Serum and cerebrospinal fluid biomarkers for risk stratification of hospitalized neonates and young infants with suspected serious bacterial infections: a secondary analysis of a prospective cohort study
TL;DR
Serum levels of TRAIL showed an exploratory association with disease severity in hospitalized neonates and young infants with suspected serious bacterial infections, and PCT was the strongest predictor of severe progression for in-hospital death.
Abstract
Background Improved risk stratification strategies for neonates and young infants are urgently needed to reduce the substantial mortality burden associated with infectious diseases, particularly in low- and middle-income settings. Evidence supporting the use of host-response biomarkers to predict disease severity in this population remains limited. Methods We conducted a secondary analysis of a prospective cohort study at a National Reference Neonatology Centre in Morocco and evaluated the prognostic performance of host-response biomarkers measured in serum and cerebrospinal fluid (CSF) to predict in-hospital mortality among hospitalized sick neonates and young infants (<2 months). Twenty-one biomarkers of immune activation, endothelial dysfunction, and neuronal injury were measured using Luminex and compared head-to-head. Results Among 179 participants with available serum and/or CSF samples included in this analysis, 9% died during hospitalization (11/136 in the serum sample set, and 12/148 in the CSF sample set). In serum, lower concentrations of TRAIL and higher concentrations of Angpt-2, IL-8, and uPAR, were associated with in-hospital death, with TRAIL showing the strongest prognostic performance (AUROC 0.86; 95% CI 0.78-0.93). In CSF, PCT was the strongest predictor of severe progression for in-hospital death (AUROC 0.87; 95% CI 0.80-0.95), whereas higher levels of IL-6, IL-12p70, TNFR1, TREM-1, Angpt-1, NGAL, and NSE were associated with higher odds of probable or laboratory-confirmed meningitis. Discussion Serum levels of TRAIL showed an exploratory association with disease severity in hospitalized neonates and young infants with suspected serious bacterial infections. Larger multicenter studies are needed to validate these findings using multiple biological matrices, characterize kinetics, and determine whether these markers may have clinical utility for risk stratification in this vulnerable population.