Metabolomics in Prenatal Medicine: A Review

Abstract

Pregnancy is a complicated and insidious state with various aspects to consider, including the well-being of the mother and child. Developing better non-invasive tests that cover a broader range of disorders with lower false-positive rates is a fundamental necessity in the prenatal medicine field, and, in this sense, the application of metabolomics could be extremely useful. Metabolomics measures and analyses the products of cellular biochemistry. As a biomarker discovery tool, the integrated holistic approach of metabolomics can yield new diagnostic or therapeutic approaches. In this review, we identify and summarize prenatal metabolomics studies and identify themes and controversies. We conducted a comprehensive search of PubMed and Google Scholar for all publications through January 2020 using combinations of the following keywords: nuclear magnetic resonance, mass spectrometry, metabolic profiling, prenatal diagnosis, pregnancy, chromosomal or aneuploidy, pre-eclampsia, fetal growth restriction, pre-term labor, and congenital defect. Metabolite detection with high throughput systems aided by advanced bioinformatics and network analysis allowed for the identification of new potential prenatal biomarkers and therapeutic targets. We took into consideration the scientific papers issued between the years 2000–2020, thus observing that the larger number of them were mainly published in the last 10 years. Initial small metabolomics studies in perinatology suggest that previously unidentified biochemical pathways and predictive biomarkers may be clinically useful. Although the scientific community is considering metabolomics with increasing attention for the study of prenatal medicine as well, more in-depth studies would be useful in order to advance toward the clinic world as the obtained results appear to be still preliminary. Employing metabolomics approaches to understand fetal and perinatal pathophysiology requires further research with larger sample sizes and rigorous testing of pilot studies using various omics and traditional hypothesis-driven experimental approaches.

Metabolomics Analysis of Amniotic Fluid in Euploid Foetuses with Thickened Nuchal Translucency by Gas Chromatography-Mass Spectrometry

“…“Omics sciences” aim at the comprehensive and quantitative analysis of wide arrays of analytes in biological samples, each demonstrating varying concentrations and physicochemical properties. Metabolomics is known to have strong potential for use in perinatal medicine [ 12 , 30 ]. Previous studies exploited this approach to investigate both physiological [ 13 , 31 ] and pathological [ 32 , 33 ] metabolic changes in AF occurring during pregnancy.…”

“…Although this phenomenon has already been widely analysed in the literature, several of its pathophysiological aspects still remain unexplained. Metabolomics could offer a fresh opportunity to explore maternal–foetal metabolism in an effort to explain its physiological and pathological mechanisms [ 12 ].…”

Metabolomics in clinical and forensic toxicology, sports anti‐doping and veterinary residues

“…Metabolomics is used for insight into the complex regulatory processes of mammalian systems through metabolic variation. [102][103][104] The majority of clinical applications has focused on studying advanced diseases with little focus on early onset diseases 102 that would be beneficial for preventative medicine. For clinical purposes, drug screening allows for the improvement of patient care with treatment guidance.…”

The relationship of maternal gestational mass spectrometry-derived metabolites with offspring congenital heart disease: results from multivariable and Mendelian randomization analyses

“…However, these studies focus on single or few biomarkers. Exploring the wider metabolome could provide opportunities to improve our understanding of the molecular mechanisms that underpin CHDs 3 . Previous work has explored metabolomics in maternal serum as a predictor of offspring CHDs and uncovered potentially relevant biological pathways 10 .…”

“…The metabolome, the complete set of metabolites in biological tissues/fluids, is influenced by both genotype and environment, and dynamically responds to environmental influences. Analyses of maternal metabolomic profiles could identify causal mechanisms leading to CHDs 3 . Because the metabolome reflects interactions of genomic, environmental (e.g., air pollution), behavioural (e.g., smoking) and pathophysiological states (e.g., body composition), examining associations of it with CHDs could help elucidate modifiable upstream risk factors and/or potential molecular targets for intervention to prevent CHDs.…”