VITAMIN C

Fetal Risk Summary

Vitamin C (ascorbic acid) is a water-soluble essential nutrient required for collagen formation, tissue repair, and numerous metabolic processes including the conversion of folic acid to folinic acid and iron metabolism (1). The National Academy of Sciences' recommended dietary allowance (RDA) for vitamin C in pregnancy is 70 mg (1).

Vitamin C is actively transported to the fetus (2,3,4 and 5). When maternal serum levels are high, placental transfer changes to simple diffusion (5). During gestation, maternal serum vitamin C progressively declines (6,7). As a consequence of this process, newborn serum vitamin C (9–22 µg/mL) is approximately 2–4 times that of the mother (4–10 µg/mL) (4,5,6,7,8,9,10,11,12,13,14,15,16,17,18 and 19).

Maternal deficiency of vitamin C without clinical symptoms is common during pregnancy (18,19 and 20). Most studies have found no association between this deficiency and maternal or fetal complications, including congenital malformations (11,12,21,22,23 and 24). When low vitamin C levels were found in women or fetuses with complications, it was a consequence of the condition and not a cause. However, a 1971 retrospective study of 1,369 mothers found that deficiency of vitamin C may have a teratogenic effect, although the authors advised caution in the interpretation of their results (25). In a later investigation, low 1st-trimester white blood cell vitamin C levels were discovered in six mothers giving birth to infants with neural tube defects (26). Folic acid, vitamin B12, and riboflavin were also low in serum or red blood cells. The low folic acid and vitamin B12 levels were thought to be involved in the etiology of the defects (see also Folic Acid, Vitamin B12, and Riboflavin).

A 1965 report suggested that high daily doses of vitamin C during pregnancy might have produced a “conditioned” scurvy in two infants (27). The mothers had apparent daily intakes of vitamin C in the 400-mg range throughout pregnancy, but both of their offspring had infantile scurvy. To study this condition, laboratory animals were given various doses of vitamin C throughout gestation. Two of 10 offspring exposed to the highest doses developed symptoms and histologic changes compatible with scurvy (27). The investigators concluded that the high in utero exposure may have induced ascorbic acid dependency. More recent reports of this condition have not been located; thus, the clinical significance is unknown.

Only one report has been found that potentially relates high doses of vitamin C with fetal anomalies. This was in a brief 1976 case report describing an anencephalic fetus delivered from a woman treated with high doses of vitamin C and other water-soluble vitamins and nutrients for psychiatric reasons (28). The relationship between the defect and the vitamins is unknown. In another study, no evidence of adverse effects was found with doses up to 2000 mg/day (29).

In summary, mild to moderate vitamin C deficiency or excessive doses do not seem to pose a major risk to the mother or fetus. Because vitamin C is required for good maternal and fetal health and an increased demand for the vitamin occurs during pregnancy, intake up to the RDA is recommended.

[* Risk Factor C if used in doses above the RDA.]

Breast Feeding Summary

Vitamin C (ascorbic acid) is excreted into human breast milk. Reported concentrations in milk vary from 24 to 158 µg/mL (30,31,32,33,34,35,36,37 and 38). In lactating women with low nutritional status, milk vitamin C is directly proportional to intake (31,32). Supplementation with 4–200 mg/day of vitamin C produced milk levels of 24–61 µg/mL (31). Similarly, in another group of women with poor vitamin C intake, supplementation with 34–103 mg/day resulted in levels of 34–55 µg/mL (32). In contrast, studies in well-nourished women consuming the RDA or more of vitamin C in their diets indicate that ingestion of greater amounts does not significantly increase levels of the vitamin in their milk (33 and 34). Even consumption of total vitamin C exceeding 1000 mg/day, 10 times the RDA, did not significantly increase milk concentrations or vitamin C intake of the infants (36). However, maternal urinary excretion of the vitamin did increase significantly. These studies indicate that vitamin C excretion in human milk is regulated to prevent exceeding a saturation level (36).

Storage of human milk in the freezer for up to 3 months did not affect vitamin C concentrations of milk obtained from preterm mothers but resulted in a significant decrease in vitamin C concentrations in milk from term mothers (39). Both types of milk, however, maintained sufficient vitamin C to meet the RDA for infants.

The RDA for vitamin C during lactation is 95 mg (1). Well-nourished lactating women consuming the RDA of vitamin C in their diets normally excrete sufficient vitamin C in their milk to reach a saturation level and additional supplementation is not required. Maternal supplementation up to the RDA is needed only in those women with poor nutritional status.

References

1. American Hospital Formulary Service. Drug Information 1997. Bethesda, MD: American Society of Health-System Pharmacists, 1997:2823–5.
2. Hill EP, Longo LD. Dynamics of maternal-fetal nutrient transfer. Fed Proc 1980;39:239–44.
3. Streeter ML, Rosso P. Transport mechanisms for ascorbic acid in the human placenta. Am J Clin Nutr 1981;34:1706–11.
4. Hamil BM, Munks B, Moyer EZ, Kaucher M, Williams HH. Vitamin C in the blood and urine of the newborn and in the cord and maternal blood. Am J Dis Child 1947;74:417–33.
5. Kaminetzky HA, Baker H, Frank O, Langer A. The effects of intravenously administered water-soluble vitamins during labor in normovitaminemic and hypovitaminemic gravidas on maternal and neonatal blood vitamin levels at delivery. Am J Obstet Gynecol 1974;120:697–703.
6. Snelling CE, Jackson SH. Blood studies of vitamin C during pregnancy, birth, and early infancy. J Pediatr 1939;14:447–51.
7. Adlard BPF, De Souza SW, Moon S. Ascorbic acid in fetal human brain. Arch Dis Child 1974;49:278–82.
8. Braestrup PW. Studies of latent scurvy in infants. II. Content of ascorbic (cevitamic) acid in the blood-serum of women in labour and in children at birth. Acta Paediatr 1937;19:328–34.
9. Braestrup PW. The content of reduced ascorbic acid in blood plasma in infants, especially at birth and in the first days of life. J Nutr 1938;16:363–73.
10. Slobody LB, Benson RA, Mestern J. A comparison of the vitamin C in mothers and their newborn infants. J Pediatr 1946;29:41–4.
11. Teel HM, Burke BS, Draper R. Vitamin C in human pregnancy and lactation. I. Studies during pregnancy. Am J Dis Child 1938;56:1004–10.
12. Lund CJ, Kimble MS. Some determinants of maternal and plasma vitamin C levels. Am J Obstet Gynecol 1943;46:635–47.
13. Manahan CP, Eastman NJ. The cevitamic acid content of fetal blood. Bull Johns Hopkins Hosp 1938;62:478–81.
14. Raiha N. On the placental transfer of vitamin C. An experimental study on guinea pigs and human subjects. Acta Physiol Scand 1958;45:Suppl 155.
15. Khattab AK, Al Nagdy SA, Mourad KAH, El Azghal HI. Foetal maternal ascorbic acid gradient in normal Egyptian subjects. J Trop Pediatr 1970;16:112–5.
16. McDevitt E, Dove MA, Dove RF, Wright IS. Selective filtration of vitamin C by the placenta. Proc Soc Exp Biol Med 1942;51:289–90.
17. Sharma SC. Levels of total ascorbic acid, histamine and prostaglandins E2 and F2a in the maternal antecubital and foetal umbilical vein blood immediately following the normal human delivery. Int J Vitam Nutr Res 1982;52:320–5.
18. Dostalova L. Correlation of the vitamin status between mother and newborn during delivery. Dev Pharmacol Ther 1982;4(Suppl 1):45–57.
19. 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.
20. Kaminetzky HA, Langer A, Baker H, Frank O, Thomson AD, Munves ED, Opper A, Behrle FC, Glista B. The effect of nutrition in teen-age gravidas on pregnancy and the status of the neonate. I. A nutritional profile. Am J Obstet Gynecol 1973;115:639–46.
21. Martin MP, Bridgforth E, McGanity WJ, Darby WJ. The Vanderbilt cooperative study of maternal and infant nutrition. X. Ascorbic acid. J Nutr 1957;62:201–24.
22. Chaudhuri SK. Role of nutrition in the etiology of toxemia of pregnancy. Am J Obstet Gynecol 1971;110:46–8.
23. Wilson CWM, Loh HS. Vitamin C and fertility. Lancet 1973;2:859–60.
24. Vobecky JS, Vobecky J, Shapcott D, Munan L. Vitamin C and outcome of pregnancy. Lancet 1974;1:630.
25. Nelson MM, Forfar JO. Associations between drugs administered during pregnancy and congenital abnormalities of the fetus. Br Med J 1971;1:523–7.
26. Smithells RW, Sheppard S, Schorah CJ. Vitamin deficiencies and neural tube defects. Arch Dis Child 1976;51:944–50.
27. Cochrane WA. Overnutrition in prenatal and neonatal life: a problem? Can Med Assoc J 1965;93:893–9.
28. Averback P. Anencephaly associated with megavitamin therapy. Can Med Assoc J 1976;114:995.
29. Korner WF, Weber F. Zur toleranz hoher Ascorbinsauredosen. Int J Vitam Nutr Res 1972;42:528–44.
30. Ingalls TH, Draper R, Teel HM. Vitamin C in human pregnancy and lactation. II. Studies during lactation. Am J Dis Child 1938;56:1011–19.
31. Deodhar AD, Rajalakshmi R, Ramakrishnan CV. Studies on human lactation. Part III. Effect of dietary vitamin supplementation on vitamin contents of breast milk. Acta Paediatr 1964;53:42–8.
32. Bates CJ, Prentice AM, Prentice A, Lamb WH, Whitehead RG. The effect of vitamin C supplementation on lactating women in Keneba, a West African rural community. Int J Vitam Nutr Res 1983;53:68–76.
33. Thomas MR, Kawamoto J, Sneed SM, Eakin R. The effects of vitamin C, vitamin B6, and vitamin B12 supplementation on the breast milk and maternal status of well-nourished women. Am J Clin Nutr 1979;32:1679–85.
34. Thomas MR, Sneed SM, Wei C, Nail PA, Wilson M, Sprinkle EE III. The effects of vitamin C, vitamin B6, vitamin B12, folic acid, riboflavin, and thiamin on the breast milk and maternal status of well-nourished women at 6 months postpartum. Am J Clin Nutr 1980;33:2151–6.
35. Sneed SM, Zane C, Thomas MR. The effects of ascorbic acid, vitamin B6, vitamin B12, and folic acid supplementation on the breast milk and maternal nutritional status of low socioeconomic lactating women. Am J Clin Nutr 1981;34:1338–46.
36. Byerley LO, Kirksey A. Effects of different levels of vitamin C intake on the vitamin C concentration in human milk and the vitamin C intakes of breast-fed infants. Am J Clin Nutr 1985;41:665–71.
37. Salmenpera L. Vitamin C nutrition during prolonged lactation: optimal in infants while marginal in some mothers. Am J Clin Nutr 1984;40:1050–6.
38. Grewar D. Infantile scurvy. Clin Pediatr 1965;4:82–9.
39. Bank MR, Kirksey A, West K, Giacoia G. Effect of storage time and temperature on folacin and vitamin C levels in term and preterm human milk. Am J Clin Nutr 1985;41:235–42.