Diagnostic Value of C-Reactive Protein, Procalcitonin and Interleukin-6 in Neonatal Sepsis: A Critical Narrative Review

Resume. Background. Early diagnosis of neonatal sepsis is difficult because symptoms overlap with noninfectious neonatal disorders and microbiological confirmation takes time. Objective. To critically assess the diagnostic contribution of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), considering sample type, timing, gestational maturity, reference standards and antibiotic stewardship. Methods. A targeted critical narrative review was developed from neonatal diagnostic studies, peer-reviewed evidence syntheses and professional guidance identified through PubMed records and original journal or institutional websites. The present review did not perform a new meta-analysis or a systematic risk-of-bias assessment. Findings. A 2024 synthesis of early-onset sepsis studies reported pooled cord-blood PCT sensitivity of 79% (95% confidence interval [CI], 71–84%) and specificity of 91% (83–96%); respective estimates for cord-blood IL-6 were 83% (71–90%) and 87% (78–93%). In a prospective study of 82 neonates with suspected early- or late-onset infection, diagnostic AUCs were 0.73 for CRP, 0.65 for PCT and 0.55 for IL-6. Such estimates cannot be ranked across studies without considering populations, assays, specimens and case definitions. Conclusion. CRP, PCT and IL-6 are complementary but imperfect diagnostic adjuncts. They should support, not replace, clinical assessment and blood cultures. Locally evaluated diagnostic pathways are necessary before routine use of multibiomarker panels.