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Abstract: 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 B6, 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. [ABSTRACT FROM AUTHOR]

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. [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]

Poor vitamin D status has been associated with increased risk and severity of respiratory tract infections. Whether or not inflammation and infection affects 25-hydroxy vitamin D (25(OH)D) concentration is controversial and is important in the interpretation of observational studies using plasma-25(OH)D as a biomarker for status. Our objectives were to measure whether 25(OH)D concentration was altered by an episode of acute lower respiratory tract infection and whether markers of inflammation predicted the 25(OH)D concentration. Children aged 2-35 months with severe (n = 43) and non-severe (n = 387) community-acquired, WHO-defined pneumonia were included. 25(OH)D concentration and inflammatory markers (cytokines, chemokines, and growth factors) were measured in plasma during the acute phase and 14, 45, and 90 days later. Predictors for 25(OH)D concentrations were identified in multiple linear regression models. Mean 25(OH)D concentration during the acute phase and after recovery (14,45, and 90 days) was 84.4 nmol/L ± 33.6, and 80.6 ± 35.4, respectively. None of the inflammatory markers predicted 25(OH)D concentration in the multiple regression models. Age was the most important predictor for 25(OH)D concentration, and there were no differences in 25(OH)D concentrations during illness and after 14, 45, and 90 days when adjusting for age. Infection and inflammation did not alter the 25(OH)D concentration in young children with acute lower respiratory tract infections. [ABSTRACT FROM AUTHOR]

Background: Describing vitamin D status and its predictors in various populations is important in order to target public health measures. Objectives: To describe the status and predictors of vitamin D status in healthy Nepalese mothers and infants. Methods: 500 randomly selected Nepalese mother and infant pairs were included in a cross-sectional study. Plasma 25(OH)D concentrations were measured by LC-MS/MS and multiple linear regression analyses were used to identify predictors of vitamin D status. Results: Among the infants, the prevalence of vitamin D insufficiency (25(OH)D <50 nmol/L) and deficiency (<30 nmol/L) were 3.6% and 0.6%, respectively, in contrast to 59.8% and 14.0% among their mothers. Infant 25(OH)D concentrations were negatively associated with infant age and positively associated with maternal vitamin D status and body mass index (BMI), explaining 22% of the variability in 25(OH)D concentration. Global solar radiation, maternal age and BMI predicted maternal 25(OH)D concentration, explaining 9.7% of its variability. Conclusion: Age and maternal vitamin D status are the main predictors of vitamin D status in infants in Bhaktapur, Nepal, who have adequate vitamin D status despite poor vitamin D status in their mothers. [ABSTRACT FROM AUTHOR]

Adequate iodine concentration in breastmilk (BMIC) is essential for optimal neonatal thyroid hormone synthesis and neurological development in breastfed infants. For many decades, iodine deficiency has been a public health problem in Nepal. However, recently, excessive iodine intakes among Nepali infants have been reported. This study aimed to measure BMIC and urinary iodine concentration (UIC) among lactating women in a peri-urban area of Nepal. Iodine concentration was measured in spot urine (n = 485) and breastmilk samples (n = 291) of 500 randomly selected lactating women. The median (p25, p75) BMIC and median UIC were 250 (130,370) µg/L and 230 (135-377) µg/L, respectively. Around 82% had BMIC > 100 µg/L, 61% had BMIC > 200 µg/L and 81% had UIC > 100 µg/L, 37% had >300 µg/L and 20% had >500 µg/L. In multiple linear regression models, time since birth (β 3.0, 95% CI (0.2, 5.0)) and UIC (β 1.0, 95% CI (0.1,2.0)) were associated with BMIC, explaining 26% of the variance. A large proportion of the women had adequate BMIC and UIC; however, a subset had high iodine concentrations. These findings emphasize the importance of carefully monitoring iodine intake to minimize the risk of iodine excess and subsequently preventing transient iodine-induced hypothyroidism in breastfed infants. [ABSTRACT FROM AUTHOR]

Vitamin deficiencies are known to be common among infants residing in low- and middle-income countries but relatively few studies have assessed several biochemical parameters simultaneously. The objective of the study was to describe the status of vitamins (A, D, E, B6, B12 and folate) in breastfed infants. We measured the plasma concentrations of trans retinol, 25 hydroxy vitamin D, α-tocopherol, pyridoxal 5′-phosphate, cobalamin, folate, methylmalonic acid, homocysteine, hemoglobin and C-reactive protein from 467 randomly selected infants. One in five (22%) was deficient in at least one vitamin. Mean (SD) plasma folate concentration was 73 (35) nmol/L, and no infant in the sample was folate deficient. Vitamin B6 deficiency and vitamin B12 deficiency was found in 22% and 17% of the infants, respectively. Elevated plasma methylmalonic acid or total homocysteine concentration was found in 82% and 62% of infants, respectively. Fifteen percent of infants were vitamin A deficient and 65% were marginally deficient in vitamin A. Fewer than 5% of infants had low plasma vitamin D concentration or vitamin E concentration (α-tocopherol <9.3 µmol/L). Our results illustrate the importance of continued supplementation campaigns and support the expansion of food fortification and dietary diversification programs that target children and women in Nepal. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 <148 pmol/L) was found among 11%, whereas 24% of the infants had plasma cobalamin concentrations between 148–221 pmol/L. Elevated total homocysteine (>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 (<10 nmol/L) was not found as the lowest value of plasma folate was 20.7 nmol/L. It is important to examine the extent to which poor cobalamin status during infancy has immediate or long-term consequences. [ABSTRACT FROM AUTHOR]

Background: More than 90% of the morbidity and mortality from chronic respiratory disease occurs in low-income and middle-income countries (LMICs), with substantial economic impact. Preserved ratio impaired spirometry (PRISm) is a prevalent lung function abnormality associated with increased mortality in high-income countries. We aimed to conduct a post-hoc analysis of a cross-sectional study to assess the prevalence of, the risk factors for, and the impact of PRISm in three diverse LMIC settings., Methods: We recruited a random, age-stratified and sex-stratified sample of the population in semi-urban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda. Quality-assured post-bronchodilator spirometry was performed to American Thoracic Society standards and PRISm was defined as a forced expiratory volume in one second (FEV 1 ) of less than 80% predicted with a FEV 1 /forced vital capacity ratio of 0·70 or more. We used t tests and χ 2 analyses to assess the relationships between demographic, biometric, and comorbidity variables with PRISm. Multivariable logistic models with random intercept by site were used to estimate odds ratios (ORs) with 95% CIs., Findings: 10 664 participants were included in the analysis, with a mean (SD) age of 56·3 (11·7) years and an equal distribution by sex. The prevalence of PRISm was 2·5% in Peru, 9·1% in Nepal, and 16·0% in Uganda. In multivariable analysis, younger age (OR for each decile of age 0·87, 95% CI 0·82-0·92) and being female (1·37, 1·18-1·58) were associated with increased odds of having PRISm. Biomass exposure was not consistently associated with PRISm across sites. Individuals with PRISm had impairment in respiratory-related quality of life as measured by the St George's Respiratory Questionnaire (OR by decile 1·18, 95% CI 1·10-1·25)., Interpretation: The prevalence of PRISm is heterogeneous across LMIC settings and associated with age, female sex, and biomass exposure, a common exposure in LMICs. A diagnosis of PRISm was associated with worse health status when compared with those with normal lung function. Health systems in LMICs should focus on all spirometric abnormalities as opposed to obstruction alone, given the disease burden, reduced quality of life, and size of the undiagnosed population at risk., Funding: Medical Research Council., Competing Interests: Declaration of interests TS reports grants or contracts from the Australian Lung Health Initiative; consulting fees from Verona Pharmaceuticals; and a leadership or fiduciary role in board, society, committee, or advocacy groups for 4D Medical. OF-F reports a Global Emerging Leader Award grant from the Fogarty International Centre. JJM reports grant support and payments made to their institution from the Alliance for Health Policy and Systems Research, Bloomberg Philanthropies, FONDECYT via CIENCIACTIVA and CONCYTEC, the British Council, British Embassy, the Newton-Paulet Fund, the UK Department for International Development, the UK Medical Research Council, the Wellcome Global Health Trials partnership, the Fogarty International Center, Grand Challenges Canada, the International Development Research Center Canada, Inter-American Institute for Global Change Research, the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Mental Health, the Swiss National Science Foundation, the UK Research and Innovation (UKRI) Biotechnology and Biological Sciences Research Council, the UKRI Engineering and Physical Sciences Research Council, the UKRI Medical Research Council, the Wellcome Trust, and the World Diabetes Foundation; a contract from Health Action International; consulting fees from the Pan American Health Organization and Bloomberg Philanthropies; participation on data safety monitoring or advisory boards for the Nigeria Sodium Study, the Intensive care bundle with blood pressure Reduction in Acute Cerebral haemorrhage Trial, the Latin American Brain Health institute, Universidad Adolfo Ibáñez (Chile), Programa de Gastronomía, Facultad de Estudios Interdisciplinarios, Pontificia Universidad Católica del Perú, and the InterAmerican Heart Foundation; being Co-chair of the Independent Group of Scientists, 2023 Global Sustainable Development Report, UN; being a member of the Scientific Expert Committee, Global Data Collaborative for CV Population Health, the World Health Federation, Microsoft, and Novartis Foundation; being a member of the Scientific and Technical Advisory Committee for the Alliance for Health Policy and Systems Research, WHO; being a member of WHO's Technical Advisory Group on non-communicable disease-related research and innovation, Non-communicable Diseases Department, WHO; and being a member of the Advisory Scientific Committee, Instituto de Investigación Nutricional, Peru. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by 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).)

Background: Globally, solid fuels are used by about 3 billion people for cooking and a smaller number use kerosene. These fuels have been associated with acute lower respiratory infection (ALRI) in children. Previous work in Bhaktapur, Nepal, showed comparable relationships of biomass and kerosene cooking fuels with ALRI in young children, compared to those using electricity for cooking. We examine the relationship of kitchen PM 2.5 concentrations to ALRI in those households., Methods: ALRI cases and age-matched controls were enrolled from a cohort of children 2-35 months old. 24-h PM 2.5 was measured once in each participant's kitchen. The main analysis was carried out with conditional logistic regression, with PM 2.5 measures specified both continuously and as quartiles., Results: In the kitchens of 393 cases and 431 controls, quartiles of increasing PM 2.5 concentration were associated with a monotonic increase in odds ratios (OR): 1.51 (95% CI: 1.00, 2.27), 2.22 (1.47, 3.34), 2.48 (1.63, 3.77), for the 3 highest exposure quartiles. The general kitchen concentration-response shape across all stoves was supralinear. There was evidence for increased risk with biomass stoves, but the slope for kerosene stoves was steeper, the highest quartile OR being 5.36 (1.35, 21.3). Evidence for increased risk was also found for gas stoves., Conclusion: Results support previous reports that biomass and kerosene cooking fuels are both ALRI risk factors, but suggests that PM 2.5 from kerosene is more potent on a unit mass basis. Further studies with larger sample sizes and preferably using electricity as the baseline fuel are needed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

Cobalamin and folate are especially important for women of childbearing age due to their ubiquitous role in fetal growth and development. Population-based data on cobalamin and folate status are lacking from Nepal, where diets are mostly vegetarian. The objectives of the study were to investigate cobalamin and folate intake and status, and to explore associations with socio-demographics, anthropometrics, anemia, and dietary habits. Following a random selection of geographical clusters, we collected blood samples from 500 non-pregnant women and 24-h dietary recalls and food frequency questionnaires from a subsample of 379 women. Twenty percent of the women did not consume any food containing cobalamin during the days recalled, and in 72% nutritional cobalamin intake was <1 μg/day. Eighty-four percent of the women had cobalamin intake lower than the estimated average requirement (EAR) (<2 μg/day). In contrast, only 12% of the women had a folate intake less than 100 μg per day, whereas 62% had intake between 100 and 320 μg. Low plasma cobalamin (<150 pmol/L) was found in 42% of the women, most of whom (88%) also had elevated levels of methylmalonic acid. Our results indicated a high prevalence of nutritional cobalamin deficiency, while folate deficiency was uncommon.

Iron deficiency anemia is still common in children under five years of age and may impair their growth and cognitive development. Diarrhea is the second most common reason for seeking medical care for young children in Nepal. However, neither screening programs nor effective preventive measures for anemia and iron deficiencies are in place among children with diarrhea in many developing countries. The aims of this study were to determine the prevalence of anemia and iron deficiency and explore their associations with clinical, socioeconomic, and anthropometric parameters in Nepalese children. This was a cross-sectional study based on 1232 children, six to 35 months old, with acute diarrhea participating in a zinc supplementation trial. The mean (SD) hemoglobin was 11.2 g/dL (1.2). Anemia was found in 493 children (40%); this estimate increased to 641 (52%) when we adjusted for the altitude of the study area (hemoglobin <11.3 g/dL). One in every three children had depleted iron stores and 198 (16%) of the children had both depleted iron stores and anemia, indicating iron deficiency anemia. The prevalence of anemia among children presenting with acute diarrhea was high but the degree of severity was mainly mild or moderate. Iron deficiency explained less than half of the total anemia, indicating other nutritional deficiencies inducing anemia might be common in this population.