Raised Plasma Neurofilament Light Protein Levels Are Associated with Abnormal MRI Outcomes in Newborns Undergoing Therapeutic Hypothermia
Aims and hypothesisHypoxic-ischemic encephalopathy (HIE) remains an important cause of death and disability in newborns. Mild therapeutic hypothermia (TH) is safe and effective; however, there are no tissue biomarkers available at the bedside to select babies for treatment. The aim of this study was...
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doaj-2c6c8138cfb74e3f9e3029c78a2666c62020-11-24T23:28:51ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-03-01910.3389/fneur.2018.00086310895Raised Plasma Neurofilament Light Protein Levels Are Associated with Abnormal MRI Outcomes in Newborns Undergoing Therapeutic HypothermiaDivyen K. Shah0Divyen K. Shah1Vennila Ponnusamy2Vennila Ponnusamy3Jane Evanson4Olga Kapellou5Georgia Ekitzidou6Neelam Gupta7Paul Clarke8Adina T. Michael-Titus9Ping K. Yip10The Royal London Hospital, Barts Health NHS Trust, London, United KingdomThe Centre for Neuroscience and Trauma, Barts and The London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, United KingdomCentre for Genomics and Child Health, Barts and The London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, United KingdomAshford and St. Peter’s Hospitals NHS Foundation Trust, Chertsey, United KingdomThe Royal London Hospital, Barts Health NHS Trust, London, United KingdomHomerton University Hospital NHS Foundation Trust, London, United KingdomHomerton University Hospital NHS Foundation Trust, London, United KingdomUniversity Hospital Southampton, Southampton, United KingdomNorfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United KingdomThe Royal London Hospital, Barts Health NHS Trust, London, United KingdomThe Royal London Hospital, Barts Health NHS Trust, London, United KingdomAims and hypothesisHypoxic-ischemic encephalopathy (HIE) remains an important cause of death and disability in newborns. Mild therapeutic hypothermia (TH) is safe and effective; however, there are no tissue biomarkers available at the bedside to select babies for treatment. The aim of this study was to show that it is feasible to study plasma neurofilament light (NfL) levels from newborns and to evaluate their temporal course. Hypothesis: Raised plasma NFL protein levels from newborns who undergo TH after HIE are associated with abnormal MRI outcomes.MethodsBetween February 2014 and January 2016, term newborns with HIE treated with TH for 72 h had plasma samples taken at three time points: (i) after the infant had reached target temperature, (ii) prior to commencing rewarming, and (iii) after completing rewarming. Infants with mild HIE who did not receive TH had a single specimen taken. NfL protein was analyzed using an enzyme-linked immunosorbent assay.ResultsTwenty-six newborns with moderate–severe HIE treated with TH were studied. Half of these had cerebral MRI predictive of an unfavorable outcome. Plasma NfL levels were significantly higher in the TH group with unfavorable outcome (median age 18 h) compared to levels from both the mild HIE group and TH group with favorable outcome (F = 25.83, p < 0.0001). Newborns who had MRIs predictive of unfavorable outcome had significantly higher NfL levels compared to those with favorable outcomes, at all three time points (mixed models, F = 27.63, p < 0.001). A cutoff NfL level >29 pg/mL at 24 h is predictive of an unfavorable outcome [sensitivity 77%, specificity 69%, positive predictive value (PPV) 67%, negative predictive value (NPV) 72%] with increasing predictive value until after rewarming (sensitivity 92%, specificity 92%, PPV 92%, NPV 86%).Interpretation of researchPlasma NfL protein levels may be a useful biomarker of unfavorable MRI outcomes in newborns with moderate–severe HIE and may assist in selecting newborns for adjunctive neuroprotective interventions. Larger studies with NfL testing at earlier time points are required.http://journal.frontiersin.org/article/10.3389/fneur.2018.00086/fullneurofilament proteinshypoxic-ischemic encephalopathytherapeutic hypothermiaMRI imagingneuroprotectionbiomarkers |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Divyen K. Shah Divyen K. Shah Vennila Ponnusamy Vennila Ponnusamy Jane Evanson Olga Kapellou Georgia Ekitzidou Neelam Gupta Paul Clarke Adina T. Michael-Titus Ping K. Yip |
spellingShingle |
Divyen K. Shah Divyen K. Shah Vennila Ponnusamy Vennila Ponnusamy Jane Evanson Olga Kapellou Georgia Ekitzidou Neelam Gupta Paul Clarke Adina T. Michael-Titus Ping K. Yip Raised Plasma Neurofilament Light Protein Levels Are Associated with Abnormal MRI Outcomes in Newborns Undergoing Therapeutic Hypothermia Frontiers in Neurology neurofilament proteins hypoxic-ischemic encephalopathy therapeutic hypothermia MRI imaging neuroprotection biomarkers |
author_facet |
Divyen K. Shah Divyen K. Shah Vennila Ponnusamy Vennila Ponnusamy Jane Evanson Olga Kapellou Georgia Ekitzidou Neelam Gupta Paul Clarke Adina T. Michael-Titus Ping K. Yip |
author_sort |
Divyen K. Shah |
title |
Raised Plasma Neurofilament Light Protein Levels Are Associated with Abnormal MRI Outcomes in Newborns Undergoing Therapeutic Hypothermia |
title_short |
Raised Plasma Neurofilament Light Protein Levels Are Associated with Abnormal MRI Outcomes in Newborns Undergoing Therapeutic Hypothermia |
title_full |
Raised Plasma Neurofilament Light Protein Levels Are Associated with Abnormal MRI Outcomes in Newborns Undergoing Therapeutic Hypothermia |
title_fullStr |
Raised Plasma Neurofilament Light Protein Levels Are Associated with Abnormal MRI Outcomes in Newborns Undergoing Therapeutic Hypothermia |
title_full_unstemmed |
Raised Plasma Neurofilament Light Protein Levels Are Associated with Abnormal MRI Outcomes in Newborns Undergoing Therapeutic Hypothermia |
title_sort |
raised plasma neurofilament light protein levels are associated with abnormal mri outcomes in newborns undergoing therapeutic hypothermia |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2018-03-01 |
description |
Aims and hypothesisHypoxic-ischemic encephalopathy (HIE) remains an important cause of death and disability in newborns. Mild therapeutic hypothermia (TH) is safe and effective; however, there are no tissue biomarkers available at the bedside to select babies for treatment. The aim of this study was to show that it is feasible to study plasma neurofilament light (NfL) levels from newborns and to evaluate their temporal course. Hypothesis: Raised plasma NFL protein levels from newborns who undergo TH after HIE are associated with abnormal MRI outcomes.MethodsBetween February 2014 and January 2016, term newborns with HIE treated with TH for 72 h had plasma samples taken at three time points: (i) after the infant had reached target temperature, (ii) prior to commencing rewarming, and (iii) after completing rewarming. Infants with mild HIE who did not receive TH had a single specimen taken. NfL protein was analyzed using an enzyme-linked immunosorbent assay.ResultsTwenty-six newborns with moderate–severe HIE treated with TH were studied. Half of these had cerebral MRI predictive of an unfavorable outcome. Plasma NfL levels were significantly higher in the TH group with unfavorable outcome (median age 18 h) compared to levels from both the mild HIE group and TH group with favorable outcome (F = 25.83, p < 0.0001). Newborns who had MRIs predictive of unfavorable outcome had significantly higher NfL levels compared to those with favorable outcomes, at all three time points (mixed models, F = 27.63, p < 0.001). A cutoff NfL level >29 pg/mL at 24 h is predictive of an unfavorable outcome [sensitivity 77%, specificity 69%, positive predictive value (PPV) 67%, negative predictive value (NPV) 72%] with increasing predictive value until after rewarming (sensitivity 92%, specificity 92%, PPV 92%, NPV 86%).Interpretation of researchPlasma NfL protein levels may be a useful biomarker of unfavorable MRI outcomes in newborns with moderate–severe HIE and may assist in selecting newborns for adjunctive neuroprotective interventions. Larger studies with NfL testing at earlier time points are required. |
topic |
neurofilament proteins hypoxic-ischemic encephalopathy therapeutic hypothermia MRI imaging neuroprotection biomarkers |
url |
http://journal.frontiersin.org/article/10.3389/fneur.2018.00086/full |
work_keys_str_mv |
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