Systematic Review and Meta-Analysis Finds IL-27 Superior to CRP for Neonatal Sepsis Diagnosis

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Frontiers in Medicine Published May 13, 2026 Medically reviewed May 13, 2026 DOI ↗ By Dr. Sofia Müller, MD · Lifespan & Whole-Person Care

Key Takeaway

Consider IL-27 as a potential biomarker for neonatal sepsis, but await further validation before routine use.

This systematic review and meta-analysis evaluated the diagnostic accuracy of interleukin-27 (IL-27) compared to C-reactive protein (CRP) for neonatal sepsis. The analysis included 495 neonates across multiple studies. The primary outcome was diagnostic accuracy, measured by sensitivity, specificity, and area under the curve (AUC).

Pooled results showed that IL-27 had a sensitivity of 0.82 (95% CI, 0.77–0.87) and specificity of 0.85 (95% CI, 0.80–0.90), both significantly higher than CRP (sensitivity 0.73 [95% CI, 0.65–0.79]; specificity 0.76 [95% CI, 0.69–0.83]). The AUC for IL-27 was 0.92, notably higher than CRP's 0.84.

The authors suggest that IL-27 may serve as a more reliable biomarker for early and accurate diagnosis of neonatal sepsis. However, the review did not report on adverse events, limitations, or funding sources. The sample size is modest, and the findings should be interpreted cautiously until confirmed in larger, prospective studies.

In practice, IL-27 could potentially assist in diagnosing neonatal sepsis, but current evidence is insufficient to recommend routine use over CRP. Clinicians should consider these results as preliminary and await further validation.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

BackgroundInterleukin-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.MethodsThis 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.ResultsA 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).ConclusionsThe 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 Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251272080.