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.
Highlights
Hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension, are major causes of maternal morbidity and mortality, and affect up to 10% of pregnant women [1,2,3].Early identification of women at high risk of preeclampsia might enable potential prophylactic treatment to reduce or avoid the onset of symptoms [4,5]
Metabolic profiles in urine and serum samples from pregnant women at 11+0–13+6 weeks gestation were significantly different between women who developed preeclampsia or gestational hypertension, and women with normotensive pregnancies
This study shows that there is potentially predictive information contained in a simple urine sample
Summary
Hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension, are major causes of maternal morbidity and mortality, and affect up to 10% of pregnant women [1,2,3].Early identification of women at high risk of preeclampsia might enable potential prophylactic treatment to reduce or avoid the onset of symptoms [4,5]. Hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension, are major causes of maternal morbidity and mortality, and affect up to 10% of pregnant women [1,2,3]. Predictive models for late onset preeclampsia have employed a combination of maternal characteristics, biochemical and biophysical markers at 11+0–13+6 weeks of gestation, to predict the syndrome at 30%–60% sensitivity [5,6,7,8]. Skråstad et al [9] have previously found a combination of mean arterial pressure (MAP), maternal age and uterine artery pulsatility index (UtAPI) to be 38.5% predictive of preeclampsia in a cohort of women at gestational weeks 11+0–13+6.
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