title: Untargeted Metabolomic Analysis of Amniotic Fluid in the Prediction of Preterm Delivery and Bronchopulmonary Dysplasia.
abstract: OBJECTIVE
  Bronchopulmonary dysplasia (BPD) is a serious complication associated with preterm birth. A growing body of evidence suggests a role for prenatal factors in its pathogenesis. Metabolomics allows simultaneous characterization of low molecular weight compounds and may provide a picture of such a complex condition. The aim of this study was to evaluate whether an unbiased metabolomic analysis of amniotic fluid (AF) can be used to investigate the risk of spontaneous preterm delivery (PTD) and BPD development in the offspring.
  
  
  METHODS
  We conducted an exploratory study on 32 infants born from mothers who had undergone an amniocentesis between 21 and 28 gestational weeks because of spontaneous preterm labor with intact membranes. The AF samples underwent untargeted metabolomic analysis using mass spectrometry combined with ultra-performance liquid chromatography. The data obtained were analyzed using multivariate and univariate statistical data analysis tools.
  
  
  RESULTS
  Orthogonally Constrained Projection to Latent Structures-Discriminant Analysis (oCPLS2-DA) excluded effects on data modelling of crucial clinical variables. oCPLS2-DA was able to find unique differences in select metabolites between term (n = 11) and preterm (n = 13) deliveries (negative ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.65; positive ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.70), and between PTD followed by the development of BPD (n = 10), and PTD without BPD (n = 11) (negative data set: R2 = 0.48, mean AUC ROC in prediction = 0.73; positive data set: R2 = 0.55, mean AUC ROC in prediction = 0.71).
  
  
  CONCLUSIONS
  This study suggests that amniotic fluid metabolic profiling may be promising for identifying spontaneous preterm birth and fetuses at risk for developing BPD. These findings support the hypothesis that some prenatal metabolic dysregulations may play a key role in the pathogenesis of PTD and the development of BPD.
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padova, Italy.|Città della Speranza Institute of Pediatric Research (IRP), Padova, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Baraldi
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padova, Italy.|Città della Speranza Institute of Pediatric Research (IRP), Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giordano
authors.affiliation: S-IN Soluzioni Informatiche, Vicenza, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Stocchero
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padova, Italy.|Città della Speranza Institute of Pediatric Research (IRP), Padova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Moschino
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padova, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zaramella
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padova, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Tran
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padova, Italy.|Città della Speranza Institute of Pediatric Research (IRP), Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Carraro
authors.affiliation: Perinatology Research Branch, NICHD, NIH, DHHS, Wayne State University/Hutzel Women's Hospital, Detroit, United States of America.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padova, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Gervasi
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism*; D019540:Area Under Curve; D001997:Bronchopulmonary Dysplasia / Q000175:diagnosis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016002:Discriminant Analysis; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D016018:Least-Squares Analysis; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics; D011247:Pregnancy; D047928:Premature Birth; D012372:ROC Curve