Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: a matched\xa0case-control study

Julie Korol Wright,Abdullah Baqui,Kevin C Kain,Azadeh Farzin,Nazma Begum,Mashuk Siddiquee,Gulam Muhammed Al Kibria,Kyla Hayford,Vanessa Tran,Ali Manajjir,Arif Mahmud

doi:10.1186/s12887-018-1087-x

Abstract

BackgroundReducing death due to neonatal sepsis is a global health priority, however there are limited tools to facilitate early recognition and treatment. We hypothesized that measuring circulating biomarkers of endothelial function and integrity (i.e. Angiopoietin-Tie2 axis) would identify young infants with sepsis and predict their clinical outcome.MethodsWe conducted a matched case-control (1:3) study of 98 young infants aged 0–59 days of life presenting to a referral hospital in Bangladesh with suspected sepsis. Plasma levels of Ang-1, Ang-2, sICAM-1, and sVCAM-1 concentrations were measured at admission. The primary outcome was mortality (n = 18); the secondary outcome was bacteremia (n = 10).ResultsAng-2 concentrations at presentation were higher among infants who subsequently died of sepsis compared to survivors (aOR 2.50, p = 0.024). Compared to surviving control infants, the Ang-2:Ang-1 ratio was higher among infants who died (aOR 2.29, p = 0.016) and in infants with bacteremia (aOR 5.72, p = 0.041), and there was an increased odds of death across Ang-2:Ang-1 ratio tertiles (aOR 4.82, p = 0.013).ConclusionsThis study provides new evidence linking the Angiopoietin-Tie2 pathway with mortality and bacteremia in young infants with suspected sepsis. If validated in additional studies, markers of the angiopoietin-Tie2 axis may have clinical utility in risk stratification of infants with suspected sepsis.

Highlights

Reducing death due to neonatal sepsis is a global health priority, there are limited tools to facilitate early recognition and treatment
In agreement with previous studies, we found the prognostic utility of typical clinical indicators of infection such as temperature, heart rate, respiratory rate, and lethargy, to be limited with no significant differences observed between infants who died of sepsis compared to those who survived (Table 1)
In this study we tested the hypothesis that circulating markers of endothelial dysfunction would identify young infants with life-threatening infections when they first present to a health care facility

Summary

Introduction

Reducing death due to neonatal sepsis is a global health priority, there are limited tools to facilitate early recognition and treatment. Recognition and initiation of antimicrobial therapy are essential to reduce the morbidity and mortality of neonatal sepsis. While the pathobiology of septic shock is complex and incompletely understood, dysregulated systemic inflammatory responses and endothelial dysfunction are believed to play key roles [5,6,7]. These altered host responses are associated with decreased systemic vascular resistance, loss of endothelial integrity, and microvascular leak, which compromise tissue perfusion and organ function [8]

Methods

Results

Discussion

Conclusion