title: First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study.
abstract: Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes related to the diseases. Metabolic profiles were obtained by nuclear magnetic resonance spectroscopy of serum and urine samples from 599 women at medium to high risk of preeclampsia (nulliparous or previous preeclampsia/gestational hypertension). Preeclampsia developed in 26 (4.3%) and gestational hypertension in 21 (3.5%) women. Multivariate analyses of the metabolic profiles were performed to establish prediction models for the hypertensive disorders individually and combined. Urinary metabolomic profiles predicted preeclampsia and gestational hypertension at 51.3% and 40% sensitivity, respectively, at 10% false positive rate, with hippurate as the most important metabolite for the prediction. Serum metabolomic profiles predicted preeclampsia and gestational hypertension at 15% and 33% sensitivity, respectively, with increased lipid levels and an atherogenic lipid profile as most important for the prediction. Combining maternal characteristics with the urinary hippurate/creatinine level improved the prediction rates of preeclampsia in a logistic regression model. The study indicates a potential future role of clinical importance for metabolomic analysis of urine in prediction of preeclampsia.
authors.affiliation: Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. marie.austdal@ntnu.no.|St. Olavs Hospital, Trondheim University Hospital, 7006 Trondheim, Norway. marie.austdal@ntnu.no.
authors.forename: Marie
authors.initials: M
authors.lastname: Austdal
authors.affiliation: St. Olavs Hospital, Trondheim University Hospital, 7006 Trondheim, Norway. line.tangeras@ntnu.no.|Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. line.tangeras@ntnu.no.
authors.forename: Line H
authors.initials: LH
authors.lastname: Tangerås
authors.affiliation: Department of Laboratory Medicine Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. ragnhild.skrastad@ntnu.no.|National Center for Fetal Medicine, Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway. ragnhild.skrastad@ntnu.no.
authors.forename: Ragnhild B
authors.initials: RB
authors.lastname: Skråstad
authors.affiliation: National Center for Fetal Medicine, Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway. pepe.salvesen@ntnu.no.|Department of Obstetrics and Gynecology, Clinical Sciences, Lund University, 221 00 Lund, Sweden. pepe.salvesen@ntnu.no.
authors.forename: Kjell
authors.initials: K
authors.lastname: Salvesen
authors.affiliation: Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. rigmor.austgulen@ntnu.no.
authors.forename: Rigmor
authors.initials: R
authors.lastname: Austgulen
authors.affiliation: Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. ann-charlotte.iversen@ntnu.no.
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Iversen
authors.affiliation: Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. tone.f.bathen@ntnu.no.
authors.forename: Tone F
authors.initials: TF
authors.lastname: Bathen
mesh_terms: D000328:Adult; D015415:Biomarkers; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism* / Q000652:urine; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: NMR spectroscopy; PLS-DA; biomarker; first-trimester screening; gestational hypertension; metabolomics; prediction; preeclampsia