Detection and Identification of Novel Metabolomic Biomarkers in Preeclampsia

Kenny, Louise C.; Broadhurst, David; Brown, Marie; Dunn, Warwick B.; Redman, Christopher W.G.; Kell, Douglas B.; Baker, Philip N.

doi:10.1177/1933719108316908

Cited by 85 publications

(73 citation statements)

References 31 publications

(34 reference statements)

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“…10 -12 We previously reported results of an anonymous metabolomic screen of plasma from women with established PE. 13,14 Subsequently, we identified highly discriminatory metabo- …”

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confidence: 99%

Robust Early Pregnancy Prediction of Later Preeclampsia Using Metabolomic Biomarkers

et al. 2010

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Abstract-Preeclampsia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preeclampsia in early pregnancy. Here, a 2-phase discovery/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using samples obtained at 15Ϯ1 weeks' gestation from 60 women who subsequently developed preeclampsia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma samples were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preeclampsia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15Ϯ1 weeks from 39 women who subsequently developed preeclampsia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preeclampsia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test. Key Words: preeclampsia Ⅲ metabolomics Ⅲ biomarkers Ⅲ screening Ⅲ hypertension P reeclampsia (PE) affects 5% of nulliparous pregnancies and globally afflicts Ϸ4 million women annually. It remains a leading cause of maternal death throughout the world and is responsible for significant baby morbidity and mortality. 1 Furthermore, PE has healthcare implications for the women later in life with an increased risk of hypertension, coronary artery disease, stroke, and type 2 diabetes mellitus. 2 Although the precise etiology of the disease is unclear, accumulating evidence suggests that the disease results from complex interaction between a poorly perfused placenta, because of defective remodeling of the uteroplacental arteries in early pregnancy, and a maternal response to placentalderived triggers, which results in widespread vascular endothelial cell dysfunction. 1,3,4 Widespread plasma alterations precede the clinical onset of PE, and there is intense interest in the identification of predictive biomarkers. 5 Numerous candidate biomarkers have been proposed for prediction of disease, including placental hormones, angiogenic factors, and lipids. 3,6 -8 To date, none (nor any combination) has emerged with the requisite specificity and sensitivity to be of clinical use. 5 Consequently, clinicians are unable to offer either targeted surveil...

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“…10 -12 We previously reported results of an anonymous metabolomic screen of plasma from women with established PE. 13,14 Subsequently, we identified highly discriminatory metabo- …”

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confidence: 99%

Robust Early Pregnancy Prediction of Later Preeclampsia Using Metabolomic Biomarkers

et al. 2010

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“…Metabolomic products have also been suggested as a investigation modality for identifying new biomarkers for preeclampsia. Kenny et al identified eight metabolomic products that with high sensitivity and specificity differentiated pregnancies with preeclampsia from control pregnancy blood [80]. Current researchers focus on the prediction of onset of preeclampsia so as to allow early management and improve the morbidity and mortality associated with this disease.…”

Section: Discussionmentioning

confidence: 99%

Prediction of the preeclampsia: a view of biochemical markers

Bostancı

Bayram

Cevrioğlu

et al. 2013

RHC

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Preeclampsia is a diverse, multiorgan group of related disease processes that occurs in up to 5%-8% of pregnancies after 20 weeks' gestation and it is one of the leading causes of maternal and fetal morbidity and mortality. Many molecular mechanisms are contributed to the pathogenesis of preeclampsia. Although it is unknown whether the mechanisms act independently or have synergistic effects. This review describes review of primary papers investigating blood based biomarker such as PAP-A, Inhibin A, sFlt1, and PP13 in general and first trimester biochemical markers and combinations of them specifically for preeclampsia.

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“…The chemical identities of these eight metabolites were established. 64 Turner et al 65 used 1 H-nuclear magnetic resonance spectroscopy to establish the metabolic profile for pre-eclampsia and to identify biomarkers that would permit a distinction between women with a normal pregnancy and those suffering from pre-eclampsia. Eleven cases and controls were used, and the plasma samples were taken at the time of disease.…”

Section: Discussionmentioning

confidence: 99%

An overview of proteomic and metabolomic technologies and their application to pregnancy research

Horgan

Clancy

Myers

et al. 2008

BJOG

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'Omic' technologies represent a strategy towards high-throughput, simultaneous analysis of thousands of biological molecules. Their development has been accelerated in the post-genomic era since these molecules represent the interaction of genes and environment or the 'functional genome'. Omic domains are of particular interest in the search for predictive disease biomarkers and have additional relevance in understanding pathophysiology and the development of molecularly targeted therapeutics. This review examines the fields of proteomics and metabolomics in the context of obstetrics and gynaecology, including a discussion of methodology, challenges, potential applications and current research.

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Detection and Identification of Novel Metabolomic Biomarkers in Preeclampsia

Abstract: In a previous study, the ability of gas chromatography time-of-

Cited by 85 publications

References 31 publications

Robust Early Pregnancy Prediction of Later Preeclampsia Using Metabolomic Biomarkers

Robust Early Pregnancy Prediction of Later Preeclampsia Using Metabolomic Biomarkers

Prediction of the preeclampsia: a view of biochemical markers

An overview of proteomic and metabolomic technologies and their application to pregnancy research

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