Int. J. Environ. Res. Public Health 2013, 10(9), 4352-4389; doi:10.3390/ijerph10094352
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Neural Tube Defects, Folic Acid and Methylation

1 Biochemistry-Hormonology Laboratory, Robert Debré Hospital, APHP, 48 bd Serrurier, Paris 75019, France 2 Metabolic Unit, Department of Clinical Chemistry, VU Free University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands
* Author to whom correspondence should be addressed.
Received: 27 July 2013; in revised form: 30 August 2013 / Accepted: 3 September 2013 / Published: 17 September 2013
(This article belongs to the Special Issue Birth Defect Prevention)
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Abstract: Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.
Keywords: neural tube defects; folate; methylation; choline; methionine; homocysteine; MTHFR; B12 vitamin

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MDPI and ACS Style

Imbard, A.; Benoist, J.-F.; Blom, H.J. Neural Tube Defects, Folic Acid and Methylation. Int. J. Environ. Res. Public Health 2013, 10, 4352-4389.

AMA Style

Imbard A, Benoist J-F, Blom HJ. Neural Tube Defects, Folic Acid and Methylation. International Journal of Environmental Research and Public Health. 2013; 10(9):4352-4389.

Chicago/Turabian Style

Imbard, Apolline; Benoist, Jean-François; Blom, Henk J. 2013. "Neural Tube Defects, Folic Acid and Methylation." Int. J. Environ. Res. Public Health 10, no. 9: 4352-4389.

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