Urine Metabolome during Parturition.

In recent years, some studies have described metabolic changes during human childbirth labor. Metabolomics today is recognized as a powerful approach in a prenatal research context, since it can provide detailed information during pregnancy and it may enable the identification of biomarkers with potential diagnostic or predictive. This is an observational, longitudinal, prospective cohort study of a total of 51 serial urine samples from 15 healthy pregnant women, aged 29-40 years, which were collected before the onset of labor (out of labor, OL). In the same women, during labor (in labor or dilating phase, IL-DP). Samples were analyzed by hydrophilic interaction ultra-performance liquid chromatography coupled with mass spectrometry (HILIC-UPLC-MS), a highly sensitive, accurate, and unbiased approach. Metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathway. This method was used to identify the potential biomarkers. The top 20 most discriminative metabolites contributing to the complete separation of OL and IL-DP were identified. Urinary metabolites displaying the largest differences between OL and IL-DP belonged to steroid hormone, particularly conjugated estrogens and amino acids much of this difference is determined by the fetal contribution. In addition, our results highlighted the efficacy of using urine samples instead of more invasive techniques to evaluate the difference in metabolic analysis between OL and IL-DP.

Urinary profiles associated with bacterial metabolites from asymptomatic pregnant women with at term or preterm premature rupture of membranes: a pilot study.

Objective: Premature rupture of membranes (PROM) and preterm premature rupture of membranes (pPROM) are frequent conditions with a not fully understood multifactorial etiology. It has been suggested that infection may be the leading cause of pPROM. Metabolomics is nowadays recognized as a successful and versatile approach for the investigation of several pathological conditions, including pregnancy-related ones. However, collecting samples such as fetal fluids or placenta poses a limit on the clinical application of this strategy. Therefore, the aim of this study was to detect urinary metabolites that could be associated with bacterial infection in PROM and pPROM and to understand its role in these different conditions, using readily available samples such as urines.Methods: Urine samples were collected from pregnant women who experienced rupture of membranes: (1) at term (≥37 weeks) not in labor (NLPROM); (2) at term in labor (LPROM); (3) preterm (<37 weeks) not in labor (pPROM). Samples were analyzed using a GC-MS platform. Student's t-test, Pearson correlation coefficient, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) were applied to observe differences between groups.Results: Results showed that lactic acid, erythritol, and ethanolamine levels were significantly higher in pPROM than in PROM (NLPROM + LPROM considered as one single group). These three metabolites might be associated with bacterial infections since they derive from bacterial metabolic processes and environments.Conclusions: This study might be useful to understand the mechanisms underlying the etiology of pPROM and PROM, and urine samples might represent a useful and readily available sample to discriminate preterm high-risk women.

PROM and Labour Effects on Urinary Metabolome: A Pilot Study.

Since pathologies and complications occurring during pregnancy and/or during labour may cause adverse outcomes for both newborns and mothers, there is a growing interest in metabolomic applications on pregnancy investigation. In fact, metabolomics has proved to be an efficient strategy for the description of several perinatal conditions. In particular, this study focuses on premature rupture of membranes (PROM) in pregnancy at term. For this project, urine samples were collected at three different clinical conditions: out of labour before PROM occurrence (Ph1), out of labour with PROM (Ph2), and during labour with PROM (Ph3). GC-MS analysis, followed by univariate and multivariate statistical analysis, was able to discriminate among the different classes, highlighting the metabolites most involved in the discrimination.

Urinary metabolomics of pregnant women at term: a combined GC/MS and NMR approach.

BACKGROUND: Physiological changes leading to parturition are not completely understood while clinical diagnosis of labour is still retrospective. Gas chromatography mass spectrometry (GC/MS) and nuclear magnetic resonance spectroscopy (NMR) represent two of the main analytical platforms used in clinical metabolomics. Metabolomics might help us to improve our knowledge about the biochemical mechanisms underlying labour. METHODS: Urine samples (n = 59), collected from pregnant women at term of gestation before and/or after the onset of labour, were analysed by GC/MS and NMR techniques in order to identify the metabolic profile. Both GC/MS and NMR data matrices containing the identified metabolites were analysed by multivariate statistical techniques in order to characterise the discriminant variables between labour (L) and not labour (NL) status. RESULTS: 18 potential metabolites (11 with (1)H-NMR, eight with GC-MS: glycine was relevant in both) were found discriminant in urine of women during labour. Taken together, the identified metabolites produced a composite biomarker pattern, a sort of barcode, capable of differentiating between labour and not labour conditions. Major discriminant metabolites for NMR and GC/MS analysis were: alanine, glycine, acetone, 3-hydroxybutiyric acid, 2,3,4-trihydroxybutyric acid and succinic acid, giving a urine metabolite signature on the late phase of labour. CONCLUSIONS: The metabolomics analysis evidenced clusters of metabolites involved in labour condition able to discriminate between urine samples collected before the onset and during labour, potentially offering the promise of a robust screening test.