Prediction of pregnancy-related hypertensive disorders using metabolomics: a systematic review

Abstract

Objective: To determine the accuracy of metabolomics in predicting hypertensive disorders in pregnancy.

Design: Systematic review of observational studies.

Data sources and study eligibility criteria: An electronic literature search was performed in June 2019 and February 2022. Two researchers independently selected studies published between 1998 and 2022 on metabolomic techniques applied to predict the condition; subsequently, they extracted data and performed quality assessment. Discrepancies were dealt with a third reviewer. The primary outcome was pre-eclampsia. Cohort or case-control studies were eligible when maternal samples were taken before diagnosis of the hypertensive disorder.

Study appraisal and synthesis methods: Data on study design, maternal characteristics, how hypertension was diagnosed, metabolomics details and metabolites, and accuracy were independently extracted by two authors.

Results: Among 4613 initially identified studies on metabolomics, 68 were read in full text and 32 articles were included. Studies were excluded due to duplicated data, study design or lack of identification of metabolites. Metabolomics was applied mainly in the second trimester; the most common technique was liquid-chromatography coupled to mass spectrometry. Among the 122 different metabolites found, there were 23 amino acids and 21 fatty acids. Most of the metabolites were involved with ammonia recycling; amino acid metabolism; arachidonic acid metabolism; lipid transport, metabolism and peroxidation; fatty acid metabolism; cell signalling; galactose metabolism; nucleotide sugars metabolism; lactose degradation; and glycerolipid metabolism. Only citrate was a common metabolite for prediction of early-onset and late-onset pre-eclampsia. Vitamin D was the only metabolite in common for pre-eclampsia and gestational hypertension prediction. Meta-analysis was not performed due to lack of appropriate standardised data.

Conclusions and implications: Metabolite signatures may contribute to further insights into the pathogenesis of pre-eclampsia and support screening tests. Nevertheless, it is mandatory to validate such methods in larger studies with a heterogeneous population to ascertain the potential for their use in clinical practice.

Prospero registration number: CRD42018097409.

Keywords: epidemiology; hypertension; maternal medicine.

Figure 1

Flow chart of study identification, screening, eligibility and inclusion. From Moher et al.

Figure 2

Characterisation of study selection regarding biological samples, sampling moment and metabolomic analysis techniques applied. GC-FID, gas-chromatography flame ionisation detector; H-NRM, hydrogen nuclear MR spectroscopy; HPLC, high-performance liquid chromatography; LC-MS, liquid-chromatography-mass spectrometry.

Figure 3

Assessment of risk of bias (left) and applicability concerns (right) of included studies.

Figure 4

Pre-eclampsia related metabolites, chemical classes and biological processes. EDC, endocrine disrupting chemical; PFAs, polyfluoroalkyl substances.