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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere0173440
JournalPLoS One
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

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hyperoxia
Brain Hypoxia
Hyperoxia
Oxygenation
Biomarkers
Brain Injuries
hypoxia
biomarkers
Brain
brain
Blood
Electroencephalography
electroencephalography
Intracranial Hemorrhages
Fatty Acid-Binding Proteins
Near infrared spectroscopy
hemorrhage
blood
Extremely Premature Infants
fatty acid-binding proteins

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Plomgaard, A. M., Alderliesten, T., Austin, T., Van Bel, F., Benders, M., Claris, O., ... Greisen, G. (2017). Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial. PLoS One, 12(3), [e0173440]. https://doi.org/10.1371/journal.pone.0173440

Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial. / Plomgaard, Anne M.; Alderliesten, Thomas; Austin, Topun; Van Bel, Frank; Benders, Manon; Claris, Olivier; Dempsey, Eugene; Fumagalli, Monica; Gluud, Christian; Hagmann, Cornelia; Hyttel-Sorensen, Simon; Lemmers, Petra; Van Oeveren, Wim; Pellicer, Adelina; Petersen, Tue H.; Pichler, Gerhard; Winkel, Per; Greisen, Gorm.

In: PLoS One, Vol. 12, No. 3, e0173440, 01.03.2017.

Research output: Contribution to journalArticle

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
Plomgaard AM, Alderliesten T, Austin T, Van Bel F, Benders M, Claris O et al. Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial. PLoS One. 2017 Mar 1;12(3). e0173440. https://doi.org/10.1371/journal.pone.0173440
Plomgaard, Anne M. ; Alderliesten, Thomas ; Austin, Topun ; Van Bel, Frank ; Benders, Manon ; Claris, Olivier ; Dempsey, Eugene ; Fumagalli, Monica ; Gluud, Christian ; Hagmann, Cornelia ; Hyttel-Sorensen, Simon ; Lemmers, Petra ; Van Oeveren, Wim ; Pellicer, Adelina ; Petersen, Tue H. ; Pichler, Gerhard ; Winkel, Per ; Greisen, Gorm. / Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial. In: PLoS One. 2017 ; Vol. 12, No. 3.
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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.",
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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

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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.

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