title: The Role of Plasma and Urine Metabolomics in Identifying New Biomarkers in Severe Newborn Asphyxia: A Study of Asphyxiated Newborn Pigs following Cardiopulmonary Resuscitation.
abstract: BACKGROUND
  Optimizing resuscitation is important to prevent morbidity and mortality from perinatal asphyxia. The metabolism of cells and tissues is severely disturbed during asphyxia and resuscitation, and metabolomic analyses provide a snapshot of many small molecular weight metabolites in body fluids or tissues. In this study metabolomics profiles were studied in newborn pigs that were asphyxiated and resuscitated using different protocols to identify biomarkers for subject characterization, intervention effects and possibly prognosis.
  
  
  METHODS
  A total of 125 newborn Noroc pigs were anesthetized, mechanically ventilated and inflicted progressive asphyxia until asystole. Pigs were randomized to resuscitation with a FiO2 0.21 or 1.0, different duration of ventilation before initiation of chest compressions (CC), and different CC to ventilation ratios. Plasma and urine samples were obtained at baseline, and 2 h and 4 h after return of spontaneous circulation (ROSC, heart rate > = 100 bpm). Metabolomics profiles of the samples were analyzed by nuclear magnetic resonance spectroscopy.
  
  
  RESULTS
  Plasma and urine showed severe metabolic alterations consistent with hypoxia and acidosis 2 h and 4 h after ROSC. Baseline plasma hypoxanthine and lipoprotein concentrations were inversely correlated to the duration of hypoxia sustained before asystole occurred, but there was no evidence for a differential metabolic response to the different resuscitation protocols or in terms of survival.
  
  
  CONCLUSIONS
  Metabolic profiles of asphyxiated newborn pigs showed severe metabolic alterations. Consistent with previously published reports, we found no evidence of differences between established and alternative resuscitation protocols. Lactate and pyruvate may have a prognostic value, but have to be independently confirmed.
authors.affiliation: Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Chemistry, University of Oslo, Oslo, Norway.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sachse
authors.affiliation: The Department of Paediatric and Adolescent Medicine, Akershus University Hospital, 1478 Lørenskog, Oslo, Norway.
authors.forename: Anne Lee
authors.initials: AL
authors.lastname: Solevåg
authors.affiliation: Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Jens Petter
authors.initials: JP
authors.lastname: Berg
authors.affiliation: The Department of Paediatric and Adolescent Medicine, Akershus University Hospital, 1478 Lørenskog, Oslo, Norway.|Institute of Clinical Medicine, Campus Akershus University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Britt
authors.initials: B
authors.lastname: Nakstad
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000097:blood* / Q000378:metabolism / Q000628:therapy / Q000652:urine*; D016887:Cardiopulmonary Resuscitation; D000860:Hypoxia / Q000150:complications; D055432:Metabolomics; D016019:Survival Analysis; D013552:Swine