Application of metabolomics to preeclampsia diagnosis

Abstract

Preeclampsia is a multifactorial disorder defined by hypertension and increased urinary protein excretion during pregnancy. It is a significant cause of maternal and neonatal deaths worldwide. Despite various research efforts to clarify pathogenies of preeclampsia and predict this disease before beginning of symptoms, the pathogenesis of preeclampsia is unclear. Early prediction and diagnosis of women at risk of preeclampsia has not markedly improved. Therefore, the objective of this study was to perform a review on metabolomic articles assessing predictive and diagnostic biomarkers of preeclampsia. Four electronic databases including PubMed/Medline, Web of Science, Sciencedirect, and Scopus were searched to identify studies of preeclampsia in humans using metabolomics from inception to March 2018. Twenty-one articles in a variety of biological specimens and analytical platforms were included in the present review. Metabolite profiles may assist in the diagnosis of preeclampsia and discrimination of its subtypes. Lipids and their related metabolites were the most generally detected metabolites. Although metabolomic biomarkers of preeclampsia are not routinely used, this review suggests that metabolomics has the potential to be developed into a clinical tool for preeclampsia diagnosis and could contribute to an improved understanding of disease mechanisms. Abbreviations: PE: preeclampsia; sFlt-1: soluble FMS-like tyrosine kinase-1; PlGF: placental growth factor; GC–MS: gas chromatography–mass spectrometry; LC–MS: liquid chromatography–mass spectrometry; NMR: nuclear magnetic resonance spectroscopy; HMDB: human metabolome database; RCT: randomized control trial; e-PE: early-onset PE; l-PE: late-onset PE; PLS-DA: partial least-squares-discriminant analysis; CRL: crown-rump length; UtPI: uterine artery Doppler pulsatility index; BMI: body mass index; MAP: mean arterial pressure; OS: oxidative stress; PAPPA: plasma protein A; FTIR: Fourier transform infrared; BCAA: branched chain amino acids; Arg: arginine; NO: nitric oxide.