Accuracy of white blood cell count, C-reactive protein, interleukin-6 and tumor necrosis factor alpha for diagnosing late neonatal sepsis

OBJECTIVE: To evaluate the diagnostic value for late neonatal sepsis of white blood cell count (WBC) and assays for C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), in isolation and in conjunction. METHODS: This was a diagnostic test validation study. Chemiluminescence was used to assay CRP, IL-6 and TNF-alpha at the time of clinical suspicion and again after 24 and 48 hours, whereas the WBC was performed only once, at the time of suspicion. Patients were classified into three groups based on clinical progress and culture results: confirmed sepsis (CS), probable sepsis (PS), and not infected (NI). Statistical analysis was performed using the Wilcoxon and chi-square tests and Friedman analysis of variance; cutoffs were defined by plotting receiver operator characteristic curves. RESULTS: The total study sample comprised 82 children, 42 of whom were classed as CS, 16 as PS and 24 as NI. At all three test times, the medians for CRP and IL-6 were significantly more elevated in the CS and PS groups, while the medians for TNF-alpha were abnormal only in the CS group. The CRP test had elevated indices of diagnostic utility at all three test times, better accuracy than the WBC and similar accuracy to the first IL-6 and TNF-alpha assays. There was no statistical difference between the cytokines, nor between them and the WBC. Combining tests did not increase diagnostic power, with the exception of the combination of WBC with CRP2 and when the sequential CRP assays were combined. CONCLUSIONS: Both CRP and WBC were useful for the diagnosis of late neonatal sepsis and comparable with IL-6 and TNF-alpha. Accuracy increased when CRP and WBC were combined and when sequential CRP assay results were used.