Choline and Risk of Neural Tube Defects in a Folate-fortified Population

  title={Choline and Risk of Neural Tube Defects in a Folate-fortified Population},
  author={Gary M. Shaw and Richard H. Finnell and Henk J Blom and Suzan L. Carmichael and Stein Emil Vollset and Wei Yang and Per Magne Ueland},
Background: Folic acid is known to reduce risk of neural tube defects (NTDs). Even so, NTDs continue to occur despite individual supplementation or population fortification with folic acid. We investigated other nutrients related to one-carbon metabolism that may affect NTD risk. Methods: This prospective study included data from more than 180,000 pregnant women in California from 2003 through 2005. Midpregnancy serum specimens were linked with delivery information regarding the presence of a… 

Neural tube defects and maternal intake of micronutrients related to one-carbon metabolism or antioxidant activity.

In addition to folic acid, other micronutrients, including thiamin, betaine, riboflavin, vitamin B(6) , vitamin C, vitamin E, niacin, iron, retinol, and vitamin A, may decrease the risk of NTD occurrence.

Neural Tube Defects, Folic Acid and Methylation

The role of methylation metabolism in the onset of neural tube defects is reviewed to raise the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk.

Is low iron status a risk factor for neural tube defects?

It is concluded that low maternal iron status during early pregnancy is not an independent risk factor for NTDs, and adding iron to folic acid for periconceptional use may improve iron status but is not likely to prevent N TDs.

The Role of Folic Acid Fortification in Neural Tube Defects: A Review

Mandatory folic acid fortification plays a significant part in the reduction of NTD prevalence, but possibly at a cost and with a portion of N TDs remaining.

Maternal choline concentrations during pregnancy and choline-related genetic variants as risk factors for neural tube defects.

The results indicate that maternal betaine and choline concentrations are not strongly associated with NTD risk, and the addition of choline to folic acid supplements may not further reduce N TD risk.

Folate-responsive birth defects: of mice and women.

  • B. Shane
  • Biology
    The American journal of clinical nutrition
  • 2012
This work reports on the first folate-responsive mouse model for NTDs due to a disruption in a gene encoding an enzyme directly involved in one-carbon metabolism, and suggests that the NTD phenotype and folate responsiveness of this mouse model were due toA defect in DNA replication rather than a defect inDNA replication.

Quantitative assessment of maternal biomarkers related to one-carbon metabolism and neural tube defects

A meta-analysis of 32 studies, involving 1,890 NTD-affected mothers and 3,995 control mothers, revealed that altered plasma levels of biomarkers related to one-carbon metabolism are associated with N TD-affected pregnancies.

One-Carbon Cofactor Intake and Risk of Neural Tube Defects Among Women Who Meet Folic Acid Recommendations: A Multicenter Case-Control Study.

It is suggested that, in the presence of folic acid, one-carbon cofactors-notably when consumed together-might reduce NTD risk.

One-carbon metabolite levels in mid-pregnancy and risks of conotruncal heart defects.

This prospective study attempted to extend information on nutrition and conotruncal heart defects by measuring analytes in mid-pregnancy sera and did not observe statistical evidence for substantial differences between cases and controls for any of the measured analytes.

Dietary intake of choline and neural tube defects in Mexican Americans.

Study findings suggest that dietary betaine may help to prevent NTDs.



Vitamin B12 and the Risk of Neural Tube Defects in a Folic-Acid-Fortified Population

There was almost a tripling in the risk for NTD in the presence of low maternal B12 status, measured by holoTC, and the benefits of adding synthetic B12 to current recommendations for periconceptional folic acid tablet supplements or folic-acid-fortified foods need to be considered.

Neural tube defects and maternal biomarkers of folate, homocysteine, and glutathione metabolism.

This metabolic profile is consistent with reduced methylation capacity and increased oxidative stress in women with affected pregnancies, and may contribute to the occurrence of NTDs.

Neural‐tube defects are associated with low concentrations of cobalamin (vitamin B12) in amniotic fluid

AF from pregnancies with NTD have lower B12 concentrations, and ratios of product to substrate(s) of homocysteine remethylation suggest impaired methionine synthase in the fetal compartment through the early second trimester.

Periconceptional dietary intake of choline and betaine and neural tube defects in offspring.

Dietary intakes of choline were associated with reduced NTD risks and study findings for dietary components other than folic acid offer additional clues about the complex etiologies of NTDs.

Vitamin B12 insufficiency and the risk of fetal neural tube defects.

  • J. RayH. Blom
  • Medicine
    QJM : monthly journal of the Association of Physicians
  • 2003
There seems to be a moderate association between low maternal B12 status and the risk of fetal NTDs, but several design limitations, and the inclusion of few study participants, may have under-represented this.

Folate, Homocysteine and Neural Tube Defects: An Overview

A dysfunctional MTHFR partly explains the observed elevated Hcy levels in women with NTD pregnancies and also, in part, the protective effect of folate on NTD.

Is disordered folate metabolism the basis for the genetic predisposition to neural tube defects?

Red cell folate levels showed a linear relationship with the number of neural tube defect pregnancies, the levels being lowest in women who had had three or four affected offspring.

Is dietary intake of methionine associated with a reduction in risk for neural tube defect-affected pregnancies?

Reductions in NTD risk were observed among women whose average daily dietary intake of methionine was above the lowest quartile of intake, and remained after adjustment for maternal race/ethnicity and education; and were observed irrespective of maternal level of folate intake.

Maternal supplemental and dietary zinc intake and the occurrence of neural tube defects in California.

It remains unclear whether increased zinc intake, or another nutrient or combination of nutrients highly correlated with zinc intake in the diet, is causally associated with reduced NTD risk, but the analyses indicate that risk of NTDs in infants and fetuses decreased with increasing maternal preconceptional zinc intake.

Vitamin deficiencies and neural tube defects.

In 6 mothers who gave birth to infants with neural tube defects, first trimester serum folate, red cell folates, white blood cell vitamin C, and riboflavin values were lower than in controls.