagnostic performance of interleukin-27 and C-reactive protein in neonatal sepsis: an updated systematic review and meta-analysis

Background Interleukin-27 (IL-27) has been proposed as a promising diagnosis marker for neonatal sepsis. However, findings across existing clinical studies remain inconsistent and inconclusive. This study aims to comprehensively evaluate and compare the diagnostic accuracy of IL-27 vs. C-reactive protein (CRP) for neonatal sepsis, based on the latest available evidence. Methods This systematic review and meta-analysis was conducted following the PRISMA guidelines and prospectively registered in PROSPERO (CRD420251272080). PubMed, Embase, and the Cochrane Library were searched for relevant studies published from January 1996 to December 2025. Eligible studies were collected and analyzed using Review Manager 5.4 and R software. Meta-Disc 1.4 was applied to calculate pooled sensitivity, specificity, and summary receiver operating characteristic (SROC) curves with corresponding area under the curve (AUC) values to evaluate overall diagnostic efficacy. Results A total of five controlled studies involving 495 neonates were ultimately included in the final analysis, all of which were judged to have acceptable methodological quality. Meta-analysis results showed that the pooled sensitivity of IL-27 for diagnosing neonatal sepsis was 0.82 95% confidence interval (CI), 0.77–0.87, which was significantly higher than that of CRP (0.73; 95% CI, 0.65–0.79). The pooled specificity of IL-27 was 0.85 (95% CI, 0.80–0.90), also exceeding that of CRP (0.76; 95% CI, 0.69–0.83). SROC curve analysis further demonstrated robust predictive value for both biomarkers, with the AUC of IL-27 (0.92) being notably higher than that of CRP (0.84). Conclusions The findings of this updated systematic review and meta-analysis indicate that IL-27 has superior diagnostic accuracy to CRP for the identification of neonatal sepsis. IL-27 may therefore serve as a more reliable biomarker to assist in the early and accurate diagnosis of neonatal sepsis in clinical practice. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251272080.