title: Urinary metabolomics of bronchopulmonary dysplasia (BPD): preliminary data at birth suggest it is a congenital disease.
abstract: OBJECTIVE
  Bronchopulmonary dysplasia (BPD) or chronic lung disease is one of the principal causes of mortality and morbidity in preterm infants. Early identification of infants at the greater risk of developing BPD may allow a targeted approach for reducing disease severity and complications. The trigger cause of the disease comprehends the impairment of the alveolar development and the increased angiogenesis. Nevertheless, the molecular pathways characterizing the disease are still unclear. Therefore, the use of the metabolomics technique, due to the capability of identifying instantaneous metabolic perturbation, might help to recognize metabolic patterns associated with the condition.
  
  
  METHODS
  The purpose of this study is to compare urinary metabolomics at birth in 36 newborns with a gestational age below 29 weeks and birth weight <1500 g (very low birth weight - VLBW), admitted in Neonatal Intensive Care Unit (NICU) divided into two groups: the first group (18 cases) consisting of newborns who have not yet developed the disease, but who will subsequently develop it and the second group (18 controls) consisting of newborns not affected by BPD. Urine samples were collected within 24-36 h of life and immediately frozen at -80 °C.
  
  
  RESULTS
  The (1)H-NMR spectra were analyzed using a partial least squares discriminant analysis (PLS-DA) model coupled with orthogonal Signal Correction. Using this approach it was possible with urine at birth to discriminate newborns that will be later have a diagnosis of BPD with a high statistics power. In particular, we found five important discriminant metabolites in urine in BPD newborns: lactate, taurine, TMAO, myoinositol (which increased) and gluconate (which decreased).
  
  
  CONCLUSIONS
  These preliminary results seem to be promising for the identification of predictor's biomarkers characterizing the BPD condition. These data may suggest that BPD is probably the result of an abnormal development (respiratory bud, vascular tree, hypodysplasia of pneumocytes) and could be considered a congenital disease (genetics plus intrauterine epigenetics). Early identification of infants at the greater risk of developing BPD may allow a targeted approach for reducing disease severity and complications.
authors.affiliation: Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, University of Cagliari , Cagliari , Italy .
authors.forename: Vassilios
authors.initials: V
authors.lastname: Fanos
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Pintus
authors.forename: Milena
authors.initials: M
authors.lastname: Lussu
authors.forename: Luigi
authors.initials: L
authors.lastname: Atzori
authors.forename: Antonio
authors.initials: A
authors.lastname: Noto
authors.forename: Mauro
authors.initials: M
authors.lastname: Stronati
authors.forename: Hercilia
authors.initials: H
authors.lastname: Guimaraes
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Marcialis
authors.forename: Gustavo
authors.initials: G
authors.lastname: Rocha
authors.forename: Corrado
authors.initials: C
authors.lastname: Moretti
authors.forename: Paola
authors.initials: P
authors.lastname: Papoff
authors.forename: Serafina
authors.initials: S
authors.lastname: Lacerenza
authors.forename: Silvia
authors.initials: S
authors.lastname: Puddu
authors.forename: Mario
authors.initials: M
authors.lastname: Giuffrè
authors.forename: Francesca
authors.initials: F
authors.lastname: Serraino
authors.forename: Michele
authors.initials: M
authors.lastname: Mussap
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corsello
mesh_terms: D015415:Biomarkers / Q000652:urine*; D001997:Bronchopulmonary Dysplasia / Q000652:urine*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D007363:Intensive Care Units, Neonatal; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D015415:Biomarkers
keywords: 1H-NMR; Bronchopulmonary dysplasia; metabolites; metabolomics; multivariate statistical analysis