Search

INTRODUCTION The World Health Organization (WHO) estimates that globally ~293 million young children and 468 million non-pregnant women suffer from anemia, among which ~50% are estimated to be attributable to [...], BACKGROUND/OBJECTIVES: Iron deficiency anemia is a widespread public health problem, particularly in low- and middle- income countries. Maternal iron status around and during pregnancy may influence infant iron status. We examined multiple biomarkers to determine the prevalence of iron deficiency and anemia among breastfed infants and explored its relationship with maternal and infant characteristics in Bhaktapur, Nepal. SUBJECTS/METHODS: In a cross-sectional survey, we randomly selected 500 mother-infant pairs from Bhaktapur municipality. Blood was analyzed for hemoglobin, ferritin, total iron-binding capacity, transferrin receptors and C-reactive protein. RESULTS: The altitude-adjusted prevalence of anemia was 49% among infants 2-6-month-old (hemaglobin (Hb) < 10.8 g/dl) and 72% among infants 7-12-month-old (Hb < 11.3 g/dl). Iron deficiency anemia, defined as anemia and serum ferritin < 20 or < 12 [micro]g/l, affected 9 and 26% of infants of these same age groups. Twenty percent of mothers had anemia (Hb < 12.3 g/dl), but only one-fifth was explained by depletion of iron stores. Significant predictors of infant iron status and anemia were infant age, sex and duration of exclusive breastfeeding and maternal ferritin concentrations. CONCLUSIONS: Our findings suggest that iron supplementation in pregnancy is likely to have resulted in a low prevalence of postpartum anemia. The higher prevalence of anemia and iron deficiency among breastfed infants compared with their mothers suggests calls for intervention targeting newborns and infants. European Journal of Clinical Nutrition (2016) 70, 456-462; doi: 10.1038/ejcn.2015.199; published online 2 December 2015

Abstract Background Promotion of proper breastfeeding practices for the first six months of life is the most cost-effective intervention for reducing childhood morbidity and mortality. However, the adherence to breastfeeding recommendations in many developing countries is not satisfactory. The aims of the study were to determine breastfeeding and infant feeding patterns at nine months of age and to assess factors influencing exclusive breastfeeding practices. Methods In Bhaktapur, Nepal, we carried out a cross-sectional survey of 325 infants who came for measles vaccination at the age of nine months. Mothers were interviewed on details regarding feeding of their child and health since birth. Results Three quarters of all mothers reported that they did not receive any information on breastfeeding during the antenatal visit. Two hundred and ninety five (91%) mothers gave colostrum and 185 (57%) initiated breastfeeding within one hour of delivery. The prevalence of exclusively breastfeeding at 1, 3 and 6 months were 240 (74%), 78 (24%) and 29 (9%), and partial feeding was initiated in 49 (15%), 124 (38%) and 257 (79%) babies, respectively. The main reason, according to the mother, for introducing other foods before six months of age was insufficient breast milk. In logistic regression analyses, mother's knowledge on how long child should be given only breast milk and not living in joint families were associated positively with exclusive or predominant breastfeeding for four months or beyond. Conclusions Despite the high proportion of mothers who initiated breastfeeding immediately after birth, continuation of exclusive breastfeeding for up to six months was not common. Very few mothers received any information on breastfeeding during the antenatal visit, indicating a need for counseling on exclusive breastfeeding. Possible options for this counseling could be during antenatal visits and at regular clinic visits for vaccination.

Objective: Different definitions of thyroid dysfunction during pregnancy may lead to under or overtreatment. The aims of this study were to (1) define population-based pregnancy-specific reference ranges for thyroid dysfunction during early pregnancy in Nepal and assess the impact of antibody positivity, (2) quantify the diagnostic impact of population-based reference ranges compared with current practice and (3) assess the determinants of thyroid function and antibody positivity., Methods: A total of 800 healthy pregnant women aged 20-40 years in the Bhaktapur municipality were included. Population-based reference ranges for thyroid hormones levels were defined as 2.5th and 97.5th percentiles using competitive immunoluminometric assay design. Thyroid disease cases and those with recommended treatment indications were calculated using current non-pregnancy new reference ranges. Multivariate regression analyses were performed to identify the determinants of thyroid hormones and antibody levels., Results: Median gestational age was 11 weeks. The reference interval was 0.05-3.69 µLU/mL for thyroid stimulating hormone (TSH) and 8.89-15.28 pg/mL for free tetraiodothyronine (fT4) after excluding thyroid peroxidase antibody-positive women. Compared with the current non-pregnancy reference ranges, the new calculations increased the number of women who required treatment from 5 to 12 (0.9% increase). We identified 19 women (2.4%) who were positive for TSH receptor antibody (TRAb). We could not identify the determinants of TRAb positivity, and TRAb positivity was not associated with TSH or fT4 levels., Conclusions: We found meaningful changes using population-based pregnancy-specific TSH and fT4 reference intervals and encourage further studies in other low- and middle-income settings. Our findings suggest that population screening for TRAb is not clinically meaningful., Trial Registration: Clinical Trial Registration: U1111-1183-4093., (© 2024 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background: The Ages and Stages Questionnaire 3rd edition (ASQ-3) could be a feasible tool in resource-poor settings. Little is known on the relationship between scores on the ASQ-3 and later intellectual abilities in these settings., Aims: To examine the relationship between ASQ-3 scores during the first and second year of life and intellectual abilities at 4 years of age in Nepalese children., Methods: In a cohort of 600 children at-risk of stunting, the ASQ-3 was performed at 6-11 and 18-23 months, and the Wechsler Preschool and Primary Scales of Intelligence, fourth edition (WPPSI-IV) at 4 years. We examined the relationship between the ASQ-3 scores and WPPSI-IV full scale IQ (FSIQ) using Spearman correlation coefficients and linear regression models., Results: Correlations between ASQ-3 total scores and FSIQ was 0.17 (95% CI 0.07, 0.27) at 6-11 and 0.34 (95% CI 0.26, 0.44) at 18-23 months explaining 2 and 12% of the variance respectively. Except for the communication subscale at 18-23 months with moderate correlations, correlations between the ASQ-3 subscales and FSIQ were weak., Conclusion: Our findings suggest a modest relationship between ASQ-3 scores in early childhood and intellectual abilities at 4 years., (© 2024. The Author(s).)

Background: Vitamin B 12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B 12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality., Objectives: The study aims to determine the effect of vitamin B 12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B 12 deficiency., Methods: The study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 -11 mo, who were supplemented with 2 μg (2-3 recommended daily allowances) vitamin B 12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B 12 status, hemoglobin, sex, and growth indices., Results: LTL at end-study did not differ between the vitamin B 12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (-0.14, 0.21). There was no effect of vitamin B 12 on LTL in any of the subgroups., Conclusions: Providing daily vitamin B 12 for 1 y during infancy in a population at risk of vitamin B 12 deficiency does not affect LTL. This trial was registered at clinicaltrials.gov as NCT02272842., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: Sleep undergoes major changes during the first year of life, but the characteristics of sleep among infants in low and middle-income countries are not well documented. This study describes sleep characteristics and changes in sleep patterns in infants at 6 and 12months of age from Bhaktapur, Nepal., Methods: This was a community-based longitudinal study comprising 735 infants. Sleep characteristics were obtained by interview with the mother using the Brief Infant Sleep Questionnaires. The stability of sleep duration and night awakenings were estimated by logistic regression analysis., Results: Cosleeping in the parent's bed at 6 and 12months of age was almost universal (>97%). At 6months of age, 254 (35%) and at 12months of age, 341 (46%) infants had a total 24-hour sleep duration <12 hours. Night awakenings >3 times per night were common (65%) both at 6 and 12months of age. Infants with frequent nightly awakenings at 6months had increased odds of frequent nightly awakenings at 12months (OR=2.2; 95% CI: 1.6, 2.9). Very few (<3%) mothers reported sleep problems in their infants at 6 and 12months of age., Conclusions: Cosleeping was almost universal among Nepalese infants, and very few of the mothers reported sleep problems in their infants. Infants at 6 and 12months had similar patterns for both sleep duration and nocturnal awakenings. For infants, there were increased odds of having similar sleep duration and nocturnal awakening at 6 and 12months., Competing Interests: Declaration of conflicts of interest The authors declare that there are no conflicts of interest regarding commercial or any financial issues., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Social withdrawal in infants may be a signal of distress and a precursor for non-optimal development., Objective: To examine the relationship between infant social withdrawal and neurodevelopment up to 4 years in Nepalese children., Methods: A total of 597 Nepalese infants 6-11 months old were assessed with the modified Alarm Distress Baby Scale (m-ADBB), and of these, 527 with the Bayley Scales of Infant and Toddler Development 3rd edition (Bayley-III) during early childhood, and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) and NEPSY-II subtests at 4 years. We examined whether social withdrawal defined by the m-ADBB was associated with neurodevelopmental scores in regression models., Results: Children socially withdrawn in infancy had lower Bayley-III language scores (-2.6 (95% CI -4.5, -0.7)) in early childhood. This association seems to be driven by the expressive communication subscale (-0.7 (95% CI -1.0, -0.3)), but not the receptive communication subscale (-0.2 (95% CI -0.6, 0.1)). There were no differences in the other Bayley-III scores or the WPPSI-IV and NEPSY-II scores at 4 years in children who were socially withdrawn or not., Conclusion: Social withdrawal in infancy was reflected in early language development but not cognitive functioning at 4 years., (© 2024. The Author(s).)

Background: Vitamin B12 is required for healthy infant growth and development, but low and marginal vitamin B12 status is endemic in low-income and middle-income countries. We aimed to measure the effect of vitamin B12 supplementation from early pregnancy until 6 months post partum on infant growth and neurodevelopment., Methods: In this community-based, double-blind, placebo-controlled trial, we randomly assigned (1:1) 800 pregnant women (aged 20-40 years) who were up to 15 weeks pregnant-recruited from home visits and outpatient departments at three hospitals in Nepal-to daily supplementation with 50 μg oral vitamin B12 or placebo until 6 months postpartum. Independent scientists generated the list that linked allocation to participants' study identification number. Participants were masked to group assignment and all investigators were masked until data cleaning was completed. The primary outcomes were length-for-age Z score (LAZ) at age 12 months and the cognitive composite score of the Bayley Scales of Infant and Toddler Development (3rd edition) at age 6 months and 12 months. The primary and secondary outcomes, including adverse events, were assessed in the intention-to-treat population, for all participants with available outcome data. This trial is registered with ClinicalTrials.gov, NCT03071666., Findings: 800 eligible pregnant women were enrolled in the trial between March 28, 2017, and Oct 15, 2020, with 400 women randomly assigned to each group. Follow-up was completed on May 18, 2022. At baseline, 569 (71%) of 800 women had plasma vitamin B12 indicating low or marginal status (<221 pmol/L). We found no effect of vitamin B12 on the primary outcomes. The mean LAZ at age 12 months were -0·57 (SD 1·03) in the B12 group and -0·55 (1.03) in the placebo group (366 infants in the vitamin B12 group vs 363 infants in the placebo group) with a mean difference of -0·02 (95% CI -0·16 to 0·13). The mean cognitive composite scores were 97·7 (SD 10·5) in the B12 group and 97·1 (10·2) in the placebo group, with a mean difference of 0·5 (95% CI -0·6 to 1·7) measured in 364 and 361 infants. Stillbirths or infant deaths occurred in three (1%) of 374 women in the vitamin B12 group and nine (2%) of 379 women in the placebo group., Interpretation: Although vitamin B12 deficiency was prevalent in our study population and vitamin B12 supplementation from early pregnancy substantially improved vitamin B12 status, supplementation did not improve infant growth or neurodevelopment. Our findings support the current WHO recommendations of no routine vitamin B12 supplementation during pregnancy., Funding: Research Council of Norway., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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)., (© 2022. The Author(s).)

Aim: In a Nepalese setting, to measure the reliability of the Test of Infant Motor Performance (TIMP) and its ability to predict development scores at 6 months., Methods: Nepalese infants (n = 705) were assessed by the TIMP when they were 8-12 weeks old and the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at 6 months. Inter-rater agreement was expressed by intraclass correlation coefficients (ICCs), the internal consistency by Cronbach's alphas and Pearson correlation coefficients. Predictive ability was estimated in linear regression models., Results: Inter-rater agreement was excellent (ICCs > 0.93). Alphas for the TIMP total scores were 0.76 for infants born to term and 0.72 in those born preterm. Correlation coefficients between TIMP total and Bayley-III subscale-scores ranged from 0.05 to 0.28 for term infants and from 0.15 to 0.43 for preterm infants. Using American norms, 56.3 % had TIMP scores within average and 43.7 % below average range. Bayley-III subscale scores were lower in children with TIMP scores below the average range, with the strongest estimates for Gross motor and Socio-emotional development., Interpretation: The reliability of the TIMP was acceptable, and the TIMP could be a feasible tool to monitor infant motor development in low-resource settings. Properties of the TIMP differed according to gestational age., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jaya S. Silpakar, Suman Ranjitkar, Catherine Schwinger, Merina Shrestha, Ram K. Chandyo and Manjeswori Ulak reports financial support was provided by Research Council of Norway through its Centres of Excellence scheme (project number 223269). Manjeswori Ulak reports financial support was provided by University of Bergen (UiB), Norway, to the Centre for Intervention Science in Maternal and Child Health (CISMAC)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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 B 12 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 B 12 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 B 12 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 B 12 on any of the other neurodevelopmental outcomes and no beneficial effect in any of the subgroups. In conclusion, providing 2 µg of vitamin B 12 for a year in infants at risk of vitamin B 12 deficiency does not improve preschool cognitive function.

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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Bayley Scales of Infant and Toddler Development is widely used worldwide. The objective of the current study was to measure the stability of the Bayley Scales during early childhood and its relationship with intellectual abilities at four years in young Nepalese children., Methods: In a prospective cohort we used the Bayley 3rd edition to measure early child development in 529 Nepalese children at 6-11, 18-23 and 30-35 months. At four years, we used the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) to measure intellectual abilities. We expressed the stability of the Bayley scores by intraclass correlation coefficients (ICCs) and concordance correlation coefficients (CCCs). The relationship between the Bayley scores and the WPPSI full-scale IQ (FSIQ) at four years was examined in regression models., Results: The ICCs between the Bayley scores across timepoints were 0.01 (95 % CI -0.06, 0.04), 0.19 (95 % CI 0.15, 0.26) and 0.22 (95 % CI 0.17, 0.28) for the Cognitive, Language and Motor composite scores. The CCC for the composite scores ranged from 0.05 to 0.20 between 6 and 11 and 30-35 months and from 0.20 to 0.36 between 18 and 23 and 30-35 months. The Bayley scores at 6-11, 18-23 and 30-35 months explained 3 %, 20 % and 36 % of the variation of the FSIQ., Conclusion: The stability of the Bayley scales is poor in early childhood, and its relationship with future intellectual abilities is poor in infancy but improves slightly with age in early childhood. Findings from this large community-based cohort of healthy at-risk children are relevant when measuring early child development worldwide., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The COVID-19 pandemic has affected many aspects of daily life worldwide, but the impact may be higher for impoverished populations. The main aim of this study is to describe the impact of the COVID-19 pandemic on different aspects of daily life in mothers in Nepal. We included 493 mothers of children aged 54-71 months participating in a randomized controlled trial on vitamin B12 supplementation. Mothers answered questions regarding the exposure and impact of the pandemic on their daily lives, and pandemic-related worries and sleep problems. We examined the extent to which worry, and sleep problems differed between mothers according to their exposure to COVID-19, socioeconomic status, and previous symptoms of depression. The mean age (SD) of the mothers was 32.3 (4.6) years and 54% had education below the secondary level. Of the mothers, 5.4% had either been exposed to someone who had tested positive or who had a family member with COVID-19. One-third of the participants responded that the pandemic had affected their economic situation, employment, and family life to a great deal. Both mothers and fathers with educational levels above 10 years or households with higher socioeconomic status had significantly higher average worry scores (maternal p = 0.020 and paternal p = 0.005). Mothers with a history of symptoms of depression had significantly more worry-related sleep problems during the pandemic (p = 0.020) than those without a history of depressive symptoms. Our study underlines the negative impact of the COVID-19 pandemic on diverse aspects of everyday life of mothers in Nepal., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Ranjitkar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Trial Registration: clinicaltrials.gov: NCT02272842., Universal Trial Number: U1111-1161-5187., Competing Interests: Conflict of interest None reported., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© The Author(s) 2021.)

Background: One-carbon metabolism (OCM) refers to the transfer of methyl groups central to DNA methylation and histone modification. Insufficient access to methyl donors and B-vitamin cofactors affects epigenetic maintenance and stability, and when occurring in early life may impact future health and neurodevelopment., Objective: The objective of this study was to examine the relative associations between one-carbon metabolites in Nepalese mother-infant pairs and child cognition measured at 5 y of age., Methods: This is a cross-sectional study from Bhaktapur, Nepal, in a population at high risk of subclinical B-vitamin deficiencies and cumulative infection burden. Venous blood samples from 500 mother-infant pairs were collected when the infants were 2 to 12 mo old, and metabolite concentrations measured by microbiological assays and GC-tandem MS. We re-enrolled 321 of these children at 5 y and assessed cognition by the Ages and Stages Questionnaire, 3rd edition, and subtests from the Developmental Neuropsychological Assessment, 2nd edition (NEPSY-II). The associations of the independent metabolites or unobserved metabolic phenotypes (identified by latent class analysis) with the cognitive outcomes were estimated by seemingly unrelated regression. We explored direct and indirect relations between the OCM pathway and the cognitive outcomes using path analysis., Results: Infant cystathionine concentration was inversely associated with 4 cognitive outcomes (standardized βs ranging from -0.22 to -0.11, P values from <0.001 to 0.034). Infants with a metabolic phenotype indicating impaired OCM and low vitamin B-12 status had poorer cognitive outcomes compared with infants with normal OCM activity and adequate vitamin B-12 status (standardized βs ranging from -0.80 to -0.40, P < 0.001 and 0.05). In the path analysis, we found several OCM biomarkers were associated with affect recognition through infant plasma cystathionine., Conclusions: Elevated plasma cystathionine during infancy reflects a metabolic phenotype of impaired OCM and low vitamin B-12 status and is associated with poorer cognitive function when the children are 5 y old., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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)., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: AMC and PMU are paid employees at Bevital AS.

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., (Copyright © 2020 Shrestha, Schwinger, Hysing, Chandyo, Ulak, Ranjitkar, Kvestad, Sharma, Shrestha and Strand.)

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/m 2 , 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/m 2 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., (Copyright © 2020 Schwinger, Chandyo, Ulak, Hysing, Shrestha, Ranjitkar and Strand.)

Cysteine is a semi-essential amino acid that has been positively associated with growth in children. However, transgenerational effects remain unclear. The aim of this analysis was to assess whether maternal plasma total cysteine (tCys) concentration is associated with various growth indicators in infants living in peri-urban settings in Bhaktapur, Nepal. We used data from the 561 mothers enrolled in an ongoing randomized controlled trial. We built linear regression models to evaluate the associations between maternal tCys and birth weight, length-for-age Z-scores (LAZ) and weight-for-length Z-scores (WLZ) at birth and six months of age. Maternal tCys was inversely associated with birth weight among boys after adjusting for confounders ( p < 0.05). In addition, there was a negative association between maternal tCys and LAZ at birth ( p < 0.01). No associations between maternal tCys and the other anthropometric indicators were found significant, although there was a tendency for maternal tCys to be associated positively with WLZ at birth among girls ( p < 0.10). This is a first study evaluating transgenerational relation of tCys on growth in infants. Further, larger and more comprehensive studies are needed to determine if and how maternal tCys alters child growth.

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., (Copyright © 2020 Ulak, Ranjitkar, Shrestha, Braarud, Chandyo, Shrestha, Guedeney, Strand and Kvestad.)

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 scores, respectively. The statistical models with the various subscale scores as dependent variables explained between 8 to 16 percent of the variability in the cognitive developmental outcomes., Conclusion: Our findings reveal important determinants for developmental scores in infancy, and underline the role of biological risk factors faced by marginalized children in low and middle income countries such as in Nepal., (Copyright © 2019 Ranjitkar, Hysing, Kvestad, Shrestha, Ulak, Shilpakar, Sintakala, Chandyo, Shrestha and Strand.)

Aim: To estimate the extent to which maternal and paternal height modify the association between length-for-age Z-score (LAZ) and neurodevelopmental outcomes assessed by the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III)., Methods: Baseline data from a clinical trial in 600 Nepalese infants aged six to 11 months with LAZ less than -1 were utilised. The primary exposure was the LAZ score, interaction variables were maternal and paternal height, and the outcomes were Bayley-III cognitive, language and motor scaled scores. Linear regression and generalised additive model (GAM) were used to identify potential interactions., Results: Linear regression analysis stratified by parental height categories showed that association between unit increase in LAZ and cognitive scaled score differed across maternal (normal height: ß 1.16, 95% CI; 0.75, 1.57 and short height: ß 0.67, 95% CI; 0.28, 1.05) and paternal (normal height: ß 1.32, 95% CI; 0.91, 1.72 and short height: ß 0.61, 95% CI; 0.03, 1.18) height categories. Maternal height also modified the association between LAZ and fine motor scaled score., Conclusion: The association between LAZ and neurodevelopmental outcomes was attenuated when maternal and paternal height was taken into account. Parental stature should be considered when using LAZ as a proxy for neurodevelopment among infants., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

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., (© 2019 John Wiley & Sons Ltd.)

Background: Many young children in developing countries do not reach their developmental potential. Traditional methods for assessing developmental outcome are time consuming, thus, physiological measures that can contribute to the prediction of developmental outcomes in high risk groups have been suggested. Vagally mediated heart rate variability (vmHRV) is considered a neurophysiological or peripheral proxy for prefrontal and executive functioning and might serve as a supplement for traditional measurements of developmental status and as a potential useful risk indicator., Aim: In the present study, we wanted to describe the vmHRV in Nepalese infants and relate it to the Bayley Scales of infant and toddler development, 3. edition (Bayley-III) subscales., Methods: 600 Nepalese infants were included in the study. At 6-11 and 17-24 months, we measured neurodevelopmental and socio-emotional outcomes by the Bayley-III. Inter-beat intervals were recorded at two measurement points when the children were 17-24 months., Results: There was a high intraclass correlation between HRV indices generated from the two measurement points. No significant associations between vmHRV and Bayley-III sub scales were found at any time., Conclusion: This study is the first to describe vmHRV in healthy infants and the relationship between Bayley-III scores. Our results suggest that vmHRV is not associated with measures of general development in infancy.

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.

Background: Many children worldwide have poor vitamin B12 status. The objective of this study was to estimate association between maternal and infant vitamin B12 status and long-term growth., Methods: We randomly selected 500 Nepali mother-infant pairs and measured maternal intake and infant and maternal vitamin B12 status using plasma cobalamin, total plasma homocysteine, and methylmalonic acid concentrations. We revisited available children when they were 5 years old and measured growth. The associations between intake and maternal and infant markers of vitamin B12 and growth were estimated in multiple linear regression models adjusting for relevant confounders (n = 331)., Results: Maternal vitamin B12 intake and status and vitamin B12 status in infancy predicted linear growth at 5 years of age, but not during infancy. Each microgram increase in the vitamin B12 intake of the mother during infancy was associated with an increase in height of 0.4 (0.2, 0.6) height-for-age z-scores and 1.7 (0.7, 2.7) cm around the child's fifth birthday., Conclusion: Vitamin B12 status and intake in early life is an important determinant for linear growth at school age. Our findings should be verified in randomized, placebo controlled trials before translated into public health recommendations.

Background: Nutrient deficiencies limit the growth and turnover of intestinal mucosa, but studies assessing whether specific nutrients protect against or improve environmental enteric dysfunction (EED) are scarce. We aimed to investigate associations between nutrient intake and EED assessed by lactulose:mannitol (L:M) ratio, anti-1-antitrypsin, myeloperoxidase (MPO), and neopterin (NEO) among children 9-24 months in Bhaktapur, Nepal., Methods: Among 231 included children, nutrient intake was assessed monthly by 24 h recalls, and 3-month usual intake was estimated using Multiple Source Method. Associations between nutrient intake and L:M ratio (measured at 15 months) were assessed using multiple linear regression, while associations between nutrient intake and fecal markers (measured quarterly) were assessed using Generalized Estimating Equations (GEE) models., Results: We found that associations between nutrient intake from complementary food and L:M ratio, alpha-1-antitrypsin (AAT), MPO and NEO were generally negative but weak. The only significant associations between nutrient intake (potassium, magnesium, phosphorous, folate, and vitamin C) and markers for intestinal inflammation were found for MPO., Conclusion: Negative but weak associations between nutrient intake and markers of intestinal inflammation were found. Significant associations between several nutrients and MPO might merit further investigation.

Objectives: Environmental enteropathy (EE) is likely associated with growth retardation in children, but the association between EE and length velocity z score (LVZ) has not been investigated. The objective of the study was to assess associations between fecal markers for intestinal inflammation and LVZ and whether these associations were influenced by micronutrient adequacy among 9 to 24 months old children in Bhaktapur, Nepal., Methods: Data were divided into 5 time slots (9-12, 12-15, 15-18, 18-21, and 21-24 months). Anthropometric measurement and dietary assessment (by 24 hour recall) were performed monthly. Mean nutrient density adequacy was calculated based on nutrient density adequacy of 10 micronutrients (thiamin, riboflavin, niacin, vitamin B6, folate, vitamin C, vitamin A, calcium, iron, and zinc). Anti-1-antitrypsin (AAT), myeloperoxidase (MPO), and neopterin (NEO) were measured in stool samples collected at the beginning of each time slot. An EE score was calculated based on all 3 fecal markers. Associations between AAT, MPO, NEO and EE score and LVZ were assessed by multiple linear regression analyses and Generalized Estimating Equations models., Results: Associations between fecal markers and EE score and LVZ were generally weak. EE score and MPO for 3-month and MPO for 6-month growth periods were significantly associated with LVZ from 9 to 24 months. These associations were slightly modified by mean nutrient density adequacy., Conclusions: EE score and MPO were significantly associated with LVZ in 9 to 24 months old Nepali children. Further studies to establish the usefulness of AAT, MPO, and NEO in assessing EE and growth retardation are warranted.

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: Long chain polyunsaturated fatty acids (LCPUFA) especially docosahexaenoic acid (DHA) and arachidonic acid (AA) are crucial for normal brain development in utero and in early infancy. Data on fatty acid status and cognitive development in infants and children from low-income countries are scarce., Methods: We examined the association between the DHA and AA status in infancy (n = 320) and developmental status and cognitive functioning five years later. At five years of age, we measured development by the Ages and Stages Questionnaire 3rd. ed. (ASQ-3) and cognitive functioning by subtests from the neuropsychological test battery NEPSY II. In addition, infant fatty acid composition in red blood cells (RBC) was analyzed. In multiple linear and logistic regression models, we estimated the associations between DHA and AA status in infancy and scores on the ASQ-3 and the NEPSY II subtests., Results: There were no notable associations between infant AA and DHA status, and the scores on the ASQ-3 and the NEPSY II subtests five years later. It should be noted that we found better than expected concentrations of erythrocyte DHA and AA among the infants, and the ASQ scores were left-skewed, which limited the ability to identify associations., Conclusion: DHA and AA status in infancy is seemingly not related to neurodevelopment measured 5 years later in this peri-urban population from Nepal.

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 (.

Prevalence of micronutrient deficiencies is high among infants and children in low- and middle income countries, but knowledge about nutrient adequacy across the complementary feeding period is limited. We investigated probability of adequacy (PA) of breast milk and complementary food combined and nutrient density adequacy (NDA) of complementary food and tracking of NDA over time among 229 children from 9-24 months of age in Bhaktapur, Nepal. Monthly, 24 h dietary recalls (16 in total) were performed and subgrouped into four 4-month time periods. Ten micronutrients (thiamin, riboflavin, niacin, vitamin B 6 , folate, vitamin C, vitamin A, calcium, iron, and zinc) were assessed. Nutrient density was defined as the amount of a nutrient in a child's complementary food per 100 kcal, whereas NDA was the nutrient density as percentage of the context specific desired nutrient density. Tracking of NDA was investigated using generalized estimating equations models. PA for B vitamins (except riboflavin), vitamin A, calcium, iron, and zinc (low absorption group) was very low (0% to 8%) at all time slots. Median (IQR) mean PA (of all 10 micronutrients) increased from 11% (9, 15) in the second to 21% (10, 35) in the last time slot. Median value for mean nutrient density adequacy of all micronutrients varied between 42% and 52%. Finally, tracking of NDA was low (correlation <0.30) or moderate (0.30-0.60) indicating poor association between the first and subsequent measurements of NDA. These findings raise grave concerns about micronutrient adequacy among young children in Nepal. Urgent interventions are needed., (© 2017 John Wiley & Sons Ltd.)

Purpose: Essential fatty acids play a critical role in the growth and development of infants, but little is known about the fatty acid status of populations in low-income countries. The objective was to describe the fatty acid composition of red blood cells (RBC) in breastfeed Nepali infants and a subsample of their mothers and to identify the main sources of fatty acids in the mother's diet, as well as the fatty acid composition of breast milk., Methods: RBC fatty acid composition was analyzed in a random sample of 303 infants and 72 mother, along with 68 breastmilk samples. Fatty acid profiles of the most important dietary fat sources were analyzed. Information on mother's diet and intake of fat was collected by three 24-h dietary recalls., Results: In infant RBC's, docosahexaenoic acid (DHA) was the main n-3 fatty acid, and arachidonic acid (AA) was the major n-6 fatty acid. Total n-6 PUFA was three times higher than total n-3 PUFA. Height-for-age (HAZ) was positively associated with DHA status and AA status in multivariable models. The concentration of all fatty acids was higher in children, compared to mothers, except Total n-6 PUFA and Linoleic acid (LA) where no differences were found. The mother's energy intake from fat was 13% and cooking oil (sesame, mustard, soybean or sunflower oil) contributed 52% of the fat intake., Conclusions: RBC-DHA levels in both infants and mother was unexpected high taking into account few dietary DHA sources and the low DHA concentrations in breastmilk.

Objective: The present study aimed to assess infant and young child feeding (IYCF) practices and the tracking of dietary diversity score (DDS), intakes of Fe- and vitamin A-rich foods and meal frequency in a peri-urban area in Nepal. Furthermore, to explore whether sociodemographic factors were associated with tracking patterns of these IYCF practices., Design: Longitudinal study. Monthly food intake was measured by 24 h recall. Four time slots were used (9-12, 13-16, 17-20 and 21-24 months). Tracking of IYCF practices was investigated using generalized estimating equations (GEE) models and Cohen's weighted kappa. Multinominal logistic regression was used to identify determinants for tracking of the IYCF practices., Setting: Bhaktapur municipality, Nepal., Subjects: Children (n 229) aged 9-24 months, randomly selected., Results: Prevalence of minimum meal frequency was higher than for minimum dietary diversity at all time slots. Tracking based on absolute measures (GEE models) was moderate for DDS (0·48) and meal frequency (0·53), and low for intakes of Fe- (0·23) and vitamin A-rich (0·35) foods. Tracking based on rank measured was moderate for DDS and meal frequency, and fair for Fe- and vitamin A-rich foods. Low socio-economic status significantly increased the odds (OR; 95 % CI) of tracking of low v. high DDS (3·31; 1·44, 7·60) and meal frequency (3·46; 1·54, 7·76)., Conclusions: Low tracking for intakes of Fe- and vitamin A-rich foods implies that interventions to improve these IYCF practices must address underlying causes for irregular intake to have sustainable effects.

Objectives: The potential growth-promoting effects of antibiotics are not well understood among undernourished children in environments with high pathogen exposure. We aimed to assess whether early antibiotic exposure duration and class were associated with growth to 2 years of age across 8 low-resource sites in the MAL-ED birth cohort study., Methods: We followed 1954 children twice per week from birth to 2 years to record maternally reported antibiotic exposures and measure anthropometry monthly. We estimated the associations between antibiotic exposure before 6 months of age and weight-for-age and length-for-age (LAZ) z scores to 2 years. We assessed the impact of class-specific exposures and duration, and compared these results to effects of antibiotic exposures after 6 months of age., Results: Antibiotic use before 6 months of age was associated with increased weight from 6 months to 2 years, whereas associations with length were less consistent across sites and antibiotic classes. Compared to unexposed children, 2 or more courses of metronidazole, macrolides, and cephalosporins were associated with adjusted increases in weight-for-age of 0.24 (95% confidence interval (CI): 0.04, 0.43), 0.23 (95% CI: 0.05, 0.42), and 0.19 (95% CI: 0.04, 0.35) from 6 months to 2 years, respectively., Conclusions: Antibiotic use in low-resource settings was most associated with the ponderal growth of children who had multiple exposures to antibiotics with broad spectrum and anaerobic activity in early infancy. Opportunities for rational and targeted antibiotic therapy in low resource settings may also promote short-term weight gain in children, although longer-term physical growth and metabolic impacts are unknown.

Introduction: Vitamin B 12 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 B 12 status. Poor vitamin B 12 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 B 12 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., Competing Interests: Competing interests: None declared., (© 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.)