scholarly journals Formate concentrations in maternal plasma during pregnancy and in cord blood in a cohort of pregnant Canadian women: relations to genetic polymorphisms and plasma metabolites

2019 ◽  
Vol 110 (5) ◽  
pp. 1131-1137 ◽  
Author(s):  
John T Brosnan ◽  
Lesley Plumptre ◽  
Margaret E Brosnan ◽  
Theerawat Pongnopparat ◽  
Shannon P Masih ◽  
...  

ABSTRACT Background One-carbon metabolism, responsible for purine and thymidylate synthesis and transmethylation reactions, plays a critical role in embryonic and fetal development. Formate is a key player in one-carbon metabolism. In contrast to other one-carbon metabolites, it is not linked to tetrahydrofolate, is present in plasma at appreciable concentrations, and may therefore be distributed to different tissues. Objective The study was designed to determine the concentration of formate in cord blood in comparison with maternal blood taken earlier in pregnancy and at delivery and to relate formate concentrations to potential precursors and key fetal genotypes. Methods Formate and amino acids were measured in plasma during early pregnancy (12–16 wk), at delivery (37–42 wk), and in cord blood samples from 215 mothers, of a prospective cohort study. Three fetal genetic variants in one-carbon metabolism were assessed for their association with cord plasma concentrations of formate. Results The formate concentration was ∼60% higher in the cord blood samples than in mothers’ plasma. The maternal formate concentrations did not differ between the early pregnancy samples and those taken at delivery. Plasma concentrations of 4 formate precursors (serine, glycine, tryptophan, and methionine) were increased in cord blood compared with the maternal samples. Cord blood formate was influenced by fetal genotype, being ∼12% higher in infants harboring the MTHFR A1298C (rs1801131) AC or CC genotypes and 10% lower in infants harboring the MTHFD1 G1958A (rs2236225) GA or AA genotypes. Conclusions The increased formate concentrations in cord blood may support the increased activity of one-carbon metabolism in infants. As such, it would support increased rates of purine and thymidylate synthesis and the provision of methionine for methylation reactions.

2014 ◽  
Vol 58 (6) ◽  
pp. 3504-3513 ◽  
Author(s):  
Mohammed H. Elkomy ◽  
Pervez Sultan ◽  
David R. Drover ◽  
Ekaterina Epshtein ◽  
Jeffery L. Galinkin ◽  
...  

ABSTRACTThe objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre- and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates.


2019 ◽  
Vol 149 (8) ◽  
pp. 1354-1362
Author(s):  
Maria F Mujica-Coopman ◽  
Dayana R Farias ◽  
Ana B Franco-Sena ◽  
Juliana S Vaz ◽  
Gilberto Kac ◽  
...  

ABSTRACTBackgroundVitamin 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.ObjectivesThe 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.DesignThis 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.ResultsMedian (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).ConclusionsThe variation of PLP concentration predicted cystathionine concentration throughout pregnancy. Increases in plasma cystathionine across trimesters may reflect maternal intracellular B-6 deficiency.


PEDIATRICS ◽  
1962 ◽  
Vol 29 (3) ◽  
pp. 369-375
Author(s):  
William M. Michener ◽  
W. Newlon Tauxe ◽  
Alvin B. Hayles

Normal values for the measurement of thyroidal function using the erythrocytic uptake of I131-labeled triiodothyronine and the thyroxine-binding capacity of the inter-alpha globulin were established. Paired maternal and cord blood samples collected at the time of delivery were studied with these methods. The erythrocytic uptake of labeled hormone was increased in cord blood as compared to maternal blood. Cord blood apparently binds exogenous triiodothyronine in a different manner than it does exogenous thyroxine. Whether this is a qualitative or quantitative difference was not shown in this study.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Anna K. Knight ◽  
Hea Jin Park ◽  
Dorothy B. Hausman ◽  
Jennifer M. Fleming ◽  
Victoria L. Bland ◽  
...  

1988 ◽  
Vol 34 (7) ◽  
pp. 1498-1499 ◽  
Author(s):  
G Liras ◽  
V Diaz ◽  
C Alvarez ◽  
J Arenas ◽  
R Sanz ◽  
...  

Abstract We studied variations in the activity of total creatine kinase (CK; EC 2.7.3.2) and of CK-B in maternal and cord-blood samples, comparing data obtained for vaginal and cesarean births. CK-B activity was determined with an immunoinhibition assay. In all cases, there was a significant postpartum increase in total CK and in CK-B activity in maternal sera, whereas cord-blood samples showed no significant differences between activities in arterial and venous blood for either vaginal or cesarean births. Statistically significant differences were found in CK-B activity, but not in total CK, between cord-blood samples from vaginal births and those from cesareans.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kattayoun Kordy ◽  
Fan Li ◽  
David J. Lee ◽  
Jason M. Kinchen ◽  
Michael H. Jew ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in western countries both in children and adults. Metabolic dysregulation associated with gut microbial dysbiosis may influence disease progression from hepatic steatosis to inflammation and subsequent fibrosis. Using a multi-omics approach, we profiled the oral and fecal microbiome and plasma metabolites from 241 predominantly Latino children with non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFL), and controls. Children with more severe liver pathology were dysbiotic and had increased gene content associated with lipopolysaccharide biosynthesis and lipid, amino acid and carbohydrate metabolism. These changes were driven by increases in Bacteroides and concomitant decreases of Akkermansia, Anaerococcus, Corynebacterium, and Finegoldia. Non-targeted mass spectrometry revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. Random forests modeling of plasma metabolites was highly predictive of non-alcoholic steatohepatitis (NASH) (97% accuracy) and hepatic fibrosis, steatosis and lobular inflammation (93.8% accuracy), and can differentiate steatohepatitis from simple steatosis (90.0% accuracy). Multi-omics predictive models for disease and histology findings revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. These results highlight the promise of non-invasive biomarkers for the growing epidemic of fatty liver disease.


2013 ◽  
Vol 1 (1) ◽  
pp. 1 ◽  
Author(s):  
Juthatip Fongsarun ◽  
Maneerat Ekkapongpisit ◽  
Mantana Paisan ◽  
Siripen Chanthachorn ◽  
Konstantinos I Papadopoulos

2021 ◽  
Author(s):  
Hyo Sub Choi ◽  
Ajay Bhat ◽  
Marshall B. Howington ◽  
Megan L. Schaller ◽  
Rebecca Cox ◽  
...  

Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans, fmo-2 expression increases lifespan and healthspan downstream of multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, contrary to its classification as a xenobiotic enzyme, fmo-2 expression leads to rewiring of endogenous metabolism principally through changes in one carbon metabolism (OCM). Using computer modeling, we identify decreased methylation as the major OCM flux modified by FMO-2 that is sufficient to recapitulate its longevity benefits. We further find that tryptophan is decreased in multiple mammalian FMO overexpression models and is a validated substrate for FMO enzymes. Our resulting model connects a single enzyme to two previously unconnected key metabolic pathways and provides a framework for the metabolic interconnectivity of longevity-promoting pathways such as dietary restriction. FMOs are well-conserved enzymes that are also induced by lifespan-extending interventions in mice, supporting a conserved and critical role in promoting health and longevity through metabolic remodeling.


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