Journal
BMC PEDIATRICS
Volume 18, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12887-018-1087-x
Keywords
Neonatal Sepsis; Endothelial activation; Angiopoietins; Biomarkers
Categories
Funding
- Canadian Institutes of Health Research (CIHR) [MOP-13721, MOP-115160, MOP-136813]
- CIHR Foundation [FDN-148439]
- Canada Research Chair Program
- Johns Hopkins (KL2) Mentored Career Development Award
- National Institute of Child Health and Human Development (NICHD) [K08 HD 073315]
- The Dr. Sydney H. Kane, Emma B. Kane, David M. Kane and Family Endowment Fund
- The Sheila S. and Lawrence C. Pakula, M.D. Endowment for Neonatal Research
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [K08HD073315] Funding Source: NIH RePORTER
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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.
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