http://www.ilsi.org/file/a5_pregnancy.pdf
Vitamin A is needed in increased amounts to support maternal reproductive processes, including fetal growth and development, and during lactation to replace losses in breast milk. The increased need during gestation is small and can be provided through a balanced diet and maternal reserves from well-nourished women.1 In areas of endemic vitamin A deficiency (VAD), however, vitamin A supplements often must supply this need. With lactation, requirements rise to replace maternal vitamin A lost daily in breast milk
and to maintain breast milk vitamin A at a level to protect the needs of rapidly growing infants during at least the first 6 months of life.2 Vitamin A requirements to support repetitive reproductive cycles may be difficult to meet from the affordable vegetarian-type diets typical of VAD areas,3 but they are easily provided through a high-dose or frequent low-dose vitamin A supplement. High doses of vitamin A given in early pregnancy can be unsafe, and it is operationally difficult to provide daily small doses in developing countries. Intervention programs to meet vitamin A needs of fertile women, therefore, must adjust dose levels and timing to ensure safety during pregnancy and lactation. Severe VAD in animals causes abortions, fetal death, resorptions, and congenital defects.4 These outcomes occur in rats when maternal tissue is depleted to the extent that reserves are decreased in the ocular system, one of the last tissues to loose its vitamin A supply.5 Case reports of adverse reproductive outcomes associated with human deficiency are rare and poorly documented. Available epidemiologic observations in human
populations where clinical vitamin A deficiency in children is common also rarely report adverse
reproductive outcomes. This is in spite of recognizing that reproductive-age women living in VAD areas frequently report night blindness during pregnancy and/or lactation6 and that nightblindness in women during periods of increased physiologic need is thought to reflect vitamin A deficiency. However, an
association of incident congenital ocular defects with VAD is suggested by a recent randomized community trial in pregnant Nepalese women. Ocular defects were reduced in their newborns by weekly low-dose vitamin A supplementation.7 High doses of vitamin A.retinol, retinyl ester, and their oxidized metabolites.given to animals in the International Vitamin A Consultative Group . IVACG
Intervention programs to meet vitamin A needs of fertile women must adjust dose levels and timing to ensure safety during pregnancy and lactation. early gestational period can cause congenital defects,8 and reports suggest impaired growth and behavioral response rates when high doses are given later in gestation.9,10 Dose and timing when adverse effects are noted are highly variable and species specific.
In humans, malformations similar to those seen in animals have been recorded when women ingested
high doses of preformed vitamin A and related compounds (particularly retinoic acid and analogues) in the first trimester.11 Retinoic acid and other oxidized metabolites are not used in VAD control programs and, in fertile women, only under medical supervision for specialized conditions when they are not pregnant. Birth defects from ingestion of retinol or retinyl ester, usually occur when the high-dose
supplement is taken daily for several days or weeks during the first gestational trimester.8 There is no
evidence of acute toxicity from ingesting ß-carotene or other carotenoids from supplements or food, especially at levels comparable to those recommended for vitamin A supplementation.11, 12 Night blindness is frequently reported in pregnant women living in areas where VAD is common in children,13 and breast milk from lactating women residing in these areas is often low in vitamin A.14 Night blindness during pregnancy has sometimes been reported to disappear without intervention following parturition, but may reappear during lactation and/or repeat pregnancies.6,13 Night blindness associated with pregnancy and lactation is reported to be only partially responsive to vitamin A supplementation,4,6,15 which suggests that other nutritional deficiencies may contribute to the problem. Breast milk levels of vitamin A in a population reflect habitual maternal vitamin A intakes, particularly when low. Low vitamin A levels have been safely increased in populations, including lactating women, when the ingestion of vitamin A. fortified food products becomes frequent16,17 and in individual mothers provided low-dose vitamin A supplements daily (2000 IU)18 or up to 300,000 IU in a single dose given within 1 month of parturition.19 Fully breast-feeding mothers are infertile for at least 8 weeks postpartum20 and, while amenorrheic, are of low susceptibility to pregnancy up to 6 months.21 The physiologic needs
for vitamin A of infants born to vitamin A.adequate mothers and fed breast milk with adequate vitamin A (in excess of 30 µg/dL or 1.05 µmol/L) are met for at least the first 6 months of life.2 The World Health Organization recently convened a group of experts to consider dose and safety issues in relationship to the
vitamin A needs of fertile women and their nursing infants.20 The consultation responded in part to a
single report questioning the safety of daily intakes during pregnancy of 10,000 IU vitamin A as a supplement given to adequately nourished women in the United States.22 Recently available global population-based information was also reviewed on the length of postpartum infertility, the period when it would be safe to give high doses of vitamin A to reproductive-age women. The review of both published and available unpublished data reconfirmed earlier recommendations of IVACG (1986) that: n It is safe to give fertile women, independent of their vitamin A status, as much as 10,000 IU (3000 µg RE) daily at any time during pregnancy. There is no evidence of acute toxicity from ingesting ß-carotene or other carotenoids from supplements or food, especially at levels comparable to those recommended for vitamin A supplementation. The recommendation was extended by noting that: n No benefits have been demonstrated from taking a supplement during gestation where habitual vitamin A intakes exceed about
three times the RDA (about 8000 IU or 2400 µg RE) from sources rich in provitamin A. The earlier recommendations of IVACG for supplementation of women residing in endemically deficient areas also were extended to include the following timing and doses: n A weekly supplement of up to 25,000 IU
(8500 µg RE) is a safe alternative to daily supplementation during pregnancy.* n A single high-dose supplement of up to 200,000 IU to breast-feeding women is safe up to 8 weeks postdelivery. n For non-breast-feeding women, a single high-dose supplement of up to 200,000 IU is safe up to 6 weeks postdelivery. Fortified food products can safely be ingested during pregnancy and lactation, and vitamin A rich natural foods, such as animal liver, consumed occasionally also can be safely ingested.20,23 There is no known teratogenic risk associated with prolonged consumption of either natural food sources or supplements rich in vitamin A.active carotenoids.8,12 *During the first 60 days following conception, the advisability of doses above 25,000 IU is uncertain. Risks are likely to diminish as gestation advances.
References
1. National Research Council/National Academy of Sciences. Recommended dietary allowances, 10th ed.
(report of the Subcommittee on the Tenth Edition of the RDAs, Food and Nutrition Board, Commission on Life Sciences). Washington, DC: National Academy Press, 1989;85
2. Underwood BA. Maternal vitamin A status and its importance in infancy and early childhood. Am J Clin Nutr 1994; 59(suppl):517S.524S
3. De Pee S et al. Lack of improvement in vitamin A status with increased consumption of dark-green leafy vegetables. Lancet 1995; 346:75.81
4. Wallingford JC, Underwood BA. Vitamin A deficiency in pregnancy, lactation, and the nursing child. In: Bauernfeind JC, ed. Vitamin A deficiency and its control. New York: Academic Press, 1986;101.152
5. Wallingford JC, Underwood BA. Vitamin A status needed to maintain vitamin A concentrations in nonhepatic tissues of the pregnant rat. J Nutr 1987;117:1410.1415
6. IVACG. Maternal night blindness: extent and associated risk factors. IVACG Statement. Washington, DC: IVACG, 1997
7. Khatry SK et al. Effect of maternal vitamin A or betacarotene supplementation on incidence of birth defects among Nepalese infants. In: Report of the XVIII IVACG Meeting, Cairo, 1997. Washington, DC: IVACG, 1998; 87
8. Hathcock JN et al. Evaluation of vitamin A toxicity. Am J Clin Nutr 1990;52:183.202
9. Hutchings DE, Gaston J. The effects of vitamin A excess administered during the mid-fetal period on learning and development in rat offspring. Dev Psychobiol 1974;71:225.233
10. Vorhees CV et al. The relationship of gestational age of vitamin A induced postnatal dysfunction. Teratology 1978;17:271.276
11. Teratology Society. Teratology Society position paper: recommendations for vitamin A use during pregnancy. Teratology 1987;35:269.275
12. Bendich A. The safety of ß-carotene. Nutr Cancer 1988;11:207.214
13. Katz J et al. Night blindness is prevalent during pregnancy and lactation in rural Nepal. J Nutr 1995;125:2122.2127
14. Newman V. Vitamin A and breastfeeding: a comparison of data from developed and developing countries. San Diego, CA: Wellstart International, 1993
15. Christian P et al. The impact of vitamin A or betacarotene
supplementation on the incidence of night blindness during pregnancy and lactation in Nepal. In:
Report of the XVIII IVACG Meeting, 1997. Washington, DC: IVACG, 1998; 86
16. Arroyave G et al. Evaluation of sugar fortification with vitamin A at the national level. Scientific Publication No. 384. Washington, DC: Pan American Health
Organization, 1979
17. Muhilal, Murdiana A, Axis I, et al. Vitamin A.fortified
monosodium glutamate and vitamin A status: a controlled field trial. Am J Clin Nutr 1988;48:1265.1270
18. Villard L, Bates CJ. Effect of vitamin A supplementation on plasma and breast milk vitamin A levels in poorly nourished Gambian women. Hum Nutr Clin Nutr 1987;


41C:47.58 Established in 1975, the International Vitamin A Consultative Group guides international activities for reducing vitamin A deficiency in the world. IVACG concentrates its efforts on stimulating and disseminating new knowledge, translating that new knowledge to assist others in its practical application, and providing authoritative policy statements and recommendations that
others can use to develop appropriate prevention and control programs. This statement was prepared at the request of the International Vitamin A Consultative Group (IVACG) by Dr. Barbara A.
Underwood, Food and Nutrition Board, Institute of Medicine, NAS, Washington, D.C., USA.

It was reviewed and approved by the IVACG Steering Committee: David Alnwick, MSc
Paul Arthur, MD, MPH, MSc
Omar Dary, PhD
Frances R. Davidson, PhD, IVACG Secretary
Abraham Horwitz, MD, MPH, IVACG Chair
Vinodini Reddy, MD, DCH, FIAP
Suttilak Smitasiri, PhD
Alfred Sommer, MD, MHSc, IVACG Steering Committee Chair
Keith P. West, Jr, DrPH

The publication of this statement is made possible by support from Opportunities for Micronutrient Interventions (OMNI), a
project of the Office of Health and Nutrition, Bureau for Global Programs, Field Support and Research, U.S. Agency for
International Development, under Contract HRN-5122-C-00-3025-00, Project 936-5122.
Printed June 1998 in the United States of America.
Additional copies of this and other IVACG publications are available free of charge to developing countries and for US$3.50 to
developed countries. Copies can be ordered from the IVACG Secretariat:
IVACG Secretariat . ILSI Research Foundation
1126 Sixteenth Street, NW . Washington, DC 20036-4810 . USA
International Vitamin A Consultative Group . IVACG
The ILSI Research Foundation.s Human Nutrition Institute serves as the IVACG Secretariat.

19. Stoltzfus RJ et al. High dose vitamin A supplementation of breast-feeding Indonesian mothers: effects on the vitamin A status of mother and infant. J Nutr 1993;123:666.675
20. World Health Organization. Safe vitamin A dosage during pregnancy and lactation: recommendations and report of a consultation. Document NUT/98.4 (available from the Nutrition Programme) Geneva: WHO, 1998
21. Kennedy KI et al. Consensus statement: lactational amenorrhea method for family planning. Int J Gynecol Obstet 1996;54:55.57
22. Rothman KJ et al. Teratogenicity of high vitamin A intake. N Engl J Med 1995; 333:1369.1373
23. Buss NE et al. The teratogenic metabolites of vitamin A in women following supplements and liver. Hum Exp Toxicol 1994;13:33.43