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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.

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.

SUBMITTER: Brosnan JT

PROVIDER: S-EPMC6821548 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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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.

Brosnan John T JT Plumptre Lesley L Brosnan Margaret E ME Pongnopparat Theerawat T Masih Shannon P SP Visentin Carly E CE Berger Howard H Lamers Yvonne Y Caudill Marie A MA Malysheva Olga V OV O'Connor Deborah L DL Kim Young-In YI

The American journal of clinical nutrition 20191101 5

<h4>Background</h4>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.<h4>Objective</h4>The study was designed to determine the concentration of forma ...[more]

PMID: 31350902

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Project description:BACKGROUND:Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies are inconsistent. OBJECTIVES:In a prospective cohort study, we investigated whether maternal urinary phthalate metabolite concentrations and phthalate mixtures measured during pregnancy were associated with thyroid hormones among pregnant women and newborns. METHODS:We measured nine phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate (MBzP), and four monoesthers of di(2-ethylhexyl) phthalate] in urine collected at approximately 16 and 26 weeks' gestation among women in the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine and triiodothyronine were measured in maternal serum at 16 weeks' gestation (n?=?202) and cord serum at delivery (n?=?276). We used multivariable linear regression to assess associations between individual urinary phthalate metabolites and concentrations of maternal or cord serum thyroid hormones. We used weighted quantile sum regression (WQS) to create a phthalate index describing combined concentrations of phthalate metabolites and to investigate associations of the phthalate index with individual thyroid hormones. RESULTS:With each 10-fold increase in 16-week maternal urinary MEP, maternal serum total thyroxine (TT4) decreased by 0.52??g/dL (95% CI: -1.01, -0.03). For each 10-fold increase in average (16- and 26-week) maternal urinary MBzP, cord serum TSH decreased by 19% (95% CI: -33.1, -1.9). Among mothers, the phthalate index was inversely associated with maternal serum TT4 (WQS beta?=?-0.60; 95% CI: -1.01, -0.18). Among newborns, the phthalate index was inversely associated with both cord serum TSH (WQS beta?=?-0.11; 95% CI: -0.20, -0.03) and TT4 (WQS beta?=?-0.53; 95% CI: -0.90, -0.16). CONCLUSION:Our results suggest that co-exposure to multiple phthalates was inversely associated with certain thyroid hormones (TT4 in pregnant women and newborns, and TSH in newborns) in this birth cohort. These findings highlight the need to study chemical mixtures in environmental epidemiology.

Project description:BACKGROUND:Animal studies suggest that organophosphate (OP) pesticides exposure affects thyroid function, but evidence in humans remains sparse and inconclusive. Gestational exposure is of particular interest, since thyroid hormone is essential for fetal brain development. OP pesticides are able to cross the placental and blood-brain barrier and may interfere with fetal development processes regulated by thyroid hormone. OBJECTIVE:To investigate the association of gestational OP pesticides exposure during pregnancy with maternal and cord blood thyroid hormone concentrations. METHODS:This study was embedded within Generation R (Rotterdam, the Netherlands), a prospective population-based birth cohort. Mother-child pairs with OP pesticides assessment and maternal (N?=?715) or cord blood (N?=?482) thyroid hormone measurements were included. OP pesticides exposure was assessed at <18, 18-25, and >25?weeks gestation by measuring six urinary dialkylphosphate (DAP) metabolites. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) were measured in maternal and cord blood. Maternal measures also included total thyroxine (TT4) and TPO antibodies (TPOAbs). To study the association of creatinine-adjusted DAP metabolite concentrations with thyroid function and TPO antibodies, multivariable linear regression models including relevant confounders were used. RESULTS:There was no association of DAP metabolites with maternal TSH, FT4, TT4 or TPOAb concentrations during pregnancy. Similarly, there was no association of DAP metabolites with cord blood TSH or FT4. Results did not change when DAP concentrations were analyzed at individual time points or as mean gestational exposure. CONCLUSION:Gestational OP pesticides exposure, as assessed by repeatedly measured urinary DAP metabolite concentrations in an urban population, was not associated with maternal or cord blood thyroid hormone concentrations. These findings do not support a mediating role for serum thyroid hormone availability in the relation of early life exposure to low levels of OP pesticides with child neurodevelopment. However, disruption of the thyroid system at tissue level cannot be excluded. In addition, this is one of the first studies on this subject and measurement error in DAP metabolites might have resulted in imprecise estimates. Future studies should use more urine samples to increase precision and should investigate specific OP pesticide metabolites.

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Project description:Although the production and use of some persistent organic pollutants (POPs) have been banned or highly restricted, human exposure remains a subject of investigation due to their environmental persistence. Physiological changes during pregnancy may affect the disposition of POPs in the mother's body, and thus fetal exposure. Changes in serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) across pregnancy trimesters, and trans-placental transfer to the fetus were investigated. Seventy-nine pregnant women in Trujillo, Peru were recruited in the first trimester of pregnancy, and provided blood samples for the analysis of 35 PCB congeners, 9 OCPs, and 11 polybrominated biphenyl diethers (PBDEs). Subsequently, maternal blood samples were collected in the second (n=64) and third trimesters (n=59), and cord blood samples (n=50) were collected at delivery. There were statistically significant changes across trimesters (p<0.05) for both fresh weight (increase) and lipid adjusted concentrations (decrease) of hexachlorobenzene (HCB), 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), PCB-74, 118, 138-158, 153, 170, 180 and 194. Fresh weight concentrations of these POPs increased from first to third trimester by 10-28%. On the other hand lipid adjusted concentrations decreased from first to third trimester by 16-28%. Serum lipids increased from first to third trimester by 53% indicating the dilution of the POPs in the lipids. Concentrations of 2,2-Bis(4-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT), its metabolite p,p'-DDE, PCB-118, 138-158, 153, 170 and 180 above their limits of detection were measured in >60% of cord serum samples. Intra-individual correlations in maternal serum concentrations were high for most of the POPs (?=0.62-0.99; p<0.05) while correlations between maternal and cord serum concentrations were also high (?=0.68-0.99; p<0.05). Results indicate that the disposition in the body and blood concentrations of POPs may change during pregnancy, and show trans-placental transfer of DDT, DDE and PCBs.

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Dataset Information

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.

Publications

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.

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