ABSTRACT
Limited data are available on the effects of pregnancy on the maternal metabolome. Therefore, the objective of this study was to use metabolomics analysis to determine pathways impacted by pregnancy followed by targeted confirmatory analysis to provide more powerful conclusions about metabolic alterations during pregnancy. Forty-seven pregnant women, 18-50 years of age were included in this study, with each subject serving as their own control. Plasma samples were collected between 25 and 28 weeks gestation and again ≥3 months postpartum for metabolomics analysis utilizing an HILIC/UHPLC/MS/MS assay with confirmatory targeted specific concentration analysis for 10 of the significantly altered amino acids utilizing an LC/MS assay. Principle component analysis (PCA) on metabolomics data clearly separated pregnant and postpartum groups and identified outliers in a preliminary assessment. Of the 980 metabolites recorded, 706 were determined to be significantly different between pregnancy and postpartum. Pathway analysis revealed three significantly impacted pathways, arginine biosynthesis (p = 2 × 10-5 and FDR = 1 × 10-3), valine, leucine, and isoleucine metabolism (p = 2 × 10-5 and FDR = 2 × 10-3), and xanthine metabolism (p = 4 × 10-5 and FDR = 4 × 10-3). Of these we focused analysis on arginine biosynthesis and branched-chain amino acid (BCAA) metabolism due to their clinical importance and interconnected roles in amino acid metabolism. In the confirmational analysis, 7 of 10 metabolites were confirmed as significant and all 10 confirmed the direction of change of concentrations observed in the metabolomics analysis. The data support an alteration in urea nitrogen disposition and amino acid metabolism during pregnancy. These changes could also impact endogenous nitric oxide production and contribute to diseases of pregnancy. This study provides evidence for changes in both the ammonia-urea nitrogen and the BCAA metabolism taking place during pregnancy.
ABSTRACT
Vitamin A is vital to maternal-fetal health and pregnancy outcomes. However, little is known about pregnancy associated changes in maternal vitamin A homeostasis and concentrations of circulating retinol metabolites. The goal of this study was to characterize retinoid concentrations in healthy women (n = 23) during two stages of pregnancy (25-28 weeks gestation and 28-32 weeks gestation) as compared to ≥3 months postpartum. It was hypothesized that plasma retinol, retinol binding protein 4 (RBP4), transthyretin and albumin concentrations would decline during pregnancy and return to baseline by 3 months postpartum. At 25-28 weeks gestation, plasma retinol (-27%), 4-oxo-13-cis-retinoic acid (-34%), and albumin (-22%) concentrations were significantly lower, and all-trans-retinoic acid (+48%) concentrations were significantly higher compared to ≥3 months postpartum in healthy women. In addition, at 28-32 weeks gestation, plasma retinol (-41%), retinol binding protein 4 (RBP4; -17%), transthyretin (TTR; -21%), albumin (-26%), 13-cis-retinoic acid (-23%) and 4-oxo-13-cis-retinoic acid (-48%) concentrations were significantly lower, whereas plasma all-trans-retinoic acid concentrations (+30%) were significantly higher than ≥3 months postpartum. Collectively, the data demonstrates that in healthy pregnancies, retinol plasma concentrations are lower, but all-trans-retinoic acid concentrations are higher than postpartum.