Value of Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) as a Diagnostic Marker for Neonatal Sepsis

Abstract

Introduction: Neonatal Sepsis (NS) is a serious clinical condition caused by a dysregulated immune response to an infection. Neonatal period is the most vulnerable time in the child’s life. Globally, approximately 7000 newborns die everyday. Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is an important receptor for the inflammatory response regulated by neutrophils. Aim: To explore the role of TREM-1 as a potential early diagnostic marker of NS compared to the conventional blood culture technique. The prognostic utility and relation of TREM-1 expression level to the clinical disease severity in septic neonates were also evaluated. Materials and Methods: The study enrolled 75 neonates with NS admitted to the Neonatal Intensive Care Unit (NICU). The studied neonates were categorised into three groups; group I: 25 neonates with an Early Onset Sepsis (EOS), group II: 25 neonates with a Late Onset Sepsis (LOS), group III: 25 neonates with septic shock. In addition, 25 age and sex-matched healthy neonates with no evidence of sepsis or any other medical illness were studied as a control group. Blood samples for conventional blood cultures and estimation of TREM-1 gene expression level in Polymorph Nuclear Neutrophils (PMNs) using quantitative Real-Time Polymerase Chain Reaction (RT-PCR) assay were synchronously collected. Data regarding clinical and laboratory findings, and risk factors of NS were also analysed. Statistical Package for the Social Sciences (SPSS) software version 20 was used to analyse the data obtained from the study. Results: The total culture-proven cases represented 24% (18/75) of all the studied neonates with NS. Klebsiella spp. was the most frequently isolated Gram-negative bacteria (4/18; 22.2%) followed by Pseudomonas spp. (3/18; 16.7%) and Acinetobacter spp. (1/18; 5.5%). Coagulase- Negative Staphylococci (CoNs), S. aureus and Candida spp. accounted for 22.2% (4/18), 16.7% (3/18) and 16.7% (3/18) of the isolated organisms respectively. No statistically significant difference was detected between the three studied groups as regards blood culture results. Significant statistical differences were detected between groups I, II and III in relation to the control group (p=0.048, p=0.049 and p<0.001) regarding TREM-1 mRNA expression level. Low Birth Weight (LBW) and prematurity were the most significant risk factors for NS. At a cut-off point of ≥0.631 TREM-1 mRNA could be considered as a potential marker for diagnosis of NS with sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of 65.33%, 96.0%, 98.0% and 48.0%, respectively. The prognostic utility of TREM-1 gene expression proved a sensitivity of 87.8% at a cut-off point >0.369. Conclusion: TREM-1 gene expression has a potential value in prognostic assessment of NS and could be considered as an early diagnostic marker.