title: Validation of metabolomic models for prediction of early-onset preeclampsia.
abstract: OBJECTIVE
  We sought to perform validation studies of previously published and newly derived first-trimester metabolomic algorithms for prediction of early preeclampsia (PE).
  
  
  METHODS
  Nuclear magnetic resonance-based metabolomic analysis was performed on first-trimester serum in 50 women who subsequently developed early PE and in 108 first-trimester controls. Random stratification and allocation was used to divide cases into a discovery group (30 early PE and 65 controls) for generation of the biomarker model(s) and a validation group (20 early PE and 43 controls) to ensure an unbiased assessment of the predictive algorithms. Cross-validation testing on the different algorithms was performed to confirm their robustness before use. Metabolites, demographic features, clinical characteristics, and uterine Doppler pulsatility index data were evaluated. Area under the receiver operator characteristic curve (AUC), 95% confidence interval (CI), sensitivity, and specificity of the biomarker models were derived.
  
  
  RESULTS
  Validation testing found that the metabolite-only model had an AUC of 0.835 (95% CI, 0.769-0.941) with a 75% sensitivity and 74.4% specificity and for the metabolites plus uterine Doppler pulsatility index model it was 0.916 (95% CI, 0.836-0.996), 90%, and 88.4%, respectively. Predictive metabolites included arginine and 2-hydroxybutyrate, which are known to be involved in vascular dilation, and insulin resistance and impaired glucose regulation, respectively.
  
  
  CONCLUSIONS
  We found confirmatory evidence that first-trimester metabolomic biomarkers can predict future development of early PE.
authors.affiliation: Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI. Electronic address: Ray.bahado-singh@beaumont.edu.
authors.forename: Ray O
authors.initials: RO
authors.lastname: Bahado-Singh
authors.affiliation: Department of Obstetrics and Gynecology, King's College Hospital, London, United Kingdom.
authors.forename: Argyro
authors.initials: A
authors.lastname: Syngelaki
authors.affiliation: Department of Obstetrics and Gynecology, King's College Hospital, London, United Kingdom.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Akolekar
authors.affiliation: Department of Biological Sciences, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Rupsari
authors.initials: R
authors.lastname: Mandal
authors.affiliation: Department of Biological Sciences, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Trent C
authors.initials: TC
authors.lastname: Bjondahl
authors.affiliation: Department of Biological Sciences, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Beomsoo
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Biological Sciences, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Edison
authors.initials: E
authors.lastname: Dong
authors.affiliation: Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bauer
authors.affiliation: Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Alpay-Savasan
authors.affiliation: Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI.
authors.forename: Stewart
authors.initials: S
authors.lastname: Graham
authors.affiliation: Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI.
authors.forename: Onur
authors.initials: O
authors.lastname: Turkoglu
authors.affiliation: Department of Biological Sciences, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Computing Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: David S
authors.initials: DS
authors.lastname: Wishart
authors.affiliation: Department of Obstetrics and Gynecology, King's College Hospital, London, United Kingdom.
authors.forename: Kypros H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism*; D011673:Pulsatile Flow; D018608:Ultrasonography, Doppler; D055988:Uterine Artery / Q000000981:diagnostic imaging*; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: early-onset preeclampsia; metabolomics