Risk Factor: A*
Fetal Risk Summary
Riboflavin (Vitamin B2), a water-soluble B complex vitamin, acts as a coenzyme in humans and is essential for tissue respiration systems (1). The National Academy of Sciences’ recommended dietary allowance (RDA) for riboflavin in pregnancy is 1.6 mg (1).
The vitamin is actively transferred to the fetus, resulting in higher concentrations of riboflavin in the newborn than in the mother (2,3,4,5,6,7,8,9,10,11 and 12). The placenta converts flavin-adenine dinucleotide existing in the maternal serum to free riboflavin found in the fetal circulation (5,6). This allows retention of the vitamin by the fetus, because the transfer of free riboflavin back to the mother is inhibited (6,12). At term, mean riboflavin values in 174 mothers were 184 ng/mL (range 80390 ng/mL) and in their newborns 318 ng/mL (range 136665 ng/mL) (7). In a more recent study, the cord serum concentration was 158 nmol/L compared with 113 nmol/L in the maternal serum (11).
The incidence of riboflavin deficiency in pregnancy is low (7,13). In two studies, no correlation was discovered between the riboflavin status of the mother and the outcome of pregnancy even when riboflavin deficiency was present (14,15). A 1977 study found no difference in riboflavin levels between infants of low and normal birth weight (10).
Riboflavin deficiency is teratogenic in animals (16). Although human teratogenicity has not been reported, low riboflavin levels were found in six mothers who had given birth to infants with neural tube defects (17). Other vitamin deficiencies present in these women were thought to be of more significance (see Folic Acid and Vitamin B12).
A mother has been described with multiple acylcoenzyme A dehydrogenase deficiency probably related to riboflavin metabolism (18). The mother had given birth to a healthy child followed by one stillbirth and six infants who had been breast-fed and died in early infancy after exhibiting a strong sweaty foot odor. In her 9th and 10th pregnancies, she was treated with 20 mg/day of riboflavin during the 3rd trimesters and delivered healthy infants. The authors thought the maternal symptoms were consistent with a mild form of acute fatty liver of pregnancy.
[*Risk Factor C if used in doses above the RDA.]
Breast Feeding Summary
Riboflavin (Vitamin B2) is excreted in human breast milk (19,20,21,22 and 23). Well-nourished lactating women were given supplements of a multivitamin preparation containing 2.0 mg of riboflavin (19). At 6 months postpartum, milk concentrations of riboflavin did not differ significantly from those in control patients not receiving supplements. In a study of lactating women with low nutritional status, supplementation with riboflavin in doses of 0.1010.0 mg/day resulted in mean milk concentrations of 200740 ng/mL (20). Milk concentrations were directly proportional to dietary intake. A 1983 English study measured riboflavin levels in pooled human milk obtained from preterm (26 mothers: 2934 weeks) and term (35 mothers: 39 weeks or longer) patients (21). Milk obtained from preterm mothers rose from 276 ng/mL (colostrum) to 360 ng/mL (615 days) and then fell to 266 ng/mL (16196 days). During approximately the same time frame, milk levels from term mothers were 288, 279, and 310 ng/mL. In a Finnish study, premature infants (mean gestational age 30.1 weeks) fed human milk, but without riboflavin supplementation, became riboflavin deficient by 6 weeks of age (24).
The National Academy of Sciences’ RDA for riboflavin during lactation is 1.8 mg (1). If the diet of the lactating woman adequately supplies this amount, supplementation with riboflavin is not needed (22). Maternal supplementation with the RDA for riboflavin is recommended for those women with inadequate nutritional intake. The American Academy of Pediatrics considers maternal consumption of riboflavin to be compatible with breast feeding (25).
- American Hospital Formulary Service. Drug Information 1997. Bethesda, MD: American Society of Health-System Pharmacists, 1997:28178.
- Hill EP, Longo LD. Dynamics of maternal-fetal nutrient transfer. Fed Proc 1980;39:23944.
- Lust JE, Hagerman DD, Villee CA. The transport of riboflavin by human placenta. J Clin Invest 1954;33:3840.
- Frank O, Walbroehl G, Thomason A, Kaminetzky H, Kubes Z, Baker H. Placental transfer: fetal retention of some vitamins. Am J Clin Nutr 1970;23:6623.
- 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;120:697703.
- Kaminetzky HA, Baker H. Micronutrients in pregnancy. Clin Obstet Gynecol 1977;20:36380.
- Baker H, Frank O, Thomason AD, Langer A, Munves ED, De Angelis B, Kaminetzky HA. Vitamin profile of 174 mothers and newborns at parturition. Am J Clin Nutr 1975;28:5965.
- Baker H, Frank O, Deangelis B, Feingold S, Kaminetzky HA. Role of placenta in maternal-fetal vitamin transfer in humans. Am J Obstet Gynecol 1981;141:7926.
- Bamji MS. Enzymic evaluation of thiamin, riboflavin and pyridoxine status of parturient women and their newborn infants. Br J Nutr 1976;35:25965.
- Baker H, Thind IS, Frank O, DeAngelis B, Caterini H, Lquria DB. Vitamin levels in low-birth-weight newborn infants and their mothers. Am J Obstet Gynecol 1977;129:5214.
- Kirshenbaum NW, Dancis J, Levitz M, Lehanka J, Young BK. Riboflavin concentration in maternal and cord blood in human pregnancy. Am J Obstet Gynecol 1987;157:74852.
- Dancis J, Lehanka J, Levitz M. Placental transport of riboflavin: differential rates of uptake at the maternal and fetal surfaces of the perfused human placenta. Am J Obstet Gynecol 1988;158:20410.
- Dostalova L. Correlation of the vitamin status between mother and newborn during delivery. Dev Pharmacol Ther 1982;4(Suppl 1):4557.
- Vir SC, Love AHG, Thompson W. Riboflavin status during pregnancy. Am J Clin Nutr 1981;34:26992705.
- Heller S, Salkeld RM, Korner WF. Riboflavin status in pregnancy. Am J Clin Nutr 1974;27:122530.
- Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:5578.
- Smithells RW, Sheppard S, Schorah CJ. Vitamin deficiencies and neural tube defects. Arch Dis Child 1976;51:94450.
- Harpey JP, Charpentier C. Acute fatty liver of pregnancy. Lancet 1983;1:5867.
- 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;33:21516.
- 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 Scand 1964;53:428.
- Ford, JE, Zechalko A, Murphy J, Brooke OG. Comparison of the B vitamin composition of milk from mothers of preterm and term babies. Arch Dis Child 1983;58:36772.
- Nail PA, Thomas MR, Eakin R. The effect of thiamin and riboflavin supplementation on the level of those vitamins in human breast milk and urine. Am J Clin Nutr 1980;33:198204.
- Gunther M. Diet and milk secretion in women. Proc Nutr Soc 1968;27:7782.
- Ronnholm KAR. Need for riboflavin supplementation in small prematures fed human milk. Am J Clin Nutr 1986;43:16.
- Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.