title: Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE): a prospective multicountry study.
abstract: BACKGROUND
  Despite cooling, adverse outcomes are seen in up to half of the surviving infants after neonatal encephalopathy. A number of novel adjunct drug therapies with cooling have been shown to be highly neuroprotective in animal studies, and are currently awaiting clinical translation. Rigorous evaluation of these therapies in phase II trials using surrogate MR biomarkers may speed up their bench to bedside translation. A recent systematic review of single-centre studies has suggested that MR spectroscopy biomarkers offer the best promise; however, the prognostic accuracy of these biomarkers in cooled encephalopathic babies in a multicentre setting using different MR scan makers is not known.
  
  
  METHODS
  The MR scanners (3 T; Philips, Siemens, GE) in all the participating sites will be harmonised using phantom experiments and healthy adult volunteers before the start of the study. We will then recruit 180 encephalopathic infants treated with whole body cooling from the participating centres. MRI and spectroscopy will be performed within 2 weeks of birth. Neurodevelopmental outcomes will be assessed at 18-24 months of age. Agreement between MR cerebral biomarkers and neurodevelopmental outcome will be reported. The sample size is calculated using the 'rule of 10', generally used to calculate the sample size requirements for developing prognostic models. Considering 9 parameters, we require 9×10 adverse events, which suggest that a total sample size of 180 is required.
  
  
  BACKGROUND
  Human Research Ethics Committee approvals have been received from Brent Research Ethics Committee (London), and from Imperial College London (Sponsor). We will submit the results of the study to relevant journals and offer national and international presentations.
  
  
  BACKGROUND
  Clinical Trials.gov Number: NCT01309711.
authors.affiliation: Centre for Perinatal Neuroscience, Imperial College London, London, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lally
authors.affiliation: Centre for Perinatal Neuroscience, Imperial College London, London, UK.
authors.forename: Shreela
authors.initials: S
authors.lastname: Pauliah
authors.affiliation: Centre for Perinatal Neuroscience, Imperial College London, London, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Montaldo
authors.affiliation: Centre for Perinatal Neuroscience, Imperial College London, London, UK.
authors.forename: Badr
authors.initials: B
authors.lastname: Chaban
authors.affiliation: Centre for Perinatal Neuroscience, Imperial College London, London, UK.
authors.forename: Vania
authors.initials: V
authors.lastname: Oliveira
authors.affiliation: Centre for Perinatal Neuroscience, Imperial College London, London, UK University College Hospital, London, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Bainbridge
authors.affiliation: Medway NHS Foundation Trust, Kent, UK.
authors.forename: Aung
authors.initials: A
authors.lastname: Soe
authors.affiliation: Medway NHS Foundation Trust, Kent, UK.
authors.forename: Santosh
authors.initials: S
authors.lastname: Pattnayak
authors.affiliation: Department of Neonatology, Norfolk and Norwich University Hospitals Foundation Trust, Norwich, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Clarke
authors.affiliation: Department of Neonatology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.
authors.forename: Prakash
authors.initials: P
authors.lastname: Satodia
authors.affiliation: Department of Neonatology, Royal Victoria Infirmary, Newcastle, UK.
authors.forename: Sundeep
authors.initials: S
authors.lastname: Harigopal
authors.affiliation: Liverpool Womens Hospital and Alderhey Hospital, Liverpool, UK.
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Abernethy
authors.affiliation: Liverpool Womens Hospital and Alderhey Hospital, Liverpool, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Turner
authors.affiliation: University College Hospital, London, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Huertas-Ceballos
authors.affiliation: Department of Neonatology, Children's Hospital of Michigan, Michigan, UK.
authors.forename: Seetha
authors.initials: S
authors.lastname: Shankaran
authors.affiliation: Centre for Perinatal Neuroscience, Imperial College London, London, UK.
authors.forename: Sudhin
authors.initials: S
authors.lastname: Thayyil
mesh_terms: D000328:Adult; D015415:Biomarkers; D001921:Brain / Q000473:pathology*; D001927:Brain Diseases / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D002657:Child Development; D002675:Child, Preschool; D002985:Clinical Protocols; D002658:Developmental Disabilities / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D011379:Prognosis; D011446:Prospective Studies; D012107:Research Design
chemical_list: D015415:Biomarkers
keywords: NEONATOLOGY; NEUROLOGY