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Folic Acid Fortification


The risk for congenital heart defects (CHDs) could be lower among pregnancies of women who regularly take a multivitamin with folic acid as long as they start before conception and continue through early pregnancy. In the only available randomized clinical trial1, the risk for heart defects in pregnancies of women taking a multivitamin with folic acid was reduced by more than half (58%). Overall risk reduction was also found in two case-control studies where the risk for heart defects was reduced by 25%. In these and other studies that looked at specific types of heart defects, the risk reduction, when present, appeared to be more marked for some, but not all, types of heart defects (see below). However, because of some inconsistencies and uncertainties among studies, more data would be helpful to confirm, modify, or expand these findings.

It is important to remember that regularly taking a multivitamin containing folic acid or folic acid alone has been conclusively shown to prevent a large fraction of some severe defects of the brain and spine, called spina bifida and anencephaly (the 'neural tube defects'). For this reason, incorporating folic acid use into a preconception plan is recommended by doctors and public health agencies in the United States and internationally. The possible protection from some heart defects that folic acid use may provide would be an additional benefit of an intervention that has established benefits on its own. Preliminary findings suggest that the effect could be greatest for selected CHDs, including d-transposition of the great arteries, tetralogy of Fallot, and ventricular septal defects4-6. However, because of scarce data, such specificity is still questionable.

Another key reason for starting folic acid use before conception is that many organs, including the heart, brain, and spine, begin forming very early in pregnancy before many women realize they are pregnant. For this reason, the recommended strategy is to start taking the supplement from before conception rather than after finding out that one is pregnant.

Strategies for Pr​​evention:

There are two important strategies for increasing the use of folic acid. The first is supplementation which involves getting essential micronutrients, ie vitamins and minerals (including trace elements), that may otherwise not be consumed in sufficient quantities by taking a product, generally multivitamins. The second is fortification which is the practice of deliberately increasing the content of an essential micronutrient in a food irrespective of whether the nutrients were originally in the food before processing or not, so as to improve the nutritional quality of the food supply and to provide a public health benefit with minimal risk to health. Both have advantages and challenges. Supplementation typically requires comparatively higher individual effort compared to fortification; women have to remember to take the supplement daily. Supplementation campaigns are typically effective in only part of the population, and often less so in minority or disadvantaged populations. Fortification typically reaches a larger fraction of the population through commonly consumed foods, requires less individual effort, can be implemented quickly (at least in theory), and can be easily sustained over time.

The majority of available information to date supports a beneficial effect of taking a multivitamin supplement containing folic acid, though some studies show no effect. Available data come mainly from one randomized clinical trial from Hungary,1 four observations studies from the United States,2,4,5 and observational study from the Netherlands.6 In all cases, the 'exposure' was a multivitamin supplement with folic acid rather than a supplement that only contained folic acid. A reduction in risk for heart defects was documented in the small, randomized study and in several, but not all, of the observational studies. Nearly all the data showing a possible protective effect of folic acid/multivitamins, come from studies of supplementation, not of diet or fortification.

The combination of baseline fortification with supplementation campaigns might be an efficient overall strategy for increasing folic acid intake for women who are pregnant or who are planning to become pregnant.

Selected Referen​​ces:

1. Czeizel AE. Periconceptional folic acid containing multivitamin supplementation. Eur J Obstet Gynecol Reprod Biol. 1998;78(2):151-161.

2. Scanlon KS, Ferencz C, Loffredo CA, et al. Preconceptional folate intake and malformations of the cardiac outflow tract. Baltimore-Washington Infant Study Group. Epidemiology. 1998;9(1):95-98.

3. Werler MM, Hayes C, Louik C, Shapiro S, Mitchell AA. Multivitamin supplementation and risk of birth defects. American Journal of Epidemiology. 1999;150(7):675-682.

4. Botto LD, Mulinare J, Erickson JD. Occurrence of congenital heart defects in relation to maternal mulitivitamin use. Am J Epidemiol. May 1 2000;151(9):878-884.

5. Shaw GM, 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(4):536-545.

6. 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. Feb 2010;31(4):464-471.​