Delivery-Associated Changes in the Levels of Inflammatory Molecules in Newborns.

Inflammation is considered a fundamental process accompanying physiological human birth, also playing a role in perinatal pathologies. The goal of the study was to assess the concentrations of inflammatory molecules with respect to the mode of delivery and dynamics of inflammatory molecules in neonatal samples in the first 48-72 hours of life. The concentrations of inflammatory cytokines were measured using the Luminex®xMAP multi-analyte profiling platform in cord blood and peripheral neonatal blood. Study groups included newborns delivered spontaneously (spontaneous group) and via elective caesarean section (elective group). Cord blood concentrations of interleukin 6 (IL-6) and procalcitonin were significantly higher (P < 0.0001) in the spontaneous group compared to the elective group. Neonatal blood concentrations of tumour necrosis factor (TNF) from the elective group were significantly higher com-pared to the spontaneous group (P = 0.0077). The concentrations of procalcitonin and TNF significantly increased within the first 48 to 72 hours following either mode of delivery. IL-6 and IL-18 were significantly higher in neonatal compared to umbilical cord blood in the elective group only, while the increase in the spontaneous group did not reach statistical significance. The concentrations of IL-1α, IL-1ß, IL-17A and IL-22 did not show significant differen-ces between the spontaneous and elective groups as well as between umbilical cord and neonatal blood. Our findings show physiological differences in the levels of inflammatory molecules following spontaneous vaginal delivery and elective caesarean section. The results can be used as baseline values for the research of various pathologies in newborns.

Spontaneous delivery is associated with increased endothelial activity in cord blood compared to elective cesarean section.

OBJECTIVES: It is suggested that delivery whether spontaneous or by elective cesarean section is associated with an inflammatory reaction which may be modified by the type of delivery. Inflammatory reactions are associated with endothelial activation. The aim of our study was to assess endothelial biomarkers in cord and neonatal blood following different modes of delivery. STUDY DESIGN: The study group consisted of term healthy newborns after uncomplicated pregnancies and either spontaneous vaginal delivery (n = 39) or elective cesarean section (n = 20). Plasma soluble biomarkers were measured using multiplex magnetic bead immunoassay. The microvesicle count and number of surface antigen-specific microvesicles were determined by flow cytometry. RESULTS: We found significantly increased concentrations of cord blood endothelial markers (sVEGFR1, Endothelin-1 and sVCAM1) and microvesicles (EPCR/CD201+, ICAM1/CD54+ and PECAM1/CD31+) in spontaneous vaginal delivery when compared to elective cesarean section. Irrespective of the delivery mode endothelial markers sVEGFR1, Endocan, Angiopoietin-2, VEGF, and sICAM1, were significantly increased in neonatal compared to cord blood. CONCLUSION: We found increased cord blood concentrations of endothelial markers and microvesicles following spontaneous vaginal delivery, which may reflect the natural activation of endothelial cells during labor. Following the delivery, most of the soluble markers increased, as a possible consequence of activation of neonatal innate immunity and postnatal cardiovascular transition.

Endothelial Microvesicles and Soluble Markers of Endothelial Injury in Critically Ill Newborns.

Neonatal systemic inflammatory response and multiple organ dysfunction syndrome are the main postnatal insults influencing mortality and morbidity. Critically ill newborns with high predicted mortality are supported by extracorporeal membrane oxygenation (ECMO). Biomarkers of inflammatory response and endothelial injury can be used for early diagnosis and treatment of critical neonatal situations. The aim of our study was to explore plasma proteins and endothelial microvesicles as markers of inflammation and endothelial activation in newborns on ECMO and to compare them with healthy neonates. Thirteen newborns on ECMO and 13 healthy newborns were included in the study. Plasma soluble biomarkers were measured using multiplex immunoassay based on Luminex® xMAP multianalyte profiling platform. The total microvesicle count and plasma level of surface antigen-specific microvesicles were determined by flow cytometry. The plasma concentration of cell-derived microvesicles was measured using annexin-V labeling, and the endothelial origin of microvesicles was determined using lineage-specific antigen labeling of endothelial cell/microvesicle markers (endoglin/CD105, PECAM1/CD31, VEGFR2/CD309, and MadCAM1). Inflammatory markers (procalcitonin, IL-1ß, IL-6, and IL-22) were increased in the ECMO group (P < 0.01). The assessment of endothelial markers showed higher concentrations of endocan and angiopoietin-2 (P < 0.01) in the ECMO group while VEGF in the ECMO group was significantly lower (P < 0.01). In the ECMO group, the concentration of annexin-V-positive microvesicles (total microvesicles) and endothelial microvesicles expressing mucosal vascular addressin cell adhesion molecule 1 (MadCAM1) was increased (P = 0.05). In summary, we found increased concentrations of soluble inflammatory and endothelial markers in the plasma of critically ill newborns with multiple organ dysfunction. Increased plasma concentrations of microvesicles may reflect the activation or damage of blood cells and vasculature including endothelial cells. The measurement of cell membrane-derived microvesicles may be added to the panel of established inflammatory markers in order to increase the sensitivity and specificity of the diagnostic process in critically ill newborns.