Background Studies in animals indicate that natural forms ofvitamin A are teratogenic. Synthetic retinoids chemically similarto vitamin A cause birth defects in humans; as in animals, thedefects appear to affect tissues derived from the cranial neuralcrest.
Methods Between October 1984 and June 1987, we identified 22,748pregnant women when they underwent screening either by measurementof maternal serum alpha-fetoprotein or by amniocentesis. Nurseinterviewers obtained information on the women's diet, medications,and illnesses during the first trimester of pregnancy, as wellas information on their family and medical history and exposureto environmental agents. We obtained information on the outcomesof pregnancy from the obstetricians who delivered the babiesor from the women themselves. Of the 22,748 women, 339 had babieswith birth defects; 121 of these babies had defects occurringin sites that originated in the cranial neural crest.
Results For defects associated with cranial-neural-crest tissue,the ratio of the prevalence among the babies born to women whoconsumed more than 15,000 IU of preformed vitamin A per dayfrom food and supplements to the prevalence among the babieswhose mothers consumed 5000 IU or less per day was 3.5 (95 percentconfidence interval, 1.7 to 7.3). For vitamin A from supplementsalone, the ratio of the prevalence among the babies born towomen who consumed more than 10,000 IU per day to that amongthe babies whose mothers consumed 5000 IU or less per day was4.8 (95 percent confidence interval, 2.2 to 10.5). Using a smoothedregression curve, we found an apparent threshold near 10,000IU per day of supplemental vitamin A. The increased frequencyof defects was concentrated among the babies born to women whohad consumed high levels of vitamin A before the seventh weekof gestation.
Conclusions High dietary intake of preformed vitamin A appearsto be teratogenic. Among the babies born to women who took morethan 10,000 IU of preformed vitamin A per day in the form ofsupplements, we estimate that about 1 infant in 57 had a malformationattributable to the supplement.
Source Information
From the Section of Preventive Medicine and Epidemiology, Evans Department of Medicine (K.J.R., L.L.M., M.R.S., U.-S.D.T.N.), and the Center for Human Genetics (A.M.), Boston University School of Medicine, Boston; and the Chair of Hygiene, Institute of Human Pathology and Social Medicine, University G. D'Annunzio, Chieti, Italy (S.M.).
Address reprint requests to Dr. Rothman at Boston University School of Medicine, B-612, 88 E. Newton St., Boston, MA 02118.
Teratogenicity of High Vitamin A Intake
Werler M. M., Lammer E. J., Mitchell A. A., Brent R. L., Hendrickx A. G., Holmes L. B., Miller R. K., Watkins M., Moore C., Mulinare J., Challem J. J., Hunt J. R., Rothman K. J., Moore L. L., Singer M. R., Milunsky A.
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N Engl J Med 1996;
334:1195-1197, May 2, 1996.
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