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.
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.
Study Objectives The objectives of this study were to evaluate the performance of renal function estimating equations compared to measured creatinine clearance (CrCl) during pregnancy and postpartum and to evaluate which body weight (pre‐pregnancy weight (PPW), actual body weight (ABW), and ideal body weight (IBW)) provides the best performance. Design A retrospective study. Setting Collections tookplace in the University of Washington clinical research unit. Patients Women (n = 166) who completed ≥1 pharmacokinetic (PK) study with a 6–24 h measured CrCl during pregnancy and/or ≥3 months postpartum were included. Intervention CrCl was estimated utilizing estimated glomerular filtration rate (eGFR) and CrCl equations with common weight descriptors. Analyses included Bland–Altman, relative accuracies within 10% and 25%, and root mean squared error (RMSE). Overall performance was determined by summation of rank for evaluation parameters. Measurements and Main Results During pregnancy, correlations between measured CrCl and estimated CrCl were between 0.5–0.8; equations with slopes closest to one were Modification of Diet in Renal Disease (MDRD2; PPW and ABW) and Cockcroft‐Gault (CG) (PPW); and y‐intercept closest to zero was Preeclampsia Glomerular Filtration Rate (PGFR). The lowest bias was seen with CG (ABW), and the highest accuracy within 25% was CG (ABW). CG (PPW) had the lowest RMSE. Postpartum, the best correlation was found with MDRD2 (PPW), Chronic Kidney Disease Epidemiology Collaboration (CKD–EPI (ABW)), and CKD–EPI 2021 (PPW). For slopes closest to one, MDRD2 (ABW) was best, whereas the equation with y‐intercept closest to zero was CKD–EPI (ABW). CG (PPW) had the highest accuracy within 25%, and 100/serum creatinine (SCr) had the lowest bias. Based on overall performance, CG (PPW) was the best followed by CG (ABW) and PGFR during pregnancy and 100/SCr followed by CG (PPW) and CG (ABW) postpartum. Conclusion The new CKD–EPI 2021 equation did not perform well during pregnancy. When 24‐h CrCls are not available during pregnancy, CG (PPW or ABW) performed the best overall, whereas at 3 months postpartum, 100/SCr performed the best overall.
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