Application of metabolomics to preeclampsia diagnosis

Gh, B. Fatemeh Nobakht M.

doi:10.1080/19396368.2018.1482968

Cited by 44 publications

(37 citation statements)

References 98 publications

(148 reference statements)

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“…However, the substantial variability in food intakes makes it difficult to assess using conventional assessment tools. Though some studies have described metabolic phenotype changes across a healthy pregnancy ( 13 – 15 ) or adverse pregnancy conditions ( 16 , 17 ), few have reported associations in dietary intake in pregnancy based on circulating metabolites that are generalizable in a multiethnic population.…”

Section: Introductionmentioning

confidence: 99%

Maternal Diet and the Serum Metabolome in Pregnancy: Robust Dietary Biomarkers Generalizable to a Multiethnic Birth Cohort

Souza

Shanmuganathan

Lamri

et al. 2020

Current Developments in Nutrition

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Background Advances in metabolomics are anticipated to decipher associations between dietary exposures and health. Replication biomarker studies in different populations are critical to demonstrate generalizability. Objectives To identify and validate robust serum metabolites associated with diet quality and specific foods in a multi-ethnic cohort of pregnant women. Design In this cross-sectional analysis of 3 multi-ethnic Canadian birth cohorts, we collected semi-quantitative food frequency questionnaires (FFQ) and serum from 900 women at the second trimester of pregnancy. We calculated a diet quality score (DQS), defined as daily servings of “healthy” minus “unhealthy” foods. Serum metabolomics was performed by multisegment injection-capillary electrophoresis-mass spectrometry, and specific serum metabolites associated with maternal diet quality scores were identified. We combined the results across all 3 cohorts using meta-analysis to classify robust dietary biomarkers (r > ± 0.1, p < 0.05). Results Diet quality was higher in the South Asian birth cohort (mean DQS = 7.1) than the two white Caucasian birth cohorts (mean DQS < 3.2). Sixty-six metabolites were detected with high frequency (> 75%) and adequate precision (CV < 30%), and 47 were common to all cohorts. Hippuric acid was positively associated with healthy diet score in all cohorts, and with the overall DQS only in the primarily white Caucasian cohorts. We observed robust correlations between: 1) proline betaine-citrus foods; 2) 3-methylhistidine-red meat, chicken, and eggs; 3) hippuric acid-fruits and vegetables; 4) trimethylamine N-oxide (TMAO)-seafood, meat, and eggs; and 5) tryptophan betaine-nuts/legumes. Conclusions Specific serum metabolites reflect intake of citrus fruit/juice, vegetables, animal foods, and nuts/legumes in pregnant women independent of ethnicity, fasting status, and delays to storage across multiple collection centers. Robust biomarkers of overall diet quality varied by cohort. Proline betaine, 3-methylhistidine, hippuric acid, TMAO, and tryptophan betaine were robust dietary biomarkers for investigations of maternal nutrition in multi-ethnic populations.

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Section: Introductionmentioning

confidence: 99%

Maternal Diet and the Serum Metabolome in Pregnancy: Robust Dietary Biomarkers Generalizable to a Multiethnic Birth Cohort

Souza

Shanmuganathan

Lamri

et al. 2020

Current Developments in Nutrition

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“…As a severe pregnancy complication, the pathophysiology of preeclampsia is not fully understood and the only effective treatment is delivery [8]. In the present study, we applied high performance liquid chromatography coupled with quadrupole-time-of light mass spectrometry (HPLC-QTOF-MS) to investigate the metabolic changes in women with preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

“…Metabolomics, as a high-throughput technique, is widely used in the systematic study of metabolites in biological samples such as plasma, serum, urine, saliva, tissue and exhaled breath [7]. It has been shown to be a valid and powerful research tool in elucidating the pathogenesis of PE [8]. For instance, it was found that branched-chain amino acids were signi cantly reduced in the serum of PE patients, which was correlated with intrauterine growth restriction in PE patients [9].…”

Section: Introductionmentioning

confidence: 99%

“…However, the results derived from the previous PE metabolomic studies typically showed poor reproducibility, which could be attributed to biological variation, external experimental conditions and availability of metabolome databases [8]. Moreover, no metabolomics studies have analyzed serum and placenta simultaneously with the liquid chromatography-mass spectrometry platform, which provides a more accurate and comprehensive way to reveal the metabolomic changes in the patients developing PE.…”

Section: Introductionmentioning

confidence: 99%

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Metabolomic analysis of serum and placenta in preeclampsia

Dong

Liu

Zhao

et al. 2020

Preprint

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Background: Preeclampsia (PE) is one of the main causes of maternal and fetal morbidity and mortality worldwide. This study was aimed to explore the potential metabolic alterations in women diagnosed with PE and reveal the underlying pathogenesis of disease.Methods: Healthy pregnant women and patients diagnosed with PE were recruited from August 2017 to February 2018. The metabolomic analysis of serum (n=90) and placenta (n=9) samples collected from the two groups were performed with the high performance liquid chromatography coupled with quadrupole-time-of light mass spectrometry (HPLC-QTOF-MS).Results: In serum, 16 metabolites that were present in different concentrations between the two groups were identified, of which pyroglutamic acid (pGlu), methionine, glutamine and taurocholic acid may be used as potential PE diagnosis biomarkers with the area under ROC curve of 0.901, 0.909, 0.892 and 0.873 respectively. Furthermore, the metabolic pathways analysis with differential metabolites in serum and placenta samples showed that linoleic acid and alpha- linolenic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, D-glutamine/D-glutamate metabolism, phenylalanine metabolism, glutathione (GSH) metabolism and tryptophan metabolism were significantly altered and might be involved in PE pathogenesis.Conclusions: These results showed the altered metabolic pathways could contribute to the pathophysiologic mechanisms of PE.

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“…Metabolomic analysis of samples collected from study subjects with/without underlying diseases is thus ideally suited for developing diagnostic tests, prognostic tools, and personalized therapeutic interventions [13][14][15] . Metabolomic studies have been conducted for the purpose of biomarker discovery for PE in a range of biological specimens (including serum, urine, and placenta) and different analytical platforms have been used to measure a number of putative biomarker molecule species including amino acid, fatty acid, organic acid, and acylcarnitine 16,17 , which have been summarized in detail elsewhere 16 . In brief, several studies with maternal blood in late pregnancy reported metabolic biomarkers for discrimination of preeclampsia [18][19][20][21] , and other previous studies suggested predictive metabolic biomarkers in early pregnancy with the use of metabolomics tools such as nuclear magnetic resonance spectroscopy (NMR), gas-/ liquid chromatography-mass spectrometry (GC-/ LC-MS), with variable sensitivities and specificities (30-100%) [22][23][24][25][26][27][28][29] .…”

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confidence: 99%

Metabolomic biomarkers in midtrimester maternal plasma can accurately predict the development of preeclampsia

Lee

Kang

Lee

et al. 2020

Sci Rep

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Early identification of patients at risk of developing preeclampsia (PE) would allow providers to tailor their prenatal management and adopt preventive strategies, such as low-dose aspirin. Nevertheless, no mid-trimester biomarkers have as yet been proven useful for prediction of PE. This study investigates the ability of metabolomic biomarkers in mid-trimester maternal plasma to predict PE. A case–control study was conducted including 33 pregnant women with mid-trimester maternal plasma (gestational age [GA], 16–24 weeks) who subsequently developed PE and 66 GA-matched controls with normal outcomes (mid-trimester cohort). Plasma samples were comprehensively profiled for primary metabolic and lipidomic signatures based on gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and liquid chromatography Orbitrap mass spectrometry (LC-Orbitrap MS). A potential biomarker panel was computed based on binary logistic regression and evaluated using receiver operating characteristic (ROC) analysis. To evaluate whether this panel can be also used in late pregnancy, a retrospective cohort study was conducted using plasma collected from women who delivered in the late preterm period because of PE (n = 13) or other causes (n = 21) (at-delivery cohort). Metabolomic biomarkers were compared according to the indication for delivery. Performance of the metabolomic panel to identify patients with PE was compared also to a commonly used standard, the plasma soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio. In the mid-trimester cohort, a total of 329 metabolites were identified and semi-quantified in maternal plasma using GC-TOF MS and LC-Orbitrap-MS. Binary logistic regression analysis proposed a mid-trimester biomarker panel for the prediction of PE with five metabolites (SM C28:1, SM C30:1, LysoPC C19:0, LysoPE C20:0, propane-1,3-diol). This metabolomic model predicted PE better than PlGF (AUC [95% CI]: 0.868 [0.844–0.891] vs 0.604 [0.485–0.723]) and sFlt-1/PlGF ratio. Analysis of plasma from the at-delivery cohort confirmed the ability of this biomarker panel to distinguish PE from non-PE, with comparable discrimination power to that of the sFlt-1/PlGF ratio. In conclusion, an integrative metabolomic biomarker panel in mid-trimester maternal plasma can accurately predict the development of PE and showed good discriminatory power in patients with PE at delivery.

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Application of metabolomics to preeclampsia diagnosis

Cited by 44 publications

References 98 publications

Maternal Diet and the Serum Metabolome in Pregnancy: Robust Dietary Biomarkers Generalizable to a Multiethnic Birth Cohort

Maternal Diet and the Serum Metabolome in Pregnancy: Robust Dietary Biomarkers Generalizable to a Multiethnic Birth Cohort

Metabolomic analysis of serum and placenta in preeclampsia

Metabolomic biomarkers in midtrimester maternal plasma can accurately predict the development of preeclampsia

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