title: Urinary gas chromatography mass spectrometry metabolomics in asphyxiated newborns undergoing hypothermia: from the birth to the first month of life.
abstract: BACKGROUND
  Perinatal asphyxia is a severe clinical condition affecting around four million newborns worldwide. It consists of an impaired gas exchange leading to three biochemical components: hypoxemia, hypercapnia and metabolic acidosis.
  
  
  METHODS
  The aim of this longitudinal experimental study was to identify the urine metabolome of newborns with perinatal asphyxia and to follow changes in urine metabolic profile over time. Twelve babies with perinatal asphyxia were included in this study; three babies died on the eighth day of life. Total-body cooling for 72 hours was carried out in all the newborns. Urine samples were collected in each baby at birth, after 48 hours during hypothermia, after the end of the therapeutic treatment (72 hours), after 1 week of life, and finally after 1 month of life. Urine metabolome at birth was considered the reference against which to compare metabolic profiles in subsequent samples. Quantitative metabolic profiling in urine samples was measured by gas chromatography mass spectrometry (GC-MS). The statistical approach was conducted by using the multivariate analysis by means of principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA). Pathway analysis was also performed.
  
  
  RESULTS
  The most important metabolites depicting each time collection point were identified and compared each other. At birth before starting therapeutic hypothermia (TH), urine metabolic profiles of the three babies died after 7 days of life were closely comparable each other and significantly different from those in survivors.
  
  
  CONCLUSIONS
  In conclusion, a plethora of data have been extracted by comparing the urine metabolome at birth with those observed at each time point collection. The modifications over time in metabolites composition and concentration, mainly originated from the depletion of cellular energy and homeostasis, seems to constitute a fingerprint of perinatal asphyxia.
authors.affiliation: Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, Cagliari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Noto
authors.affiliation: Neonatal Intensive Care, Neonatology, ASO S. Croce e Carle, Cuneo, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Pomero
authors.affiliation: Laboratory Medicine Service, IRCCS AOU San Martino-IST, University-Hospital, Genoa, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Mussap
authors.affiliation: Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Barberini
authors.affiliation: Department of Chemical and Geological Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fattuoni
authors.affiliation: Department of Chemical and Geological Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Palmas
authors.affiliation: Neonatal Intensive Care, Neonatology, ASO S. Croce e Carle, Cuneo, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Dalmazzo
authors.affiliation: Neonatal Intensive Care, Neonatology, ASO S. Croce e Carle, Cuneo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Delogu
authors.affiliation: Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, Cagliari, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Dessì
authors.affiliation: Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, Cagliari, Italy.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Fanos
authors.affiliation: Neonatal Intensive Care, Neonatology, ASO S. Croce e Carle, Cuneo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gancia
keywords: Metabolomics; biomarkers; hypoxic-ischemic-encephalopathy; metabolites; newborns; perinatal asphyxia; urine