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.

Applications of metabolomics in the study and management of preeclampsia: a review of the literature

“…The remaining studies used urine (n = 1) (Diaz, Barros, Goodfellow, Duarte, Galhano, Pita, Almeida et al 2013), urine and serum (n = 2) (Austdal, Skråstad, Gundersen, Austgulen, Iversen, Bathen 2014; Austdal, Tangerås, Skråstad, Salvesen, Austgulen, Iversen, Bathen 2015), or breast milk (n=1) (Dangat, Upadhyay, Kilari, Sharma, Kemse, Mehendale, Lalwani et al 2016). Sixteen studies performed metabolic profiling with Mass Spectrometry (MS), while 12 used a form of nuclear magnetic resonance spectroscopy (NMR).…”

“…The minimum number of metabolites for inclusion in the review was five (Sohlberg, Wikström, Olovsson, Lindgren, Axelsson, Mulic-Lutvica, Weis et al), while as many as 8000 features, as defined by their mass (mz) and retention time (rt) were included in the untargeted studies (Kelly, Croteau-Chonka, Dahlin, Mirzakhani, Wu, Wan, McGeachie et al 2016). Of the prospective studies and nested case-control studies, seven analyzed first trimester metabolites (Austdal, Tangerås, Skråstad, Salvesen, Austgulen, Iversen, Bathen 2015; Bahado-Singh, Akolekar, Mandal, Dong, Xia, Kruger, Wishart et al 2012; Bahado-Singh, Akolekar, Mandal, Dong, Xia, Kruger, Wishart et al 2013; Bahado-Singh, Syngelaki, Akolekar, Mandal, Bjondahl, Han, Dong et al 2015; Koster, Vreeken, Harms, Dane, Kuc, Schielen, Hankemeier et al 2015; Kuc, Koster, Pennings, Hankemeier, Berger, Harms, Dane et al 2014; Odibo, Goetzinger, Odibo, Cahill, Macones, Nelson, Dietzen 2011), while only three analyzed second trimester metabolites (Diaz, Barros, Goodfellow, Duarte, Galhano, Pita, Almeida et al 2013; Kenny, Broadhurst, Dunn, Brown, North, McCowan, Roberts et al 2010; Pinto, Maciel, Melo, Domingues, Galhano, Pita, Almeida et al 2014) (Figure 2). …”

“…Seven studies compared metabolomic profiles of biological samples between controls and cases of any time of onset (Austdal, Tangerås, Skråstad, Salvesen, Austgulen, Iversen, Bathen 2015; Diaz, Barros, Goodfellow, Duarte, Galhano, Pita, Almeida et al 2013; Kelly, Croteau-Chonka, Dahlin, Mirzakhani, Wu, Wan, McGeachie et al 2016; Kenny, Broadhurst, Dunn, Brown, North, McCowan, Roberts et al 2010; Koster, Vreeken, Harms, Dane, Kuc, Schielen, Hankemeier et al 2015; Kuc, Koster, Pennings, Hankemeier, Berger, Harms, Dane et al 2014; Odibo, Goetzinger, Odibo, Cahill, Macones, Nelson, Dietzen 2011). Lactate was consistently shown to be decreased in the blood of women who went on to develop preeclampsia, while histidine was consistently increased.…”

Recent Advances in NMR-Based Metabolomics

“…A fairly large study used both urine and serum metabolite profiles to evaluate the potential of metabolomics to predict preeclampsia and gestational hyper-tension in early pregnancy. 129 It showed that urinary metabolites provide higher sensitivity than serum metabolite profiles for the prediction of preeclampsia and gestational hypertension. The sensitivity was 51.3% (from urine) vs 15% (serum) for preeclampsia and 40% (urine) vs 33% (serum) for gestational hypertension.…”

Efficacy and Safety of Labetalol in the Management of Moderate Gestation Hypertension - A Prospective Observational Study

“…15,16,17 These agents have been most widely studied in Randomized Controlled Trials (RCTs), although systematic reviews have failed to reveal clear differences between agents. 18,19 Once blood pressure rises above a certain level; however, there is a risk of direct damage to the blood vessel wall, regardless of what caused the rise. This risk is not specific to pregnancy, as it is similar for non-pregnant people with very high blood pressure.…”