Background Vitamin B12 deficiency is common and affects cell division and differentiation, erythropoiesis, and the central nervous system. Several observational studies have demonstrated associations between biomarkers of vitamin B12 status with growth, neurodevelopment, and anemia. The objective of this study was to measure the effects of daily supplementation of vitamin B12 for 1 year on neurodevelopment, growth, and hemoglobin concentration in infants at risk of deficiency. Methods and findings This is a community-based, individually randomized, double-blind placebo-controlled trial conducted in low- to middle-income neighborhoods in Bhaktapur, Nepal. We enrolled 600 marginally stunted, 6- to 11-month-old infants between April 2015 and February 2017. Children were randomized in a 1:1 ratio to 2 μg of vitamin B12, corresponding to approximately 2 to 3 recommended daily allowances (RDAs) or a placebo daily for 12 months. Both groups were also given 15 other vitamins and minerals at around 1 RDA. The primary outcomes were neurodevelopment measured by the Bayley Scales of Infant and Toddler Development 3rd ed. (Bayley-III), attained growth, and hemoglobin concentration. Secondary outcomes included the metabolic response measured by plasma total homocysteine (tHcy) and methylmalonic acid (MMA). A total of 16 children (2.7%) in the vitamin B12 group and 10 children (1.7%) in the placebo group were lost to follow-up. Of note, 94% of the scheduled daily doses of vitamin B12 or placebo were reported to have been consumed (in part or completely). In this study, we observed that there were no effects of the intervention on the Bayley-III scores, growth, or hemoglobin concentration. Children in both groups grew on an average 12.5 cm (SD: 1.8), and the mean difference was 0.20 cm (95% confidence interval (CI): −0.23 to 0.63, P = 0.354). Furthermore, at the end of the study, the mean difference in hemoglobin concentration was 0.02 g/dL (95% CI: −1.33 to 1.37, P = 0.978), and the difference in the cognitive scaled scores was 0.16 (95% CI: −0.54 to 0.87, P = 0.648). The tHcy and MMA concentrations were 23% (95% CI: 17 to 30, P < 0.001) and 30% (95% CI: 15 to 46, P < 0.001) higher in the placebo group than in the vitamin B12 group, respectively. We observed 43 adverse events in 36 children, and these events were not associated with the intervention. In addition, 20 in the vitamin B12 group and 16 in the placebo group were hospitalized during the supplementation period. Important limitations of the study are that the strict inclusion criteria could limit the external validity and that the period of vitamin B12 supplementation might not have covered a critical window for infant growth or brain development. Conclusions In this study, we observed that vitamin B12 supplementation in young children at risk of vitamin B12 deficiency resulted in an improved metabolic response but did not affect neurodevelopment, growth, or hemoglobin concentration. Our results do not support widespread vitamin B12 supplementation in marginalized infants from low-income countries. Trial registration ClinicalTrials.gov NCT02272842 Universal Trial Number: U1111-1161-5187 (September 8, 2014) Trial Protocol: Original trial protocol: PMID: 28431557 (reference [18]; study protocols and plan of analysis included as Supporting information).

BackgroundVitamin B12 deficiency is one of the most common micronutrient deficiencies and is associated with poor cognitive development and growth. Vitamin B12 is crucial for normal cell division and differentiation, and it is necessary for the development and myelination of the central nervous system. The aim of the present study is to measure the effect of daily supplementation of vitamin B12 on the neurodevelopment and growth of young children in Nepal.Methods/designWe are conducting an individually randomized, double-blind, placebo-controlled trial with 600 marginally stunted children 6–11 months old (length for age less than −1 z-score). Children are randomized to receive a lipid-based paste containing vitamin B12 or placebo daily for 12 months. The main outcomes are changes in growth (z-scores) and in neurodevelopment measured by the Bayley Scales of Infant and Toddler Development, Third Edition, from baseline until the end of the study.DiscussionIf vitamin B12 supplementation benefits early child development and growth, this will have consequences for dietary recommendations for malnourished children worldwide.Trial registrationsClinicalTrials.gov Identifier: NCT02272842. Registered on 21 October 2014.Universal Trial Number: U1111-1161-5187. Registered on 8 September 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1937-0) contains supplementary material, which is available to authorized users.

Background: The Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) is the most widely used developmental assessment tool for infants and toddlers worldwide, but less is known about its psychometric properties and feasibility in low and middle-income countries.Aim: To assess the psychometric properties and feasibility of the Bayley-III when used in a large scale randomized controlled intervention trial in Nepal.Methods: The participating infants were part of a randomized, doubled blind, placebo-controlled trial to measure the efficacy of vitamin B12 supplementation on growth and neurodevelopment. A total of 600 children aged 6–11 months were enrolled and included for developmental assessment. The Bayley-III measures child development across five domains: cognition, receptive and expressive language, fine and gross motor skills. Some items were culturally adapted. To measure and ensure appropriate inter-observer agreement, standardization exercises were performed during the initial training, and double scoring of 7% of test sessions were conducted throughout the study by two examiners.Results: The inter-rater agreement was excellent for both the standardization exercises before the start of the study, and for the quality control throughout the study with intraclass correlation coefficient ranging from 0.95 to 0.99. The internal consistency measured by the Cronbach’s alpha coefficient ranged between 0.57 and 0.87. The subtests raw scores as well as scaled scores were significantly correlated (p < 0.001). The means and SDs of the scaled scores compared with American norms were similar to the distribution in the American sample, with the exception of the receptive (Mean = 7.7, SD = 2.2) and expressive (Mean = 7.3, SD = 1.9) language subtests that were lower than the American norms.Conclusion: The inter-rater reliability between the scorers on the Bayley-III was excellent both during standardization and for the quality control. The distributions for the cognitive and motor subscales are comparable to the American norms, while caution is needed in the interpretation of the language scales. The results suggest that Bayley-III is a feasible tool for the assessment of neurodevelopmental status in nutritional studies in low resource settings such as Nepal. Cultural adaptations, training and standardization are prerequisites for a valid and reliable assessment using the Bayley-III.

Background: Children in low and middle income countries may have many risk factors for poor cognitive development, and are accordingly at a high risk of not reaching their developmental potential. Determinants for cognitive development in early life can be found among biological and socioeconomic factors, as well as in stimulation and learning opportunities.Objective: The present study aimed to identify determinants of cognitive, language and motor development in 6-11 months old Nepalese infants.Methods: Six hundred infants with a length-for-age z-score <-1 were assessed with the Bayley Scales of Infant and Toddler development, 3rd edition (Bayley-III). Information on socioeconomic factors, child and maternal demographics, clinical and biological factors, and the home environment were collected. In a manual stepwise variable selection procedure, we examined the association between selected biological, socioeconomic and stimulation and learning opportunity variables and the Bayley-III cognitive, language and motor development subscale scores in multiple linear regression models. Results:The length-for-age z-scores was positively associated with the cognitive composite score [standardized beta (ß): 0.22, p < 0.001] and the motor composite score [(ß): 0.14, p = 0.001]. Children born with low birth weight (<2500 g) scored significantly lower on all subscale scores. Diarrheal history was associated with poor language composite scores, and females had higher language composite scores than boys [(ß): 0.11, p = 0.015]. Children who had been hospitalized during the first month of life had also lower cognitive and motor composite scores than those who had not been hospitalized. Parental reports of physical punishment and lack of spontaneous vocalization were associated with poor cognitive and language composite

Introduction: Nepal suffered from major earthquakes in April 2015 resulting in great damage to the society. The objective of the current study is to describe the earthquake exposure, the impact on family’s daily life and the symptoms of post-traumatic stress disorder (PTSD) and their association in Nepalese mothers 20 months following the earthquakes. Methods: In a clinical trial in Bhaktapur, Nepal, 558 mothers responded to an inventory on earthquake exposure and the Impact of Event Scale – Revised (IES-R) 20 months after the earthquakes. In multiple linear regression models, we estimated the associations between the earthquake exposure and the impact on the families’ life and the IES-R score. Results: Over 60% reported that the earthquakes had a great deal of negative impact on their family’s life. In 4.7%, close family members died, and in 10.5%, family members were injured. 24% had IES-R scores indicating PTSD symptoms within clinical concern or a possible diagnosis. Lower levels of education were associated with higher scores on the total IES-R. Mothers who report that the earthquakes had a great deal of negative impact had higher total IES-R scores [9.8, 95% CI (5.9, 13.6)] compared to mothers that reported no such negative impact. Mothers with family members who were killed had higher IES-R scores [3.6, 95% CI (1.6, 5.5)] than those with no family members who died. Mothers assisting in rescue efforts had lower IES-R scores [2.8, 95% CI (0.8, 4.8)] than those not assisting. Conclusion: Our study demonstrates high levels of exposure to traumatic events, large negative impact on the everyday life of the families, and a high level of PTSD symptoms. There was a consistent and graded association between the exposure variables and PTSD symptoms. The large impact of the earthquakes on these Nepalese mothers underscore the importance of awareness of mental disorders following major natural catastrophes for marginalized families.