Teratogenicity of high vitamin A intake

• Published in: The New England journal of medicine Vol. 333; no. 21; pp. 1369 - 1373
• Main Authors: Rothman, K.J. (Boston University School of Medicine, Boston, MA.), Moore, L.L, Singer, M.R, Nguyen, U.S.D.T, Mannino, S, Milunsky, A
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 23.11.1995
• Subjects: Abnormalities, Drug-Induced - epidemiology; Abnormalities, Drug-Induced - etiology; BEBES; Biological and medical sciences; Birth defects; CHOIX DE LA DATE; DIETA; Dietary supplements; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; ELECCION DE LA EPOCA; ENFANT EN BAS AGE; EXCES DE SUBSTANCE NUTRITIVE; EXCESO DE NUTRIENTES; Facial Bones - abnormalities; Female; FEMME; GESTACION; GESTATION; Heart Defects, Congenital - chemically induced; Humans; Infant, Newborn; INGESTION DE NUTRIENTES; INGESTION DE SUBSTANCES NUTRITIVES; Medical research; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); MUJERES; Neural Tube Defects - chemically induced; NUTRIENTES; Pharmacology. Drug treatments; Pregnancy; Prevalence; Prospective Studies; REGIME ALIMENTAIRE; RETINOL; SISTEMA NERVIOSO CENTRAL; Skull - abnormalities; SUBSTANCE NUTRITIVE; SYSTEME NERVEUX CENTRAL; TRASTORNOS GENETICOS; TROUBLE GENETIQUE; Vitamin A; Vitamin A - administration & dosage; Vitamin A - adverse effects; Women; Consumption; Human; Teratogen; Toxicity; High dose; Retinol
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM199511233332101

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 affect tissues derived from the cranial neural crest. Methods. 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. Results. 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. Conclusions. High dietary intake of preformed vitamin A appears to be teratogenic