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Randomized Controlled Trial
. 2017 Mar 22;12(3):e0173440.
doi: 10.1371/journal.pone.0173440. eCollection 2017.

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

Anne M Plomgaard  1 , Thomas Alderliesten  2 , Topun Austin  3 , Frank van Bel  2 , Manon Benders  2 , Olivier Claris  4 , Eugene Dempsey  5 , Monica Fumagalli  6 , Christian Gluud  7 , Cornelia Hagmann  8 , Simon Hyttel-Sorensen  1 , Petra Lemmers  2 , Wim van Oeveren  9 , Adelina Pellicer  10 , Tue H Petersen  11 , Gerhard Pichler  12 , Per Winkel  7 , Gorm Greisen  1
Affiliations
Randomized Controlled Trial

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

Anne M Plomgaard et al. PLoS One. .

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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Conflict of interest statement

Competing Interests: Author WvO received funding from HaemoScan, a commercial company, for this study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Flowchart.
Flow of participants through the SafeBoosC II study.
Fig 2
Fig 2. Risk for adverse outcomes for infants with a burden of cerebral hypoxia within or below the 4th quartile.
Odds ratio (OR) and 95% confidence interval.
Fig 3
Fig 3. Risk for adverse outcomes for infants with a burden of cerebral hyperoxia within or below the 4th quartile.
Odds ratio (OR) and 95% confidence interval.
See this image and copyright information in PMC

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