Risk Factor: A*
Fetal Risk Summary
Vitamin B12 (cyanocobalamin), a water-soluble B complex vitamin, is an essential nutrient required for nucleoprotein and myelin synthesis, cell reproduction, normal growth, and the maintenance of normal erythropoiesis (1). The National Academy of Sciences’ recommended dietary allowance (RDA) for vitamin B12 in pregnancy is 2.2 g (1).
Vitamin B12 is actively transported to the fetus (2,3,4,5 and 6). This process is responsible for the progressive decline of maternal levels that occurs during pregnancy (6,7,8,9,10,11,12,13 and 14). Fetal demands for the vitamin have been estimated to be approximately 0.3 g/day (0.2 nmol/day) (15). Similar to other B complex vitamins, higher concentrations of B12 are found in the fetus and newborn than in the mother (5,6,7,8 and 9,16,17,18,19,20,21,22,23 and 24). At term, mean vitamin B12 levels in 174 mothers were 115 pg/mL and in their newborns 500 pg/mL, a newborn:maternal ratio of 4.3 (16). Comparable values have been observed by others (5,7,21,22 and 23). Mean levels in 51 Brazilian women, in their newborns, and in the intervillous space of their placentas were approximately 340, 797, and 1074 pg/mL, respectively (24). The newborn:maternal ratio in this report was 2.3. The high levels in the placenta may indicate a mechanism by which the fetus can accumulate the vitamin against a concentration gradient. This study also found a highly significant correlation between vitamin B12 and folate concentrations. This is in contrast to an earlier report that did not find such a correlation in women with megaloblastic anemia (25).
Maternal deficiency of vitamin B12 is common during pregnancy (16,17,26,27). Tobacco smoking reduces maternal levels of the vitamin even further (28). Megaloblastic anemia may result when the deficiency is severe, but it responds readily to therapy (29,30,31 and 32). On the other hand, tropical macrocytic anemia during pregnancy responds erratically to vitamin B12 therapy and is better treated with folic acid (32,33).
Megaloblastic (pernicious) anemia may be a cause of infertility (30,31,34). One report described a mother with undiagnosed pernicious anemia who had lost her 3rd, 9th, and 10th pregnancies (30). A healthy child resulted from her 11th pregnancy following treatment with vitamin B12. In another study, eight infertile women with pernicious anemia were treated with vitamin B12 and seven became pregnant within 1 year of therapy (31). One of three patients in still another report may have had infertility associated with very low vitamin B12 levels (34).
Vitamin B12 deficiency was associated with prematurity (as defined by a birth weight of 2500 g or less) in a 1968 paper (9). However, many of the patients who delivered prematurely had normal or elevated vitamin B12 levels. No correlation between vitamin B12 deficiency and abruptio placentae was found in two studies published in the 1960s (35,36). Two reports found a positive association between low birth weight and low vitamin B12 levels (21,37). In both instances, however, folate levels were also low and iron was deficient in one. Others could not correlate low vitamin B12 concentrations with the weight at delivery (11,26). Based on these reports, it is doubtful whether vitamin B12 deficiency is associated with any of the conditions.
In experimental animals, vitamin B12 deficiency is teratogenic (7,38). Investigators studying the cause of neural tube defects measured very low vitamin B12 levels in three of four mothers of anencephalic fetuses (39). Additional evidence led them to conclude that the low vitamin B12 resulted in depletion of maternal folic acid and involvement in the origin of the defects. In contrast, two other reports have shown no relationship between low levels of vitamin B12 and congenital malformations (9,19).
No reports linking high doses of vitamin B12 with maternal or fetal complications have been located. Vitamin B12 administration at term has produced maternal levels approaching 50,000 pg/mL with corresponding cord blood levels of approximately 15,000 pg/mL (4,5). In fetal methylmalonic acidemia, large doses of vitamin B12, 10 mg orally initially then changed to 5 mg IM, were administered daily to a mother to treat the affected fetus (40). On this dosage regimen, maternal levels rose as high as 18,000 pg/mL shortly after a dose. This metabolic disorder is not always treatable with vitamin B12: one study reported a newborn with the vitamin B12unresponsive form of methylmalonic acidemia (41).
In summary, severe maternal vitamin B12 deficiency may result in megaloblastic anemia with subsequent infertility and poor pregnancy outcome. Less severe maternal deficiency apparently is common and does not pose a significant risk to the mother or fetus. Ingestion of vitamin B12 during pregnancy up to the RDA either via the diet or by supplementation is recommended.
[*Risk Factor C if used in doses above the RDA.]
Breast Feeding Summary
Vitamin B12 is excreted into human breast milk. In the first 48 hours after delivery, mean colostrum levels were 2431 pg/mL and then fell rapidly to concentrations comparable to those of normal serum (42). One group of investigators also observed very high colostrum levels ranging from 6 to 17.5 times that of milk (2). Milk:plasma ratios are approximately 1.0 during lactation (19). Reported milk concentrations of vitamin B12 vary widely (43,44,45 and 46). Mothers supplemented with daily doses of 1200 g had milk levels increase from a level of 79 to a level of 100 pg/mL (43). Milk concentrations were directly proportional to dietary intake. In a study using 8-g/day supplements, mean milk levels of 1650 pg/mL at 1 week and 1100 pg/mL at 6 weeks were measured (44). Corresponding levels in unsupplemented mothers were significantly different at 1220 and 610 pg/mL, respectively. Other investigators also used 8-g/day supplements and found significantly different levels compared with women not receiving supplements: 910 vs. 700 pg/mL at 1 week and 790 vs. 550 pg/mL at 6 weeks (45). In contrast, others found no difference between supplemented and unsupplemented well-nourished women with 5100 g/day (46). The mean vitamin B12 concentration in these latter patients was 970 pg/mL. A 1983 English study measured vitamin B12 levels in pooled human milk obtained from preterm (26 mothers: 2934 weeks) and term (35 mothers: 39 weeks or longer) patients (47). Milk from preterm mothers decreased from 920 pg/mL (colostrum) to 220 pg/mL (16196 days), whereas milk from term mothers decreased over the same period from a level of 490 to a level of 230 pg/mL.
Vitamin B12 deficiency in the lactating mother may cause severe consequences in the nursing infant. Several reports have described megaloblastic anemia in infants exclusively breast-fed by vitamin B12deficient mothers (48,49,50,51 and 52). Many of these mothers were vegetarians whose diets provided low amounts of the vitamin (49,50,51 and 52). The adequacy of vegetarian diets in providing sufficient vitamin B12 has been debated (53,54 and 55). However, a recent report measured only 1.4 g of vitamin B12 intake/day in lactovegetarians (56). This amount is approximately 54% of the RDA for lactating women in the United States (1). Moreover, a 1986 case of vitamin B12induced anemia supports the argument that the low vitamin B12 intake of some vegetarian diets is inadequate to meet the total needs of a nursing infant for this vitamin (57). The case involved a 7-month-old male infant, exclusively breast-fed by a strict vegetarian mother, who was diagnosed as suffering from macrocytic anemia. The infant was lethargic, irritable, and failing to thrive. His vitamin B12 level was less than 100 pg/mL (normal 180960 pg/mL), but iron and folate levels were both within normal limits. The anemia responded rapidly to administration of the vitamin, and he was developing normally at 11 months of age (57).
The National Academy of Sciences’ RDA for vitamin B12 during lactation is 2.6 g (1). If the diet of the lactating woman adequately supplies this amount, maternal supplementation with vitamin B12 is not needed. Supplementation with the RDA for vitamin B12 is recommended for those women with inadequate nutritional intake. The American Academy of Pediatrics considers maternal consumption of the vitamin to be compatible with breast feeding (58).
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