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      Marcadores inflamatórios e oxidativos em sangue de cordão umbilical como preditores de gravidade em sepse neonatal Translated title: Inflammatory and oxidative cord blood parameters as predictors of neonatal sepsis severity

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          Abstract

          OBJETIVOS: Sepse neonatal corresponde a uma síndrome complexa, causada por resposta inflamatória sistêmica descontrolada, associada a um foco infeccioso que pode determinar disfunção ou falência de um ou mais órgãos ou mesmo a morte. Apresenta incidência elevada em neonatos prematuros, sendo importante correlacionarmos fatores prognósticos para otimizar nosso diagnóstico precoce e resposta a terapêutica nestes pacientes. Este estudo teve por objetivo determinar a relação entre marcadores inflamatórios e parâmetros oxidativos com fatores prognósticos em sepse neonatal precoce. MÉTODOS: Foi realizado um estudo observacional, prospectivo e foram coletados os dados de 120 pacientes, da maternidade de hospital universitário. Foram incluídos na pesquisa neonatos prematuros (< 37 semanas de gestação) com pelo menos um outro fator de risco para sepse neonatal. Foram determinados os níveis de interleucina (IL)-6, IL-10, substâncias reativas ao ácido tiobarbitúrico e de proteínas carboniladas em sangue do cordão umbilical e sua relação com gravidade de sepse. RESULTADOS: Os níveis das substâncias reativas ao ácido tiobarbitúrico e IL-6, mas não IL-10 e proteínas carboniladas, apresentaram correlação significativa com o escore de gravidade SNAPPE-II (r=0,385, p=0,017 e r=0,435 / p=0,02, respectivamente). Não houve relação dos marcadores com a mortalidade dos pacientes. CONCLUSÃO: Substâncias reativas ao ácido tiobarbitúrico e IL-6 têm uma correlação de média a moderada com o escore de gravidade SNAPPE-II, mas não com mortalidade.

          Translated abstract

          OBJECTIVES: Neonatal sepsis is a complex syndrome involving an uncontrolled systemic inflammatory response associated with an infection. It may result in the dysfunction or failure of one or more organs or even death. Given its high incidence in premature neonates, the identification of prognostic factors to optimize the early diagnosis and therapeutic interventions are highly desirable. This objective study determine the relationship between inflammatory markers and oxidative parameters as prognostic factors in early neonatal sepsis. METHODS: We conducted a prospective observational study by collecting data from 120 patients in the maternity unit of a university hospital. Preterm (<37 weeks of pregnancy) infants with at least one additional risk factor for neonatal sepsis were included. The levels of interleukin (IL)-6, IL-10, thiobarbituric acid reactive species (TBARS) and protein carbonyls and their association with sepsis severity were determined in the cord blood. RESULTS: Levels of IL-6 and TBARS, but not IL-10 and protein carbonyls, demonstrated a mild to moderate correlation with the SNAPPE-II severity score (r=0.435, p=0.02 and r = 0.385, p = 0.017, respectively). No correlations were found between these markers and mortality. CONCLUSION: TBARS and IL-6 have a mild to moderate correlation with SNAPPE-II, but none of the studied markers were able to predict mortality in our sample.

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          Most cited references 24

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          Oxidative stress in the newborn--a 30-year perspective.

           Ola Saugstad (2004)
          In this review the development of the concept 'hypoxia-reoxygenation injury' is outlined. An update of some important factors and mechanisms related to oxidative stress injury in newborn infants is presented, including the metabolism of glutathione, the role of antioxidants, iron and nitric oxide, and how these may influence health and disease in the newborn and contribute to 'oxygen radical disease of the newborn'. New insight into how hyperoxia and hypoxia may induce changes leading to retinopathy of prematurity by vascular endothelial growth factor acting in concert with insulin-like growth factor is briefly summarized. Inflammation and oxidative stress seem to be two sides of the same coin in newborn babies both contributing to injury partly through similar mechanisms. Copyright (c) 2005 S. Karger AG, Basel.
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            Diagnostic markers of infection in neonates.

             P C Ng (2004)
            Diagnostic markers of infection are useful indicators of neonatal sepsis. Serial measurements of infection markers can improve diagnostic sensitivity, and the use of multiple markers can enhance diagnostic accuracy. Current evidence suggests that promising markers may be useful for early termination of antimicrobial treatment, but none of the current diagnostic tests are sensitive and specific enough to influence the clinical decision for withholding antibiotic treatment at the onset of suspected infection.
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              Proteomics Mapping of Cord Blood Identifies Haptoglobin “Switch-On” Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

              Background Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns. Methodology/Principal Findings We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1st-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (P<0.001). Western blot concurred in determining that EONS babies had conspicuous Hp&HpRP bands in cord blood (“switch-on pattern”) as opposed to non-EONS newborns who had near-absent “switch-off pattern” (P<0.001). Fetal Hp phenotype independently impacted Hp&HpRP. A Bayesian latent-class analysis (LCA) was further used for unbiased classification of all 180 cases based on probability of “antenatal IAI exposure” as latent variable. This was then subjected to 2nd-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage. Conclusions/Significance Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the selection of newborns for prompt and targeted treatment at birth.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                rbti
                Revista Brasileira de Terapia Intensiva
                Rev. bras. ter. intensiva
                Associação de Medicina Intensiva Brasileira - AMIB (São Paulo )
                1982-4335
                March 2012
                : 24
                : 1
                : 30-34
                Affiliations
                [1 ] Universidade do Extremo Sul Catarinense Brazil
                Article
                S0103-507X2012000100005
                10.1590/S0103-507X2012000100005

                http://creativecommons.org/licenses/by/4.0/

                Product
                Product Information: SciELO Brazil
                Categories
                CRITICAL CARE MEDICINE

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