title: Prevention of neural-tube defects with periconceptional folic acid, methylfolate, or multivitamins?
abstract: OBJECTIVE
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary. czeizel@interware.hu
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Czeizel
authors.forename: István
authors.initials: I
authors.lastname: Dudás
authors.forename: László
authors.initials: L
authors.lastname: Paput
authors.forename: Ferenc
authors.initials: F
authors.lastname: Bánhidy
mesh_terms: D003276:Contraceptives, Oral / Q000008:administration & dosage; D004032:Diet / Q000009:adverse effects; D019587:Dietary Supplements / Q000032:analysis; D004338:Drug Combinations; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D005527:Food, Fortified / Q000032:analysis; D006801:Humans; D039382:Maternal Nutritional Physiological Phenomena; D009436:Neural Tube Defects / Q000209:etiology / Q000517:prevention & control*; D016742:Preconception Care; D055502:Secondary Prevention; D013763:Tetrahydrofolates / Q000008:administration & dosage / Q000627:therapeutic use*; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D003276:Contraceptives, Oral; D004338:Drug Combinations; D013763:Tetrahydrofolates; D014815:Vitamins; D005492:Folic Acid; C005984:5-methyltetrahydrofolate