title: Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial.
abstract: OBJECTIVE
  To determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy (NIRS) oximetry.
  
  
  METHODS
  Phase II randomised, single blinded, parallel clinical trial.
  
  
  METHODS
  Eight tertiary neonatal intensive care units in eight European countries.
  
  
  METHODS
  166 extremely preterm infants born before 28 weeks of gestation: 86 were randomised to cerebral NIRS monitoring and 80 to blinded NIRS monitoring. The only exclusion criterion was a decision not to provide life support.
  
  
  METHODS
  Monitoring of cerebral oxygenation using NIRS in combination with a dedicated treatment guideline during the first 72 hours of life (experimental) compared with blinded NIRS oxygenation monitoring with standard care (control).
  
  
  METHODS
  The primary outcome measure was the time spent outside the target range of 55-85% for cerebral oxygenation multiplied by the mean absolute deviation, expressed in %hours (burden of hypoxia and hyperoxia). One hour with an oxygenation of 50% gives 5%hours of hypoxia. Secondary outcomes were all cause mortality at term equivalent age and a brain injury score assessed by cerebral ultrasonography.
  
  
  METHODS
  Allocation sequence 1:1 with block sizes 4 and 6 in random order concealed for the investigators. The allocation was stratified for gestational age (<26 weeks or ≥ 26 weeks).
  
  
  METHODS
  Cerebral oxygenation measurements were blinded in the control group. All outcome assessors were blinded to group allocation.
  
  
  RESULTS
  The 86 infants randomised to the NIRS group had a median burden of hypoxia and hyperoxia of 36.1%hours (interquartile range 9.2-79.5%hours) compared with 81.3 (38.5-181.3) %hours in the control group, a reduction of 58% (95% confidence interval 35% to 73%, P<0.001). In the experimental group the median burden of hypoxia was 16.6 (interquartile range 5.4-68.1) %hours, compared with 53.6 (17.4-171.3) %hours in the control group (P=0.0012). The median burden of hyperoxia was similar between the groups: 1.2 (interquartile range 0.3-9.6) %hours in the experimental group compared with 1.1 (0.1-23.4) %hours in the control group (P=0.98). We found no statistically significant differences between the two groups at term corrected age. No severe adverse reactions were associated with the device.
  
  
  CONCLUSIONS
  Cerebral oxygenation was stabilised in extremely preterm infants using a dedicated treatment guideline in combination with cerebral NIRS monitoring.Trial registration ClinicalTrial.gov NCT01590316.
authors.affiliation: Department of Neonatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Hyttel-Sorensen
authors.affiliation: Department of Neonatology, La Paz University Hospital, Madrid, Spain.
authors.forename: Adelina
authors.initials: A
authors.lastname: Pellicer
authors.affiliation: University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Alderliesten
authors.affiliation: Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: Topun
authors.initials: T
authors.lastname: Austin
authors.affiliation: University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.affiliation: University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, Netherlands Centre of the Developing Brain, King's College London, London, UK.
authors.forename: Manon
authors.initials: M
authors.lastname: Benders
authors.affiliation: Department of Neonatology, Hopital Femme Mere Enfants, Bron, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Claris
authors.affiliation: Department of Paediatrics and Child Health, University College Cork, Cork, Republic of Ireland.
authors.forename: Eugene
authors.initials: E
authors.lastname: Dempsey
authors.affiliation: Department of Neonatology, University Children's Hospital Tübingen, Tübingen, Germany.
authors.forename: Axel R
authors.initials: AR
authors.lastname: Franz
authors.affiliation: NICU, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Fumagalli
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.affiliation: Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Berit
authors.initials: B
authors.lastname: Grevstad
authors.affiliation: Division of Neonatology, University of Zurich, Zurich, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hagmann
authors.affiliation: University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Lemmers
authors.affiliation: Haemoscan, Groningen, Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: van Oeveren
authors.affiliation: Department of Pediatrics, Medical University of Graz, Graz, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Pichler
authors.affiliation: Department of Neonatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Anne Mette
authors.initials: AM
authors.lastname: Plomgaard
authors.affiliation: Department of Neonatology, La Paz University Hospital, Madrid, Spain Center for Biomedical Technology, Technical University of Madrid, Madrid, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Riera
authors.affiliation: Department of Neonatology, La Paz University Hospital, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Sanchez
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Winkel
authors.affiliation: Biomedical Optics Research Laboratory, Division of Neonatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Department of Neonatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Gorm
authors.initials: G
authors.lastname: Greisen
mesh_terms: D001921:Brain / Q000098:blood supply*; D002560:Cerebrovascular Circulation; D002985:Clinical Protocols; D005060:Europe; D019983:Guideline Adherence; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis* / Q000473:pathology; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D015931:Intensive Care, Neonatal; D008991:Monitoring, Physiologic / Q000379:methods*; D010092:Oximetry / Q000379:methods; D017410:Practice Guidelines as Topic; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013997:Time Factors; D016896:Treatment Outcome