Feed the Future
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Vitamin B12 Status in Infancy is Positively Associated With Poorer Development and Cognitive Functioning Five Years Later in Nepalese Children

This post was written by Andrew Thorne-Lyman, an Associate Scientist at the Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health and an Adjunct Lecturer at the Center for Human Nutrition, Harvard School of Public Health.
Malnutrition comes in many forms. In recent years, much of the attention in the nutrition world has focused on stunting. Why? One reason is that early childhood stunting is associated with poorer childhood development, educational attainment and ultimately lifetime earnings capacity. [1, 2] One recent estimate placed the global economic cost of growth faltering at USD $178 billion per birth cohort using nominal exchange rates or USD $616 billion at purchasing parity-adjusted exchange rates. [1] Although such impacts are substantial and present a strong economic case for intervention, they likely represent an underestimate of the true cost of early childhood malnutrition, as deficiencies in vitamins, minerals or essential fatty acids can impair brain development and adversely impact health or birth outcomes without necessarily impairing linear growth or the prevalence of stunting.
The brain is the body’s most complex organ and its development in infancy is influenced by many environmental factors, including nurture and stimulation and the availability of the building blocks needed for its development. There is still much to learn about the nutritional influences on brain development during infancy. [3] Yet some micronutrients are widely acknowledged to be of critical importance. Perhaps most salient is iodine deficiency, an easily preventable condition that has been estimated to globally cost 10-15 IQ points at a population level. [4] 
It has been argued that vitamin B12 (cobalamin) may rank among the world’s most prevalent deficiencies as the few natural dietary sources are largely restricted to animal source foods such as fish, meat, milk and eggs, foods that are not widely consumed amongst poor or vegetarian populations. Infants are at particularly great risk when they are born with low stores and their mothers are deficient. Yet, relatively few studies have been undertaken to explore the links between vitamin B12 deficiency and child brain development. Research in low income settings where nutritional deficiencies and adverse child development outcomes are most prevalent has been limited, in part due to the difficulty in measuring both exposures and outcomes. 
A study published last month in the American Journal of Clinical Nutrition (link), and funded by the USAID Feed the Future Innovation Lab for Nutrition, the Research Council of Norway, GC Rieber Funds, and the South-Eastern Norway Regional Health Authority, examined for the first time the prospective association between lower vitamin B12 status in infancy and measures of development later in childhood. [5] Researchers measured cobalamin status using multiple biomarkers among 321 infants in Nepal who were then revisited five years later to administer tests to evaluate different aspects of their development including the Ages and Stages Questionnaire (3rd edition) (ASQ-3) and the Developmental Neuropsychological Assessment, 2nd edition (NEPSY II). Key findings from the study included:
  • Better vitamin B12 status, assessed using three biomarkers, showed a significant positive association with total child development using the ASQ-3 after adjusting for potential confounders.   
  • Higher B12 status was associated with social perception abilities and visuospatial processing skill, measured using the NEPSY II, but not with domains of attention, executive function or sensorimotor functioning. 
  • Only about 15 percent of infants of had cobalamin concentrations below the cutoff for deficiency (<148 pmol/L).
This was an observational study, with key strengths including its prospective longitudinal design, the use of multiple measures of B12 status and child development, and control for confounding. The main limitation was the use of tools that have not yet been formally validated to measure child development in Nepal. 
Implications and Next Steps
The findings of this study are largely aligned with other studies conducted among other age groups and settings. It is also important to note that plausible biological mechanisms for the effects of B12 on the central nervous system and brain have been described elsewhere including a role in myelination. [6, 7] Given the observational design of the study, further research using a randomized trial design is needed to establish the causality of vitamin B12 in infancy on child development outcomes. Still, given the high global prevalence of B12 deficiency, it is worthwhile considering policy options and how food systems could be developed to address this problem. 
Food fortification is an often-discussed policy option for addressing vitamin B12 deficiency on a population level. [8] Dietary diversification with animal source foods is another complementary strategy that can also can address many of the nutrient deficiencies common in settings where consumption of animal source foods is low as many animal source foods are also good sources of iron, zinc and vitamin A. Fish and shellfish are among the richest dietary sources of B12, suggesting a potential role for aquaculture and fisheries, which are sometimes neglected by agricultural strategies. [9] Follow-on work is being conducted in rural Nepal through the USAID Feed the Future Nutrition Innovation Lab to explore the associations between animal source food production and consumption and indicators of child development.    
1. Fink G, Peet E, Danaei G, Andrews K, McCoy DC, Sudfeld CR, et al. Schooling and wage income losses due to early-childhood growth faltering in developing countries: national, regional, and global estimates. The American journal of clinical nutrition. 2016;104(1):104-12.
2. Sudfeld CR, McCoy DC, Danaei G, Fink G, Ezzati M, Andrews KG, et al. Linear growth and child development in low- and middle-income countries: a meta-analysis. Pediatrics. 2015;135(5):e1266-75.
3. Prado EL, Dewey KG. Nutrition and brain development in early life. Nutrition reviews. 2014;72(4):267-84.
4. Delange F. Iodine deficiency as a cause of brain damage. Postgraduate medical journal. 2001;77(906):217-20.
5. Kvestad I, Hysing M, Shrestha M, Ulak M, Thorne-Lyman AL, Henjum S, et al. Vitamin B-12 status in infancy is positively associated with development and cognitive functioning 5 y later in Nepalese children. The American journal of clinical nutrition. 2017;105(5):1122-31.
6. Dror DK, Allen LH. Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Nutrition reviews. 2008;66(5):250-5.
7. Stabler SP. Vitamin B12 deficiency. The New England journal of medicine. 2013;368(21):2041-2.
8. Quay T, Lamers Y. Food fortification with vitamin B12: Potential benefits and open questions. Sight & Life Magazine. 2012;26(2):28-38.
9. Watanabe F. Vitamin B12 sources and bioavailability. Experimental biology and medicine (Maywood, NJ). 2007;232(10):1266-74.