Drugs in Pregnancy and Lactation: Tenth Edition

VITAMIN E

Vitamin

PREGNANCY RECOMMENDATION: Compatible

BREASTFEEDING RECOMMENDATION: Compatible

PREGNANCY SUMMARY

Neither deficiency nor excess of vitamin E has been associated with maternal or fetal complications during pregnancy. One study did find a lower birth weight in infants of women taking high doses of vitamin E during pregnancy, but the reduced weight was not thought to be clinically significant and may have been due to other factors. However, in well-nourished women, adequate vitamin E is consumed in the diet and supplementation is not required. If dietary intake is poor, supplementation up to the recommended daily allowance (RDA) for pregnancy is recommended.

FETAL RISK SUMMARY

Vitamin E (tocopherols) is comprised of a group of fat-soluble vitamins that are essential for human health, although their exact biologic function is unknown (1). The National Academy of Sciences’ RDA for vitamin E in pregnancy is 10 mg (1).

Vitamin E concentrations in mothers at term are approximately 4–5 times that of the newborn (28). Levels in the mother rise throughout pregnancy (3). Maternal blood vitamin E level usually ranges between 9 and 19 mcg/mL with corresponding newborn levels varying from 2 to 6 mcg/mL (29). Supplementation of the mother with 15–30 mg/day had no effect on either maternal or newborn vitamin E concentrations at term (4). Use of 600 mg/day in the last 2 months of pregnancy produced about a 50% rise in maternal serum vitamin E (+8 mcg/mL) but a much smaller increase in the cord blood (+1 mcg/mL) (7). Although placental transfer is by passive diffusion, passage of vitamin E to the fetus is dependent on plasma lipid concentrations (810). At term, cord blood is low in β-lipoproteins, the major carriers of vitamin E, in comparison with maternal blood; as a consequence, it is able to transport less of the vitamin (8). Because vitamin E is transported in the plasma by these lipids, recent investigations have focused on the ratio of vitamin E (in milligrams) to total lipids (in grams) rather than on blood vitamin E concentrations alone (9). Ratios above about 0.6–0.8 are considered normal depending on the author cited and the age of the patients (9,11,12).

A 2005 prospective, observational study reported the pregnancy outcomes of 82 women who had taken high-dose vitamin E (≥400 IU/day) in the 1st trimester and compared them with 130 matched controls exposed to agents not known to cause embryo–fetal harm (13). The reason given by the women for taking high doses was that large amounts of vitamins were part of a healthy lifestyle, but none took large doses of vitamins A and D. The two groups were enrolled in the study at a mean gestational age of 13.1 and 6.2 weeks’, respectively. In the subject group, doses of 400, 800, or 1200 IU/day were taken by 74, 7, and 1 women, respectively. The mean duration was 6 months and 44 (54%) took a high dose throughout gestation. There were no differences in the outcomes between the groups in terms of live births, spontaneous abortions, elective abortions, stillbirths, gestational age at delivery, prematurity, and malformations. The mean birth weight, however, was lower in subjects than in controls, 3173 vs. 3417 g, respectively (p = 0.0015). Because only two infants had a birth weight <2500 g, the difference was thought to have a questionable clinical significance. Moreover, vigorous exercise was thought to be part of a “healthy lifestyle” and it might also reduce birth weight (13).

Vitamin E deficiency is relatively uncommon in pregnancy, occurring in less than 10% of all patients (3,4,14). No maternal or fetal complications from deficiency or excess of the vitamin have been identified. Doses far exceeding the RDA have not proved to be harmful (7,15,16). Early studies used vitamin E in conjunction with other therapy in attempts to prevent abortion and premature labor, but no effect of the vitamin therapy was demonstrated (17,18). Premature infants born with low vitamin E stores may develop hemolytic anemia, edema, reticulocytosis, and thrombocytosis if not given adequate vitamin E in the first months following birth (16,19,20). In two studies, supplementation of mothers with 500–600 mg of vitamin E during the last 1–2 months of pregnancy did not produce values significantly different from controls in the erythrocyte hemolysis test with hydrogen peroxide, a test used to determine adequate levels of vitamin E (7,16).

BREASTFEEDING SUMMARY

Vitamin E is excreted into breast milk (11,12,21,22). Human milk is more than 5 times richer in vitamin E than cow’s milk and is more effective in maintaining adequate serum vitamin E and vitamin E:total lipid ratio in infants up to 1 year of age (11,22). A 1985 study measured 2.3 mcg/mL of the vitamin in mature milk (21). Milk obtained from preterm mothers (gestational age 27–33 weeks) was significantly higher (8.5 mcg/mL) during the first week and then decreased progressively over the next 6 weeks to 3.7 mcg/mL (21). The authors concluded that milk from preterm mothers plus multivitamin supplements would provide adequate levels of vitamin E for very low-birth-weight infants (<1500 g and appropriate for gestational age).

Japanese researchers examined the pattern of vitamin E analogs (α-, γ-, δ-, and β-tocopherols) in plasma and red blood cells from breastfed and bottle-fed infants (23). Several differences were noted, but the significance of these findings to human health is unknown.

Vitamin E applied for 6 days to the nipples of breastfeeding women resulted in a significant rise in infant serum levels of the vitamin (24). The study group, composed of 10 women, applied the contents of one 400-IU vitamin E capsule to both areolae and nipples after each nursing. Serum concentrations of the vitamin rose from 4 to 17.5 mcg/mL and those in a similar group of untreated controls rose from 3.4 to 12.2 mcg/mL. The difference between the two groups was statistically significant (p <0.025). Although no adverse effects were observed, the authors cautioned that the long-term effects were unknown.

The National Academy of Sciences’ RDA of vitamin E during lactation is 12 mg (1). Maternal supplementation is recommended only if the diet does not provide sufficient vitamin E to meet the RDA.

References

1.American Hospital Formulary Service. Drug Information 1997. Bethesda, MD: American Society of Health-System Pharmacists, 1997:2832–3.

2.Moyer WT. Vitamin E levels in term and premature newborn infants. Pediatrics 1950;6:893–6.

3.Leonard PJ, Doyle E, Harrington W. Levels of vitamin E in the plasma of newborn infants and of the mothers. Am J Clin Nutr 1972;25:480–4.

4.Baker H, Frank O, Thomson AD, Langer A, Munves ED, De Angelis B, Kaminetzky HA. Vitamin profile of 174 mothers and newborns at parturition. Am J Clin Nutr 1975;28:59–65.

5.Dostalova L. Correlation of the vitamin status between mother and newborn during delivery. Dev Pharmacol Ther 1982;4(Suppl l):45–57.

6.Kaminetzky HA, Baker H. Micronutrients in pregnancy. Clin Obstet Gynecol 1977;20:363–80.

7.Mino M, Nishino H. Fetal and maternal relationship in serum vitamin E level. J Nutr Sci Vitaminol 1973;19:475–82.

8.Haga P, Ek J, Kran S. Plasma tocopherol levels and vitamin E/B-lipoprotein relationships during pregnancy and in cord blood. Am J Clin Nutr 1982;36:1200–4.

9.Martinez FE, Goncalves AL, Jorge SM, Desai ID. Vitamin E in placental blood and its interrelationship to maternal and newborn levels of vitamin E. J Pediatr 1981;99:298–300.

10.Hill EP, Longo LD. Dynamics of maternal-fetal nutrient transfer. Fed Proc 1980;39:239–44.

11.Martinez FE, Jorge SM, Goncalves AL, Desai ID. Evaluation of plasma tocopherols in relation to hematological indices of Brazilian infants on human milk and cows’ milk regime from birth to 1 year of age. Am J Clin Nutr 1984;39:969–74.

12.Mino M, Kitagawa M, Nakagawa S. Red blood cell tocopherol concentrations in a normal population of Japanese children and premature infants in relation to the assessment of vitamin E status. Am J Clin Nutr 1985;41:631–8.

13.Boskovic R, Gargaun L, Oren D, Djulus J, Koren G. Pregnancy outcome following high doses of vitamin E supplementation. Reprod Toxicol 2005;20:85–8.

14.Kaminetzky HA, Langer A, Baker O, Frank O, Thomson AD, Munves ED, Opper A, Behrle FC, Glista B. The effect of nutrition in teenage gravidas on pregnancy and the status of the neonate. I. A nutritional profile. Am J Obstet Gynecol 1973;115:639–46.

15.Hook EB, Healy KM, Niles AM, Skalko RG. Vitamin E: teratogen or anti-teratogen? Lancet 1974;1:809.

16.Gyorgy P, Cogan G, Rose CS. Availability of vitamin E in the newborn infant. Proc Soc Exp Biol Med 1952;81:536–8.

17.Kotz J, Parker E, Kaufman MS. Treatment of recurrent and threatened abortion. Report of two hundred and twenty-six cases. J Clin Endocrinol 1941;1:838–49.

18.Shute E. Vitamin E and premature labor. Am J Obstet Gynecol 1942;44:271–9.

19.Oski FA, Barness LA. Vitamin E deficiency: a previously unrecognized cause of hemolytic anemia in the premature infant. J Pediatr 1967;70:211–20.

20.Ritchie JH, Fish MB, McMasters V, Grossman M. Edema and hemolytic anemia in premature infants. A vitamin E deficiency syndrome. N Engl J Med 1968;279:1185–90.

21.Gross SJ, Gabriel E. Vitamin E status in preterm infants fed human milk or infant formula. J Pediatr 1985;106:635–9.

22.Friedman Z. Essential fatty acids revisited. Am J Dis Child 1980;134:397–408.

23.Mino M, Kijima Y, Nishida Y, Nakagawa S. Difference in plasma- and red blood cell-tocopherols in breastfed and bottle-fed infants. J Nutr Sci Vitaminol 1980;26:103–12.

24.Marx CM, Izquierdo A, Driscoll JW, Murray MA, Epstein MF. Vitamin E concentrations in serum of newborn infants after topical use of vitamin E by nursing mothers. Am J Obstet Gynecol 1985;152:668–70.