International Journal of Medical Sciences
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18 April 2014

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The primary prevention of birth defects: Multivitamins or folic acid?

Int J Med Sci 2004; 1:50-61 ©Ivyspring International Publisher

The primary prevention of birth defects: Multivitamins or folic acid?

Andrew E. Czeizel

Foundation for the Community Control of Hereditary Diseases, 1148 Budapest, Bolgárkerék u. 3. Hungary

Abstract

Periconceptional use of folic acid alone or in multivitamin supplements is effective for the primary prevention of neural-tube defects. The Hungarian randomized and two-cohort controlled trials showed that periconceptional multivitamin supplementation can reduce the occurrence of some other structural birth defects, i.e. congenital abnormalities. These findings were supported by many, but not all observational studies. Recently there have been two main debated questions. The first one is whether the use of folic acid alone or folic acid-containing multivitamins is better. The second one is connected with the dilemma of whether high dose of folic acid (e.g. 5 mg) might be better than a daily multivitamin with 0.4 – 0.8 mg of folic acid. Comparison of the pooled data of two Hungarian trials using a multivitamin containing 0.8 mg folic acid and the data of the Hungarian Case-Control Surveillance of Congenital Abnormalities using high dose of folic acid seemed to be appropriate to answer these questions. Multivitamins containing 0.4 – 0.8 mg of folic acid were more effective for the reduction of neural-tube defects than high dose of folic acid. Both multivitamins and folic acid can prevent some part of congenital cardiovascular malformations. Only multivitamins were able to reduce the prevalence at birth of obstructive defects of urinary tract, limb deficiencies and congenital pyloric stenosis. However, folic acid was effective in preventing some part of rectal/anal stenosis/atresia, and high dose of folic acid had effect in preventing some orofacial clefts. The findings are consistent that periconceptional multivitamin and folic acid supplementation reduce the overall occurrence of congenital abnormalities in addition to the demonstrated effect on neural-tube defects.

Keywords: Folic acid, multivitamins, prevention, neural-tube defects, other congenital abnormalities

How to cite this article:
Czeizel AE. The primary prevention of birth defects: Multivitamins or folic acid?. Int J Med Sci 2004; 1:50-61. http://www.medsci.org/v01p0050.htm
multivitamin

Multivitamins containing folic acid appear to be more effective at preventing neural tube defects than high dose folic acid supplements, suggests a new study, attempting to resolve the debate over how women should consume the essential nutrient.

It concludes that multivitamins should contain between 0.4 - 0.8 mg of folic acid for pregnant women to prevent neural tube defects and some other congenital abnormalities.

During periods of rapid growth, such as pregnancy and foetal development, the body's requirement for folic acid increases and insufficient levels of the vitamin in mothers have been linked to higher risk of neural tube defects, causing the permanently disabling disease spina bifida, in offspring.

Each year about 3 per cent of all new births around the world are affected with major structural birth defects, according to the new study, or more than 4 million each year, and these are the major cause of infant mortality and disabilities among children in industrialized countries.

In Canada, which introduced folic acid fortification of grain-based foods in 1998, the prevalence of neural-tube defects among both unborn and newborn children has been halved and it has also seen a similar benefit on incidence of the deadly childhood cancer neuroblastoma.

baby

But aside from those living in Chile and the US, most women must rely on self-supplementation around the time of conception to prevent birth defects in their offspring. Now a review of three major trials suggests that multivitamins containing between 0.4 and 0.8 mg of folic acid is the best way of achieving this prevention.

Recent research in this area has debated whether the use of folic acid alone or folic acid-containing multivitamins is better. Researchers have also questioned whether a high dose of folic acid (eg 5mg) might be more effective than a daily multivitamin with low dose (0.4 - 0.8 mg) folic acid.

In a paper published in the International Journal of Medical Sciences, Professor Andrew E. Czeizel, receiver of the 2002 award of the US National Council on Folic Acid for Excellence in Research in the Field of Folic Acid and Birth Defects Prevention, compares two intervention trials and a case-control surveillance of congenital abnormalities that involve very large population.

The pooled findings of these trials indicate that approximately 92 per cent of neural tube defects may be prevented by supplemented multivitamins containing 0.8 mg of folic acid.

The first intervention trial is a randomized controlled trial involving 2,819 participants supplemented with multivitamins containing 0.8 mg of folic acid, and 2,683 unsupplemented participants. The second trial is a two-cohort controlled trial involving 3,069 participants supplemented with the same multivitamins, and 3,069 unsupplemented participants. The case-control surveillance of congenital abnormalities includes 30,054 pregnant women who received high dose (in general 6 mg) folic acid supplementation - in a much larger racially homogeneous European-Caucasican population.

A comparison of these results shows that multivitamins containing 0.8 mg of folic acid were more effective for the reduction of neural-tube defects than high dose folic acid supplements.

While both multivitamins and folic acid can prevent some part of congenital cardiovascular malformations, only multivitamins were able to reduce the prevalence at birth of obstructive defects of urinary tract, limb deficiencies and congenital pyloric stenosis. Folic acid was effective in preventing some part of rectal/anal stenosis/atresia, and high dose of folic acid had effect in preventing some orofacial clefts.

In a separate study, Smithells et al used a multivitamin containing 0.36 mg of folic acid and they were able to prevent 91 per cent of recurrent neural tube defects.

In light of these findings, Czeizel recommends the daily use of a multivitamin containing 0.4 - 0.8 mg of folic acid for pregnant women.

Details see the paper published by International Journal of Medical Sciences. Full PDF can be downloaded from http://www.medsci.org/v01p0050.htm


czeizel

Contact:
Prof. Andrew E. Czeizel
Foundation for the Community Control of Hereditary Diseases
Tel: (36-1) 3635272, 3944712
Fax: (36-1) 3838477
e-mail: czeizel@interware.hu

Int. J. Med Sci. featured article [2004-5-1] http://www.medsci.org/press/birthdefect.html