RESUMO
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.
Assuntos
Cesárea , Interleucina-6 , Gravidez , Recém-Nascido , Humanos , Feminino , Pró-Calcitonina , Parto Obstétrico/métodos , Fator de Necrose Tumoral alfa , Sangue FetalRESUMO
Mortality and morbidity of newborns with sepsis can be improved by early and accurate diagnosis and targeted therapy. To evaluate the early molecular events associated with inflammation and infection, we evaluated markers of endothelial activation and injury and circulating plasma miRNAs in preterm newborns with sepsis. The study group consisted of newborns with gestational age ≤ 32 weeks, with culture-positive early-onset neonatal sepsis (sepsis group, N = 8), and as a control group, we enrolled newborns without sepsis (control group, N = 12). Soluble markers of inflammation were measured using Luminex-based multiplex assay. Platelet-free plasma RNA was used to construct the library for miRNA sequencing analysis. Normalized counts were calculated and used to measure differential expression of individual detected miRNAs. We found a significant increase of interleukin 18 (IL-18) in the cord blood of the sepsis group (mean ± SEM, 104.7 ± 30.4 pg/ml vs 52.7 ± 5.6 pg/ml, P = 0.02). In peripheral blood of sepsis group patients, we found a significant increase of VEGF-A compared to controls (196.0 ± 70.5 pg/ml vs 59.6 ± 8.5 pg/ml, P = 0.02). In the cord blood plasma, eight miRNAs had significantly differential expression (P < 0.05), four miRNAs were up-regulated and four miRNAs down-regulated. In peripheral blood plasma, all nine miRNAs with significant differential expression were up-regulated. In conclusion, in early-onset neonatal sepsis, IL-18 and VEGF-A might be considered in diagnostic workup. Early-onset sepsis in preterm newborns is associated with significant changes in the circulating miRNA pattern.
Assuntos
MicroRNAs , Sepse Neonatal , Sepse , Humanos , Recém-Nascido , Lactente , MicroRNAs/genética , Sepse Neonatal/diagnóstico , Interleucina-18 , Fator A de Crescimento do Endotélio Vascular , Biomarcadores/metabolismo , Sepse/diagnóstico , Sepse/genética , InflamaçãoRESUMO
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.