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

• Main Authors: Julie Korol Wright, Kyla Hayford, Vanessa Tran, Gulam Muhammed Al Kibria, Abdullah Baqui, Ali Manajjir, Arif Mahmud, Nazma Begum, Mashuk Siddiquee, Kevin C. Kain, Azadeh Farzin
• Format: Article
• Language: English
• Published: BMC 2018-03-01
• Series: BMC Pediatrics
• Subjects: Neonatal Sepsis; Endothelial activation; Angiopoietins; Biomarkers
• Online Access: http://link.springer.com/article/10.1186/s12887-018-1087-x

Abstract Background Reducing 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. Methods We 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). Results Ang-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). Conclusions This 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.