title: A metabolomic approach in an experimental model of hypoxia-reoxygenation in newborn piglets: urine predicts outcome.
abstract: Perinatal asphyxia is one of the leading causes of morbidity and mortality in the neonatal period. Response to oxygen treatment is unpredictable and the optimum concentration of oxygen in neonatal resuscitation is still a matter of debate among neonatologists. A metabolomic approach was used to characterize the metabolic profiles of newborn hypoxic-reoxygenated piglets. Urine samples were collected from newborn piglets (n = 40) undergoing hypoxia followed by resuscitation at different oxygen concentrations (ranging from 18% to 100%) and analyzed by ¹H NMR spectroscopy. Despite reoxygenation 7 piglets, out of 10 which became asystolic, did not respond to resuscitation. Profiles of the ¹H NMR spectra were submitted to unsupervised (principal component analysis) and supervised (partial least squares-discriminant analysis) multivariate analysis. The supervised analyses showed differences in the metabolic profile of the urine collected before the induction of hypoxia between survivors and deaths. Metabolic variations were observed in the urine of piglets treated with different oxygen concentrations comparing T0 (basal value) and end of the experiment (resuscitation). Some of the individual metabolites discriminating between these groups were urea, creatinine, malonate, methylguanidine, hydroxyisobutyric acid. The metabolomic approach appears a promising tool for investigating newborn hypoxia over time, for monitoring the response to the treatment with different oxygen concentrations, and might lead to a tailored management of the disorder.
authors.affiliation: Department of Toxicology, University of Cagliari, Cagliari, Italy. latzori@unica.it
authors.forename: Luigi
authors.initials: L
authors.lastname: Atzori
authors.forename: Theodoros
authors.initials: T
authors.lastname: Xanthos
authors.forename: Luigi
authors.initials: L
authors.lastname: Barberini
authors.forename: Roberto
authors.initials: R
authors.lastname: Antonucci
authors.forename: Federica
authors.initials: F
authors.lastname: Murgia
authors.forename: Milena
authors.initials: M
authors.lastname: Lussu
authors.forename: Filippia
authors.initials: F
authors.lastname: Aroni
authors.forename: Marianna
authors.initials: M
authors.lastname: Varsami
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.forename: Adolfo
authors.initials: A
authors.lastname: Lai
authors.forename: Ernesto
authors.initials: E
authors.lastname: D'Aloja
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Iacovidou
authors.forename: Vassilios
authors.initials: V
authors.lastname: Fanos
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D004195:Disease Models, Animal; D000860:Hypoxia / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000652:urine; D008297:Male; D055442:Metabolome / Q000187:drug effects; D055432:Metabolomics / Q000379:methods*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D010102:Oxygen Inhalation Therapy / Q000379:methods / Q000662:veterinary; D011379:Prognosis; D015424:Reperfusion / Q000662:veterinary; D012151:Resuscitation / Q000379:methods; D013552:Swine / Q000378:metabolism*; D016896:Treatment Outcome; D016482:Urinalysis / Q000379:methods*
chemical_list: D010100:Oxygen