Search

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: 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defined by the m-ADBB was associated with neurodevelopmental scores in regression models., Results: Children socially withdrawn in infancy had lower Bayley-III language scores (-2.6 (95% CI -4.5, -0.7)) in early childhood.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differences in the other Bayley-III scores or the WPPSI-IV and NEPSY-II scores at 4 years in children who were socially withdrawn or not., Conclusion: Social withdrawal in infancy was reflected in early language development but not cognitive functioning at 4 years., (© 2024.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).)

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.)

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.)

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: 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.

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: 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: 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.

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.)

Background: Poor vitamin B-12 (cobalamin) status is widespread in South Asia. Insufficient vitamin B-12 status has been linked to poor neurodevelopment in young children. Objective: We measured the associations between vitamin B-12 status in infancy (2-12 mo) and the development and cognitive functioning in Nepalese children 5 y later. Design: Vitamin B-12 status was assessed in infancy with the use of plasma cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). At 5 y of age, we measured development with the use of the Ages and Stages Questionnaire, 3rd edition (ASQ-3), and cognitive functioning by using the Developmental Neuropsychological Assessment, 2nd edition (NEPSY II), in 320 children. In regression models, we estimated the associations between vitamin B-12 status, including a combined indicator of vitamin B-12 status (3cB12) and scores on the ASQ-3 and NEPSY II subtests. Results: All markers of vitamin B-12 status with the exception of plasma cobalamin were significantly associated with the total ASQ-3 scores in the multiple regression models. A 1-unit increase in the 3cB12 score was associated with an increase in the total ASQ-3 score of 4.88 (95% CI: 2.09, 7.68; P = 0.001). Increases in both plasma tHcy and MMA (indicating poorer status) were associated with a decrease in scores on the NEPSY II affect recognition and geometric puzzle subtests. Each unit increment in 3cB12 scores was associated with increases of 0.82 (95% CI: 0.49, 1.14; P < 0.0005), 0.59 (95% CI: 0.10, 1.09; P = 0.020), and 0.24 (95% CI: 0.02, 0.47; P = 0.035) in the affect recognition, geometric puzzle, and block construction scores, respectively. Conclusions: Vitamin B-12 status in infancy is associated with development and performance on social perception tasks and visuospatial abilities at 5 y of age. The long-term effects of poor vitamin B-12 status in infancy need further investigation in randomized controlled trials., (© 2017 American Society for Nutrition.)

Background: Vitamin B 12 deficiency is one of the most common micronutrient deficiencies and is associated with poor cognitive development and growth. Vitamin B 12 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 B 12 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 B 12 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 B 12 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.

Background Poor growth in early childhood has been associated with increased risk of mortality and morbidity, as well as long-term deficits in cognitive development and economic productivity. Objectives Data from the MAL-ED cohort study were used to identify factors in the first 2 y of life that are associated with height-for-age, weight-for-age, and body mass index z -scores (HAZ, WAZ, BMIZ) at 5 y of age. Methods A total of 1017 children were followed from near birth until 5 y of age at sites in Bangladesh, Brazil, India, Nepal, Peru, South Africa, and Tanzania. Data were collected on their growth, environmental enteric dysfunction (EED), micronutrient status, enteric pathogen burden, illness prevalence, dietary intake, and various other socio-economic and environmental factors. Results EED biomarkers were related to size at 5 y. Mean lactulose:mannitol z -scores during the first 2 y of life were negatively associated with all of the growth measures (HAZ: −0.11 [95% CI: −0.19, −0.03]; WAZ: −0.16 [95% CI: −0.26, −0.06]; BMIZ: −0.11 [95% CI: −0.23, 0.0]). Myeloperoxidase was negatively associated with weight (WAZ: −0.52 [95% CI: −0.78, −0.26] and BMIZ: −0.56 [95% CI: −0.86, −0.26]); whereas α-1-antitrypsin had a negative association with HAZ (−0.28 [95% CI: −0.52, −0.04]). Transferrin receptor was positively related to HAZ (0.18 [95% CI: 0.06, 0.30]) and WAZ (0.21 [95% CI: 0.07, 0.35]). Hemoglobin was positively related to HAZ (0.06 [95% CI: 0.00, 0.12]), and ferritin was negatively related to HAZ (−0.08 [95% CI: −0.12, −0.04]). Bacterial density in stool was negatively associated with HAZ (−0.04 [95% CI: −0.08, 0.00]), but illness symptoms did not have any effect on size at 5 y. Conclusions EED markers, bacterial density, and iron markers are associated with growth at 5 y of age. Interventions to reduce bacterial burden and EED may improve long-term growth in low-income settings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]