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Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes

BACKGROUND: Neonatal encephalopathy (NE) contributes substantially to child mortality and disability globally. We compared cytokine profiles in term Ugandan neonates with and without NE, with and without perinatal infection or inflammation and identified biomarkers predicting neonatal and early chil...

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Autores principales: Pang, Raymand, Mujuni, Brian M., Martinello, Kathryn A., Webb, Emily L., Nalwoga, Angela, Ssekyewa, Julius, Musoke, Margaret, Kurinczuk, Jennifer J., Sewegaba, Margaret, Cowan, Frances M., Cose, Stephen, Nakakeeto, Margaret, Elliott, Alison M., Sebire, Neil J., Klein, Nigel, Robertson, Nicola J., Tann, Cally J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411052/
https://www.ncbi.nlm.nih.gov/pubmed/33674741
http://dx.doi.org/10.1038/s41390-021-01438-1
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author Pang, Raymand
Mujuni, Brian M.
Martinello, Kathryn A.
Webb, Emily L.
Nalwoga, Angela
Ssekyewa, Julius
Musoke, Margaret
Kurinczuk, Jennifer J.
Sewegaba, Margaret
Cowan, Frances M.
Cose, Stephen
Nakakeeto, Margaret
Elliott, Alison M.
Sebire, Neil J.
Klein, Nigel
Robertson, Nicola J.
Tann, Cally J.
author_facet Pang, Raymand
Mujuni, Brian M.
Martinello, Kathryn A.
Webb, Emily L.
Nalwoga, Angela
Ssekyewa, Julius
Musoke, Margaret
Kurinczuk, Jennifer J.
Sewegaba, Margaret
Cowan, Frances M.
Cose, Stephen
Nakakeeto, Margaret
Elliott, Alison M.
Sebire, Neil J.
Klein, Nigel
Robertson, Nicola J.
Tann, Cally J.
author_sort Pang, Raymand
collection PubMed
description BACKGROUND: Neonatal encephalopathy (NE) contributes substantially to child mortality and disability globally. We compared cytokine profiles in term Ugandan neonates with and without NE, with and without perinatal infection or inflammation and identified biomarkers predicting neonatal and early childhood outcomes. METHODS: In this exploratory biomarker study, serum IL-1α, IL-6, IL-8, IL-10, TNFα, and VEGF (<12 h) were compared between NE and non-NE infants with and without perinatal infection/inflammation. Neonatal (severity of NE, mortality) and early childhood (death or neurodevelopmental impairment to 2.5 years) outcomes were assessed. Predictors of outcomes were explored with multivariable linear and logistic regression and receiver-operating characteristic analyses. RESULTS: Cytokine assays on 159 NE and 157 non-NE infants were performed; data on early childhood outcomes were available for 150 and 129, respectively. NE infants had higher IL-10 (p < 0.001), higher IL-6 (p < 0.017), and lower VEGF (p < 0.001) levels. Moderate and severe NE was associated with higher IL-10 levels compared to non-NE infants (p < 0.001). Elevated IL-1α was associated with perinatal infection/inflammation (p = 0.013). Among NE infants, IL-10 predicted neonatal mortality (p = 0.01) and adverse early childhood outcome (adjusted OR 2.28, 95% CI 1.35–3.86, p = 0.002). CONCLUSIONS: Our findings support a potential role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy. IMPACT: Neonatal encephalopathy is a common cause of child death and disability globally. Inflammatory cytokines are potential biomarkers of encephalopathy severity and outcome. In this Ugandan health facility-based cohort, neonatal encephalopathy was associated with elevated serum IL-10 and IL-6, and reduced VEGF at birth. Elevated serum IL-10 within 12 h after birth predicted severity of neonatal encephalopathy, neonatal mortality, and adverse early childhood developmental outcomes, independent of perinatal infection or inflammation, and provides evidence to the contribution of the inflammatory processes. Our findings support a role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy in a sub-Saharan African cohort.
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spelling pubmed-94110522022-08-27 Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes Pang, Raymand Mujuni, Brian M. Martinello, Kathryn A. Webb, Emily L. Nalwoga, Angela Ssekyewa, Julius Musoke, Margaret Kurinczuk, Jennifer J. Sewegaba, Margaret Cowan, Frances M. Cose, Stephen Nakakeeto, Margaret Elliott, Alison M. Sebire, Neil J. Klein, Nigel Robertson, Nicola J. Tann, Cally J. Pediatr Res Clinical Research Article BACKGROUND: Neonatal encephalopathy (NE) contributes substantially to child mortality and disability globally. We compared cytokine profiles in term Ugandan neonates with and without NE, with and without perinatal infection or inflammation and identified biomarkers predicting neonatal and early childhood outcomes. METHODS: In this exploratory biomarker study, serum IL-1α, IL-6, IL-8, IL-10, TNFα, and VEGF (<12 h) were compared between NE and non-NE infants with and without perinatal infection/inflammation. Neonatal (severity of NE, mortality) and early childhood (death or neurodevelopmental impairment to 2.5 years) outcomes were assessed. Predictors of outcomes were explored with multivariable linear and logistic regression and receiver-operating characteristic analyses. RESULTS: Cytokine assays on 159 NE and 157 non-NE infants were performed; data on early childhood outcomes were available for 150 and 129, respectively. NE infants had higher IL-10 (p < 0.001), higher IL-6 (p < 0.017), and lower VEGF (p < 0.001) levels. Moderate and severe NE was associated with higher IL-10 levels compared to non-NE infants (p < 0.001). Elevated IL-1α was associated with perinatal infection/inflammation (p = 0.013). Among NE infants, IL-10 predicted neonatal mortality (p = 0.01) and adverse early childhood outcome (adjusted OR 2.28, 95% CI 1.35–3.86, p = 0.002). CONCLUSIONS: Our findings support a potential role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy. IMPACT: Neonatal encephalopathy is a common cause of child death and disability globally. Inflammatory cytokines are potential biomarkers of encephalopathy severity and outcome. In this Ugandan health facility-based cohort, neonatal encephalopathy was associated with elevated serum IL-10 and IL-6, and reduced VEGF at birth. Elevated serum IL-10 within 12 h after birth predicted severity of neonatal encephalopathy, neonatal mortality, and adverse early childhood developmental outcomes, independent of perinatal infection or inflammation, and provides evidence to the contribution of the inflammatory processes. Our findings support a role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy in a sub-Saharan African cohort. Nature Publishing Group US 2021-03-05 2022 /pmc/articles/PMC9411052/ /pubmed/33674741 http://dx.doi.org/10.1038/s41390-021-01438-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Clinical Research Article
Pang, Raymand
Mujuni, Brian M.
Martinello, Kathryn A.
Webb, Emily L.
Nalwoga, Angela
Ssekyewa, Julius
Musoke, Margaret
Kurinczuk, Jennifer J.
Sewegaba, Margaret
Cowan, Frances M.
Cose, Stephen
Nakakeeto, Margaret
Elliott, Alison M.
Sebire, Neil J.
Klein, Nigel
Robertson, Nicola J.
Tann, Cally J.
Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes
title Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes
title_full Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes
title_fullStr Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes
title_full_unstemmed Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes
title_short Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes
title_sort elevated serum il-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes
topic Clinical Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411052/
https://www.ncbi.nlm.nih.gov/pubmed/33674741
http://dx.doi.org/10.1038/s41390-021-01438-1
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