Biomarkers of endothelial activation predict sepsis severity and outcomes in adults but their role in early newborn sepsis has not been reported. We hypothesize that these circulating biomarkers will identify young infants with sepsis and predict their clinical outcome.
420 infants aged 0-60 days of life with suspected sepsis were recruited on presentation to a referral hospital in Bangladesh. Serum was collected at admission and Ang-1, Ang-2, sICAM and sVCAM concentrations were determined by ELISA. The primary outcome was mortality (n=18); the secondary outcome was bacteremia (n=11). Using a 1:3 matched case-control design, infants who died or had culture-confirmed bacteremia (cases) were matched on birthweight and age with survivor/non-bacteremic infants (control).
Serum Ang-2 concentration at presentation was higher among infants who subsequently died of sepsis compared to survivors (5.4 pg/mL vs 3.3, adjusted OR 2.19, p=0.014) and the relative odds of death increased across Ang-2 tertiles (p-trend = 0.0156). Similarly, the serum Ang-2:Ang-1 ratio was higher among infants who died compared to survivors (0.5 vs 0.2, aOR 2.90, p=0.008) and the relative odds of death increased across tertiles of Ang 2:Ang-1 (p-trend = 0.0254). Among infants with bacteremia, Ang-2:Ang-1 was higher compared to controls (0.25 vs 0.20. aOR 5.82, p=0.044). sICAM levels trended with bacteremia (262.0 pg/mL vs 158.5 pg/mL, aOR 2.38, p=0.053) but not with mortality.
This is the first study to demonstrate an association between biomarkers of endothelial dysfunction and mortality in young infants with suspected sepsis. If validated in additional studies, their use in rapid point-of-care tests could risk-stratify infants with suspected sepsis. Since these markers are mediators of endothelial function, they also represent potential targets for intervention to improve clinical outcomes.
V. Tran, None
G. M. A. Kibria, None
A. Baqui, None
A. Mahmud, None
K. Kain, None
A. Farzin, None
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