Homocysteine Metabolism in Pregnancies Complicated by Neural-Tube Defects

Mills, James L.; McPartlin, Joseph; Kirke, Peadar N.; Lee, Young Jong; Conley, Mary; Weir, Donald G.; Scott, John M.

doi:10.1097/00006254-199508000-00005

Cited by 137 publications

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“…The combination of measuring serum vitamin B 12 and its metabolites would well define the interrelation between nutrition status and embryonic risks for NTD formation (20) . Most recently, it was found that a significantly low vitamin B 12 concentration in the mother increased the risk of orofacial clefts in the offspring (21) . It is well-documented that a functional shortage of folate and vitamin B 12 may lead to a disturbed homocysteine metabolism, affecting DNA synthesis and transcription, especially in cellular differentiation during embryogenesis (18) .…”

Section: Discussionmentioning

confidence: 99%

“…It is well-documented that a functional shortage of folate and vitamin B 12 may lead to a disturbed homocysteine metabolism, affecting DNA synthesis and transcription, especially in cellular differentiation during embryogenesis (18) . Mills et al found that hyperhomocysteinaemia was present in women of offspring with NTD, which indicated an abnormality in methionine synthase involving vitamin B 12 as a cofactor in one-carbon unit metabolism (21) . Similar trend was observed in the present study, which means that the mean serum tHcy concentration in mothers of offspring with NTD was higher than that of control subjects.…”

Section: Discussionmentioning

confidence: 99%

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Maternal serum vitamin B₁₂, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China

Zhang

Xin

et al. 2009

Public Health Nutr.

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Objective: To examine the association between the risk of neural tube defects (NTD) and maternal serum vitamin B 12 , folate and homocysteine in a high-risk area of China. Design: A case-control study was carried out in Luliang mountain area of Shanxi Province. Subjects/setting: A total of eighty-four NTD pregnancies and 110 matched controls were included in the study; their serum vitamin B 12 and folate concentrations were measured by chemiluminescent immunoenzyme assay and total homocysteine concentrations by fluorescent polarisation immunoassay. Results: Serum vitamin B 12 and folate concentrations were lower in NTD-affected pregnant women than in controls (P , 0?01). Serum total homocysteine was higher in the NTD group than in controls at less than 21 weeks of gestation (P , 0?01). Adjusted odds ratios revealed that women with lower vitamin B 12 (adjusted OR54?96; 95 % CI 1?94, 12?67) and folate (adjusted OR53?23; 95 % CI 1?33, 7?85) concentrations had a higher risk of NTD compared to controls. Based on dietary analysis, less consumption of meat, egg or milk, fresh vegetables and fruit intake would increase the risk of NTD. Conclusions: Lower serum concentrations of folate and vitamin B 12 are related to the increased risk of NTD in high-risk populations. Both folate and vitamin B 12 intake insufficiency could contribute to the increased risk of NTD. A dietary supplement, combining folate and vitamin B 12 , might be an effective measure to decrease the NTD incidence in these areas.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Maternal serum vitamin B₁₂, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China

Zhang

Xin

et al. 2009

Public Health Nutr.

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“…Many studies suggest a positive connection between folate deficiencies, elevated Hcys levels, and increased risk of congenital defects, not only in animal models, but also in humans (Steegers-Theunissen et al, 1994;Mills et al, 1995;van der Put et al, 1997;Nelen et al, 1998;van Rooij et al, 2003;Hobbs et al, 2005). Whether the defects are a direct consequence of folate loss or an increase in Hcys levels because of folate deficiency, is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Homocysteine enhances cardiac neural crest cell attachment in vitro by increasing intracellular calcium levels

Heidenreich

Reedy

Brauer

2008

Developmental Dynamics

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Elevated homocysteine (Hcys) increases the risk of neurocristopathies. Previous studies show Hcys inhibits neural crest (NC) cell migration in vivo. However, the mechanisms responsible for this effect are unknown. Here, we evaluated the effect of Hcys on NC cell attachment in vitro and determined if any of the effects were due to altered Ca 2؉ signaling. We found Hcys enhanced NC cell attachment in a dose and substratedependent manner. Ionomycin mimicked the effect of Hcys while BAPTA-AM and 2-APB blocked the effect of Hcys on NC attachment. In contrast, inhibitors of plasma membrane Ca 2؉ channels had no effect on NC attachment. Hcys also increased the emission of the intracellular Ca 2؉ -sensitive probe, Fluo-4. These results show Hcys alters NC attachment by triggering an increase in intracellular Ca 2؉ possibly by generating inositol triphosphate. Hence, the teratogenic effect ascribed to Hcys may be due to perturbation of intracellular Ca 2؉ signaling.

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“…Elevated total serum homocysteine concentration in pregnant women is an important issue as it is known to be related to many adverse pregnancy outcomes including birth defects (Mill et al, 1995;Rosenquist et al, 1995), pre-eclampsia (Leeda et al, 1998), placental abruption (Goddijn-Wessel et al, 1996), spontaneous abortion (Wouters et al, 1993), low birth weight (Burke et al, 1992), and other maternal or fetal complications (Aubard et al, 2000;Scholl & Johnson, 2000).…”

Section: Introductionmentioning

confidence: 99%

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Kim

Chang

2003

Eur J Clin Nutr

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Objective: The purpose of this study was to investigate the effect of the interaction between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and serum levels of B vitamins on serum homocysteine levels in pregnant women. Design: A cross-sectional study. Setting: Ewha Womans University Hospital, Seoul, Korea. Subjects: A total of 177 normal pregnant women, 24.671.1 weeks of gestation, in a 6-month period during [2001][2002]. Interventions: Serum vitamin B 2 , vitamin B 6 , and homocysteine analyses were conducted using high-performance liquid chromatography methods. Serum folate and vitamin B 12 concentrations were determined using a radioimmunoassay kit. MTHFR gene mutation was investigated by the polymerase chain reaction of a genomic DNA fragment. Results: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR gene (Po0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes (Po0.001), and the correlation between the two serum levels was the strongest in the T/T genotype. Serum homocysteine was higher in the subjects with the T/T MTHFR genotype only when the serum folate was below the median level. Explanatory power of B vitamin status as predictors of serum homocysteine levels was more pronounced in the T/T genotypes (68.5%) compared with the C/T (37.9%) or C/C genotypes (20.6%). Conclusions: Serum homocysteine levels in pregnant women varied significantly with MTHFR genotype and the serum B vitamin status. Higher serum folate, vitamin B 2 , and vitamin B 12 concentrations may lessen the MTHFR genotypic effect on serum homocysteine levels.

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Homocysteine Metabolism in Pregnancies Complicated by Neural-Tube Defects

Cited by 137 publications

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Maternal serum vitamin B₁₂, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China

Maternal serum vitamin B₁₂, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China

Homocysteine enhances cardiac neural crest cell attachment in vitro by increasing intracellular calcium levels

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

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Homocysteine Metabolism in Pregnancies Complicated by Neural-Tube Defects

Cited by 137 publications

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Maternal serum vitamin B12, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China

Maternal serum vitamin B12, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China

Homocysteine enhances cardiac neural crest cell attachment in vitro by increasing intracellular calcium levels

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

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Maternal serum vitamin B₁₂, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China

Maternal serum vitamin B₁₂, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China