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Teratology Society Publications. Teratology. Society Position Paper: Recommendations For Vitamin A Use During Pregnancy. TERATOLOGY. 3. 5: 2. LISS, INC. Contents. RECOMMENDATIONSIt. A is an essential nutrient for normal.
Vitamin. A deficiency is a worldwide problem of great magnitude. It should. be noted that . Carotene, e. g., beta- carotene, has not been associated. A toxic effects; accordingly the warning contained. A preparations (as retinol or retinyl.
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Supplements that contain 2. International. Units (IU) or more of vitamin A per capsule are available as over- the- counter. The risk of birth defects owing to synthetic. A analogs has already been documented in humans, and recently. A (2. 5,0. 00 IU or more) as retinol/retinyl. It is with this caution that the following.
A supplements as retinol/retinyl. The National Research Council's recommended dietary. A during pregnancy is 1,0. RE)/day, which is equivalent to 3,3.
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IU as retinol or 5,0. IU. of vitamin A obtained from the typical American diet as a combination. An average balanced.
IU of vitamin A derived. Therefore, women who are at risk for becoming. A before. taking supplements. The USRDA (recommended daily allowance) established. Food and Drug Administration is 8,0. IU/day. Supplementation. IU vitamin A (as retinol/retinyl esters) per day should.
High. dosages of vitamin A as retinol/retinyl esters (2. IU or more). are not recommended, since these dosages are not necessary as a. With over- the- counter preparations, a major concern is the. The public perception of . In addition, studies of dose- response relationships. INTRODUCTIONVitamin.
A . is important in maintaining normal growth, regulating proliferation. Goodman, '8. 4). Vitamin A analogs (retinoids). More than 1,5. 00 retinoids. Bollag and Matter, '8.
Bollag, '8. 3). The use of vitamin A and retinoids in the United States. Ingestion of excess. The purpose of this paper is to express. A during pregnancy could.
A large volume. of literature documents the experimental use of these compounds. Case reports of malformed children of mothers. A are accumulating. Isotretinoin (1. 3- cis- retinoic.
Accutane. Retinoids. A activity. and synthetic analogs of retinoic acid. Comprehensive reviews of. A and retinoids have appeared. Bauernfeind, '8. 3; Olsen et al., '8. Wolf, '8. 4; Goodman.
Sporn et al., '8. New York Academy of Sciences (De. Luca and Shapiro, '8. Chronic. intake of vitamin A that greatly exceeds the recommended daily allowance.
A with toxic. effects to the central nervous system, liver, bone, and skin (Goodman. The toxicity of retinoids has been reviewed (Underwood, '8. Howard and Willhite, '8.
Sources. as retinol and beta- carotene are widely used as vitamin A supplements. It is important. to determine the type of vitamin A consumed, since beta- carotene.
A. Beta- carotene. A toxicity in animals. Underwood, '8. 4).
Thus, such lack of vitamin A toxicity. To. understand the biologic effectiveness of vitamin A, its synthetic. One international unit (IU) of vitamin A is. A retinol equivalent. RE) is used to convert all sources of vitamin A and carotenoids. Thus, 1 mcg of all- trans- retinol equals.
RE. For comparison by readers accustomed to international units. IU of vitamin A is equivalent to 7. Retinoic acid is absorbed through the portal. Retinyl esters. on the other hand, are usually hydrolyzed in the intestinal lumen. The retinyl. esters in the form of chylomicron remnants are removed from the.
Ingestion of high- retinol doses. Goodman et al., '8. Doses of retinol which yield high.
Vitamin. A deficiency is a worldwide problem of much greater magnitude than. A; accordingly, the warning contained in this paper. A preparations. readily available to the public. EXPERIMENTAL STUDIESThe.
A in laboratory animals was first. Cohlan ('5. 3). He fed pregnant. IU vitamin A per day on days 2- 1. Subsequently, other.
A (Geelen. '7. 9). Experimental. teratologists began studying synthetic retinoids in the mid' sixties. Kochhar, '6. 7) because unlike natural vitamin A compounds, they. Subsequently, these retinoids were found to affect. Geelen, '7. 9). Shenefelt.
The anomalies were. Kochhar, '7. 3. Geelen, '7. Willhite and Balogh- Nair, '8. Webster et al., '8. Most. investigators have used a single high dose of retinoids given to. The literature on the minimal teratogenic. Such information is important.
Table 1). The doses of retinoids in this table are those commonly. Cognitive. and behavioral abnormalities were detected in rat offspring (Hutchings. Vorhees et al., '7. Mooney et al., '8. How. does vitamin A or the retinoid molecule interfere with embryonic. No definite answers are available. Experimental studies on mouse.
Webster et al.. '8. Goulding and Pratt., '8. Irving et al., '8. Thorogood et. al.
Other experimental. Kwasigroch and Kochhar. Morriss, '7. 6). Stage- dependent. Cell death, interference with some aspect of cell multiplication.
Changes in pattern formation have been. Maden and Summerbell, '8. Diverse. cell types, both normal and transformed, are responsive to retinoids. Sporn and Roberts, '8. Some evidence suggests that the.
Two cellular binding proteins, one specific. CRBP) and cellular retinoic acid binding. CRABP), respectively—are present in various tissues. Chytil and Ong, '8. The presence of CRABP has been detected in. Kwarta et al., '8.
Maden and Summerbell. The role of these binding proteins or of changes in gene transcription. A is not well defined. HUMAN STUDIESThe. RDA) of vitamin A during pregnancy. RE, which is equal to 3,3.
IU of retinol or retinyl esters. U in an average U. S. The. RDA of vitamin A during pregnancy was established by extrapolating.
RE/day or 4,0. 00. IU/day). The International Vitamin A Consultative Group (IVACG). RE/kg plus 1. 00 RE during pregnancy. Underwood, '8. 6); this is approximately 6. RE/day (1,8. 00 IU/day). A for a 5. 5- kg woman.
The World Health Organization (WHO). IVACG state that a daily supplemental dose of 3,0. RE (1. 0,0. 00. IU) of vitamin A is appropriate in geographical areas or under conditions. A intake is known to be inadequate and when diet cannot. Food and. Drug Administration (FDA) as a standard for nutrition labeling. Most prenatal. vitamin preparations contain 8,0. IU/capsule of vitamin A as a.
Dietary surveys in the U. S., however, have defined. IU/day of vitamin A (Russell- Briefel et al., '8. Therefore, women. A before taking supplements.
TABLE. 2. These authors have also presented. Adverse Drug Reaction Reports. A during pregnancy that were. FDA. Almost all of the FDA cases are brief, retrospective. IU/day or more of vitamin A during pregnancy.
The biases. that contributed to the decision to report or publish these cases. A- exposed infants are unknown but are probably. Some of these infants have malformations similar to. At best, it can be said that.
A- exposed infants fit the. The malformations involved craniofacial.
Isotretinoin- exposed. The brain malformations included. Cardiac malformations included aorticopulmonary. Lammer. and Opitz, '8. Craniofacial malformations included malformed external. Most of the mothers of affected infants.
Lammer. et al., '8. Can. we extrapolate from the known teratogenic daily dose of isotretinoin. A? Probably not at this time. Yet the pharmacologic. A and isotretinoin make it difficult.
For example, the. Finally, in a single case, regardless. A intake, one cannot impute the cause of birth defects. A based upon present knowledge. CONCLUSIONSIn. summary, the review of vitamin A has raised questions concerning. It is essential to evaluate these concerns.
Shepard '7. 3 '8. Wilson '7. 7; Brent '7. Stein et al., '8. Hemminki and Vineis '8. Although not conclusive.
A may be teratogenic. Yes–for animal studies. Since isotretinoin and. A (retinol and retinyl esters) induce similar patterns of.
Currently. there is no evidence to suggest that vitamin A should act differently. Beta- carotene, a provitamin. A, does not produce vitamin A toxicity nor does it produce teratogenicity.
All of these data are consistent with a specific vitamin. A- related teratogenic response. LITERATURE CITEDEditorial. Vitamin A and teratogenesis Lancet, I: 3. Bauernfeind. J. C. Diet, 4. 1: 1. 00–1. Brent. R. L. Teratology 3.
Brent. R. L. In Clinics in Perinatology, R. L. Brent, and D. A., Beckman.
Saunders, Philadelphia, vol. Bollag. W. From nutrition to pharmacology.
Lancet I: 8. 60–8. Bollag. W., and A. Matter (1. 98. 1) From vitamin A to retinoids in experimental. Achievements, failures and outlook. Sci., 3. 59: 9–2.
Chytil. F., and D. Ong (1. 98. 4) Cellular retinoid- binding proteins. Goodman, (eds.). Academic Press, New York, pp. Cohan. S. Q. Science, 1. Davis. A. New American Library, Bergenfield.
NJ. De. Luca. Sci.. Food. and Nutrition Board (1. Recommended Daily Allowances, National. Academy of Sciences. Geelen. J. A. G. Toxicol., 6: 3. Goodman. D. S. Med., 3. Goodman. G. E., D.
S. Meyskens (1. 98. Phase. I trial of retinol in cancer patients. Oncol., 1: 3. 94–3.
Goulding. E. H., and R. M. Pratt (1. 98. 6) Isotretinoin teratogenicity in mouse.
Biol., 6: 9. 9–1. Hemminki. K., and P. Vinels (1. 98. 5) Extrapolation of the evidence on teratogenicity. Chemicals. other than drugs. Teratogenesis Carcinogen.
Mutagen., 5: 2. 51–2. Howard. W. B., and C. C. Willhite (1. 98.
Toxicity of retinoids in humans. Rev.; 5: 5. 5–9. 4. Hutchings. D. E., J. Kauffman (1. 97. 3) Maternal vitamin A excess. Psychobiol., 6: 4.
Irving. D. W., C. C. Burk (1. 98. 6) Morphogenesis of isotretinoin- induced. Dermatol., 6: 6. 52–6. Kamm. J. J., K. O. Ehmann (1. 98. 4) Preclinical and. Academic Press. New York, vol. Kochhar. D. M., (1.
Teratogenic activity of retinoic acid. Scand., 7. 0: 3. 98–4. Kochhar. D. M. I Analysis of teratogenic. Teratology, 7: 2. Kochhar. D. M., and W. G. Mc. Bride (1. 98. Isotretinoin metabolism and its.
Teratology, 3. 3: 4. C. Kwarta. R. F., C. A. Slikker (1. 98. Identification. of the cellular retinoic acid- binding protein (CRABP) within the.
CD- 1) limb bud. Teratology 3. Kwasigrouch. T. E., and D. M. Kochhar (1. 97. Locomotory behavior of limb bud. Effects of excess vitamin A in vivo and in vitro. Opitz (1. 98. 6) The Di.
George anomaly as a developmental.
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