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Folic Acid and Prevention of Birth Defects-Reply

Leslie E. Daly, PhD; Peadar N. Kirke, FFPHMI; Anne Molloy, PhD; Donald G. Weir, MD, FRCP; John M. Scott, DSc
JAMA. 1996;275(21):1635-1636. doi:10.1001/jama.1996.03530450025019.
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In Reply.  —The letter by Dr Czeizel about the protective effect of a multivitamin preparation containing folic acid on NTDs and other congenital malformations raises an important public health issue.It is now accepted that periconceptional folic acid prevents both the recurrence and occurrence of NTDs. However, we wish to emphasize that the evidence to date regarding the effects of folic acid in preventing other birth defects, cardiovascular disease, or some cancers is much more tenuous. Most of the studies examining these questions were observational rather than randomized, and the protective effects, in the main, were related to multivitamins that happened to include folic acid. In particular, the protective effects on birth defects noted in the letter by Czeizel, though based on a randomized trial, were for a preparation that contained folic acid as just 1 of many ingredients. The efficacy of folic acid per se in conditions other than


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