Journal Mobile Options
Table of Contents
Vol. 59, No. 1, 2011
Issue release date: November 2011
Ann Nutr Metab 2011;59:38–40

Periconceptional Folic Acid-Containing Multivitamin Supplementation for the Prevention of Neural Tube Defects and Cardiovascular Malformations

Czeizel A.E.
Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


The prevention of neural tube defects with periconceptional folic acid or folic acid-containing multivitamin supplementation is accepted by the scientific community; here the possible prevention of cardiovascular malformations is discussed. The aim of this presentation is to show the main findings of trials and studies that resulted in the prevention of neural tube defects and particularly cardiovascular malformations by folic acid-containing multivitamins or folic acid supplementation in order to stimulate the incorporation of folic acid-containing multivitamins or folic acid in the prevention of cardiovascular malformations.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Czeizel AE, Dudás I: Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327:1832–1835.
  2. Czeizel AE, Dobó M, Vargha P: Hungarian cohort controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities. Birth Defects Res A Clin Mol Teratol 2004;70:853–861.
  3. Berry RJ, Li Z, Erickson JD, Moore CA, Wang H, Li S, Moore CA, Wang H, Mulinare J, Zhao P, Wong LY, Gindler J, Hong SX, Correa A: Prevention of neural-tube defects with folic acid in China: China-US Collaborative Project for Neural Tube Defect Prevention. N Engl J Med 1999;341:1485–1490.
  4. Smithells RW, Sheppard S, Wild J, Schorah CJ: Prevention of neural tube defect recurrences in Yorkshire: final report. Lancet 1989;2:498–499.
  5. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study – MRC Vitamin Study Research Group. Lancet 1991;338:131–137.
  6. Czeizel AE: Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 1996;62:179–183.
  7. Czeizel AE: Periconceptional folic acid-containing multivitamin supplementation. Eur J Obstet Gynecol Reprod Biol 1998;75:151–161.

    External Resources

  8. Botto LD, Khoury MJ, Mulinare J, Erickson JD: Periconceptional multivitamin use and the occurrence of conotruncal heart defects: results from a population-based case-control study. Pediatrics 1996;98:911–917.
  9. Botto LD, Mulinare J, Erickson JD: Occurrence of congenital heart defects in relation to maternal multivitamin use. Am J Epidemiol 2000;151:878–884.
  10. Botto LD, Mulinare J, Erickson JD: Do multivitamin or folic acid supplementation reduce the risk for congenital heart defects? Evidence and gaps. Am J Med Genet 2003;121A:95–101.
  11. Shaw CM, O’Malley CD, Wasserman CR, Tolarova MM, Lammer EJ: Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring. Am J Med Genet 1995;59:536–545.
  12. Czeizel AE, Tóth M, Rockenbaer M: Population-based case control study of folic acid supplementation during pregnancy. Teratology 1996;53:345–351.
  13. Werler MM, Hayes C, Louik S, Shapiro S, Mitchell AA: Multivitamin supplementation and risk of birth defects. Am J Epidemiol 1999;150:675–682.
  14. Scanion KS, Ferencz C, Loffredo CA, Wilson PD, Correa-Villasenor A, Khoury MJ, Willett WC: Periconceptional folate intake and malformations of the cardiac outflow tract – Baltimore-Washington Infant Study Group. Epidemiology 1998;9:95–98.
  15. van Beynum IM, Kapusta L, Bakker MK, den Heijer M, Blom HJ, de Walle HE: Protective effect of periconceptional folic acid supplements on the risk of congenital heart defects: a registry-based case-control study in the northern Netherlands. Eur Heart J 2010;31:464–471.
  16. Ionescu-Ittu R, Marelli AJ, Mackie AS, Pilote L: Prevalence of severe congenital heart disease after folic acid fortification of grain products: time trend analysis in Quebec, Canada. BMJ 2009;338:b1673.

    External Resources

  17. Botto LD, Olney RS, Erickson JD: Vitamin supplement and the risk for congenital anomalies other than neural tube defects. Am J Med Genet 2004;125C:12–21.
  18. Goh YI, Bollano E, Einarson TR, Koren G: Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis. J Obstet Gynaecol Can 2006;28:690–689.

    External Resources

  19. Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA: Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343:1608–1614.
  20. Czeizel AE, Rockenbaer M, Sorensen HT, Olsen J: The teratogenic risk of trimethoprim-sulfonamides: a population-based case-control study. Reprod Toxicol 2001;15:637–646.
  21. Czeizel AE, Puho E, Sorensen HT, Olsen J: Possible association between congenital abnormalities and use of different sulfonamides during pregnancy. Congenit Anom 2004;44:79–86.
  22. van Beynum IM, Kapusta L, den Heijer M, Vermeulen SH, Kouwenberg M, Dani LS, Blom HJ: Maternal MTHFR C>T is a risk factor for congenital heart defects: effect modification by periconceptional folate supplementation. Eur Heart J 2006;27:981–987.
  23. van Beynum IM, den Heijer M, Kapusta L, Blom HJ: The MTHFR 677C-T polymorphism and the risk of congenital heart defects: a literature review and meta-analysis. QMJ 2007;100:743–753.
  24. Hobbs CA, Cleves MA, Karim MA: Maternal folate-related gene environment interactions and congenital heart defects. Obstet Gynecol 2010;116:316–322.
  25. Botto LD, Correa A, Erickson JD: Racial and temporal variation in the prevalence of heart defect. Pediatrics 2001;107:E32.
  26. Mészáros M, Nagy A, Czeizel AE: Incidence of congenital heart disease in Hungary. Hum Hered 1975;25:513–519.
  27. Boneva RS, Botto LD, Moore CA, Yang O, Correa A, Erickson JD: Mortality associated with congenital heart defects in the United States: trends and racial disparities, 1979–1997. Circulation 2001;103:2376–2381.
  28. Czeizel AE, Révész C: Major malformations of the central nervous system in Hungary. Br J Prev Soc Med 1970;24:205–222.
  29. Tarusco D (ed): Folic Acid: From Research to Public Health Practice. Rome, Rapporti ISTISAN, 2004.
  30. Oakley GP: Inertia on folic acid fortification: Public health malpractice. Teratology 2002;66:44–54.

Pay-per-View Options
Direct payment This item at the regular price: USD 33.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 23.00