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Background Biomass fuels are still in use for cooking by many households in resource poor countries such as Nepal and is a major source of household air pollution (HAP). Chronic exposure to HAP has been shown to be associated with shorter telomere length in adults. Objectives To measure the association between exposure related to household biomass fuel in infancy and leukocyte telomere length (LTL) at 18–23 months of age among 497 children from Bhaktapur, Nepal. Methods In a prospective cohort study design, we have collected information on household cooking fuel use and several clinical, anthropometric, demographic, and socioeconomic variables. We estimated the association between biomass fuel use and the relative LTL in multiple linear regression models. Results Most of the families (78%) reported liquified petroleum gas (LPG) as the primary cooking fuel, and 18.7% used biomass. The mean relative (SD) LTL was 1.03 (0.19). Children living in households using biomass fuel had on average 0.09 (95% CI: 0.05 to 0.13) units shorter LTL than children in households with no biomass fuel use. The observed association was unaltered after adjusting for relevant confounders. The association between LTL and biomass use was strongest among children from households with ≤2 rooms and without separate kitchen. Significance Exposure to biomass fuel use in early life might have consequences for longevity, and risk of chronic illnesses reflected in shortening of the telomeres. Our findings support the ongoing effort to reduce exposure to biomass fuel in low-resource settings. Impact statements Biomass for cooking is a leading source of household air pollution in low and middle-income countries, contributing to many chronic diseases and premature deaths. Chronic exposure to biomass fuel through oxidative stress and inflammation has been associated with a shortening of the telomeres, a “biological marker” of longevity. This prospective cohort study describes the association between household biomass fuel use and leukocyte telomere length among 497 toddlers. Leukocyte telomere length was significantly shorter among children living in households with biomass fuel than in children from homes where mainly LPG was used for cooking. Clinical Trial registration Clinicaltrials.gov: NCT02272842, registered October 21, 2014, Universal Trial Number: U1111-1161-5187 (September 8, 2014)

The most critical period for brain development is before a child’s second birthday. Standardised tests measuring neurodevelopment are more reliable when administered after this period. Severe vitamin B12 deficiency affects brain development and function. In a randomised, double-blind, placebo-controlled trial in 600 Nepalese infants (6–11 months at enrolment), we found no effect of 2 µg vitamin B12 daily for a year on neurodevelopment. The primary objective of the current study was to measure the effect of the intervention on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) full scale intelligence quotient (FSIQ). We measured the effect on the Bayley Scales of Infant and Toddler Development 3rd edition at age 30–35 months (n 555). At age 42–47 months (n 533), we used the WPPSI-IV and subtests from the Neuropsychological Assessment, 2nd edition (NEPSY-II). We also used the FSIQ to estimate subgroup specific effects. The mean (sd) WPPSI-IV FSIQ in the vitamin B12 group was 84·4 (8·4) and 85·0 (8·6) in the placebo group (mean difference −0·5 (95 % CI -1·97, 0·94), P = 0·48). There were no effect of the vitamin B12 on any of the other neurodevelopmental outcomes and no beneficial effect in any of the subgroups. In conclusion, providing 2 µg of vitamin B12 for a year in infants at risk of vitamin B12 deficiency does not improve preschool cognitive function.

Background There are still many people in the world who prepare their meals on open fires or stoves using solid fuels from biomass, especially in low-and middle-income countries. Although biomass cooking fuels have been associated with adverse health impacts and diseases, the association with child linear growth remains unclear. Objectives In a cohort design, we aimed to describe the association between the use of biomass cooking fuels and linear growth in children aged 18–23 months living in the urban and peri-urban community of Bhaktapur, situated in the Kathmandu valley in Nepal. Methods Caretakers of 600 marginally stunted children aged 6–11 months were interviewed about their source of cooking fuel and other socio-demographic characteristics at enrolment into a randomized controlled trial. Children’s body length was measured when children were 18–23 months old. In linear regression models, we estimated the association between the use of biomass fuel and length-for-age Z-scores (LAZ), adjusted for relevant confounders. We repeated these analyses in pre-defined sub-groups and different percentiles of LAZ using quantile regression models. Results Among study participants, 101 (18%) used biomass as cooking fuel. The association between biomass fuel and LAZ was not statistically significant in the full sample (adjusted regression coefficient: –0.14, 95% CI: −0.28, 0.00). The association was stronger in some of the sub-groups and in the lower tail of the LAZ distribution (those who are stunted), but neither reached statistical significance. Discussion Children from households in poor, urban neighborhoods in Nepal which used biomass fuel for cooking were on average slightly shorter than other children, although the association only approached statistical significance. As this was an observational study, residual confounding cannot be excluded. Further studies are needed to confirm these associations, in particular those seen in certain sub-groups. publishedVersion

Background Biomass fuel use for cooking is widespread in low to middle income countries. Studies on the association between biomass fuel use and cognitive abilities in children are limited. Objective To examine the association between biomass fuel use for cooking and cognitive abilities in Nepalese children at 4 years of age. Methods In a cohort design we have information on biomass fuel use in the households of 533 children in infancy and cognitive abilities when they were 4 years old from a community-based sample. Cognitive abilities were measured by the Wechsler Preschool and Primary Scale of Intelligence, 4th edition (WPPSI-IV) and the NEPSY-II. We examined the associations between biomass fuel use and scores on the WPPSI-IV Full-Scale IQ (FSIQ) (primary outcome), and WPPSI index and NEPSY-II subtest scores in multiple linear regression models. The associations were also examined in predefined subgroups. Results Ninety-nine (18.6%) of the families used biomass fuel for cooking. Children in these families had lower mean FSIQ than children in families with no biomass use (83.3 (95%CI 81.7, 85.0) vs. 85.3 (95%CI 84.5, 86.0)), with a mean difference of −2.2 (95%CI -3.9, −0.5) adjusting for demographics and socio-economic status. The association between biomass fuel use and cognitive abilities was strongest in subgroups of children from households with more than three rooms, with separate kitchen and bedroom, and with higher wealth-score. These interactions were significant for number of rooms in the home (p = 0.04), if the household had separate bedroom and kitchen (p = 0.05), and for the wealth-score (p = 0.03). Conclusion Biomass fuel use for cooking in Nepalese families was associated with lower overall cognitive abilities at 4 years. Uncertainties include exposure misclassification and unmeasured confounding. The associations between biomass fuel use and neurodevelopment in children needs further investigation with more precise measurements of the exposure. publishedVersion

Background Vitamin B12 deficiency is common worldwide and has been associated with poor sleep. The effect of vitamin B12 supplementation on sleep in infants is not known. Aims To measure the effect of daily supplementation of vitamin B12 for one year on sleep in infants at risk of deficiency. Methods This was an individually randomized double-blind placebo-controlled trial in 600 infants in low-to middle-income neighborhoods in Bhaktapur, Nepal of daily supplementation of vitamin B12 for one year. Infants were included if they were 6–11 month year-old and with a length-for-age less than one z-score. Sleep was a predefined, secondary outcome, and was measured by actigraphy including sleep duration at night and total sleep duration (day and night), sleep onset latency (SOL), and wake after sleep onset (WASO). The effect of vitamin B12 on sleep was additionally assessed in predefined subgroups defined by stunting, underweight, vitamin B12 status, low birthweight, anemia and exclusive breastfeeding for 3 months. Results There was no effect of vitamin B12 supplementation on sleep duration at night, total sleep duration, or WASO. There was a small significant negative effect for SOL. None of the included subgroup analyses revealed effect modification on any of the sleep outcomes. Conclusion Overall, vitamin B12 supplementation did not have an effect on sleep in infants or for high-risk subgroups, with the exception of a small negative effect for SOL. The present study does not support vitamin B12 supplementation to improve sleep in infants. publishedVersion

Background Children born with low birth weight (LBW) tend to have lower neurodevelopmental scores compared to term normal birth weight children. It is important to determine factors that influence neurodevelopment in these low birth weight children especially in the first 2–3 years of life that represents a period of substantial brain development. Methods This secondary data analysis was conducted using data from LBW infants enrolled soon after birth in an individually randomized controlled trial (RCT) and followed up till end of 1st year. Neurodevelopmental assessment was done at 12 months of corrected age by trained psychologists using Bayley Scales of Infant and Toddler Development 3rd edition (Bayley-III). Factors influencing cognitive, motor and language scores were determined using multivariable linear regression model. Results Linear growth (i.e., length for age z score, LAZ) [cognitive: Standardized ẞ-coefficient = 2.19, 95% CI; 1.29, 3.10; motor: 2.41, 95% CI; 1.59, 3.23; language: 1.37, 95% CI; 0.70, 2.04], stimulation at home [cognitive: 0.21, 95% CI; 0.15, 0.27; motor: 0.12, 95% CI; 0.07, 0.17; language: 0.21, 95% CI; 0.16, 0.25] and number of diarrhoeal episodes [cognitive: -2.87, 95% CI; -4.34, -1.39; motor: -2.62, 95% CI; -3.93, -1.29; language: -2.25, 95% CI; -3.32, -1.17] influenced the composite scores in all three domains i.e., cognitive, language and motor. While increase in LAZ score and stimulation led to increase in composite scores; an increase in number of diarrhoeal episodes was associated with decrease in scores. Weight for height z scores (WHZ) were associated with motor and language but not with cognitive scores. Additionally, a negative association of birth order with cognitive and language scores was noted. Conclusions The findings indicate the possible importance of promoting nutrition and preventing diarrhoea as well as ensuring optimal stimulation and nurturance at home for enhancing child development in LBW infants.

The demand for cobalamin (vitamin B12) and folate is increased during pregnancy, and deficiency during pregnancy may lead to complications and adverse outcomes. Yet, the status of these micronutrients is unknown in many populations. We assessed the concentration of cobalamin, folate and their functional biomarkers, total homocysteine (tHcy) and methylmalonic acid (MMA), in 561 pregnant women enrolled in a community-based randomised controlled trial in Bhaktapur, Nepal. Plasma concentrations of cobalamin, folate, tHcy and MMA were measured and a combined indicator of vitamin B12 status (3cB12) was calculated. We report mean or median concentrations and the prevalence of deficiency according to commonly used cut-offs, and assessed their association with indicators of socio-economic status, and maternal and dietary characteristics by linear regression. Among the women at gestational week less than 15, deficiencies of cobalamin and folate were seen in 24 and 1 %, respectively. Being a vegetarian was associated with lower plasma cobalamin, and a higher socio-economic status was associated with a better micronutrient status. We conclude that cobalamin deficiency defined by commonly used cut-offs was common in Nepalese women in early pregnancy. In contrast, folate deficiency was rare. As there is no consensus on cut-off points for vitamin B12 deficiency during pregnancy, future studies are needed to assess the potential functional consequences of these low values.

BackgroundCOVID-19 is an infectious disease caused by a newly discovered, with more than 24 million cases worldwide. Geometrically increasing numbers of cases and deaths from COVID 19 in the world, both medical staff and the public have been experiencing psychological problems, which can cause disability and functional impairment of the individual. This study aimed to determine the burden of stress anxiety and depression among health care workers.MethodologyA hospital-based cross-sectional study was carried out among all the employees of Hospital for Children Eye ENT and Rehabilitation Services Bhaktapur during the COVID-19 pandemic lockdown using an online questionnaire. The tools used were adopted from Hospital Anxiety and Depression scale (HADS) Nepali version and WHO Disability Assessment Schedule (WHODAS2.0).ResultsThe mean age (SD) of the participants (n=86) was 32.53 (7.92) years. Male and female participants were equal in number. The point prevalence of anxiety and depression was 25.6% and 14.0%, respectively. Females had a higher prevalence of both anxiety (39.5% vs 11.6%, pConclusionAnxiety and depression during COVID-19 pandemic lockdown were highly prevalent both in clinical and non-clinical employees, without causing significant functional impairment among health care workers.

BackgroundCOVID-19 is an infectious disease caused by a newly discovered coronavirus that is pandemic, with more than 338 thousand cases worldwide. Geometrically increasing numbers of cases and deaths from COVID 19 in the world, both medical staff and the public have been experiencing psychological problems, including anxiety, depression, and stress, which can cause disability and functional impairment of the individual. One of the most stressful situations is the unpredictability of the situation and the uncertainty of when to control the disease and the seriousness of the risk. These challenges and stress can trigger a common mental disorder. This study aimed to determine the burden of stress anxiety and depression among all employees of Eye and ENT hospitals.MethodologyA hospital-based cross-sectional study was carried out among all the employees of Hospital for Children Eye ENT and Rehabilitation Services Bhaktapur during the COVID-19 pandemic lockdown using an online self-administered questionnaire through Google forms. The tools were adopted from Hospital Anxiety and Depression scale (HADS) Nepali version on a Likert's scale of 0 to 3 validated by Risal A. et al. and WHO Disability Assessment Schedule (WHODAS S2.0) on a Likert's scale of 1 to 5 to assess functional impairment.ResultsThe mean age (SD) of the participants (n=86) was 32.53 (7.92) years. Male and female participants was equal in number. The point prevalence of anxiety and depression was 25.6% and 14.0%, respectively. Females had a higher prevalence of both anxiety (39.5% vs 11.6%, pConclusionAnxiety and depression during COVID-19 pandemic lockdown were highly prevalent both in clinical and non-clinical employees, causing mild to moderate functional impairment.

Introduction: There is an increase in the double burden of malnutrition globally, with a particular rise documented in Asia. In Nepal, undernutrition has been prevalent for decades. Today, however, the incidence of overweight and obesity (OWOB) in the country has increased substantially. There is a need to conduct local studies reporting on the concurrent burden of both underweight and OWOB across adult populations. This study addresses this need by describing the distribution of body mass index (BMI) in a defined population of adults living in the peri-urban community of Bhaktapur, Nepal. Material and methods: For this cross-sectional analysis, we used data that were available from 600 women and 445 men whose children were enrolled in an individually randomized, double-blind, placebo-controlled trial assessing the effect of daily vitamin B12 supplementation. Upon enrolment of their 6–11-month old children, mothers and fathers were interviewed about their socio-demographic details. In addition, their weight and height were measured by trained field workers. Each parent's BMI was calculated as the ratio of body weight (in kg) and height squared (in m), expressed as kg/m2, and categorized according to the WHO recommendation. We used linear and multinomial logistic regression models to assess associations between the BMI of the mothers and fathers, and their baseline characteristics. Results: The mean BMI was 23.7 kg/m2 for both the mothers and fathers with a standard deviation (SD) of 3.6 and 3.7, respectively. The proportion categorized as underweight, overweight, and obese was also similar in the two groups with around 5% being underweight, 30% being overweight and 5% being obese. Age was positively associated with BMI in both groups. Those categorized as daily wage earner had a lower mean BMI than those in other occupational groups. Conclusion: Our results contribute to documenting the burden of both under- and overnutrition in a selected group of young adults living in a peri-urban community in Nepal. As Nepal is undergoing an improvement in its economic situation, as well as a nutrition transition, it is important to provide sufficient information to enable timely action, and evidence-based decision-making to prevent a further increase in Nepal's growing double burden of malnutrition. publishedVersion

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)., Tor A. Strand and colleagues measure the effects of daily supplementation of vitamin B12 for one year on neurodevelopment, growth, and hemoglobin concentration in infants at risk of deficiency., Author summary Why was this study done? Many marginalized children fail to reach their cognitive and growth potential. Subclinical vitamin B12 deficiency, which is poor vitamin B12 status without overt clinical symptoms, is common in this population in Nepal. Vitamin B12 deficiency in children is associated with anemia (low hemoglobin concentration), stunted growth, and poor neurodevelopment. What did the researchers do and find? In this population-based, double-blind, randomized controlled trial (RCT), we measured the effects of daily supplementation of vitamin B12 for 1 year in 600 infants. The primary outcomes were neurodevelopment, growth, and hemoglobin concentration. We targeted stunted infants as these children are at risk of vitamin B12 deficiency. Daily supplementation of vitamin B12 for a year resulted in a metabolic profile reflecting substantially improved B12 status (lower total homocysteine (tHcy) and methylmalonic acid (MMA) concentrations) but did not affect neurodevelopment, growth, or hemoglobin concentration. What do these findings mean? In spite of the improved metabolic profile following vitamin B12 supplementation, the findings do not support widespread vitamin B12 supplementation to improve short-term growth, neurodevelopment, or hemoglobin concentration in infants.

Background: The Ages and Stages Questionnaires, Third Edition (ASQ-3) is becoming a widely used developmental assessment tool. The ASQ-3 can be completed by the caregivers (referred to as “mail out”), or by trained personnel under direct observation of the children (referred to as “home procedure”). Aim: The study was carried out to compare results obtained by the ASQ mail out with those of the ASQ home procedure in a community setting of Bhaktapur, Nepal. Methods: Trained fieldworkers (FWs) performed developmental assessment of 134 children aged 9 months in their homes using the ASQ home procedure. A few days before these assessments, mothers were asked to fill in the same ASQ-3 questionnaire. The concordance correlation coefficient (CCC) was calculated to measure their agreement. Result: The agreement between the ASQ mail out and home procedure was fair for the total score (CCC = 0.54). For the sub-scales, the agreement was good for the gross motor (CCC = 0.65), for the remaining subscales agreement was poor (CCC < 0.4). Conclusion: In resource limited setting like Nepal, the ASQ mail out represents an easy method to assess child development by caretakers at home; however, with the poor agreement between different methods of assessments, we cannot conclude that a single method is superior or most optimal and this question should be investigated further. When either of the method home procedure or mail out is opted, the results should be interpreted with cautions. publishedVersion

Background Vitamin 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/design We 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. Discussion If vitamin B12 supplementation benefits early child development and growth, this will have consequences for dietary recommendations for malnourished children worldwide. Trial registrations ClinicalTrials.gov Identifier: NCT02272842. Registered on 21 October 2014. Universal Trial Number: U1111-1161-5187. Registered on 8 September 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1937-0) contains supplementary material, which is available to authorized users.

Background: Sustained social withdrawal in infancy may have organic and nonorganic causes and could hinder normal development. The Alarm Distress Baby (ADBB) scale is a widely validated screening tool of social withdrawal in children 2-24 months. The aim of the current study was to evaluate the full and modified ADBB in Nepalese infants in a community-based study. Methods: We enrolled 600 infants who were video recorded during a pediatric examination. The 36 infants first enrolled were scored by an expert rater, and the subsequent 64 infants were scored by two trained staff with the full ADBB scale. Of the 600 enrolled infants, 597 videos (including the 100 infants scored with the full ADBB) were scored with the modified ADBB (m-ADBB) scale by the trained staff, with 7% double scoring. We measured the interrater agreement and psychometric properties of both scales. Results: In the 64 infants scored with the full ADBB by two raters, the concordance correlation coefficients (CCCs) indicated poor interrater agreement. For the m-ADBB, the CCCs were better indicating acceptable agreement between raters. The greatest lower bound (GLB) for reliability coefficient for the full ADBB scored by an expert rater indicated good internal consistency, whereas the GLB coefficient for the m-ADBB indicated poorer internal consistency. The Spearman correlation coefficient between the total scores of the two versions was 0.82 (P < 0.001). Among the infants scored with the full ADBB, 25% had a score above cutoff (≥5). Scored with the m-ADBB in the full sample, 11.4% of the infants had a score above the suggested cutoff (≥2). In both versions, children achieved high scores on vocalization. Conclusion: Our findings suggest that the m-ADBB is an acceptable approach to achieve adequate interrater agreement in a large community-based study in Nepal. Results indicate high prevalence of social withdrawal in this population. There are, however, uncertainties on the internal consistency of the scales in this setting, and the validity of the scales needs to be investigated further. More effective training strategies for administration and additional cultural-specific instructions could be important measures to explore before implementing the scale further in this setting. Keywords: ADBB; Nepal; feasibility; infant; social withdrawal. Copyright © 2020 Ulak, Ranjitkar, Shrestha, Braarud, Chandyo, Shrestha, Guedeney, Strand and Kvestad. publishedVersion

Background: The Ages and Stages Questionnaire Third Edition (ASQ-3) may be a feasible and cost-effective tool to screen children's development in resource poor settings. We have assessed the feasibility of the ASQ-3 "home procedure" when conducted by fieldworkers in a community-based nutritional interventional trial on early child development in Nepal. Method: Six hundred children aged 6-11 months at risk of stunting were assessed by trained fieldworkers in their homes by the ASQ-3. Three fieldworkers performed standardization exercises and were double scored with a gold standard during the study period. Intraclass correlations (ICCs) were calculated to measure the interrater agreement. The internal consistency was expressed by standardized Cronbach's alphas. The association between total ASQ score and gestation, low birth weight, and stunted children is presented to give an estimate of the construct validity of the tool. Result: Mean scores of the 600 Nepalese children were consistently lower than in the American norm sample. The ICCs from the standardization exercises were initially good to excellent but declined throughout the study period. The standardized alphas for the total score in the different age groups indicate good internal consistency but varied in the subscales. Children who were preterm, children with low birth weight, and children who were stunted scored substantially lower on the total ASQ score than those who were not. Conclusion: Although the ASQ-3 "home procedure" is low at cost and easily accessible in a Nepalese context, the tool requires rigorous and stringent training to achieve acceptable interrater agreement. Further adjustment is required to achieve satisfactory internal consistency. GC Rieber Funds Thrasher Research Fund. Grant Number: 11512

Cobalamin and folate are crucial micronutrients during infancy and they are required for growth and cognitive development. Due to the monotonous and predominantly vegetarian-based complementary feeding and poor maternal micronutrient status, infants from low- and middle-income countries are susceptible to cobalamin deficiency. However, data on plasma cobalamin and folate and the functional markers methylmalonic acid and total homocysteine from breastfed infants in Nepal are still needed. We collected plasma samples from 316 6–11-month-old breastfed infants with a length-for-age of less than minus one z-score and analyzed blood for plasma folate, cobalamin, methylmalonic acid and total homocysteine concentrations. Cobalamin deficiency (plasma cobalamin 10 µmol/L) and methylmalonic acid (>0.28 µmol/L) indicating functional cobalamin deficiency were found among 53% and 75% of the infants, respectively. Based on a combined indicator of cobalamin status, 58% were found to have low cobalamin status. However, folate deficiency (

INTRODUCTION: Vitamin B12 is crucial for normal cell division and differentiation, and necessary for the development and myelination of the central nervous system. Pregnant mothers in resource poor settings are at risk for poor vitamin B12 status. Poor vitamin B12 status in infancy is linked to poor growth and neurodevelopment. Brain development starts from conception, and pregnancy is a period of rapid growth and development for the brain. METHODS AND ANALYSIS: The study is an individually randomised double-blind placebo controlled trial in 800 pregnant Nepalese women randomised in a 1:1 ratio. A daily dose of 50 µg of vitamin B12 or placebo is given to women from early pregnancy, not later than week 15, until 6 months after birth. Weekly visits are conducted in order to record compliance, growth and morbidity. The primary outcomes are scores on the cognitive, language and motor subscales of the Bayley Scales of Infant and Toddler Development, Third Edition, measured at 6 and 12 months of age, and growth (length and weight) measured at 6 and 12 months of age. ETHICS AND DISSEMINATION: National Health and Research Council, Nepal (NHRC 253/2016) and Regional Committee for Medical and Health Research Ethics of Western Norway (2016/1620/REK vest) have approved the study. Investigators who have contributed to the conceptualising, conducting, as well as being involved in the data analyses and manuscript writing will be eligible for authorship and be responsible to share outcomes with different stakeholders through publications and workshops. The results from this study may support new dietary guidelines for Nepalese and possibly South Asian pregnant women that can lead to improved pregnancy outcomes, neurodevelopment and cognitive functioning in children. TRIAL REGISTRATION NUMBER: Universal Trial Number: U1111-1183-4093. TRIAL REGISTRATION: clinicaltrials.gov: NCT03071666. Protocol date: version 1.2, 1 June 2017. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. KEYWORDS: Cobalamin; Nepal; Pregnancy; Supplementation Funding This study has been granted funding from the Centre of Excellence Scheme and the University of Bergen (UiB), Norway to the Centre for Intervention Science in Maternal and Child Health (CISMAC; project number 223269).