Assessment of Urinary Interleukin-18 and Serum Amyloid A Efficacies against C-Reactive Protein in Diagnosis and Follow-up of Neonatal Sepsis

Abstract

Objective: infection is a leading cause of morbidity and mortality in neonates. The aim of this study was to evaluate the diagnostic and prognostic performances of urinary interleukin-18 (uIL-18) and serum amyloid A (SAA) in neonatal sepsis parallel to C- reactive protein (CRP). Subjects and methods: A total of 275 neonates were included in this case-control study. This study was conducted in neonatal intensive care unit at both Minia University Hospital for obstetric and pediatrics as well as Qena University hospital (Egypt). Among those 275 neonates, 150 non septic neonates - who had neither clinical signs nor laboratory findings suggestive of sepsis - were involved as a non-septic control group (Group II) and 125 septic neonates were classified as a septic group (group I). Blood and urine samples were obtained before initiation of antibiotic therapy. Full sepsis screen was performed at the time of sepsis onset plus measurement of SAA and uIL-18 by Enzyme Immune Assay (EIA). A second blood and urine samples were collected 72 hours later. The effectiveness of these 3 biomarkers as diagnostic ones was determined by using receiver operating characteristic (ROC) curve analysis. We also calculated the sensitivity, specificity, and positive, and negative predictive values. Results: The levels of uIL-18 and SAA were significantly elevated in septic neonates than in control group. The two markers showed significant decrease in their levels after 72 hours which matched with clinical improvement but not CRP. Moreover, very high levels of these markers were observed in neonates who died later on. The area under ROC curve (AUC) was used to evaluate the diagnostic efficacies of these markers. The superiority of SAA over both uIL-18 and CRP was obvious in the diagnosis of neonatal sepsis [AUC: 0.995] versus [AUC: 0.934 (uIL-18) and 0.871 (CRP)]. However in discriminating late onset sepsis (LOS), both uIL-18 and SAA have equal diagnostic capacities [AUC: 44 0.991] which are better than that of CRP [AUC: 0.866]. As to EOS, SAA has the most efficient performance as well but CRP is advanced than uIL-18. The specificities and sensitivities of either SAA or uIL-18 were higher than that of CRP in differentiating neonatal sepsis mainly LOS from controls. Conclusion: Both uIL-18 and SAA have enhanced performance over CRP for distinguishing neonatal sepsis mostly for LOS. Thus, they could be promising biomarkers for the screening and follow up of neonatal sepsis. This warrants further assessment of their prognostic values.