Maternal Plasma Pyridoxal 5′-Phosphate Concentration Is Inversely Associated with Plasma Cystathionine Concentration across All Trimesters in Healthy Pregnant Women

Abstract

Background Vitamin B-6 (B-6), in the form of pyridoxal 5′phosphate (PLP), is critical for one-carbon metabolism reactions and cellular function. Plasma PLP concentration decreases throughout pregnancy, but the functional consequences of this have not been studied. Plasma cystathionine is a sensitive indicator of suboptimal B-6 status in healthy adults. Objectives The aim of this study was to determine the relation between plasma PLP and cystathionine concentrations, and to assess longitudinal changes in plasma concentrations of metabolites of one-carbon metabolism, including total homocysteine (tHcy), cysteine, methionine, glycine, serine, and glutathione, over the course of pregnancy. Design This was a prospective cohort study of 186 healthy Brazilian pregnant women (20–40 y). Plasma PLP and metabolite concentrations were quantified in fasting maternal blood samples collected between 5–13, 20–26, and 30–36 weeks of gestation. Linear mixed regression models were used to determine the association of 1) first-trimester PLP tertiles, and 2) the variation of PLP concentration throughout pregnancy, with related metabolite concentrations across weeks of gestation. Results Median (IQR) PLP concentration decreased from 36.2 (29.2–44.5) to 21.0 (15.9–26.0) to 16.8 (12.9–21.4) nmol/L in the first, second, and third trimester, respectively, whereas cystathionine concentration increased from 63.2 (49.7–78.9) to 122 (98.0–167) to 143 (114–193) nmol/L, respectively (both P < 0.001). The variation of PLP throughout pregnancy was inversely associated with cystathionine concentration across weeks of gestation, after adjusting for confounding factors; β (95% CI) = −0.387 (−0.752, −0.219), P = 0.04. This association significantly differed by trimester and was strongest in the third trimester. Plasma concentrations of glycine, serine, methionine, cysteine, and tHcy decreased, and that of glutathione increased, between the first and second trimesters (all P < 0.05). Conclusions The variation of PLP concentration predicted cystathionine concentration throughout pregnancy. Increases in plasma cystathionine across trimesters may reflect maternal intracellular B-6 deficiency.

Longitudinal Analysis of One-Carbon Metabolism-Related Metabolites in Maternal and Cord Blood of Japanese Pregnant Women

“…However, these results appear contradictory because theoretically, Hcy should decrease due to changes in OCM enzyme activity caused by increased estrogen during pregnancy, along with increased maternal circulating blood volume and decreased albumin levels [ 6 ]. Moreover, previous studies have reported a decrease in tHcy from early to mid-pregnancy [ 27 , 28 , 57 , 58 , 59 ]. Conversely, some studies have indicated an increase in tHcy from mid to late pregnancy [ 28 , 29 , 34 , 58 , 60 , 61 , 62 , 63 ].…”

“…Moreover, previous studies have reported a decrease in tHcy from early to mid-pregnancy [ 27 , 28 , 57 , 58 , 59 ]. Conversely, some studies have indicated an increase in tHcy from mid to late pregnancy [ 28 , 29 , 34 , 58 , 60 , 61 , 62 , 63 ]. Therefore, this study did not include measurements during mid-pregnancy, which may have missed the potential decrease in tHcy during this period.…”

“…Serum tCys decreased significantly in late pregnancy in this study ( Table 1 ), but results from previous studies are inconsistent. Some studies have reported a decrease from early to mid-pregnancy followed by a plateau [ 51 ], a decrease from early to mid-pregnancy with a slight increase from mid to late pregnancy [ 58 ], a decrease from mid to late pregnancy [ 64 ], and in some cases, no change [ 29 ]. Further studies are required to systematically investigate changes in tCys levels during pregnancy.…”

Longitudinal Urine Metabolic Profiling and Gestational Age Prediction in Pregnancy

“…Investigation of longitudinal maternal metabolomic alternations over the course of pregnancy has the potential to be a highly informative approach for mechanistic investigation and a breakthrough tool for GA dating. This approach has recently attracted more attention ( 21,33,34 ) but has relied mostly on maternal blood samples ( 21,35–37 ). Use of maternal urine for GA dating and metabolic profiling has yet to be explored and may provide a cost effective and non-invasive method that could be easily translated into clinical settings.…”