Markers of endothelial cell activation in suspected late onset neonatal sepsis in Surinamese newborns: a pilot study.

BACKGROUND: Serum levels of markers of endothelial cell activation are associated with bacteremia and mortality in sepsis in adults, children, and newborns with early onset sepsis. We hypothesize that levels of these markers are associated with these outcomes in hospitalized newborns with suspected late onset neonatal sepsis (LONS). METHODS: In this prospective cohort study, newborns admitted to the tertiary neonatal care facility of Suriname were included upon clinical suspicion of LONS and before start of antibiotic treatment, between April 1, 2015 and May 31, 2016. Serum concentrations of angiopoietin-1, angiopoietin-2, and soluble isoforms of P-selectin, E-selectin, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), platelet and endothelial cell adhesion molecule-1 (sPECAM-1), matrix metalloproteinase-9 (MMP-9), neutrophil elastase, and tissue-inhibitor of metalloproteinases-1 (TIMP-1) were measured. RESULTS: Twenty-thee newborns were included. Baseline characteristics were similar between newborns with and without bacteremia and between non-survivors and survivors. Only soluble E-selectin (sE-selectin) was higher in newborns with bacteremia versus non-bacteremia (P=0.04) and lower in non-survivors (P=0.04). No conclusions could be made for sVCAM-1 due to high serum concentrations. CONCLUSIONS: In conclusion, the data from this pilot study indicate that serum levels of markers of endothelial cell activation are poorly associated with bacteremia and mortality.

Serum concentrations of endothelial cell adhesion molecules and their shedding enzymes and early onset sepsis in newborns in Suriname.

BACKGROUND: Early onset sepsis (EOS) is defined as onset of sepsis within 72 hours after birth. Leucocyte-endothelial interactions play a pivotal part in EOS pathophysiology. Endothelial cell adhesion molecules (CAMs) orchestrate these interactions and their soluble isoforms (sCAMs) are released into the vasculature by enzymes called sheddases. PURPOSE: This study was undertaken to explore further the pathophysiology of EOS and to investigate the potential of sCAM and their sheddases as potential biomarkers for EOS. METHODS: Stored serum aliquots were used from 71 Surinamese newborns suspected of EOS and 20 healthy newborns from an earlier study. Serum had been collected within 72 hours after birth and six (8.6%) newborns had a positive blood culture with gram-negative pathogens. Concentrations of sCAMs sP-selectin, sE-selectin, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and platelet and endothelial cell adhesion molecule-1, sheddases matrix metalloproteinase-9 (MMP-9) and neutrophil elastase (NE) and sheddase antagonist tissue-inhibitor of metalloproteinases-1 (TIMP-1) were measured simultaneously with Luminex and ELISA. RESULTS: MMP-9 and TIMP-1 levels were measured in serum of n=91 newborns and sCAMs and NE levels in serum of n=80 newborns, respectively. We found no differences in median concentrations of sCAMs, MMP-9 and TIMP-1 or NE between blood culture positive EOS, blood culture negative EOS and control groups at start of antibiotic treatment. CONCLUSIONS: Our data indicate that serum concentrations of sCAMs and their sheddases have no clinical utility as biomarkers for EOS. TRIAL REGISTRATION NUMBER: NCT02486783. Results.

Low Serum Angiopoietin-1, High Serum Angiopoietin-2, and High Ang-2/Ang-1 Protein Ratio are Associated with Early Onset Sepsis in Surinamese Newborns.

PURPOSE: Vascular inflammation and leakage in sepsis is mediated by Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) and their phosphorylation of the endothelial Tie-2 receptor. This study investigates levels of Ang-1 and Ang-2 in newborns to gain insight in the vascular pathophysiology of early onset sepsis (EOS) within 72 h after birth. METHODS: A prospective cohort study was performed among 71 Surinamese newborns treated with antibiotics for suspected EOS and 20 control newborns. Newborns with suspected EOS were divided in two groups: blood culture negative and positive EOS. Ang-1 and Ang-2 levels were measured in serum obtained at the start of antibiotic treatment and at re-evaluation after 48 to 72 h. RESULTS: In this cohort 8.5% of newborns had a positive blood culture. At the start of antibiotic treatment Ang-1 serum levels were lower (P < 0.01), and Ang-2 and Ang-2/Ang-1 serum protein ratios were higher (P < 0.01 and P < 0.01, respectively) in newborns with blood culture positive EOS than in controls. These levels were not dependent on timing of first blood draw after birth. After 48 to 72 h levels of Ang-1 further decreased in blood culture positive EOS, while in the other groups no change was observed. CONCLUSIONS: Our findings support the hypothesis that a disbalance in the Angiopoietins plays a role in the vascular pathophysiology of EOS.