Prevention of Neural-Tube Defects with Periconceptional Folic Acid, Methylfolate, or Multivitamins?

Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary.
Annals of Nutrition and Metabolism (Impact Factor: 2.62). 08/2011; 58(4):263-71. DOI: 10.1159/000330776
Source: PubMed


To review the main results of intervention trials which showed the efficacy of periconceptional folic acid-containing multivitamin and folic acid supplementation in the prevention of neural-tube defects (NTD).
The main findings of 5 intervention trials are known: (i) the efficacy of a multivitamin containing 0.36 mg folic acid in a UK nonrandomized controlled trial resulted in an 83-91% reduction in NTD recurrence, while the results of the Hungarian (ii) randomized controlled trial and (iii) cohort-controlled trial using a multivitamin containing 0.8 mg folic acid showed 93 and 89% reductions in the first occurrence of NTD, respectively. On the other hand, (iv) another multicenter randomized controlled trial proved a 71% efficacy of 4 mg folic acid in the reduction of recurrent NTD, while (v) a public health-oriented Chinese-US trial showed a 41-79% reduction in the first occurrence of NTD depending on the incidence of NTD.
Translational application of these findings could result in a breakthrough in the primary prevention of NTD, but so far this is not widely applied in practice. The benefits and drawbacks of 4 main possible uses of periconceptional folic acid/multivitamin supplementation, i.e. (i) dietary intake, (ii) periconceptional supplementation, (iii) flour fortification, and (iv) the recent attempt for the use of combination of oral contraceptives with 6S-5-methytetrahydrofolate (methylfolate), are discussed. Obviously, prevention of NTD is much better than the frequent elective termination of pregnancies after prenatal diagnosis of NTD fetuses.

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    • "A specific focus is to illustrate how mouse models have been used to uncover interactions between nutritional status and molecular mechanisms that underlie birth defect risk. In recent years, evidence has emerged that the risk for neural tube defects can be modulated by maternal nutrition, providing the basis for strategies that aim to prevent neural tube defects by manipulation of maternal diet [Czeizel et al., 2011]. The success of supplementation and food fortification with the micronutrient folic acid [Obican et al., 2010] attests that dietary approaches can be effective: after mandatory fortification of the grain and flour supply in the United States, the incidence of neural tube defects was reduced by 30% [Mosley et al., 2009]. "
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