Scientific basis: Globally, vitamin B12 deficiency is one of the most common micronutrient
deficiencies. The only relevant source of vitamin B12 is animal-source foods. Vitamin B12 is
crucial for normal cell division and differentiation and is necessary for the development and
initial myelination of the central nervous system as well as for the maintenance of its
normal function. Deficiency is also associated with impaired infant and child growth.
In a previous clinical trial, we demonstrated that vitamin B12 administration over a period
of six months enhanced growth and neurodevelopment in young Indian children. The overall
effect on growth was significant but small. We saw an effect on both ponderal (weight for age
z scores) and linear (height for age z scores) growth. However, the overall effects were
driven by the effects in the subgroups of children who were wasted, underweight or stunted at
baseline, and no effect in the children who were not malnourished at baseline. This effect
modification was significant for all three (stunting, wasting, and underweight) baseline
variables. Similarly, the effect of the intervention on neurodevelopmental scores was also
strongest in the subgroup of children that were stunted.
We have for the last 15 years undertaken studies on dietary intake and status in women and
children in Bhaktapur, Nepal. In this site, vitamin B12 deficiency is very common. The
objective of the proposed study is to measure to what extent administration of 2 RDA of
vitamin B12 to stunted children from the last half of infancy and for 12 months affect
neurodevelopment, growth and hemoglobin concentration.
Hypothesis: Daily supplementation of 2 RDA of vitamin B12 in young Nepali children for 12
months improves neurodevelopment, growth and hemoglobin concentration.
Study design: Individually randomized placebo controlled, double blind trial. Children will
be identified in the community and stunted children will be randomized to daily receive a
paste containing vitamin B12 or a placebo paste. The paste will be delivered by trained field
workers every day and by the caregivers on Saturdays and public holidays.
Study participants and site: 600 stunted children aged 6 to 11 months in Bhaktapur
municipality and surrounding areas.
Intervention: Daily administration of a paste containing vitamin B12 or placebo for 12
months.
Comparator: Placebo, identical to the vitamin B12 supplements.
Data: Primary outcomes: (i) neurodevelopmental scores measured by Bayley Scales of Infant and
Toddler Development 3rd edition and the Ages and Stages Questionnaire 3rd edition after 6 and
12 months of supplementation (ii) growth measured by change in height for age, weight for age
and weight for height z-score from study start to end study and growth velocity z scores
during the six first and six last months of supplementation (iii) hemoglobin concentration
after 12 months of supplementation. Secondary: (i) cognitive development in children measured
approximately 3 and 6 years after enrollment, (ii) linear and ponderal growth measured 2 and
3 years after enrollment, (iii) hemoglobin concentration measured 2 and 3 years after
enrollment. All secondary outcomes require additional funding.
Relevance for programs and public health: Improved learning ability and growth in young
malnourished children. If the supplementation is effective this will have consequences for
dietary recommendation to malnourished children worldwide. In contrast to most other relevant
nutritional interventions, vitamin B12 is inexpensive and our body has the ability to store
vitamin B12, up to years. Thus, improving the status of this nutrient for a limited time
period may have impact on learning and productivity beyond the time of administration and
help to lift poor children out of the vicious cycle of poverty and malnutrition.