Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial

Anne M. Plomgaard; Thomas Alderliesten; Topun Austin; Frank Van Bel; Manon Benders; Olivier Claris; Eugene Dempsey; Monica Fumagalli; Christian Gluud; Cornelia Hagmann; Simon Hyttel-Sorensen; Petra Lemmers; Wim Van Oeveren; Adelina Pellicer; Tue H. Petersen; Gerhard Pichler; Per Winkel; Gorm Greisen

doi:10.1371/journal.pone.0173440

Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial

Anne M. Plomgaard, Thomas Alderliesten, Topun Austin, Frank Van Bel, Manon Benders, Olivier Claris, Eugene Dempsey, Monica Fumagalli, Christian Gluud, Cornelia Hagmann, Simon Hyttel-Sorensen, Petra Lemmers, Wim Van Oeveren, Adelina Pellicer, Tue H. Petersen, Gerhard Pichler, Per Winkel, Gorm Greisen

Department of Clinical Medicine

25 Citations (Scopus)

88 Downloads (Pure)

Abstract

Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the intervention and the control group. The primary outcome was the reduction in the burden of cerebral hypo- and hyperoxia between the two groups. In this study we describe the associations between the burden of cerebral hypo- and hyperoxia, regardless of allocation to intervention or control group, and the biomarkers of brain injury from birth till term equivalent age that was collected as secondary and explorative outcomes in the SafeBoosC II trial. Methods Cerebral oxygenation was continuously monitored during the first 72h of life in 166 extremely preterm infants. Cranial ultrasound was performed at day 1,4,7,14, and 35 and at term. Electroencephalogram (EEG) was recorded at 64h. Blood-samples taken at 6 and 64 hours were analysed for the brain injury biomarkers; S100beta, brain-fatty-acid-binding-protein, and neuroketal. All analyses were conducted post hoc. Results Significantly more infants with a cerebral burden of hypoxia within the 4^th quartile versus infants within quartile 1-3 were diagnosed with severe intracranial haemorrhage (11/39 versus 11/117, p = 0.003), had low burst rate on EEG (12/28 versus 21/103, p = 0.015), or died (14/41 versus 18/123, p = 0.006), whereas none of these events were significantly associated with cerebral hyperoxia. The blood biomarkers were not significantly associated with the burden of cerebral hypo- or hyperoxia. Conclusions The explorative analysis showed that early burden of cerebral hypoxia, but not hyperoxia was significantly associated with low brain electrical activity and severe intracranial haemorrhage while none of the three blood biomarkers were associated with the burden of either cerebral hypo- or hyperoxia.

Original language	English
Article number	e0173440
Journal	PLoS ONE
Volume	12
Issue number	3
Number of pages	15
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0173440
Publication status	Published - Mar 2017

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Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trialFinal published version, 1.64 MBLicence: CC BY

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Plomgaard, A. M., Alderliesten, T., Austin, T., Van Bel, F., Benders, M., Claris, O., Dempsey, E., Fumagalli, M., Gluud, C., Hagmann, C., Hyttel-Sorensen, S., Lemmers, P., Van Oeveren, W., Pellicer, A., Petersen, T. H., Pichler, G., Winkel, P., & Greisen, G. (2017). Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial. PLoS ONE, 12(3), Article e0173440. https://doi.org/10.1371/journal.pone.0173440

Plomgaard, AM, Alderliesten, T, Austin, T, Van Bel, F, Benders, M, Claris, O, Dempsey, E, Fumagalli, M, Gluud, C, Hagmann, C, Hyttel-Sorensen, S, Lemmers, P, Van Oeveren, W, Pellicer, A, Petersen, TH, Pichler, G, Winkel, P & Greisen, G 2017, 'Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial', PLoS ONE, vol. 12, no. 3, e0173440. https://doi.org/10.1371/journal.pone.0173440

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title = "Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial",

abstract = "Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the intervention and the control group. The primary outcome was the reduction in the burden of cerebral hypo- and hyperoxia between the two groups. In this study we describe the associations between the burden of cerebral hypo- and hyperoxia, regardless of allocation to intervention or control group, and the biomarkers of brain injury from birth till term equivalent age that was collected as secondary and explorative outcomes in the SafeBoosC II trial. Methods Cerebral oxygenation was continuously monitored during the first 72h of life in 166 extremely preterm infants. Cranial ultrasound was performed at day 1,4,7,14, and 35 and at term. Electroencephalogram (EEG) was recorded at 64h. Blood-samples taken at 6 and 64 hours were analysed for the brain injury biomarkers; S100beta, brain-fatty-acid-binding-protein, and neuroketal. All analyses were conducted post hoc. Results Significantly more infants with a cerebral burden of hypoxia within the 4th quartile versus infants within quartile 1-3 were diagnosed with severe intracranial haemorrhage (11/39 versus 11/117, p = 0.003), had low burst rate on EEG (12/28 versus 21/103, p = 0.015), or died (14/41 versus 18/123, p = 0.006), whereas none of these events were significantly associated with cerebral hyperoxia. The blood biomarkers were not significantly associated with the burden of cerebral hypo- or hyperoxia. Conclusions The explorative analysis showed that early burden of cerebral hypoxia, but not hyperoxia was significantly associated with low brain electrical activity and severe intracranial haemorrhage while none of the three blood biomarkers were associated with the burden of either cerebral hypo- or hyperoxia.",

author = "Plomgaard, {Anne M.} and Thomas Alderliesten and Topun Austin and {Van Bel}, Frank and Manon Benders and Olivier Claris and Eugene Dempsey and Monica Fumagalli and Christian Gluud and Cornelia Hagmann and Simon Hyttel-Sorensen and Petra Lemmers and {Van Oeveren}, Wim and Adelina Pellicer and Petersen, {Tue H.} and Gerhard Pichler and Per Winkel and Gorm Greisen",

year = "2017",

month = mar,

doi = "10.1371/journal.pone.0173440",

language = "English",

volume = "12",

journal = "PLoS ONE",

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publisher = "Public Library of Science",

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TY - JOUR

T1 - Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial

AU - Plomgaard, Anne M.

AU - Alderliesten, Thomas

AU - Austin, Topun

AU - Van Bel, Frank

AU - Benders, Manon

AU - Claris, Olivier

AU - Dempsey, Eugene

AU - Fumagalli, Monica

AU - Gluud, Christian

AU - Hagmann, Cornelia

AU - Hyttel-Sorensen, Simon

AU - Lemmers, Petra

AU - Van Oeveren, Wim

AU - Pellicer, Adelina

AU - Petersen, Tue H.

AU - Pichler, Gerhard

AU - Winkel, Per

AU - Greisen, Gorm

PY - 2017/3

Y1 - 2017/3

N2 - Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the intervention and the control group. The primary outcome was the reduction in the burden of cerebral hypo- and hyperoxia between the two groups. In this study we describe the associations between the burden of cerebral hypo- and hyperoxia, regardless of allocation to intervention or control group, and the biomarkers of brain injury from birth till term equivalent age that was collected as secondary and explorative outcomes in the SafeBoosC II trial. Methods Cerebral oxygenation was continuously monitored during the first 72h of life in 166 extremely preterm infants. Cranial ultrasound was performed at day 1,4,7,14, and 35 and at term. Electroencephalogram (EEG) was recorded at 64h. Blood-samples taken at 6 and 64 hours were analysed for the brain injury biomarkers; S100beta, brain-fatty-acid-binding-protein, and neuroketal. All analyses were conducted post hoc. Results Significantly more infants with a cerebral burden of hypoxia within the 4th quartile versus infants within quartile 1-3 were diagnosed with severe intracranial haemorrhage (11/39 versus 11/117, p = 0.003), had low burst rate on EEG (12/28 versus 21/103, p = 0.015), or died (14/41 versus 18/123, p = 0.006), whereas none of these events were significantly associated with cerebral hyperoxia. The blood biomarkers were not significantly associated with the burden of cerebral hypo- or hyperoxia. Conclusions The explorative analysis showed that early burden of cerebral hypoxia, but not hyperoxia was significantly associated with low brain electrical activity and severe intracranial haemorrhage while none of the three blood biomarkers were associated with the burden of either cerebral hypo- or hyperoxia.

AB - Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the intervention and the control group. The primary outcome was the reduction in the burden of cerebral hypo- and hyperoxia between the two groups. In this study we describe the associations between the burden of cerebral hypo- and hyperoxia, regardless of allocation to intervention or control group, and the biomarkers of brain injury from birth till term equivalent age that was collected as secondary and explorative outcomes in the SafeBoosC II trial. Methods Cerebral oxygenation was continuously monitored during the first 72h of life in 166 extremely preterm infants. Cranial ultrasound was performed at day 1,4,7,14, and 35 and at term. Electroencephalogram (EEG) was recorded at 64h. Blood-samples taken at 6 and 64 hours were analysed for the brain injury biomarkers; S100beta, brain-fatty-acid-binding-protein, and neuroketal. All analyses were conducted post hoc. Results Significantly more infants with a cerebral burden of hypoxia within the 4th quartile versus infants within quartile 1-3 were diagnosed with severe intracranial haemorrhage (11/39 versus 11/117, p = 0.003), had low burst rate on EEG (12/28 versus 21/103, p = 0.015), or died (14/41 versus 18/123, p = 0.006), whereas none of these events were significantly associated with cerebral hyperoxia. The blood biomarkers were not significantly associated with the burden of cerebral hypo- or hyperoxia. Conclusions The explorative analysis showed that early burden of cerebral hypoxia, but not hyperoxia was significantly associated with low brain electrical activity and severe intracranial haemorrhage while none of the three blood biomarkers were associated with the burden of either cerebral hypo- or hyperoxia.

U2 - 10.1371/journal.pone.0173440

DO - 10.1371/journal.pone.0173440

M3 - Journal article

C2 - 28328980

AN - SCOPUS:85015981730

SN - 1932-6203

VL - 12

JO - PLoS ONE

JF - PLoS ONE

IS - 3

M1 - e0173440

ER -

Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial

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