Urine Metabolome during Parturition

Abstract

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.

Keywords: amino acid; conjugated estrogens; dilating phase; estrogens; in labor; out of labor; urine metabolomic profile.

Figure 1

PLS-DA 3D plot based on normalized and mean-centered data. Each data point represents the metabolome of a single individual. In red are expressed sample collected in OL. In green are expressed samples collected in IL-DP. In blue are expressed QC.

Figure 2

Metabolic Pathway Analysis (MetPA). All the matched pathways are displayed as circles. The color and size of each circle are based on the p-value and pathway impact value, respectively. The graph was obtained by plotting on the y-axis the −log of p-values from the pathway enrichment analysis and on the x-axis the pathway impact values derived from the pathway topology analysis.