To the Editor:
The policy statement from the American College of Medical Genetics on folic acid and neural tube defects1 singles out the 1992 randomized controlled trial by Czeizel and Dudas2 as the “most definitive.” That characterization actually is more appropriate for the Medical Research Council study, which was published the preceding year.3 The factorial design of the MRC study, coupled with its large number of pregnancies affected by neural tube defects, allowed folic acid to be definitively pinpointed as the active agent and set the stage for governments in various areas of the world to fortify the food supply. The study by Czeizel and Dudas2 provided useful supplementary evidence, but the intervention group received only a multivitamin preparation. Being confident that folic acid was the active agent, therefore, required knowledge of results from the MRC study.
In making its recommendations for an appropriate intake of folic acid, the Policy and Practice Guidelines Committee did not consider the modeled calculations published by Wald et al.4 in 2001, showing a dose-response reduction for neural tube defects with folic acid intakes up to 5 mg/day. The authors concluded that all women planning pregnancy would achieve greatest risk reduction at this dose level, rather than limiting folic acid doses in this range to high-risk women. It would be reasonable for the committee to acknowledge this analysis.
REFERENCES
Toriello HV . Policy statement on folic acid and neural tube defects. Genet Med 2011; 13: 593–596.
Czeizel AE, Dudas I . Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992; 327: 1832–1835.
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991; 338: 131–137.
Wald NJ, Law MR, Morris JK, Wald DS . Quantifying the effect of folic acid. Lancet 2001; 358: 2069–2073.
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Haddow, J. Folic acid and neural tube defects. Genet Med 13, 849 (2011). https://doi.org/10.1097/GIM.0b013e31822a49db
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DOI: https://doi.org/10.1097/GIM.0b013e31822a49db