PEDIATRICS Vol. 108 No. 4 October 2001, pp. 1048

The Unnecessary Epidemic of Folic Acid-Preventable Spina Bifida and Anencephaly

To the Editor.

The commentary by Brent et al in the October 2000 issue of Pediatrics has a title that should invoke no disagreement: "The Unnecessary Epidemic of Folic Acid-Preventable Spina Bifida and Anencephaly." The authors allowed for the association of valproic acid exposure and maternal insulin-dependent diabetes making up a portion of the neural tube defects, but the vast majority were attributable to folic acid deficiency. Or, at least, prevention was associated with folic acid intake. The folic acid issue seems to be: "How much and in what form?"

Supplementation was evaluated with varying reliability, from a telephone survey to data from countries with higher compliance rates than could be expected in this country. Whether a study was based on intake from natural folic acid sources, suboptimal supplementation, the accepted standard of 400 µg/day, enrichment of flour with 200 versus 400 µg, or whether supplementation was started before conception or during the first trimester, confounding variables are rampant in such studies. How can we evaluate the intake from natural sources or the absolute intake from the ingestion of supplemented white flour?

My disagreement is with the authors' stance that commonly eaten foods should be fortified so that "prevention occurs without the need for a behavior change." If neural tube defects are attributed to maternal elevated homocysteine levels, as are strokes and heart disease, as the authors state, we should think of all the "big 3 Bs"folic acid, B12, and pyridoxine. The first two enhance methylation in the conversion of homocysteine to methionine, while pyridoxine enhances sulfuration to reduce homocysteine levels (as in the treatment for the pediatric disease homocysteinuria. My thought is that we should encourage the intake of these B vitamins plus the antioxidants and bioflavonoids found in folic acid-rich foods. In the face of the appalling rise of the incidence of childhood obesity and noninsulin-dependent diabetes, we must think of changing the behavior of children and young adults by encouraging them to exchange some of their favorite deficient foods, such as white flour and pop, for nutrient-dense foods.

Isolating a nutrient from a whole food that is responsible for a nutritional deficiency disease and incorporating it into a food that is a staple in the diet is not the same as leaving a healthy food unadulterated and educating people of its value and of how to prepare it in an attractive form. If this goal can't be met, answer the authors' plea, and throw some money into the equation that could supply supplementation along with nutrition education. But certainly we should not encourage the consumption of high-glycemic-index "enriched flour."

Ralph K. Campbell, MD, FAAP
Polson, MT 59860

In Reply.

We very much appreciated Dr Campbell's thoughtful letter concerning our commentary¹ entitled "The Unnecessary Epidemic of Folic Acid-Preventable Spina Bifida and Anencephaly." Your letter is evidence of your broad interest in the problems of children. If we had written a commentary about Haemophilus influenzae meningitis 10 years after the vaccine was approved complaining that the vaccine was not being administered, we would probably have received 200 angry letters from pediatricians demanding that a program should be initiated that would enable every child to be vaccinated. Apparently, the epidemic of neural tube defects does not evoke an angry response from our colleagues. We believe that support for higher folic acid supplementation from the pediatric community could significantly reduce the frequency of neural tube defects.

We agree with Dr Campbell that we should encourage healthy diets for children and adults alike. We also think that no child should be born with folic acid-preventable spina bifida and anencephaly. The best evidence we have today suggests that we would make very substantial strides to the total prevention of these birth defects if all women of the world consumed 400 µg of synthetic folic acid daily above whatever natural folate they consume. Adding enough folic acid to commonly eaten foods would be a very effective way to achieve this goal. We do not encourage individuals to eat more foods with enriched flour. We suggested that enriched flour should contain more folic acid.

The March of Dimes has been very active in publicizing the importance of taking folic acid as part of their national campaign to prevent birth defects. Part of their campaign has included surveying the population to determine whether their message is reaching the public. There has been a steady but slow improvement of awareness over the past 5 years. But the following information tells us that more education is needed. In 2000, 75% of the population have heard of folic acid; 14% know that it prevents birth defects; 10% know that folic acid must be taken before a woman becomes pregnant; 32% consume folic acid on a daily basis; 54% have heard about folic acid from the media; and 20% have heard about folic acid from their health care provider.

Since we wrote our commentary, the National Center for Health Statistics has published data showing that the current fortification of enriched grains had made a remarkable increase in the median serum folate among American women of reproductive age.² The median increased from 4.8 to 14.5 ng/mL.¹ In the United States we must determine whether or not to add more folic acid to grains. In countries that have not fortified grains with enough folic acid, the unnecessary epidemic of folic acid-preventable birth defects continues unabated. We note in closing that the Institute of Medicine in 1998 recommended that those over 50 consume 2.4 µg of synthetic vitamin B12. We remain puzzled as to why the Food and Drug Administration has not moved to add vitamin B12 to enriched grains. It seems long overdue to us.

Robert L. Brent, MD, PhD, DSc
Jefferson Medical College and Alfred I. duPont Hospital for Children
Wilmington, DE 19899

Godfrey P. Oakley Jr, MD
Emory University
Atlanta, GA 30345

Donald R. Mattison, MD
March of Dimes
White Plains, NY 10605

REFERENCES

1. Brent RL, Oakley GP Jr, Mattison DR The unnecessary epidemic of folic acid-preventable spina bifida and anencephaly [commentary]. Pediatrics. 2000; 106:825-827 [Abstract/Free Full Text]
2. Centers for Disease Control and Prevention Folate status in women of childbearing ageUnited States, 1999. MMWR Morb Mortal Wkly Rep. 2000; 49:962-965 [Medline]