Assessing the Strength of Serum Cytokines as Compared to Traditional Markers in the Diagnosis of Culture-positive Neonatal Sepsis in Premature Infants

Background: Neonatal sepsis remains a major cause of morbidity in premature infants, with traditional clinical markers like the neonatal sequential organ failure assessment (nSOFA) score and C-reactive protein (CRP) lacking diagnostic precision. Given the subtle and non-specific presentation of sepsis, early and accurate diagnosis is critical. Recent studies suggest that cytokine profiling, particularly IL-27, IL-6, IL-10, and MCP-1, may enhance early sepsis detection by identifying inflammatory responses.

Objectives: To assess whether cytokine profiling strengthens the diagnostic utility of existing clinical factors in distinguishing culture-positive sepsis from non-culture-positive cases in premature infants

Design/Methods: 167 premature infants born between 22 0/7 - 32 6/7 weeks’ gestational age undergoing sepsis evaluations were grouped based on blood culture results (culture-positive vs. culture-negative). Clinical factors, including nSOFA score, CRP, white blood cell count (WBC), and left shift were collected by review of the medical record at the time of each sepsis evaluation for included infants. Residual clinical serum samples were collected from included infants at the time of initial evaluation. Serum concentrations of cytokines and chemokines (IL-1, IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1a, and TNF) were measured using a multiplex protein assay. Statistical analyses included Mann-Whitney U tests and multivariate logistic regression models, with diagnostic performance assessed using AUC.

Results: The clinical markers did not show statistically significant differences between culture-positive and culture-negative groups, however, there were significantly elevated serum concentrations of cytokines and chemokines in the culture-positive cohort. Univariate analysis showed that IL-1β, IL-6, IL-8, and IP-10 had moderate accuracy in predicting culture-positive sepsis. Multivariate models combining CRP with serum cytokines gave the highest diagnostic accuracy (AUC=0.81), outperforming the models with clinical factors alone (AUC=0.69).

Conclusions: This study highlights the limited utility of traditional clinical markers in differentiating culture-positive neonatal sepsis from culture-negative cases in premature infants. Serum cytokine profiling, on the other hand, particularly IL-1β, IL-6, IL-8, and IP-10, demonstrated potential in enhancing diagnostic accuracy. Further research is needed to validate these findings and explore their utilization in clinical settings.