First-Trimester Serum Acylcarnitine Levels to Predict Preeclampsia: A Metabolomics Approach.

Maria P H Koster,Amy C Harms,Thomas Hankemeier,Adrie D Dane,Rob J Vreeken,Peter C J I Schielen,Sylwia Kuc,Ruud Berger,Jeroen L A Pennings,Gerard H A Visser

doi:10.1155/2015/857108

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). Conclusion. 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.

Highlights

Preeclampsia (PE) is a hypertensive complication that occurs in approximately 3% of all pregnancies and may lead to poor pregnancy outcomes of both mother and fetus [1, 2]
Maternal blood was drawn at 8+0–13+6 weeks of gestational age (GA) and stored at −80∘C until metabolomics analysis
Multiparous women with PE more often had a history of hypertensive pregnancy disorders (EO-PE 30.8%, p = 0.009 and LO-PE 37.0%, p < 0.001) compared to multiparous controls

Summary

Introduction

Preeclampsia (PE) is a hypertensive complication that occurs in approximately 3% of all pregnancies and may lead to poor pregnancy outcomes of both mother and fetus [1, 2]. It is thought that in women with PE a complex interaction between placental factors, maternal constitutional factors, and pregnancy-specific vascular and immunological adaptation occurs already in the first trimester of their pregnancy [3,4,5]. Early recognition of women at risk and timely intervention ahead of clinical onset might enable tailored pregnancy care and better pregnancy outcomes. Several studies have been performed focusing on the detection of markers to predict preeclampsia [6]. At present the most promising marker for the prediction

Methods

Results

Conclusion