Cargando…
Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial
BACKGROUND: In the Preterm Erythropoietin (Epo) NeUroproTection (PENUT) Trial, potential biomarkers of neurological injury were measured to determine their association with outcomes at two years of age and whether Epo treatment decreased markers of inflammation in extremely preterm (<28 weeks’ ge...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498235/ https://www.ncbi.nlm.nih.gov/pubmed/34619638 http://dx.doi.org/10.1016/j.ebiom.2021.103605 |
_version_ | 1784580126305943552 |
---|---|
author | Wood, Thomas R. Parikh, Pratik Comstock, Bryan A. Law, Janessa B. Bammler, Theo K. Kuban, Karl C. Mayock, Dennis E. Heagerty, Patrick J. Juul, Sandra |
author_facet | Wood, Thomas R. Parikh, Pratik Comstock, Bryan A. Law, Janessa B. Bammler, Theo K. Kuban, Karl C. Mayock, Dennis E. Heagerty, Patrick J. Juul, Sandra |
author_sort | Wood, Thomas R. |
collection | PubMed |
description | BACKGROUND: In the Preterm Erythropoietin (Epo) NeUroproTection (PENUT) Trial, potential biomarkers of neurological injury were measured to determine their association with outcomes at two years of age and whether Epo treatment decreased markers of inflammation in extremely preterm (<28 weeks’ gestation) infants. METHODS: Plasma Epo was measured (n=391 Epo, n=384 placebo) within 24h after birth (baseline), 30min after study drug administration (day 7), 30min before study drug (day 9), and on day 14. A subset of infants (n=113 Epo, n=107 placebo) had interferon-gamma (IFN-γ), Interleukin (IL)-6, IL-8, IL-10, Tau, and tumour necrosis factor-α (TNF-α) levels evaluated at baseline, day 7 and 14. Infants were then evaluated at 2 years using the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III). FINDINGS: Elevated baseline Epo was associated with increased risk of death or severe disability (BSID-III Motor and Cognitive subscales <70 or severe cerebral palsy). No difference in other biomarkers were seen between treatment groups at any time, though Epo appeared to mitigate the association between elevated baseline IL-6 and lower BSID-III scores in survivors. Elevated baseline, day 7 and 14 Tau concentrations were associated with worse BSID-III Cognitive, Motor, and Language skills at two years. INTERPRETATION: Elevated Epo at baseline and elevated Tau in the first two weeks after birth predict poor outcomes in infants born extremely preterm. However, no clear prognostic cut-off values are apparent, and further work is required before these biomarkers can be widely implemented in clinical practice. FUNDING: PENUT was funded by the National Institute of Neurological Disorders and Stroke (U01NS077955 and U01NS077953). |
format | Online Article Text |
id | pubmed-8498235 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84982352021-10-12 Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial Wood, Thomas R. Parikh, Pratik Comstock, Bryan A. Law, Janessa B. Bammler, Theo K. Kuban, Karl C. Mayock, Dennis E. Heagerty, Patrick J. Juul, Sandra EBioMedicine Research paper BACKGROUND: In the Preterm Erythropoietin (Epo) NeUroproTection (PENUT) Trial, potential biomarkers of neurological injury were measured to determine their association with outcomes at two years of age and whether Epo treatment decreased markers of inflammation in extremely preterm (<28 weeks’ gestation) infants. METHODS: Plasma Epo was measured (n=391 Epo, n=384 placebo) within 24h after birth (baseline), 30min after study drug administration (day 7), 30min before study drug (day 9), and on day 14. A subset of infants (n=113 Epo, n=107 placebo) had interferon-gamma (IFN-γ), Interleukin (IL)-6, IL-8, IL-10, Tau, and tumour necrosis factor-α (TNF-α) levels evaluated at baseline, day 7 and 14. Infants were then evaluated at 2 years using the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III). FINDINGS: Elevated baseline Epo was associated with increased risk of death or severe disability (BSID-III Motor and Cognitive subscales <70 or severe cerebral palsy). No difference in other biomarkers were seen between treatment groups at any time, though Epo appeared to mitigate the association between elevated baseline IL-6 and lower BSID-III scores in survivors. Elevated baseline, day 7 and 14 Tau concentrations were associated with worse BSID-III Cognitive, Motor, and Language skills at two years. INTERPRETATION: Elevated Epo at baseline and elevated Tau in the first two weeks after birth predict poor outcomes in infants born extremely preterm. However, no clear prognostic cut-off values are apparent, and further work is required before these biomarkers can be widely implemented in clinical practice. FUNDING: PENUT was funded by the National Institute of Neurological Disorders and Stroke (U01NS077955 and U01NS077953). Elsevier 2021-10-04 /pmc/articles/PMC8498235/ /pubmed/34619638 http://dx.doi.org/10.1016/j.ebiom.2021.103605 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Wood, Thomas R. Parikh, Pratik Comstock, Bryan A. Law, Janessa B. Bammler, Theo K. Kuban, Karl C. Mayock, Dennis E. Heagerty, Patrick J. Juul, Sandra Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial |
title | Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial |
title_full | Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial |
title_fullStr | Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial |
title_full_unstemmed | Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial |
title_short | Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial |
title_sort | early biomarkers of hypoxia and inflammation and two-year neurodevelopmental outcomes in the preterm erythropoietin neuroprotection (penut) trial |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498235/ https://www.ncbi.nlm.nih.gov/pubmed/34619638 http://dx.doi.org/10.1016/j.ebiom.2021.103605 |
work_keys_str_mv | AT woodthomasr earlybiomarkersofhypoxiaandinflammationandtwoyearneurodevelopmentaloutcomesinthepretermerythropoietinneuroprotectionpenuttrial AT parikhpratik earlybiomarkersofhypoxiaandinflammationandtwoyearneurodevelopmentaloutcomesinthepretermerythropoietinneuroprotectionpenuttrial AT comstockbryana earlybiomarkersofhypoxiaandinflammationandtwoyearneurodevelopmentaloutcomesinthepretermerythropoietinneuroprotectionpenuttrial AT lawjanessab earlybiomarkersofhypoxiaandinflammationandtwoyearneurodevelopmentaloutcomesinthepretermerythropoietinneuroprotectionpenuttrial AT bammlertheok earlybiomarkersofhypoxiaandinflammationandtwoyearneurodevelopmentaloutcomesinthepretermerythropoietinneuroprotectionpenuttrial AT kubankarlc earlybiomarkersofhypoxiaandinflammationandtwoyearneurodevelopmentaloutcomesinthepretermerythropoietinneuroprotectionpenuttrial AT mayockdennise earlybiomarkersofhypoxiaandinflammationandtwoyearneurodevelopmentaloutcomesinthepretermerythropoietinneuroprotectionpenuttrial AT heagertypatrickj earlybiomarkersofhypoxiaandinflammationandtwoyearneurodevelopmentaloutcomesinthepretermerythropoietinneuroprotectionpenuttrial AT juulsandra earlybiomarkersofhypoxiaandinflammationandtwoyearneurodevelopmentaloutcomesinthepretermerythropoietinneuroprotectionpenuttrial AT earlybiomarkersofhypoxiaandinflammationandtwoyearneurodevelopmentaloutcomesinthepretermerythropoietinneuroprotectionpenuttrial |