TERATOGENICITY OF HIGH VITAMIN-A INTAKE

Background. Studies in animals indicate that natural forms of vitamin A are teratogenic. Synthetic retinoids chemically similar to vitamin A cause birth defects in humans; as in animals, the defects appear to a ffect tissues derived from the cranial neural crest. Methods. Between October 1984 and June 1987, we identified 22,748 pregnant women when t hey underwent screening either by measurement of maternal serum alpha- fetoprotein or by amniocentesis. Nurse interviewers obtained informati on on the women's diet, medications, and illnesses during the first tr imester of pregnancy, as well as information on their family and medic al history and exposure to environmental agents. We obtained informati on on the outcomes of pregnancy from the obstetricians who delivered t he babies or from the women themselves. Of the 22,748 women, 339 had b abies with birth defects; 121 of these babies had defects occurring in sites that originated in the cranial neural crest. Results. For defec ts associated with cranial-neural-crest tissue, the ratio of the preva lence among the babies born to women who consumed more than 15,000 IU of preformed vitamin A per day from food and supplements to the preval ence among the babies whose mothers consumed 5000 IU or less per day w as 3.5 (95 percent confidence interval, 1.7 to 7.3). For vitamin A fro m supplements alone, the ratio of the prevalence among the babies born to women who consumed more than 10,000 IU per day to that among the b abies whose mothers consumed 5000 IU or less per day was 4.8 (95 perce nt confidence interval, 2.2 to 10.5). Using a smoothed regression curv e, we found an apparent threshold near 10,000 IU per day of supplement al vitamin A. The increased frequency of defects was concentrated amon g the babies born to women who had consumed high levels of vitamin A b efore the seventh week of gestation. Conclusions. High dietary intake of preformed vitamin A appears to be teratogenic. Among the babies bor n to women who took more than 10,000 IU of preformed vitamin A per day in the form of supplements, we estimate that about 1 infant in 57 had a malformation attributable to the supplement.