title: First-Trimester Serum Acylcarnitine Levels to Predict Preeclampsia: A Metabolomics Approach.
abstract: OBJECTIVE
  To expand the search for preeclampsia (PE) metabolomics biomarkers through the analysis of acylcarnitines in first-trimester maternal serum.
  
  
  METHODS
  This was a nested case-control study using serum from pregnant women, drawn between 8 and 14 weeks of gestational age. Metabolites were measured using an UPLC-MS/MS based method. Concentrations were compared between controls (n = 500) and early-onset- (EO-) PE (n = 68) or late-onset- (LO-) PE (n = 99) women. Metabolites with a false discovery rate <10% for both EO-PE and LO-PE were selected and added to prediction models based on maternal characteristics (MC), mean arterial pressure (MAP), and previously established biomarkers (PAPPA, PLGF, and taurine).
  
  
  RESULTS
  Twelve metabolites were significantly different between EO-PE women and controls, with effect levels between -18% and 29%. For LO-PE, 11 metabolites were significantly different with effect sizes between -8% and 24%. Nine metabolites were significantly different for both comparisons. The best prediction model for EO-PE consisted of MC, MAP, PAPPA, PLGF, taurine, and stearoylcarnitine (AUC = 0.784). The best prediction model for LO-PE consisted of MC, MAP, PAPPA, PLGF, and stearoylcarnitine (AUC = 0.700).
  
  
  CONCLUSIONS
  This study identified stearoylcarnitine as a novel metabolomics biomarker for EO-PE and LO-PE. Nevertheless, metabolomics-based assays for predicting PE are not yet suitable for clinical implementation.
authors.affiliation: Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht (UMCU), 3508 AB Utrecht, Netherlands.
authors.forename: Maria P H
authors.initials: MP
authors.lastname: Koster
authors.affiliation: Leiden Academic Centre for Drug Research, Division of Analytical Biosciences, Leiden University, 2300 RA Leiden, Netherlands ; Discovery & Exploratory BA, Pharmacokinetics, Dynamics & Metabolism, Discovery Sciences, Janssen Pharmaceutica, Beerse, Belgium.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vreeken
authors.affiliation: Leiden Academic Centre for Drug Research, Division of Analytical Biosciences, Leiden University, 2300 RA Leiden, Netherlands.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Harms
authors.affiliation: Leiden Academic Centre for Drug Research, Division of Analytical Biosciences, Leiden University, 2300 RA Leiden, Netherlands.
authors.forename: Adrie D
authors.initials: AD
authors.lastname: Dane
authors.affiliation: Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht (UMCU), 3508 AB Utrecht, Netherlands.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Kuc
authors.affiliation: Centre for Infectious Diseases Research, Diagnostics and Screening (IDS), National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, Netherlands.
authors.forename: Peter C J I
authors.initials: PC
authors.lastname: Schielen
authors.affiliation: Netherlands Metabolomics Centre, 3501 DE Utrecht, Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
authors.affiliation: Netherlands Metabolomics Centre, 3501 DE Utrecht, Netherlands.
authors.forename: Ruud
authors.initials: R
authors.lastname: Berger
authors.affiliation: Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht (UMCU), 3508 AB Utrecht, Netherlands.
authors.forename: Gerard H A
authors.initials: GH
authors.lastname: Visser
authors.affiliation: Centre for Health Protection (GZB), National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, Netherlands.
authors.forename: Jeroen L A
authors.initials: JL
authors.lastname: Pennings
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; C116917:acylcarnitine; D002331:Carnitine