title: Brain injury in the international multicenter randomized SafeBoosC phase II feasibility trial: cranial ultrasound and magnetic resonance imaging assessments.
abstract: BACKGROUND
  Abnormal cerebral perfusion during the first days of life in preterm infants is associated with higher grades of intraventricular hemorrhages and lower developmental score. In SafeBoosC II, we obtained a significant reduction of cerebral hypoxia by monitoring cerebral oxygenation in combination with a treatment guideline. Here, we describe (i) difference in brain injury between groups, (ii) feasibility of serial cranial ultrasound (cUS) and magnetic resonance imaging (MRI), (iii) local and central cUS assessment.
  
  
  METHODS
  Hundred and sixty-six extremely preterm infants were included. cUS was scheduled for day 1, 4, 7, 14, and 35 and at term-equivalent age (TEA). cUS was assessed locally (unblinded) and centrally (blinded). MRI at TEA was assessed centrally (blinded). Brain injury classification: no, mild/moderate, or severe.
  
  
  RESULTS
  Severe brain injury did not differ significantly between groups: cUS (experimental 10/80, control 18/77, P = 0.32) and MRI (5/46 vs. 3/38, P = 0.72). Kappa values for local and central readers were moderate-to-good for severe and poor-to-moderate for mild/moderate injuries. At TEA, cUS and MRI were assessed in 72 and 64%, respectively.
  
  
  CONCLUSIONS
  There was no difference in severe brain injury between groups. Acquiring cUS and MRI according the standard operating procedures must be improved for future trials. Whether monitoring cerebral oxygenation during the first 72 h of life prevents brain injury should be evaluated in larger multicenter trials.
authors.affiliation: Department of Neonatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Plomgaard
authors.affiliation: Clinic 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, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Alderliesten
authors.affiliation: Rosie Maternity 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, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.affiliation: Department of Neonatology, Hospital 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, Ireland.
authors.forename: Eugene
authors.initials: E
authors.lastname: Dempsey
authors.affiliation: Department of Neonatology, University of Tuebingen, Tübingen, Germany.
authors.forename: Axel
authors.identifier: http://orcid.org/0000-0001-5066-0857
authors.initials: A
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: Department of Neonatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Gorm
authors.initials: G
authors.lastname: Greisen
authors.affiliation: Department of Neonatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Hyttel-Sorensen
authors.affiliation: University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Lemmers
authors.affiliation: Department of Neonatology, La Paz University Hospital, Madrid, Spain.
authors.forename: Adelina
authors.initials: A
authors.lastname: Pellicer
authors.affiliation: Department of Pediatrics, Medical University of Graz, Graz, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Pichler
authors.affiliation: University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Manon
authors.identifier: http://orcid.org/0000-0001-5491-9168
authors.initials: M
authors.lastname: Benders
mesh_terms: D001724:Birth Weight; D001930:Brain Injuries / Q000000981:diagnostic imaging* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000473:pathology; D002560:Cerebrovascular Circulation; D005240:Feasibility Studies; D005865:Gestational Age; D006470:Hemorrhage / Q000503:physiopathology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000000981:diagnostic imaging* / Q000473:pathology; D007391:International Cooperation; D008279:Magnetic Resonance Imaging; D015588:Observer Variation; D010100:Oxygen / Q000737:chemistry; D010477:Perfusion; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography
chemical_list: D010100:Oxygen