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

Abstract

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.

Evaluation of plasma angiopoietin‐2 and vascular endothelial growth factor in healthy dogs and dogs with systemic inflammatory response syndrome or sepsis

“…Given its good overall performance, plasma Ang‐2 concentration may be a promising prognostic biomarker in dogs with SIRS and sepsis. In the human medical literature, the Ang‐2 to Ang‐1 ratio sometimes is reported to be of even higher prognostic value than Ang‐2 alone . However, there is currently is no validated assay for measurement of Ang‐1 in dogs.…”

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

“…For this study, we used a Surinamese cohort of 20 healthy newborns and 71 newborns with suspected EOS from an earlier reported study. 15 All newborns were included after admission between 1 April 2015 and 31 May 2016 to the neonatal care facility of Academic Pediatric Center Suriname at the Academic Hospital Paramaribo in Suriname. Included were newborns with a gestational age equal to or above 34 weeks in whom antibiotics were started within the first 72 hours of life for suspected EOS.…”

“…The management of these patients was described before. 15 In short, healthy control newborns and newborns suspected of EOS were included at start of antibiotic treatment within 72 hours after birth. At start of antibiotic treatment, blood was collected for separation and storage of serum.…”

“…In the previous study, serum had been collected from whole blood collected after insertion of a venous cannula in newborns suspected of EOS and after capillary collection in controls. 15 Frozen serum samples had been transported on dry ice to the Netherlands and aliquoted and frozen again on arrival. A stored aliquot was used for the measurement of sP-selectin, sE-selectin, vascular cell adhesion molecule-1 (sVCAM-1), sICAM-1 and sPECAM-1 using the Human Magnetic Bead Adhesion 6-plex panel performance assay (LHC0016M, Thermo Scientific, Waltham, Massachusetts, USA) according to the manufacturer’s instructions.…”

“…Recently, we showed in a cohort of near term and term Surinamese newborns that a systemic disbalance in Ang-2/Ang-1 concentrations was associated with blood culture positive EOS. 15 This study was undertaken to examine if this disbalance is paralleled by increased serum concentrations of sCAMs and sheddases in this cohort of newborns with EOS to explore further the pathophysiology of EOS. We hypothesised that sCAM and sheddases concentrations measured at start of antibiotic treatment for suspected EOS are higher in newborns with blood culture positive EOS than in healthy controls.…”