SCN NEWS NO. 15 sees the start of a new section
"Letters to the Editor". This section aims to encourage positive
discussion and debate about current issues in the field of international
nutrition, including reponses to articles published in SCN News Your letters and
comments would be most welcome
By Rafael Pérez-Escamilla, Department of Nutritional Sciences, University of Connecticut, U.S.A.
In the recent SCN News article entitled "The Nutrition Challenge in the Twenty-First Century: What Role for the United Nations?" (SCN News No. 14), it is stated '... [Folic Acid] Supplementation of women before conception will reduce the incidence of neural tube defects... The beneficial effects of folate are obtained at alt levels well above usual intake'. In a review article (1) published in 1995,1 argued that massive folic acid (FA) supplementation or fortification of the food supply for the prevention of neural tube defects (NTDs) is unwarranted. First and foremost, it is essential to recognize that the FA-NTD connection is not based on a 'typical' nutritional deficiency paradigm. In contrast with health (e.g., low birth weight, infant mortality) and nutritional (e.g., stunting, iron, iodine and vitamin A deficiency) indicators, the distribution of NTDs does not seem to follow a developed vs. developing country spacial distribution pattern. This is not surprising, because FA-sensitive NTDs are the result of a genetic defect in the metabolism of FA and/or other nutrients such as vitamin B-12 and methionine. This genetic disorder is partially overcome by additional FA consumption. Thus, FA deficiency is not the primary cause of NTD's and this is why blood FA levels appear similar when comparing women who develop vs. those who do not develop NTDs. Second, whereas over a billion people suffer from undernutrition and parasitic infestations, the estimated annual occurrence of NTDs worldwide is approximately 350 000 births.
To put this number in perspective, in a country the size of the USA (about 250 million inhabitants and 4 million annual births), it has been estimated that a policy of FA fortification of cereal based products would prevent only about 1000 NTD cases per year. Even though reasonable solutions have existed for decades to prevent some micronutrient deficiencies (e.g., iron supplementation, sugar fortification with vitamin A, salt iodization) and some progress has recently been made, these public health problems still afflict hundreds of millions of individuals. Should we then embark on trying to implement an exceedingly difficult intervention to prevent a relatively small number of NTD cases per year? Implementing an FA supplementation policy is very difficult because sexually active women would have to take the supplement throughout their reproductive life. This is because additional FA can prevent NTDs only if consumed during the periconceptional period (i.e., at a time when most women do not even know that they are pregnant). In addition Demographic and Health Survey data indicate that in many developing countries over half of the women become pregnant when they were not planning to have another child. Third, it is true that the MRC randomized clinical trial (2) used 4mg FA per day (about 10 times the US RDA for pregnant women) to demonstrate that periconceptional supplementation with this vitamin can indeed significantly reduce the recurrence of NTDs. This dosage, however, was intentionally chosen to be high to avoid the possibility of negative findings due to an insufficiency level of FA exposure. There is a substantial body of observational and quasi-experimental evidence indicating that 0.4mg FA per day may be enough to prevent NTDs. This is why the US Public Health Service bases its recommendation for women without a previous history of NTDs on this low dosage approach. The implications are that women may be able to obtain additional FA through their diets (e.g., by increasing consumption of beans, oranges, green leafy vegetables) or food fortification - an also less than optimal approach - without exposing the population to unsafe FA dosages. In addition to the possibility of PA masking B-12 deficiency, there is limited but worrisome data indicating that additional FA could interfere with the action of some malaria medications and even increase the susceptibility for the development of this disease. In summary, the finding that FA supplementation can prevent the development of some NTDs is a remarkable and landmark finding in the history of developmental nutrition. The implications of these findings for developing countries are not clear due to the difficulty of implementing a FA supplementation policy to prevent the occurrence of a relatively rare outcome. All women in developing countries should be informed about the FA-NTDs findings and be advised on how to increase the consumption of this water soluble vitamin through their diets. It is clear that women who are at risk of NTD recurrence should follow the USA Center for Disease Control and Prevention (CDC) policy (i.e., 4mg of FA perday under the supervision of a physician when they plan to become pregnant). This policy, unfortunately does not reach the majority of women as most NTDs are occurrent (i.e., first time event), and the policy may also be difficult to implement in some developing country settings. Meanwhile, it seems clear that it is currently unwarranted for United Nations agencies to invest precious resources on massive FA supplementation for the prevention of NTDs. Improving our understanding of the epidemiology of FA deficiency and NTDs in developing countries, and hunting for the genetic marker(s) that accurately predict risk of FA-sensitive NTD's should be a priority. Perhaps in the not too distant future we will be able to identify women who are at NTD risk before they enter their reproductive years and follow them up accordingly and with much better targeted efforts.
1. Pérez-Escamilla R. Periconceptional Folic Acid and Neural Tube Defects: Public Health Issues, Bulletin of PAHO 1995; 29:250-263.
2. MRC Vitamin Study Research Group. Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet 1991; 338:131-137.
Rafael Pérez-Escamilla, Assistant Professor & Extension Nutrition Specialist, Department of Nutritional Sciences, University of Connecticut, 3624 Horsebarn Rd Ext, Storrs, CT 06269-4017, U.S.A. Tel: 860 4865073 Fax: 860 486 3674 Email: email@example.com.