Avaliação de biomarcadores associados a sepse no período neonatal

Abstract

Introduction: Neonatal sepsis continues to be a challenge because of its high incidence and lethality and difficult diagnosis, especially among preterm newborns (NB) with very low birth weight. Early diagnosis and initiation of appropriate treatment play a crucial role in improving the survival of these newborns. Objective: Evaluate the presence of biomarkers in umbilical and peripheral cord blood of very low birth weight newborns that may aid in the prediction of neonatal sepsis. Methods: Twenty-seven biomarkers were measured with a high precision kit (Bio-Plex Pro Human Cytokyne 27-plex Assay) in umbilical cord blood and peripheral blood at the 2nd, 7th, 14th and 28th days of life of the newborns of gestational age of less than 34 weeks and birth weight of less than 1,500 g, without major congenital malformations, who were born during a period of 8 months. The newborns were followed up and divided into 2 groups: the control group and the sepsis group according to the presence of sepsis. For the markers with statistical difference, the ROC curve was performed and the best cutoff was found to help predict sepsis. The sensitivity, specificity, accuracy, positive and negative predictive value were also calculated. Results: 48 eligible infants were born during the study period. In the analysis of umbilical cord blood, 9 newborns were excluded because they were not able to collect blood at birth, the others were divided in 2 groups: control group (n = 12) and sepsis group (n = 27). In the sepsis group, the sepsis was clinical sepsis in 15 (56%) and proved sepsis in 12 (44%), with average age on day of sepsis of 7 days. NB with sepsis had lower concentrations of MCP-1 than the control group. NB with MCP-1 values lower than 130.2 pg / mL in umbilical cord blood presented a 9-fold higher chance of sepsis during the neonatal period with sensitivity of 81.2% and specificity of 66.6%. In the peripheral blood of 2 days of life there was an inverse behavior. NB with MCP-1 values greater than 111.3 pg / mL had a 7.2-fold higher chance of sepsis in the neonatal period with a sensitivity of 70.8% and specificity of 75%. In the analysis of the peripheral blood of the newborn, NB with early sepsis (n = 5) and those who died before the 7th day of life (n = 5) were excluded and after divided into 2 groups: control group (n = 14) and late-onset sepsis group (n = 24). In the sepsis group, the sepsis was clinical sepsis in 14 (58.3%) and proven sepsis in 10 (41.7%), with average age on the day of sepsis of 11.1 days. Blood samples from the 2nd and 7th day of life of the newborn, before the diagnosis of sepsis, were then selected for analysis. On the second day of life, the NB of the late-onset sepsis group had higher concentrations of IL1-ra, IL-6, IP-10, and MCP-1 and lower concentrations of FGF basic, IFN-γ, IL-4, IL-5 , IL-7, IL-9, IL-10, IL-12p70, IL-13, IL-17A, PDGF-BB and TNF-α. On the 7th day of life, they had higher concentrations of VEGF, IL-8, IL-15 and IL1-ra and lower concentrations of IL-6, IL-13, IP-10 and IL-5. We highlight IL-5 and IL-6 in the second day of life that presented the highest values of odds ratio (55 and 53.3) and accuracy (83.6 and 87.6) and VEGF on the 7th day of life (odds ratio 46.2 and accuracy 84.8). Conclusion: We concluded that some biomarkers may help to predict sepsis, especially MCP-1 in the umbilical cord, IL-5 and IL-6 in the second day of life and VEGF in the 7th day of life. All of these markers, with the exception of IL-6, are still poorly explored in neonatal sepsis, deserving special attention in new studies.