TY - JOUR
T1 - Teratogenicity of high vitamin a intake
AU - Rothman, Kenneth J.
AU - Moore, Lynn L.
AU - Singer, Martha R.
AU - Nguyen, Uyen sa D.t.
AU - Mannino, Salvatore
AU - Milunsky, Aubrey
PY - 1995/11/23
Y1 - 1995/11/23
N2 - 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 affect tissues derived from the cranial neural crest. Between October 1984 and June 1987, we identified 22,748 pregnant women when they underwent screening either by measurement of maternal serum alpha-fetoprotein or by amniocentesis. Nurse interviewers obtained information on the women's diet, medications, and illnesses during the first trimester of pregnancy, as well as information on their family and medical history and exposure to environmental agents. We obtained information on the outcomes of pregnancy from the obstetricians who delivered the babies or from the women themselves. Of the 22,748 women, 339 had babies with birth defects; 121 of these babies had defects occurring in sites that originated in the cranial neural crest. For defects associated with cranial-neural-crest tissue, the ratio of the prevalence 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 prevalence among the babies whose mothers consumed 5000 IU or less per day was 3.5 (95 percent confidence interval, 1.7 to 7.3). For vitamin A from 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 babies whose mothers consumed 5000 IU or less per day was 4.8 (95 percent confidence interval, 2.2 to 10.5). Using a smoothed regression curve, we found an apparent threshold near 10,000 IU per day of supplemental vitamin A. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the seventh week of gestation. High dietary intake of preformed vitamin A appears to be teratogenic. Among the babies born 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.
AB - 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 affect tissues derived from the cranial neural crest. Between October 1984 and June 1987, we identified 22,748 pregnant women when they underwent screening either by measurement of maternal serum alpha-fetoprotein or by amniocentesis. Nurse interviewers obtained information on the women's diet, medications, and illnesses during the first trimester of pregnancy, as well as information on their family and medical history and exposure to environmental agents. We obtained information on the outcomes of pregnancy from the obstetricians who delivered the babies or from the women themselves. Of the 22,748 women, 339 had babies with birth defects; 121 of these babies had defects occurring in sites that originated in the cranial neural crest. For defects associated with cranial-neural-crest tissue, the ratio of the prevalence 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 prevalence among the babies whose mothers consumed 5000 IU or less per day was 3.5 (95 percent confidence interval, 1.7 to 7.3). For vitamin A from 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 babies whose mothers consumed 5000 IU or less per day was 4.8 (95 percent confidence interval, 2.2 to 10.5). Using a smoothed regression curve, we found an apparent threshold near 10,000 IU per day of supplemental vitamin A. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the seventh week of gestation. High dietary intake of preformed vitamin A appears to be teratogenic. Among the babies born 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.
UR - http://www.scopus.com/inward/record.url?scp=0028881748&partnerID=8YFLogxK
U2 - 10.1056/NEJM199511233332101
DO - 10.1056/NEJM199511233332101
M3 - Article
C2 - 7477116
AN - SCOPUS:0028881748
SN - 0028-4793
VL - 333
SP - 1369
EP - 1373
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 21
ER -