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

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; ß (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.

Polymorphisms of Leptin (G2548A) and Leptin Receptor (Q223R and K109R) Genes and Blood Pressure During Pregnancy and the Postpartum Period: A Cohort.

BACKGROUND: The genetic component related to blood pressure (BP) changes during pregnancy is still not elucidated. Thus, the aim of the study was to evaluate the association between leptin and leptin receptor polymorphisms and systolic (SBP) and diastolic BP (DBP) variation during pregnancy and the postpartum period. METHODS: Prospective cohort of 146 women followed at a Public Health Center in Rio de Janeiro, Brazil, during pregnancy and the postpartum. SBP and DBP (mm Hg) were measured using an automatic sphygmomanometer. DNA was extracted by phenol-chloroform protocol and leptin (G2548A) and leptin receptor genes (Q223R and K109R) polymorphisms were genotyped using real-time PCR method. Statistical analyses included longitudinal linear mixed-effect models. RESULTS: Adjusted longitudinal models showed that women carrying the G-allele of leptin gene's polymorphism began pregnancy with higher BP levels compared to the AA genotype and their levels remained higher throughout pregnancy and the postpartum period (ß SBP = 4.5; 95% confidence interval (CI) = 1.0-8.0; P = 0.012; ß DBP = 2.9; 95% CI = 0.1-5.8; P = 0.040). There was a significant interaction between leptin gene polymorphism and body mass index (BMI), in which the effect of BMI on increasing BP was steeper in women homozygous for the A-allele, compared with those who had at least one G-allele (ß G-allele#BMI = -0.8; 95% CI = -1.5 to -0.1; P = 0.022). We did not find significant associations between leptin receptor polymorphisms and BP changes. CONCLUSIONS: The G-allele of leptin gene polymorphism (G2548A) was associated with increased BP levels during pregnancy and the postpartum. Furthermore, leptin polymorphism genotypes seem to modify the well-known effect of BMI on BP.

Vitamin B-6 Status in Unsupplemented Pregnant Women Is Associated Positively with Serum Docosahexaenoic Acid and Inversely with the n-6-to-n-3 Fatty Acid Ratio.

BACKGROUND: Vitamin B-6-deficient diets decrease plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) concentrations in healthy adults. These fatty acids (FAs) are important for fetal neurodevelopment, but the relation between vitamin B-6 status and circulating polyunsaturated FAs (PUFAs) during pregnancy is unknown. OBJECTIVE: We sought to assess the relation between plasma pyridoxal 5' phosphate (PLP; the active form of vitamin B-6) and serum DHA, EPA, AA, linoleic acid, eicosadienoic, and α-linolenic acid concentrations during pregnancy. METHODS: A prospective cohort study in 186 healthy pregnant Brazilian women (aged 20-40 y) who were not using supplements was conducted in Rio de Janeiro, Brazil. Participants were enrolled in the first trimester of pregnancy (5-13 gestational weeks) and were followed up twice between 20-26 and 30-36 wk of gestation. Longitudinal linear mixed-effects regression models were used to evaluate the associations between 1) first-trimester PLP and PUFA concentrations across pregnancy and 2) ΔPLP (i.e., difference between third- and first-trimester plasma PLP concentrations) and PUFA concentrations across pregnancy. Models were adjusted for gestational week, first-trimester body mass index, smoking habit, and dietary intakes of vitamin B-6, fish, total fat, and PUFAs. RESULTS: Plasma PLP concentrations (median, IQR) substantially declined during pregnancy from 35.8 nmol/L (28.6-44.3 nmol/L) in the first trimester to 21.0 nmol/L (15.8-26.3 nmol/L) in the second trimester, and 16.8 nmol/L (12.9-20.3 nmol/L) in the third trimester (both P < 0.0001). Changes in plasma PLP concentrations across trimesters were positively associated with serum DHA concentrations (ß = 0.252, P = 0.012) and inversely associated with serum n-6-to-n-3 (ω-6-to-ω-3) FA ratio (ß = -0.010; P = 0.015), after adjustments for confounders. CONCLUSIONS: Maternal vitamin B-6 status during pregnancy was positively associated with the circulating concentration of DHA and inversely associated with n-6:n-3 FAs in Brazilian women who were not taking vitamin supplements. Further study is required to determine the impact of poor vitamin B-6 status on fetal neurodevelopment.

Total cholesterol and leptin concentrations are associated with prospective changes in systemic blood pressure in healthy pregnant women.

BACKGROUND: Lipids and leptin have been associated with high blood pressure (BP) levels during pregnancy. The aim was to evaluate the associations between serum lipids and leptin concentrations during the first trimester and longitudinal changes of SBP and DBP in healthy pregnancies. METHODS: Prospective cohort of pregnant women followed at a public healthcare center in Rio de Janeiro, Brazil. SBP and DBP were obtained at the ≤13th, 20-26th, and 30-36th weeks of gestation and were the dependent variables. Serum lipids and plasma leptin concentrations were collected at 13 weeks or less of gestation and were the main independent variables. Statistical analyses included longitudinal linear mixed-effects regression models, with (ß) coefficients and their 95% confidence intervals (CI). RESULTS: Mean BPs were 109.8/66.9, 107.8/64.3, and 111.2/66.9  mmHg, respectively in the 1st, 2nd, and 3rd trimester. Multiple longitudinal regressions revealed that leisure time physical activity before pregnancy (ß(SBP) = -3.003, 95% CI = -5.034 to -0.971; ß(DBP) = -2.620, 95% CI = -4.177 to -1.064), baseline BMI (ß(SBP) = 4.003, 95% CI = 1.924-6.081; ß(DBP) = 1.862, 95% CI = 0.252-3.412), parity (ß(SBP) = -2.778, 95% CI = -4.627 to -0.929; ß(DBP) = -1.780, 95% CI = -3.168 to -0.392), and Homeostasis model of assessment-Insulin Resistance (HOMA-IR; ß(SBP) = 2.554, 95% CI = 0.552-4.557; ß(DBP) = 2.962, 95% CI = 1.436-4.489) were the covariates independently associated with SBP and DBP changes. Monthly per-capita family income (ß(SBP) = -0.006, 95% CI = -0.010 to -0.001), total cholesterol (ß(SBP) = 2.094, 95% CI = 0.223-3.965), and leptin (ß(SBP) = 2.211, 95% CI = 0.159-4.263) were associated only with SBP changes. CONCLUSION: Serum total cholesterol and leptin concentrations, HOMA-IR, and BMI were positively associated with changes in BP during healthy pregnancies, whereas physical activity, parity, and family income were negatively associated.