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Int. J. Mol. Sci. 2015, 16(9), 21520-21538; doi:10.3390/ijms160921520

First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study

1
Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway
2
St. Olavs Hospital, Trondheim University Hospital, 7006 Trondheim, Norway
3
Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway
4
Department of Laboratory Medicine Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway
5
National Center for Fetal Medicine, Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
6
Department of Obstetrics and Gynecology, Clinical Sciences, Lund University, 221 00 Lund, Sweden
*
Author to whom correspondence should be addressed.
Academic Editor: Philip Newton Baker
Received: 29 June 2015 / Revised: 17 August 2015 / Accepted: 26 August 2015 / Published: 8 September 2015
(This article belongs to the Special Issue Prediction, Diagnostics and Prevention of Pregnancy Complications)
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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. View Full-Text
Keywords: NMR spectroscopy; preeclampsia; metabolomics; PLS-DA; gestational hypertension; prediction; first-trimester screening; biomarker NMR spectroscopy; preeclampsia; metabolomics; PLS-DA; gestational hypertension; prediction; first-trimester screening; biomarker
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Austdal, M.; Tangerås, L.H.; Skråstad, R.B.; Salvesen, K.; Austgulen, R.; Iversen, A.-C.; Bathen, T.F. First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study. Int. J. Mol. Sci. 2015, 16, 21520-21538.

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