title: Metabolomic and bioinformatic analyses in asphyxiated neonates.
abstract: OBJECTIVE
  We tested the application of bioinformatic algorithms in studying the metabolomic profiles of neonatal urine samples with clinical evidence of severe asphyxia at birth and subsequent neurodevelopmental handicap.
  
  
  METHODS
  The clinical outcomes of 256 newborns that required direct admission to neonatal intensive care unit for respiratory support or did not require direct admission were studied. Urinary metabolite profiles were measured by high throughput mass spectrometry and analyzed by bioinformatic methods.
  
  
  RESULTS
  We found a positive relationship between suppressed biochemical networks involved in macromolecular synthesis and birth asphyxia associated with significant neonatal oxidative stress and morbidity. The metabolomic discriminators between good neonatal outcome and poor neonatal outcome were established using hierarchical clustering analysis. Concentrations of eight urinary organic acids in distinct biochemical pathways were elevated and significantly associated with the prognosis of neurodevelopmental handicap with high sensitivity and specificity: ethylmalonate, 3-hydroxy-3-methylglutarate, 2-hydroxy-glutarate and 2-oxo-glutarate were associated with good neonatal outcome, whereas glutarate, methylmalonate, 3-hydroxy-butyrate and orotate were associated with poor outcome.
  
  
  CONCLUSIONS
  The data demonstrated the potential application of bioinformatics methods in this metabolomic study and proved its clinical relevance.
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Ching Yan
authors.initials: CY
authors.lastname: Chu
authors.forename: Xin
authors.initials: X
authors.lastname: Xiao
authors.forename: Xiao Guang
authors.initials: XG
authors.lastname: Zhou
authors.forename: Tze Kin
authors.initials: TK
authors.lastname: Lau
authors.forename: Michael Scott
authors.initials: MS
authors.lastname: Rogers
authors.forename: Tai Fai
authors.initials: TF
authors.lastname: Fok
authors.forename: Lap Kay
authors.initials: LK
authors.lastname: Law
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Wang
mesh_terms: D001238:Asphyxia Neonatorum / Q000378:metabolism* / Q000652:urine; D002264:Carboxylic Acids / Q000652:urine; D016022:Case-Control Studies; D016000:Cluster Analysis; D019295:Computational Biology; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008423:Maternal Age; D009017:Morbidity; D009774:Obstetrics; D011237:Predictive Value of Tests; D011247:Pregnancy; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D002264:Carboxylic Acids