This case of a 5-month-old Italian infant with severe pancytopenia and neurological impairment born to a vegan mother who had received B12 supplementation during pregnancy but not during lactation seems to be particularly interesting for various reasons.
The first is the fact that it is very important to be aware that vitamin B12 and iron deficiency can frequently occur in infants born to vegan mothers (who are increasing in number in these last years) and these deficits are a preventable cause of neurodevelopmental delay. The second is the fact that the mother was treated with a multivitamin preparation that provided 2.5
μg/day of vitamin B12, an amount that is quite similar to the 2.6
μg/day recommended for pregnant women by health authorities [5
]. Despite this, the infant showed clinical signs clearly attributable to vitamin B12 deficiency (such as a failure to thrive and pallor) in the first months of life, which suggests that the recommended amount of vitamin B12 is not enough to avoid the early development of disease in the infants of strictly vegetarian women. Moreover, the concomitant presence of substantial iron deficiency modified the characteristics of the anemia and may also justify several symptoms (i.e., lethargy and irritability) and signs (i.e., demyelination and poor developmental progression). Instead of significant megaloblastosis, we found red blood cells with a normal MCV, a finding that initially made it more difficult to reach a correct diagnosis. This also underlines the need to determine vitamin B12 and iron levels in all cases of otherwise unexplained severe anemia occurring in the first months of life. Finally, the MRI data confirmed the view of Lovblad et al
] that the most important neurological damage due to vitamin B12 deficiency is reduced myelination, which can persist for several months even after the start of supplementation therapy.
The possible development of severe clinical signs of vitamin B12 deficiency in infants born to undernourished mothers has been repeatedly described. A recent review of 134 cases of childhood vitamin B12 deficiency published over the last 20
years found that 69 were due to maternal B12 deficiency, and that more than 50% of these were directly related to an inadequate consumption of meat and other animal products such as that usually characterising strict vegetarians [7
]. The children of women with low vitamin B12 levels during pregnancy and lactation may have smaller stores of the vitamin at birth [8
], and its concentration in breast milk is likely to be low [9
]. Such children tend to develop signs of vitamin B12 deficiency generally not before the fourth month of life, although neonatal cases have also been reported [10
Childhood vitamin B12 deficiency is probably significantly more frequent than usually thought. Various studies carried out in the developing world or in countries where vegetarian diets are common have shown that a large number of mothers and children have low serum vitamin B12 levels that closely correlate with albeit mild clinical problems mainly involving the central nervous system. It has been reported that approximately one-third of low-income women and children in Guatemala have deficient (<148 pmol/L) or marginal (148–220 pmol/L) plasma vitamin B12 concentrations, and that the lowest levels are strictly related to poor growth and development [11
]. In India, where people tend to be vegetarians, vitamin B12 deficiency during pregnancy is common [12
], and the infants of deficient mothers are affected by a syndrome including mild developmental regression and alterations in skin pigmentation [13
Vitamin B12 supplementation in pregnant and lactating women, and the greater use of complementary vitamin B12-rich foods in infants aged >6
months are frequently suggested strategies for reducing the risk of major clinical signs of deficiency [14
]. However, it is difficult to implement preventive programs in the developing world as economic problems may profoundly impact the consumption of meat and other animal products. In industrialised countries, where the problem is less frequent and only vegans are at risk, a correct evaluation of the mother’s nutritional history and systematic supplementation during pregnancy and lactation can easily prevent the problem. Unfortunately, there is a lack of information concerning the optimal formulation of micronutrient supplements for pregnant women, and the need to continue their administration after delivery is not recognised in many situations in which maternal and infant health might benefit [16
Despite a low vitamin B12 intake and significant deficiency, pregnant women generally show no related signs or symptoms because they usually consume large amounts of vegetables containing high folate concentrations that may mask the hematological effects of vitamin B12 deficiency. Furthermore, the neuropsychiatric symptoms of vitamin B12 deficiency are usually mild in adolescents and adults, and may therefore be overlooked.
On the contrary, young infants frequently have multiple deficiencies and so, particularly when they are exclusively breastfed, they develop hematological disease with anemia and (in the most severe cases) pancytopenia. As the developing central nervous system seems to be more sensitive to vitamin B12 deficiency than that of adults [17
], breastfed infants born to vegan mothers may experience substantial neurological damage with developmental delay, irritability, tremor and convulsions. Furthermore, these may persist and lead to long-term cognitive and developmental delay despite adequate therapy and the complete disapperance of hematological problems [18
As in our case, treated vitamin B12 and iron deficient infants tend to improve rapidly: hematological values quickly return to normal, and the neurological signs progressively decrease. However, in most of the severe cases described thus far [18
], some neurological problems may be permanent.
In conclusion, this case underlines the importance of adequate maternal vitamin B12 intake during pregnancy by means of supplementation which, in the case of vegans, should be significantly greater than that usually given. Moreover, the supplementation should be continued during lactation in order to avoid the development of signs of deficiency that may be associated with persistent neurological problems in infancy. This case also highlights the need to consider vitamin B12 deficiency in infants with severe anemia even if their hematological parameters do not indicate megaloblastic anemia because the concomitant presence of substantial iron deficiency may modify the characteristics of the anemia.