Avaliação de biomarcadores associados a sepse no período neonatal

Detalhes bibliográficos
Autor(a) principal: Barros, Lidia Mayrink de
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFU
Texto Completo: https://repositorio.ufu.br/handle/123456789/24743
http://dx.doi.org/10.14393/ufu.te.2019.1213
Resumo: 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.
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spelling Avaliação de biomarcadores associados a sepse no período neonatalEvaluation of biomarkers associated to neonatal sepsisSepse neonatalNeonatal sepsisRecém-nascido pré-termo de muito baixo pesoVery low weight preterm newbornCitocinasCytokinesBiomarcadoresBiomarkersCordão umbilicalUmbilical cordProteína quimiotática de monócitos 1 MCP-)Monocyte chemotactic protein 1 MCP-1Interleucina 5 IL-5Interleukin 5 IL-5Interleucina 6 IL-6Interleukin 6 IL-6Fator de crescimento endotelial vascular VEGFVascular endothelial growth factor VEGFCiências médicasCNPQ::CIENCIAS DA SAUDE::MEDICINA::SAUDE MATERNO-INFANTILIntroduction: 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.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorCNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo a Pesquisa do Estado de Minas GeraisTese (Doutorado)Introdução: A sepse neonatal continua sendo um desafio pela alta incidência e letalidade e pela dificuldade no diagnóstico, especialmente entre os recém-nascidos (RN) pré-termo de muito baixo peso. O diagnóstico precoce e o início do tratamento apropriado têm um papel crucial na melhoria da sobrevida destes recém-nascidos. Objetivo: Avaliar a presença de biomarcadores em sangue de cordão umbilical e periférico de recém-nascidos pré-termo de muito baixo peso que possam auxiliar na predição da sepse neonatal. Método: Foram dosados 27 biomarcadores com um kit de alta precisão (Bio-Plex Pro Human Cytokyne 27-plex Assay) em sangue do cordão umbilical e no sangue periférico no 2º, 7º, 14º e 28º dias de vida, dos RN com idade gestacional menor que 34 semanas e peso de nascimento inferior a 1.500g, sem malformações congênitas maiores, que nasceram durante um período de 8 meses. Os RN foram acompanhados e divididos em 2 grupos: grupo controle e grupo sepse de acordo com a presença de sepse. Para os marcadores com diferença estatística foi realizado a curva ROC e encontrado o melhor cutoff que poderia ajudar a predizer a sepse e calculado a sensibilidade, especificidade, acurácia, valor preditivo positivo e negativo. Resultados: Durante o período estudado nasceram 48 RN elegíveis. Na análise do sangue do cordão umbilical foram excluídos 9 RN por não ter sido possível a coleta do sangue no momento do nascimento, e divididos em 2 grupos: grupo controle (n=12) e grupo sepse (n=27), sendo 15 (56%) sepse clínica e 12 (44%) sepse comprovada, com média da idade no dia da sepse de 7 dias. Os RN do grupo sepse apresentaram menores concentrações de MCP-1 do que os RN do grupo controle. Os RN com valores de MCP-1 menores que 130,2 pg/mL no sangue do cordão umbilical apresentaram chance 9 vezes maior de sepse no período neonatal com sensibilidade de 81,2% e especificidade de 66,6%. Já no sangue periférico de 2 dias de vida houve um comportamento inverso. Os RN com valores de MCP-1 maiores que 111,3 pg/mL apresentaram chance 7,2 vezes maior de sepse no período neonatal com sensibilidade de 70,8% e especificidade de 75%. Na análise do sangue periférico do RN, foram excluídos os RN com sepse precoce (n=5), e os que faleceram antes do 7º dia de vida (n=5), e após divididos em 2 grupos: grupo controle (n=14) e grupo sepse tardia (n=24), sendo 14 (58,3%) sepse clínica e 10 (41,7%) sepse comprovada, com média da idade no dia da sepse de 11,1 dias. Foram então escolhidos para análise as amostras de sangue do 2º e 7º dia de vida do RN, antes do diagnóstico de sepse. No 2º dia de vida, os RN do grupo sepse tardia apresentaram maiores concentrações de IL1-ra, IL-6, IP-10, e MCP-1 e menores concentrações de FGF basic, IFN-γ, IL-4, IL-5, IL-7, IL-9, IL-10, IL-12p70, IL-13, IL-17A, PDGF-BB e TNF-α. No 7º dia de vida apresentaram maiores concentrações de VEGF, IL-8, IL-15 e IL1-ra e menores concentrações de IL-6, IL-13, IP-10 e IL-5. Destacamos a IL-5 e a IL-6 no 2º dia de vida que apresentaram os maiores valores de odds ratio (55 e 53,3) e acurácia (83,6 e 87,6) e o VEGF no 7º dia de vida (odds ratio 46,2 e acurácia 84,8). Conclusão: Concluímos que alguns biomarcadores podem ajudar a predizer a sepse, em especial o MCP-1 no cordão umbilical, a IL-5 e a IL-6 no 2º dia de vida e o VEGF no 7º dia de vida. Todos esses marcadores, com exceção da IL-6 são ainda muito pouco explorados na sepse neonatal, merecendo atenção especial em novos estudos.Universidade Federal de UberlândiaBrasilPrograma de Pós-graduação em Ciências da SaúdeAbdallah, Vânia Olivetti Steffenhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794569U1Ferreira, Daniela Marques de Lima Motahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4767722Z8Goulart Filho, Luiz Ricardohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4781012P8Vergara, Mario León Silvahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4799608Y0Moura, Magda Regina Silvahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4420624H7Maia, Yara Cristina de Paivahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4133677P3Bonini, Marília Martins Pradohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4515747T6Barros, Lidia Mayrink de2019-03-29T18:22:57Z2019-03-29T18:22:57Z2019-02-08info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfBARROS, Lidia Mayrink de. Avaliação de biomarcadores associados a sepse no período neonatal. 2019. 122 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2019. DOI http://dx.doi.org/10.14393/ufu.te.2019.1213https://repositorio.ufu.br/handle/123456789/24743http://dx.doi.org/10.14393/ufu.te.2019.1213porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2019-03-30T06:07:51Zoai:repositorio.ufu.br:123456789/24743Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2019-03-30T06:07:51Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false
dc.title.none.fl_str_mv Avaliação de biomarcadores associados a sepse no período neonatal
Evaluation of biomarkers associated to neonatal sepsis
title Avaliação de biomarcadores associados a sepse no período neonatal
spellingShingle Avaliação de biomarcadores associados a sepse no período neonatal
Barros, Lidia Mayrink de
Sepse neonatal
Neonatal sepsis
Recém-nascido pré-termo de muito baixo peso
Very low weight preterm newborn
Citocinas
Cytokines
Biomarcadores
Biomarkers
Cordão umbilical
Umbilical cord
Proteína quimiotática de monócitos 1 MCP-)
Monocyte chemotactic protein 1 MCP-1
Interleucina 5 IL-5
Interleukin 5 IL-5
Interleucina 6 IL-6
Interleukin 6 IL-6
Fator de crescimento endotelial vascular VEGF
Vascular endothelial growth factor VEGF
Ciências médicas
CNPQ::CIENCIAS DA SAUDE::MEDICINA::SAUDE MATERNO-INFANTIL
title_short Avaliação de biomarcadores associados a sepse no período neonatal
title_full Avaliação de biomarcadores associados a sepse no período neonatal
title_fullStr Avaliação de biomarcadores associados a sepse no período neonatal
title_full_unstemmed Avaliação de biomarcadores associados a sepse no período neonatal
title_sort Avaliação de biomarcadores associados a sepse no período neonatal
author Barros, Lidia Mayrink de
author_facet Barros, Lidia Mayrink de
author_role author
dc.contributor.none.fl_str_mv Abdallah, Vânia Olivetti Steffen
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794569U1
Ferreira, Daniela Marques de Lima Mota
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4767722Z8
Goulart Filho, Luiz Ricardo
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4781012P8
Vergara, Mario León Silva
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4799608Y0
Moura, Magda Regina Silva
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4420624H7
Maia, Yara Cristina de Paiva
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4133677P3
Bonini, Marília Martins Prado
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4515747T6
dc.contributor.author.fl_str_mv Barros, Lidia Mayrink de
dc.subject.por.fl_str_mv Sepse neonatal
Neonatal sepsis
Recém-nascido pré-termo de muito baixo peso
Very low weight preterm newborn
Citocinas
Cytokines
Biomarcadores
Biomarkers
Cordão umbilical
Umbilical cord
Proteína quimiotática de monócitos 1 MCP-)
Monocyte chemotactic protein 1 MCP-1
Interleucina 5 IL-5
Interleukin 5 IL-5
Interleucina 6 IL-6
Interleukin 6 IL-6
Fator de crescimento endotelial vascular VEGF
Vascular endothelial growth factor VEGF
Ciências médicas
CNPQ::CIENCIAS DA SAUDE::MEDICINA::SAUDE MATERNO-INFANTIL
topic Sepse neonatal
Neonatal sepsis
Recém-nascido pré-termo de muito baixo peso
Very low weight preterm newborn
Citocinas
Cytokines
Biomarcadores
Biomarkers
Cordão umbilical
Umbilical cord
Proteína quimiotática de monócitos 1 MCP-)
Monocyte chemotactic protein 1 MCP-1
Interleucina 5 IL-5
Interleukin 5 IL-5
Interleucina 6 IL-6
Interleukin 6 IL-6
Fator de crescimento endotelial vascular VEGF
Vascular endothelial growth factor VEGF
Ciências médicas
CNPQ::CIENCIAS DA SAUDE::MEDICINA::SAUDE MATERNO-INFANTIL
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019-03-29T18:22:57Z
2019-03-29T18:22:57Z
2019-02-08
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv BARROS, Lidia Mayrink de. Avaliação de biomarcadores associados a sepse no período neonatal. 2019. 122 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2019. DOI http://dx.doi.org/10.14393/ufu.te.2019.1213
https://repositorio.ufu.br/handle/123456789/24743
http://dx.doi.org/10.14393/ufu.te.2019.1213
identifier_str_mv BARROS, Lidia Mayrink de. Avaliação de biomarcadores associados a sepse no período neonatal. 2019. 122 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2019. DOI http://dx.doi.org/10.14393/ufu.te.2019.1213
url https://repositorio.ufu.br/handle/123456789/24743
http://dx.doi.org/10.14393/ufu.te.2019.1213
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Uberlândia
Brasil
Programa de Pós-graduação em Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal de Uberlândia
Brasil
Programa de Pós-graduação em Ciências da Saúde
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFU
instname:Universidade Federal de Uberlândia (UFU)
instacron:UFU
instname_str Universidade Federal de Uberlândia (UFU)
instacron_str UFU
institution UFU
reponame_str Repositório Institucional da UFU
collection Repositório Institucional da UFU
repository.name.fl_str_mv Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)
repository.mail.fl_str_mv diinf@dirbi.ufu.br
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