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.
ObjectiveTo explore the potential of magnetic resonance (MR) metabolomics for study of preeclampsia, for improved phenotyping and elucidating potential clues to etiology and pathogenesis.MethodsUrine and serum samples from pregnant women with preeclampsia (n = 10), normal pregnancies (n = 10) and non-pregnant women (n = 10) matched by age and gestational age were analyzed with MR spectroscopy and subjected to multivariate analysis. Metabolites were then quantified and compared between groups.ResultsUrine and serum samples revealed clear differences between women with preeclampsia and both control groups (normal pregnant and non-pregnant women). Nine urine metabolites were significantly different between preeclampsia and the normal pregnant group. Urine samples from women with early onset preeclampsia clustered together in the multivariate analysis. The preeclampsia serum spectra showed higher levels of low and very-low density lipoproteins and lower levels of high-density lipoproteins when compared to both non-pregnant and normal pregnant women.ConclusionThe MR determined metabolic profiles in urine and serum from women with preeclampsia are clearly different from normal pregnant women. The observed differences represent a potential to examine mechanisms underlying different preeclampsia phenotypes in urine and serum samples in larger studies. In addition, similarities between preeclampsia and cardiovascular disease in metabolomics are demonstrated.
Objective-Gestational hypertension and preeclampsia involve dysregulated maternal inflammatory responses to pregnancy, but whether such responses differ between the disorders has not been determined. We aimed to investigate disease-specific early pregnancy serum cytokine profiles of women subsequently developing gestational hypertension or preeclampsia for new insight into the underlying pathogeneses and differences between the disorders. Approach and Results-The study cohort consisted of 548 pregnant Norwegian women who were either multiparous with previous gestational hypertension or preeclampsia or were nulliparous. Maternal sera at gestational weeks 11 0 -13 6 were assayed for 27 cytokines, C-reactive protein, total cholesterol, high-density lipoprotein, triglyceride, creatinine, calcium, uric acid, and placental growth factor. Compared with normotensive women, women with both hypertensive conditions presented an atherogenic lipid profile at early gestation, but only those later developing gestational hypertension had significantly higher serum levels of interleukin (IL)-5 and IL-12. Comparing the 2 hypertensive pregnancy disorders, women subsequently developing gestational hypertension had higher serum levels of IL-1β, IL-5, IL-7, IL-8, IL-13, basic fibroblast growth factor, and vascular endothelial growth factor than the women subsequently developing preeclampsia. Conclusions-This study identifies early pregnancy differences in serum cytokine profiles for gestational hypertension and preeclampsia.
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