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Objectives: To assess the impact of nutritional and multiple-micronutrient supplementation to lactating mothers on the micronutrient status of mother-infant dyad at 6 months of age postnatally., Design: This study was a trial that aimed to investigate the impact of maternal nutritional supplementation on infant growth. A secondary objective was to assess the effect on the micronutrient status of mother-infant pairs. The intervention group mothers received snacks with 600 kcal energy, 20 g protein and daily micronutrient tablets., Setting: Blood samples were collected from both mothers and infants at 6 months., Participants: The participants in this study were mother-infant pairs. The micronutrient status of these pairs was assessed through blood samples, focusing on vitamins A, D, B 12 , ferritin, Zn and folate., Results: Micronutrient analysis of serum samples from 600 mother-infant pairs showed that mothers in the intervention group had higher levels of serum ferritin (mean difference (MD) 14·7 ng/ml), retinol (MD 0·6 μmol/l), folate (MD 3·3 ng/ml) and vitamin D (1·03 ng/ml) at 6 months postpartum. Additionally, the supplementation was associated with a higher mean ± sd of serum ferritin (MD 8·9 ng/ml) and vitamin A (MD 0·2 μmol/l) levels in infants at 6 months., Conclusions: The study found that supplementing maternal nutrition with additional dietary and micronutrient intakes during lactation improved maternal micronutrient status and slightly increased ferritin and vitamin A levels in infants at 6 months. The findings highlight the importance of nutritional interventions for improving the micronutrient health of mother-infant pairs, with significant public health implications.Trial registered at www.clinicaltrials.gov (CTRI/2018/04/013095).

Background: Protein quality, evaluated using Digestible Indispensable Amino Acid Score (DIAAS) requires ileal digestibility values of individual indispensable amino acids (IAA) in each protein. However, true tryptophan (Trp) digestibility has rarely been quantified in humans., Objective: To measure the true Trp digestibility and DIAAS of 2 H-intrinsically labelled plant and animal protein sources in humans, using the dual isotope tracer technique., Methods: The true Trp digestibility of 2 H intrinsically labelled plant proteins such as whole mung bean (n=6) and dehulled mung bean (n=6), chickpea (n=5), and yellow pea (n=5), and protein from animal source foods such as egg white (n=6), whole egg (n=6), chicken meat (n=6) and goat milk (n=7) was determined against the known digestibility of U- 13 C spirulina whole cell protein as reference, except for goat milk protein which was measured against free crystalline 13 C-Trp as reference. Banked samples from earlier studies conducted to determine true IAA digestibility of different protein sources were used for the analysis. DIAAS was calculated for each test protein using digestibility corrected IAA scores (mg IAA/g of protein) in comparison to the IAA requirement score for adults., Results: The true Trp digestibility of whole mung bean, dehulled mung bean, chickpea, yellow pea, egg white, whole egg, chicken meat, and goat milk were 67.6±3.7%, 74.5±4.4%, 72.6±2.3%, 72.5±2.2%, 89.7±2.5%, 91.4±2.6%, 95.9±2.2%, and 92.8±2.9% respectively. The true Trp digestibility of plant protein sources was significantly lower than that of animal protein sources (p<0.05). Trp was not a limiting IAA in all the tested proteins., Conclusion: The true Trp digestibility determined in the present study ranged from 67.6±3.7% to 95.9 ± 2.2% for whole mung bean and chicken meat respectively, and adds to the database of individual true IAA digestibility of different protein sources. This study was registered in Clinical Trials Registry of India (CTRI) with registration number: CTRI/2017/11/010468, CTRI/2020/04/024512, CTRI/2018/03/012265., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Anura V Kurpad reports financial support was provided by Wellcome Trust DBT India Alliance. Anura V Kurpad reports financial support was provided by International Atomic Energy Agency. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Accurate assessment of body composition during infancy is an important marker of early growth. This study aimed to develop anthropometric models to predict body composition in 3-24-month-old infants from diverse socioeconomic settings and ethnic groups., Methods: An observational, longitudinal, prospective, multi-country study of infants from 3 to 24 months with body composition assessed at three monthly intervals using deuterium dilution (DD) and anthropometry. Linear mixed modelling was utilized to generate sex-specific fat mass (FM) and fat-free mass (FFM) prediction equations, using length(m), weight-for-length (kg/m), triceps and subscapular skinfolds and South Asian ethnicity as variables. The study sample consisted of 1896 (942 measurements from 310 girls) training data sets, 941 (441 measurements from 154 girls) validation data sets of 3-24 months from Brazil, Pakistan, South Africa and Sri Lanka. The external validation group (test) comprised 349 measurements from 250 (185 from 124 girls) infants 3-6 months of age from South Africa, Australia and India., Results: Sex-specific equations for three age categories (3-9 months; 10-18 months; 19-24 months) were developed, validated on same population and externally validated. Root mean squared error (RMSE) was similar between training, validation and test data for assessment of FM and FFM in boys and in girls. RMSPE and mean absolute percentage error (MAPE) were higher in validation compared to test data for predicting FM, however, in the assessment of FFM, both measures were lower in validation data. RMSE for test data from South Africa (M/F-0.46/0.45 kg) showed good agreement with validation data for assessment of FFM compared to Australia (M/F-0.51/0.33 kg) and India(M/F-0.77/0.80 kg)., Conclusions: Anthropometry-based FFM prediction equations provide acceptable results. Assessments based on equations developed on similar populations are more applicable than those developed from a different population., (© 2024. The Author(s).)

The changing global climate brings a gradual yet constant and adverse shift in crop production. Grain crop plants, particularly cereals and legumes, respond varyingly to adverse climate, including reduction in grain yield and changes to their nutrient densities. An understanding of specific changes to crop systems under differing climatic conditions can help in planning diets to meet human nutrient sufficiency. Grain protein content is also affected by adverse environmental factors. Deficits in protein yield, linked to changes in grain or seed protein and antinutrient concentrations, have been reported in major food crops when exposed to elevated carbon dioxide, high temperature, drought, and humidity. These changes, in addition to affecting the quantity of indispensable or essential amino acids (IAA), also impact their bioavailability. Therefore, it is important to assess consequences of climate change on grain protein quality. An important tool to measure grain protein quality, is measuring its digestibility at the level of the ileum and its IAA concentration, linked to a metric called the Digestible IAA Score (DIAAS). A minimally invasive technique called the dual isotope tracer technique, which measures IAA digestibility after simultaneous administration of two different intrinsically labelled protein sources, one a test protein ( 2 H/ 15 N) and one a reference protein ( 13 C) of predetermined digestibility, has been used in evaluation of grain protein IAA digestibility, and promises more in the evaluation of changes based on climate. This review discusses climate induced changes to grain protein quality through the prism of IAA digestibility, using the dual isotope tracer technique., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kashyap, Reddy, Devi and Kurpad.)

Background & Aims: Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of metformin is often associated with a decrease in vitamin B 12 (B 12 ) levels in patients with DM. Few studies have shown that this effect could be mitigated with calcium supplementation. In the present study, we quantified the effect of metformin, and metformin co-administered with calcium on B 12 absorption using a novel stable isotope [ 13 C] cyanocobalamin tracer., Methods: A pilot crossover study was conducted to estimate the bioavailability of B 12 in healthy subjects, using [ 13 C] cyanocobalamin as a tracer. In the study, [ 13 C] cyanocobalamin was administered orally to the participants followed by hourly venous sampling to measure the concentration of the tracer and estimate bioavailability. This protocol was followed for three experiment days, each separated by a one month wash out period. As part of the study, all participants received the tracer alone for the control day (C), metformin 850 mg along with the tracer for the metformin day (M) and metformin 850 mg with calcium 500 mg and the tracer for the metformin calcium day (MC)., Results: Seven participants completed all three experiment days. The mean B 12 bioavailability (±SD, n = 7) was 42.6 ± 10.2% for the control day (C), 30.8 ± 15.3% for the metformin day (M) and 46.4 ± 8.6% for the metformin-calcium day (MC). Repeated measures ANOVA was done and the pairwise comparison showed a significant difference in the B 12 bioavailability between control and metformin day (C vs M p = 0.010), and between the metformin and metformin with calcium day (M vs MC p = 0.003)., Conclusion: B 12 bioavailability reduced significantly from baseline (C) when metformin (M) was administered and this reduction was reversed when calcium was co-administered (MC) in healthy participants. In patients using metformin, calcium supplementation as a strategy to prevent B 12 deficiency needs to be further studied., Competing Interests: Declaration of competing interest No potential conflicts of interests to declare., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) resulted in a pandemic with huge death toll and economic consequences. The virus attaches itself to the human epithelial cells through noncovalent bonding of its spike protein with the angiotensin-converting enzyme-2 (ACE2) receptor on the host cell. Based on in silico studies we hypothesized that perturbing the functionally active conformation of spike protein through the reduction of its solvent accessible disulfide bonds, thereby disintegrating its structural architecture, may be a feasible strategy to prevent infection by reducing the binding affinity towards ACE2 enzyme. Proteomics data showed that N-acetyl cysteine (NAC), an antioxidant and mucolytic agent been widely in use in clinical medicine, forms covalent conjugates with solvent accessible cysteine residues of spike protein that were disulfide bonded in the native state. Further, in silico analysis indicated that the presence of the selective covalent conjugation of NAC with Cys525 perturbed the stereo specific orientations of the interacting key residues of spike protein that resulted in threefold weakening in the binding affinity of spike protein with ACE2 receptor. Interestingly, almost all SARS-CoV-2 variants conserved cystine residues in the spike protein. Our finding results possibly provides a molecular basis for identifying NAC and/or its analogues for targeting Cys-525 of the viral spike protein as fusion inhibitor and exploring in vivo pharmaco-preventive and its therapeutic potential activity for COVID-19 disease. However, in-vitro assay and animal model-based experiment are required to validate the probable mechanism of action.Communicated by Ramaswamy H. Sarma.

Background: In large supplementary feeding programs for children, it is challenging to create and sustain contextual, acceptable, nutritionally complete, and diverse supplemental foods. For example, the Indian Supplementary Nutrition Program (SNP) supplements the dietary intake of children, pregnant and lactating women, and severely acutely malnourished (SAM) children by offering dry take home rations (THRs) or hot cooked meals (HCMs) across India, but an optimization tool is necessary to create local contextual recipes for acceptable and nutritionally adequate products., Objectives: This study aimed to create a linear programming (LP) model to optimize diverse food provisions for a SNP to meet its program guidelines, using locally available foods, within budgetary allocations., Methods: A LP algorithm with appropriate constraints was used to generate an optimal THR based on raw foods, or an optimal weekly HCM menu comprised of a lunch meal with mid-morning snacks, based on user choices of foods and recipes. The database of foods used was created by a prospective survey conducted across all states of India for this purpose, such that the recipe and food optimization was diverse and specific to the guidelines for each beneficiary group., Results: An interactive web-based app, which can optimize feeding programs at any population level, was developed for use by program implementers and is hosted at https://www.datatools.sjri.res.in/SNP/. In the Indian example analyzed here, the recommended optimized diets met the guidelines for diversified and nutritionally complete SNP provision but at a cost that was almost 25% higher than the present Indian budget allocation., Conclusions: The optimization model developed demonstrates that contextual SNP diets can be created to meet macronutrient and most essential micronutrient needs of large-scale feeding programs, but appropriate diversification entails additional costs., (© 2024 The Authors.)

The World Health Organization has recently updated the guideline on the prevention and management of wasting and nutritional oedema (acute malnutrition) in infants and children under 5 years. Apart from differences with regard to the nutritional framework that defines the quantity of energy required as Ready-to-Use Therapeutic Food (RUTF) for the outpatient treatment of severe wasting and/or nutritional oedema, there are also important gaps in the practical guidance. Instead of the recommended energy intake of 150-185 kcal/kg/day, our alternative calculations indicate the requirement to be only 105-120 kcal/kg/day. If true, the implementation of such caloric overfeeding can have adverse consequences. Gaps in practical guidance also need to be addressed, including the timing of transition to home-based diets, maximal duration of therapeutic feeding, especially in non-responders (∼50% in South Asia), and the role of augmented home foods as the primary therapeutic food option., Competing Interests: We declare no competing interests., (© 2024 The Author(s).)

Objective: We aimed to develop anthropometric growth references for Indian children and adolescents, based on available 'healthy' child data from multiple national surveys., Methodology: Data on 'healthy' children, defined by comparable WHO's Multicentre Growth Reference Study (MGRS) selection criteria, were extracted from four Indian surveys over the last 2 decades, viz, NFHS-3, 4, and 5 and Comprehensive National Nutrition Survey (CNNS). Reference distributions of height-for-age for children up to 19 years, weight-for-age for children up to 9y, weight-for-height for children less than 5 years and BMI for age for children between 5-19 y were estimated by GAMLSS with Box-Cox Power Exponential (BCPE) family. The national prevalence of growth faltering was also estimated by the NFHS-5 and CNNS data., Results: The distributions of the new proposed Indian growth references are consistently lower than the WHO global standard, except in the first 6 months of age. Based on these references, growth faltering in Indian children and adolescents reduced > 50% in comparison with the WHO standard., Conclusion: The study findings revealed that the WHO one-standard-fits-all approach may lead to inflated estimates of under nutrition in India and could be a driver of misdirected policy and public health expenditure in the Indian context. However, these findings need validation through prospective and focussed studies for more robust evidence base.

Competing Interests: This research was funded by the Drivers of Food Choice (DFC) Competitive Grants Program, which is funded by the UK Government's Department for International Development and the Bill & Melinda Gates Foundation, and managed by the University of South Carolina, Arnold School of Public Health, USA; however, the views expressed do not necessarily reflect the UK Government's official policies. SK receives research funding from Medical Research Council UK, University of Chiang Mai Thailand, and Ministry of AYUSH Gov of India. PM receives research funding from Medical Research Council UK and Ministry of AYUSH Gov of India. JL receives research funding from Medical Research Council, UK. HW receives research funding from Public Health England, the Health Services Research Initiative, and Helen Keller International, and has received honoraria from University of the Western Cape and ANH (Agriculture, Nutrition, & Health) Academy. All authors declare no conflicts of interest.

Introduction: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants., Research Design and Methods: We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher's exact test., Results: Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs)., Conclusions: Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Milk is an important source of protein for many Indian households. However, milk intake is very low. Hence, it is necessary to examine production-consumption linkages of milk within the paradigm of accessibility, availability, and affordability., Objectives: This study examined linkages between milk consumption and production, accounting for sales and factors associated with production investments in rural Bihar, a major milk-producing state of India with very poor nutritional status., Methods: A panel of households from the Gaya and Nalanda districts of Bihar were surveyed: the first round in July and August 2019 ( n = 2026 households) and the second round from December 2019 to January 2020 ( n = 2001 households). Data were collected on household consumption, production, and sale of milk, as well as other foods. The study examines the consumption-production linkage of milk and the association of dietary diversity with consumption from own production, with households as the unit of analysis. Ordinary least square regression analysis of average monthly household milk consumption was used to identify factors associated with milk consumption, particularly milk production., Results: The median (Quartile 1, Quartile 3) per capita milk consumption per day was 83.3 (41.6, 166.6) mL in the milk-consuming households. Average monthly household milk consumption in liters was higher in milk-producing households [β: 7.1; 95% confidence interval (CI): 6.1, 8.1] than households relying on market purchases. Household milk consumption was higher in the third tertile of milk production than the first tertile of production (β: 14.3 L/wk; 95% CI: 12.1, 17.2) and lower in the highest tertile of household sale quantity (β: -8.8 L/wk in tertile 3, 95% CI: -12.7, -5) than the first tertile of household sale quantity of milk., Conclusions: The study provides evidence that consumption of milk in rural households is associated with own production such that households with higher production consume more. However, sale preferences restrict the quantity of milk consumed in milk-producing households., (© 2024 The Authors.)

Background: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers., Methods: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively., Results: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin., Conclusions: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5)., (Copyright © 2024 Massachusetts Medical Society.)

Objective: Anaemia affects more than half of Indian women and children, but the contribution of its causes remains unquantified. We examined interrelationships between Hb and nutritional, environmental, infectious and genetic determinants of anaemia in non-pregnant mothers and children in Uttar Pradesh (UP)., Design: We conducted a cross-sectional survey of households in twenty-five districts of UP between October and December 2016. We collected socio-demographic data, anthropometry and venous blood in 1238 non-pregnant mothers and their children. We analysed venous blood samples for malaria, Hb, ferritin, retinol, folate, Zn, vitamin B 12 , C-reactive protein, α 1-acid glycoprotein (AGP) and β -thalassaemia. We used path analysis to examine pathways through which predictors of anaemia were associated with Hb concentration., Setting: Rural and urban households in twenty-five districts of UP., Participants: Mothers 18-49 years and children 6-59 months in UP., Results: A total of 36·4 % of mothers and 56·0 % of children were anaemic, and 26·7 % of women and 44·6 % of children had Fe deficiency anaemia. Ferritin was the strongest predictor of Hb ( β (95 % CI) = 1·03 (0·80, 1·27) g/dL in women and 0·90 (0·68, 1·12) g/dL in children). In children only, red blood cell folate and AGP were negatively associated with Hb and retinol was positively associated with Hb., Conclusions: Over 70 % of mothers and children with anaemia had Fe deficiency, needing urgent attention. However, several simultaneous predictors of Hb exist, including nutrient deficiencies and inflammation. The potential of Fe interventions to address anaemia may be constrained unless coexisting determinants are jointly addressed.

Introduction: Prevalence of undernutrition continues to be high in India and low household wealth is consistently associated with undernutrition. This association could be modified through improved dietary intake, including dairy consumption in young children. The beneficial effect of dairy on child growth has not been explored at a national level in India. The present analyses aimed to evaluate the direct and indirect (modifying association of household level per adult female equivalent milk and milk product consumption) associations between household wealth index on height for age (HAZ) and weight for age (WAZ) in 6-59 months old Indian children using data from of nationally representative surveys., Methods: Two triangulated datasets of two rounds of National Family Health Survey, (NFHS-3 and 4) and food expenditure (National Sample Survey, NSS61 and 68) surveys, were produced by statistical matching of households using Non-Iterative Bayesian Approach to Statistical Matching technique. A Directed Acyclic Graph was constructed to map the pathways in the relationship of household wealth with HAZ and WAZ based on literature. The direct association of wealth index and its indirect association through per adult female equivalent dairy consumption on HAZ and WAZ were estimated using separate path models for each round of the surveys., Results: Wealth index was directly associated with HAZ and WAZ in both the rounds, but the association decreased from NFHS-3 (β HAZ : 0.145; 95% CI: 0.129, 0.16) to NFHS-4 (β HAZ : 0.102; 95%CI: 0.093, 0.11). Adult female equivalent milk intake (increase of 10gm/day) was associated with higher HAZ (β&#95;NFHS-3=0.001;95% CI: 0, 0.002; β&#95;NFHS-4=0.002;95% CI: 0.002, 0.003) but had no association with WAZ. The indirect association of wealth with HAZ through dairy consumption was 2-fold higher in NFHS-4 compared to NFHS-3., Conclusions: The analysis of triangulated survey data shows that household level per- adult female equivalent dairy consumption positively modified the association between wealth index and HAZ, suggesting that regular inclusion of milk and milk products in the diets of children from households across all wealth quintiles could improve linear growth in this population., (© 2024. The Author(s).)

Background: Given the importance of infancy for establishing growth trajectories, with later-life health consequences, we investigated longitudinal body composition among infants from six economically and ethnically diverse countries., Methods: We recruited mother-infant dyads using the WHO Multicenter Growth Reference Study criteria. We measured fat-free mass (FFM) in 1393 (49% female) infants from birth to 6 months of age (Australia, India, and South Africa; n = 468), 3-24 months of age (Brazil, Pakistan, South Africa, and Sri Lanka; n = 925), and derived fat mass (FM), fat mass index (FMI), and fat-free mass index (FFMI). Height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length (WHZ) Z-scores were computed. Sex differences were assessed using a t-test, and country differences using a one-way analysis of covariance. We further compared subsamples of children with average (-0.25 > HAZ < +0.25), below-average (≤-0.25) and above-average (≥+0.25) HAZ., Results: HAZ performed well between 0 and 6 months, but less so between 3 and 24 months. The stunting prevalence peaked at 10.3% for boys and 7.8% for girls, at 24 months. By 24 months, girls had greater FMI (10%) than boys. There were significant differences in FFM (both sexes in all countries) and FM (Brazilian boys, Pakistani and South African girls) by 24 months of age between infants with average, above-average, and below-average HAZ., Conclusion: In a multi-country sample representing more ideal maternal conditions, body composition was heterogeneous even among infants who exhibited ideal length. Having a mean HAZ close to the median of the WHO standard for length reduced FFM between-country heterogeneity but not FM, suggesting that other factors may influence adiposity., (© 2024. The Author(s).)

In response to the continuing high prevalence of anaemia recorded in the National Family Health Survey-5, the Indian government launched a policy for mandatory iron fortification of the rice provided through public nutrition programmes in India. This was done even though a rigorous evidence analysis had already concluded that rice fortification was not effective in preventing anaemia or iron deficiency at the population level. Fortification also poses a potential risk of iron toxicity over time, but there is no stated time period for the policy's implementation. The risk is particularly high in segments of the population who already have a high habitual iron intake, and who could be exposed to simultaneous fortification in different staples and food commodities along with the ongoing weekly Iron and Folic Acid tablets supplementation programme. Finally, this fortification policy also requires significant additional funding and resources to implement. It is crucial to examine such mandatory health actions, and to weigh the benefits and risks of harm, using the principles of public health ethics.

Background and Aims: Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology affecting the enteric nervous system (ENS). Since the early gestational development of the ENS is dependent on the prenatal maternal metabolic environment, the objective of this pilot study was to explore the role of specific maternal plasma metabolites in the etiology of HSCR., Methods: In this cross-sectional study, postnatal (as a surrogate for prenatal) plasma samples were obtained from mothers of children diagnosed with HSCR ( n = 7) and age-matched mothers of normal children ( n = 6). The plasma metabolome was analyzed by ultra-high-pressure liquid chromatography and mass spectrometry. Metabolites were identified by mzCloud using Compound Discoverer software. Using an untargeted metabolomics workflow, metabolites with case versus control group differences were identified., Results: A total of 268 unique plasma metabolites were identified and annotated in maternal plasma. Of these, 57 were significantly different between case and control groups ( P < 0.05, t -test). Using a false discovery rate corrected cutoff of 10% to adjust for multiple comparisons, 19 metabolites were significantly different in HSCR cases, including carnitines, medium-chain fatty acids, and glutamic acid. Pathways affected were for amino acid and lipid metabolism., Conclusion: Disordered prenatal metabolic pathways may be involved in the etiopathogenesis of HSCR in the developing fetus. This is the first study to assess maternal plasma metabolomics in HSCR., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Indian Association of Pediatric Surgeons.)

Background: Clinical and biochemical vitamin B 12 (B 12 ) deficiency is lower than anticipated in vegetarians. Extraileal absorption, such as from the colon, as well as reduced daily excretion, may be adaptive mechanisms to maintain B 12 homeostasis with marginal intakes., Objective: To measure the absorption of B 12 from the small and large intestine, and its daily rate of excretion from the body, using a [ 13 C]-cyanocobalamin tracer., Methods: Oral B 12 bioavailability was measured over 12 h after administration of [ 13 C]-cyanocobalamin tracer (2.5 μg) in normal participants. The colonic B 12 bioavailability was evaluated by direct instillation of [ 13 C]-cyanocobalamin (5 μg) into the ascending colon. Bioavailability was calculated from 2-compartmental modeling of the tracer appearance in plasma. The excretion rate of B 12 was measured from [ 13 C]-cyanocobalamin elimination from the body over 4 wk after oral dosing (5 μg)., Results: The oral B 12 bioavailability (n = 11) was 63% ± 10% measured over 12 h. A late absorption peak, accounting for 12% of the absorption, was observed after an average lag time of 8.7 h from dosing. The colonic B 12 bioavailability (n = 10) was 7% ± 5% over 4 h. The daily B 12 excretion rate (n = 4) was 0.7 ± 0.2 μg/d. The minimum daily requirement of B 12 in these participants was derived at 1 μg /d., Conclusions: B 12 is absorbed in the human colon. This observation confirms the potential contribution of the colon in daily B 12 nutriture, and along with a possible lower requirement, could explain the absence of clinical deficiency in populations with marginal B 12 intakes., Trial Registration Number: This study was registered in Clinical Trials Registry of India (CTRI) with the registration number CTRI/2018/04/012957, available from https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49319&EncHid=&userName=029108., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: There is limited data in term low birth weight neonates from urban poor settings on the incidence of and recovery from undernutrition and co-existence of its different forms, under conditions of appropriate health and nutrition care counselling., Objectives: To determine the longitudinal growth and undernutrition burden among term low birth weight newborns reared in adverse conditions, but with appropriate counselling., Methods: The study reports follow-up data from DIVIDS trial. 2079 term low birth weight (1800-2499 grams) newborns from an urban poor setting were followed-up for growth from 0 to 26 weeks (n=1282) and at 2.8-6.8 years (n=912). Using Cole LMS approach, age- and sex-specific internal z scores were computed and subsequently adjusted for the effect of a vitamin D intervention and potential bias due to attrition. Back-transformed measurements were then used to compute WHO z scores for height for age (HAZ), weight for age (WAZ), and BMI for age (BMIZ)., Results: HAZ remained fairly stable: mean changes from birth till 6 weeks, 26 weeks and 3-7 years were 0.07, 0.04 and 0.2 SD, respectively. BMIZ and WAZ showed considerable catch-up; 0.69 SD, 1.84 SD and 1.38 SD for BMIZ, and 0.25 SD, 0.89 SD and 0.60 SD for WAZ, respectively. 60-92% had at least one form of undernutrition and co-existence was frequent. Half the children remained stunted till 5 years, while underweight and wasting declined considerably from 0-6 months., Conclusion: With appropriate counselling of parents, term low birth weight infants reared under adverse socioeconomic conditions show substantial catch-up growth in BMIZ and WAZ but not in HAZ. The long-term consequences of this excess weight over length gain need focused evaluation.

Background: The deuterium dose-to-mother (DTM) method measures the human milk intake of breastfed children. Recently, the use of this method has been expanded to classify babies objectively as exclusively breast fed (EBF) or not (non-EBF) based on quantification of non-milk oral water intake (NMOI). However, the calculation of NMOI estimates involves atmospheric temperature and humidity., Objective: To evaluate the effects of atmospheric temperature and humidity on NMOI calculation and the classification of exclusive breastfeeding., Methods: The effect of indoor temperature and relative humidity on NMOI and the estimated prevalence of non-EBF were examined in two existing data sets of DTM in children by varying temperature in the range of 15 to 35°C and relative humidity in the range of 20 to 80% representing the maximum span of indoor conditions expected. Population-level estimates of NMOI distributions were derived using the rstan package for R v2.21.2., Results: The NMOI decreased at a rate of -1.15 g/day per °C increase and at a rate of -1.01 g/day per percent increase in relative humidity; this was due to variations in non-oral water intake from the atmosphere, a component of the calculation of NMOI, which is dependent on temperature and humidity. For the various locations considered, the mean calculated NMOI varied between 24.6 and 53.3 g/day using the same input data. In the mixed-fed sample of babies, the prevalence of non-EBF based on the earlier defined NMOI cut-off of 86.6 g/day was reduced by 19% when relative humidity was increased by 60%., Conclusions: Atmospheric conditions are essential factors in the computation of NMOI, used in the objective classification of babies as exclusively breast fed or not, and should be considered when the DTM method is used to classify exclusive breastfeeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Baby, Kaestel, Preston, Duffull, Liu, Diana, Houghton, Kurpad and Thomas.)

While studies on ambient fine particulate matter (PM 2.5 ) exposure effect on child health are available, the differential effects, if any, of exposure to PM 2.5 species are unexplored in lower and middle-income countries. Using multiple logistic regression, we showed that for every 10 μg m -3 increase in PM 2.5 exposure, anaemia, acute respiratory infection, and low birth weight prevalence increase by 10% (95% uncertainty interval, UI: 9-11), 11% (8-13), and 5% (4-6), respectively, among children in India. NO 3 - , elemental carbon, and NH 4 + were more associated with the three health outcomes than other PM 2.5 species. We found that the total PM 2.5 mass as a surrogate marker for air pollution exposure could substantially underestimate the true composite impact of different components of PM 2.5 . Our findings provide key indigenous evidence to prioritize control strategies for reducing exposure to more toxic species for greater child health benefits in India., (© 2023. The Author(s).)

Objective: To examine the accuracy of World Health Organization (WHO) growth standard in under-5 year Indian children, and identify a method to contextualize the WHO standard for India., Participants: Data of Healthy children, defined by WHO selection criteria, extracted from nationally representative Indian surveys (National Family Health Surveys, NFHS-3, NFHS-4, NFHS-5 and Comprehensive National Nutrition Survey, CNNS)., Design: Height for age z score (HAZ) and weight for age z score (WAZ) and weight for height z score (WHZ) distributions in healthy sample were compared against the standard normal. If deviant, age-specific correction factors for z scores were estimated by hierarchical linear mixed effects mean and variance polynomial models. A new term, excess mean risk of growth faltering (EMRGF), was introduced to describe growth faltering., Main Outcome: Measure of deviation of HAZ, WAZ and WHZ from standard normal distribution. Correction of WHO growth standards for India leading to accurate prevalence of stunting, underweight and wasting in Indian children using NFHS-5 data., Results: Data on 10,384 healthy under-5 year children were extracted, of which 5377 were boys. Across surveys and metrics, the mean z scores were significantly lower than zero (-0.52 to -0.79). HAZ and WHZ variability (1.16, 1.07) were significantly higher than 1. Derived age-specific corrections reduced the NFHS-5 prevalence of growth faltering by 50%. The national EMRGF (after applying the age-specific correction) for height for age was 15.5% (95%CI:15.3-15.8), and weight for age was 15.0% (95%CI:14.8-15.3), respectively, in NFHS-5., Conclusion: The WHO growth standards need contextual customization for accurate estimation of the burden of growth faltering in under-5 year children in India. When corrected, the burden of growth faltering is lower, by half or more, in all the three indices.

Background/objectives: Two compartment (2 C) models of body composition, including Air Displacement Plethysmography (ADP) and Deuterium Dilution (DD), assume constant composition of fat-free mass (FFM), while 3-compartment (3 C) model overcomes some of these assumptions; studies are limited in infants. The objective of the present study is to compare 3 C estimates of body composition in 6-mo. old infants from Australia, India, and South Africa, including FFM density and hydration, compare with published literature and to evaluate agreement of body composition estimates from ADP and DD., Methods: Body volume and water were measured in 176 healthy infants using ADP and DD. 3C-model estimates of fat mass (FM), FFM and its composition were calculated, compared between countries (age and sex adjusted) and with published literature. Agreement between estimates from ADP and DD were compared by Bland-Altman and correlation analyses., Results: South African infants had significantly higher % FM (11.5%) and density of FFM compared to Australian infants. Australian infants had significantly higher % FFM (74.7 ± 4.4%) compared to South African infants (71.4 ± 5.0) and higher FFMI (12.7 ± 0.8 kg/m 2 ) compared to South African (12.3 ± 1.2 kg/m 2 ) and Indian infants (11.9 ± 1.0 kg/m 2 ). FFM composition of present study differed significantly from literature. Pooled three country estimates of FM and FFM were comparable between ADP and DD; mean difference of -0.05 (95% CI: -0.64, +0.55) kg and +0.05 (95% CI: -0.55, +0.64) kg., Conclusions: 3C-model estimates of body composition in infants differed between countries; future studies are needed to confirm these findings and investigate causes for the differences., (© 2023. The Author(s).)

Background: Agronomic zinc biofortification of wheat by foliar application increases wheat zinc content and total zinc absorption in humans., Objectives: To assess the effect of agronomically biofortified whole wheat flour (BFW) on plasma zinc (PZC) compared with a postharvest fortified wheat (PHFW) and unfortified control wheat (CW) when integrated in a midday school meal scheme., Methods: We conducted a 20-wk double-blind intervention trial in children (4-12 y, n = 273) individually randomly assigned to 3 groups to receive a daily school lunch consisting of 3 chapattis prepared with the 3 different wheat flour types. Measurements of anthropometry, blood biochemistry, and leukocyte DNA strand breaks were conducted. We applied sparse serial sampling to monitor PZC over time, and analysis was performed using linear mixed-effects models., Results: Mean zinc content in BFW, PHFW, and CW were 48.0, 45.1, and 21.2 ppm, respectively (P < 0.001). Mean (standard deviation) daily zinc intakes in the study intervention in BFW, PHFW, and CW groups were 4.4 (1.6), 5.9 (1.9) and 2.6 (0.6) mg Zn/d, respectively, with intake in groups PHFW and BFW differing from CW (P < 0.001) but no difference between BFW and PHFW. There were no time effect, group difference, or group × time interaction in PZC. Prevalence of zinc deficiency decreased in the BFW (from 14.1%-11.2%), PHFW (from 8.9%-2.3%), and CW (9.8%-8.8%) groups, but there was no time × treatment interaction in the prevalence of zinc deficiency (P = 0.191). Compliance with consuming the study school meals was associated with PZC (P = 0.006). DNA strand breaks were not significantly associated with PZC (n = 51; r = 0.004, P = 0.945)., Conclusions: Consumption of either PHFW or BFW provided an additional ∼1.8 to 3.3 mg Zn/d, but it did not affect PZC or zinc deficiency, growth, or DNA strand breaks. This trial was registered on clinicaltrials.gov as NCT02241330 and ctri.nic.in as CTRI/2015/06/005913., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Protein quality of the red kidney bean (RKB), a common source of dietary protein, has been assessed using the protein digestibility-corrected amino acid score (PDCAAS) determined in animal models using mainly oro-fecal digestibility. More recently, the FAO recommended to use digestible indispensable amino acid score (DIAAS) instead of PDCAAS but highlighted insufficient data on true ileal indispensable amino acid (IAA) digestibility of proteins because amino acids are absorbed in the ileum., Objectives: Using a recently developed dual stable isotope tracer method, we aimed to measure each IAA digestibility as representation of true ileal digestibility of the RKB, Phaseolus vulgaris, in humans consuming a typical Jamaican meal., Methods: RKB-IAAs were intrinsically labeled by adding 2 H 2 O to the plants. Uniformly labeled-[ 13 C]-spirulina (standard protein) was added to a meal prepared with the labeled RKB and fed to 10 healthy adults (5 males, 5 females) in a nonrandomized trial as primed/intermittent doses to achieve a steady state IAA enrichment in plasma. Enrichment of 2 H- and 13 C-labeled IAA in plasma and the bean was measured by mass spectrometry. Each IAA digestibility (except tryptophan and histidine) was calculated as the ratio of plasma 2 H-IAA to meal 2 H-IAA divided by the ratio of plasma 13 C-IAA to meal 13C-IAA adjusted for loss of 2 H-atom during transamination and digestibility of spirulina., Results: Adequate IAA labeling (>1000 ppm 2 H excess) and plasma plateau isotopic enrichment were achieved. Mean RKB-IAA digestibility (%) was 79.4 ± 0.5, ranging from 69.0 ± 1.2 (threonine) to 85.7 ± 1.7 (lysine)., Conclusion: The dual stable isotope tracer digestibility data are similar to published oro-fecal digestibility supporting substantial nitrogen exchange in the colon. The individual IAA digestibility is useful to derive DIAAS to replace PDCAAS. Using published RKB-IAA composition, extrapolated DIAAS was 0.63 based on the lowest score for methionine., Clinical Trial Registration: https://register., Clinicaltrials: gov; ID: NCT-04118517., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: The persistent high prevalence of anaemia among Indian women of reproductive age (WRA) despite aggressive long-term iron supplementation could be related to over-diagnosis from an inappropriately high haemoglobin (Hb) diagnostic cut-off. To develop an appropriate cut-off for Indian WRA, we hypothesized that during iron-folic acid (IFA) supplementation to a mixed (anaemic/non-anaemic) WRA population, the positive slope of the Hb-plasma ferritin (PF) response in anaemic women would inflect into a plateau (zero-response) as a non-anaemic status is reached. The 2.5th percentile of the Hb distribution at this inflection point will be the diagnostic Hb cut-off for iron-responsive anaemia., Method: A hierarchical mixed effects model, with a polynomial mean and variance model to account for intraclass correlation due to repeated measures, was used to estimate the response curve of Hb to PF, or body iron stores, in anaemic and non-anaemic WRA (without inflammation), who were receiving a 90-day IFA supplementation., Results: The Hb response curve at low PF values showed a steep increase, which inflected into a plateau at a PF of 10.1 µg/L and attained a steady state at a PF of 20.6 µg/L. The Hb distribution at the inflection was a normal probability distribution, with a mean of 12.3 g/dL. The 2.5th percentile value of this distribution, or the putative diagnostic Hb cut-off for anaemia, was 10.8 g/dL (~11 g/dL)., Conclusion: The derived Hb cut-off is lower than the current adult values of 12 g/dL and could partly explain the persistently high prevalence of anaemia., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: /Objective: The extent of exocrine pancreatic insufficiency (EPI) in the paediatric population with acute pancreatitis (AP) is unknown. The primary objective was to use a 6 h stable-isotope breath test to determine the prevalence of EPI in children with AP. The secondary objective was to determine the diagnostic ability of a 4 h abbreviated breath test in the detection of EPI., Methods: 13 C-mixed triglyceride (MTG) breath test was used to measure fat digestibility in 12 children with AP and 12 normal children. EPI was diagnosed based on a cumulative dose percentage recovery (cPDR) cut-off value < 26.8% present in literature. To reduce the test burden, the diagnostic accuracy of an abbreviated 4 h test was evaluated, using a cPDR cut-off that was the 2.5 th percentile of its distribution in control children., Results: The cPDR of cases was significantly lower than that of controls (27.71 ± 7.88% vs 36.37 ± 4.70%, p = 0.005). The cPDR during acute illness was not significantly different to that at 1 month follow up (24.69 ± 6.83% vs 26.98 ± 11.10%, p = 0.52). The 4 h and 6 h breath test results correlated strongly (r = 0.93, p < 0.001) with each other. The new 4 h test had 87.5% sensitivity and 93.8% specificity for detecting EPI., Conclusion: Two-thirds (66.7%) of this sample of children with AP had EPI during admission, which persisted at 1 month follow up. The 4 h abbreviated 13 C-MTG breath test has good diagnostic ability to detect EPI in children and may improve its clinical utility in this age group., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Introduction: The gene-environment interaction of the REarranged during Transfection ( RET ) gene with vitamin A in the etiopathogenesis of Hirschsprung disease (HSCR) has been suggested in rodents. The aim of this study was to evaluate vitamin A status in mothers of children with HSCR and to assess its association with pathogenic variants of the RET gene in affected children., Methods: This was a case-control study of stable isotope-based vitamin A measurement stores of mothers of children diagnosed with HSCR (within 8 months from birth, n = 7) and age-matched mothers of normal children (n = 6). Next-generation sequencing of RET exons, along with their upstream promoter region, was performed in the 7 HSCR proband-parent triads to evaluate pathogenic variants., Results: Maternal vitamin A stores in the HSCR group was almost 50% that of those in controls, tending toward significance (0.50 ± 0.17 vs 0.89 ± 0.51 μmol/g respectively, P = 0.079). Two novel pathogenic de novo mutations were identified in 2 cases, and a rare single-nucleotide deletion was detected in the 3.5-kb RET upstream region, in a heterozygous state, in all 7 proband-parent triads. Low-penetrance RET haplotypes associated with HSCR were detected in 5 cases., Discussion: Mothers with children with HSCR had lower vitamin A liver stores than mothers with normal children, and the children who were affected had HSCR despite having no established pathogenic RET variants. Lower maternal vitamin A status may increase the penetrance of genetic mutations in RET , and vitamin-A mediated gene-environment interactions may underpin some of the etiology of HSCR., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background/objective: Available evidence on infant body composition is limited. This study aimed to investigate factors associated with body composition at 6 and 24 months., Subjects/methods: Multicenter study with data from a 0 to 6-mo cohort (Australia, India and South Africa) and a 3 to 24-mo cohort (Brazil, Pakistan, South Africa, and Sri Lanka). For the 0-6-mo cohort, body composition was assessed by air-displacement plethysmography (ADP) and for the 3-24-month cohort by the deuterium dilution (DD) technique. Fat mass (FM), fat-free mass (FFM), FM index (FMI), and FFM index (FFMI) were calculated. Independent variables comprised the Gini index of the country, maternal and infant characteristics, and breastfeeding pattern at 3 months. For the 3-24-mo cohort, breastfeeding, and minimum dietary diversity (MDD) at 12 months were also included. Crude and adjusted analyses stratified by sex were conducted by multilevel modelling using mixed models., Results: At 6 months, every 1 kg increase in birth weight was associated with an increase of 0.716 kg in FFM and 0.582 kg/m 2 in FFMI in girls, whereas in boys, the increase was of 0.277 kg in FFM. At 24 months, compared to those weaned before 12 months, girls still breastfed at 12 months presented a decrease of 0.225 kg in FM, 0.645 kg in FFM and 0.459 kg/m 2 in FFMI, and in boys the decreases were of 0.467 kg in FM, 0.603 kg in FFM and 0.628 kg/m 2 in FFMI., Conclusion: Birth weight and breastfeeding are independent predictors of body composition in early life, irrespective of sex., (© 2023. The Author(s).)

Providing all infants with the best start to life is a universal but challenging goal for the global community. Historically, the size and shape of infants, quantified by anthropometry and commencing with birthweight, has been the common yardstick for physical growth and development. Anthropometry has long been considered a proxy for nutritional status during infancy when, under ideal circumstances, changes in size and shape are most rapid. Developed from data collected in the Multicentre Growth Reference Study (MGRS), WHO Child Growth Standards for healthy infants and children have been widely accepted and progressively adopted. In contrast, and somewhat surprisingly, much less is understood about the 'quality' of growth as reflected by body composition during infancy. Recent advances in body composition assessment, including the more widespread use of air displacement plethysmography (ADP) across the first months of life, have contributed to a progressive increase in our knowledge and understanding of growth and development. Along with stable isotope approaches, most commonly the deuterium dilution (DD) technique, the criterion measure of total body water (TBW), our ability to quantify lean and fat tissue using a two-compartment model, has been greatly enhanced. However, until now, global reference charts for the body composition of healthy infants have been lacking. This paper details some of the historical challenges associated with the assessment of body composition across the first two years of life, and references the logical next steps in growth assessments, including reference charts., (© 2023. The Author(s).)

There has been recent advocacy for food fortification with zinc in India. However, there are three important conditions that should be established before fortifying food with any micronutrient, which requires that there should be i) Established high prevalence of biochemical or sub-clinical deficiency (≥20%), ii) Low dietary intakes that increase the risk of deficiency, and iii) Evidence of efficacy of supplementation from clinical trials. For zinc, all three conditions are not satisfied. The prevalence of low serum zinc concentrations in Indian children is well below 20% (~6%), signifying that zinc deficiency is not a public health problem. There is no risk of dietary zinc inadequacy in Indian populations where intake has been measured. Finally, there is no robust evidence that zinc-fortified foods improve functional outcomes, even if the serum zinc concentration is increased. Thus, contemporary evidence does not justify the need for food fortification with zinc in India.

Milk and legumes are good source of protein foods used to sustain muscle mass, but their effects on postprandial glucose homeostasis and energy metabolism may be different. This is relevant, for example, in the dietetic response to obesity or diabetes, where the intake of high-quality protein is often increased significantly. The objective of this study was to characterize the acute effect of whey and soy protein (15% vs. 30%) on glucose homeostasis, energy metabolism, and satiety. Healthy, normal body mass index (BMI) Indian adult males aged 20-35 years ( n  = 15) received 4 test meals (2 proteins (soy vs. whey) and 2 doses (15% vs. 30% protein: energy ratio)). Blood samples were collected serially after the meal to calculate the incremental area under the curve for plasma glucose and insulin. Energy expenditure and substrate oxidation were measured after the meal. Satiety was measured with a visual analogue scale. The insulin response, represented by the incremental area under the curve, was significantly higher for the 30% whey compared to the 30% soy protein meal ( p < 0.01) but was not significantly different between the 15% protein doses. There were no differences in the plasma glucose response across protein sources or doses. The mean peak fat and carbohydrate oxidation, satiety, and energy expenditure did not differ between the protein sources and doses. In conclusion, at higher doses, whey protein has a greater insulinogenic response, compared to soy protein, and exhibits a dose-response effect. However, at lower doses, whey and soy protein elicit similar insulinogenic responses, making them equally effective protein sources in relation to glucose homoeostasis., Competing Interests: At the time of this study, Cope M and Mukherjea R (coauthors) were part of DuPont Nutrition & Biosciences, St Louis, MO, USA., (Copyright © 2023 Sucharita Sambashivaiah et al.)

Deficiencies of vitamin B 12 (B 12 ) and folate (FA) are of particular interest due to their pleiotropic role in 1-carbon metabolism. In addition to adverse birth outcomes, deficiencies of B 12 and FA, or an imbalance in FA/B 12 status, are linked to metabolic disorders. Indian diets that are predominantly plant food-based could be deficient in these vitamins, but there are no national estimates of the prevalence of B 12 and FA deficiency in Indian children and adolescents, nor their associations with age, sex and growth indicators. The recent Comprehensive National Nutrition Survey (CNNS-2016-18) provided estimates of the prevalence of B 12 and FA deficiency at the national and state levels among preschool (1-4 years: 9976 and 11,004 children, respectively), school-age children (5-9 years: 12,156 and 14,125) and adolescents (10-19 years: 11,748 and 13,621). Serum B 12 and erythrocyte FA were measured by the direct chemiluminescence method and their deficiency was defined using WHO cut-offs. The prevalence of B 12 and FA deficiency was high among adolescents (31.0%, CI: 28.7-33.5 and 35.6%, CI: 33.1-8.2) compared to school-age (17.3%, CI: 15.4-19.3 and 27.6%, CI: 25.5-29.9) and preschool children (13.8%, CI: 11.7-16.2 and 22.8%, CI: 20.5-25.2, respectively). The prevalence of both B 12 and FA deficiency was significantly higher by 8% and 5%, respectively, in adolescent boys compared to girls. There was no association between anthropometric undernutrition and B 12 and FA deficiency. There was wide regional variation in the prevalence of B 12 and FA deficiency, but no rural-urban differences were observed across all age groups. The national prevalence of B 12 deficiency among preschool or school-age children was <20% (the cut-off that indicates a public health problem). However, FA deficiency in these age groups and both FA and B 12 deficiencies in adolescents were >20%, warranting further investigation.

Background: The digestion and absorption of ingested protein may be reduced in children with environmental enteric dysfunction (EED), reducing systemic amino acid availability for protein synthesis with resultant growth faltering. This has not been directly measured in children with EED and associated growth faltering., Objectives: To evaluate the systemic availability of algal (spirulina) and legume (mung bean) indispensable amino acids (IAAs) in children with EED., Methods: Indian children (18-24 mo) from urban slums were assigned to EED (n = 24) or no-EED (control, n = 17) groups based on the lactulose rhamnose test, where the lactulose rhamnose ratio cutoff for diagnosing EED (≥0.068) was the mean + 2SD of its distribution in healthy, age-, and sex-matched children of high socioeconomic status. Fecal biomarkers of EED were also measured. Systemic IAA availability was calculated from the plasma: meal IAA enrichment ratio for each protein. True ileal mung bean IAA digestibility was measured by the dual isotope tracer method using spirulina protein as reference. Co-administration of free 13 C 6 -phenylalanine allowed for estimating true ileal phenylalanine digestibility of both proteins, and a phenylalanine absorption index., Results: There was no significant difference (independent t-test) in the systemic IAA availability from spirulina or mung bean protein between EED and no-EED groups. There was no between-group difference in true ileal phenylalanine digestibility and its absorption index, or in mung bean IAA digestibility., Conclusions: The systemic IAA availability of algal and legume protein, or the latter's IAA/phenylalanine digestibility, is not significantly reduced in children with EED and does not correlate with linear growth. This study was registered in Clinical Trials Registry of India (CTRI) with registration number: CTRI/2017/02/007921., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Body composition assessment in the first 2 y of life provides important insights into child nutrition and health. The application and interpretation of body composition data in infants and young children have been challenged by a lack of global reference data., Objectives: We aimed to develop body composition reference charts of infants aged 0-6 mo based on air displacement plethysmography (ADP) and those aged 3-24 mo based on total body water (TBW) by deuterium dilution (DD)., Methods: Body composition was assessed by ADP in infants aged 0-6 mo from Australia, India, and South Africa. TBW using DD was assessed for infants aged 3-24 mo from Brazil, Pakistan, South Africa, and Sri Lanka. Reference charts and centiles were constructed for body composition using the lambda-mu-sigma method., Results: Sex-specific reference charts were produced for FM index (FMI), FFM index (FFMI), and percent FM (%FM) for infants aged 0-6 mo (n = 470 infants; 1899 observations) and 3-24 mo (n = 1026 infants; 3690 observations). When compared with other available references, there were observable differences but similar patterns in the trajectories of FMI, FFMI, and %FM., Conclusions: These reference charts will strengthen the interpretation and understanding of body composition in infants across the first 24 mo of life., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: We declare no competing interests.

Background/objectives: Chronic immune activation in Environmental Enteric Dysfunction (EED) could lead to increased fed-state metabolic rate (MR) or total energy expenditure (TEE) and limit the energy available for optimal linear growth. In a secondary analysis, MR and TEE were compared in young Indian children from urban slums, with and without stunting or EED., Subjects/methods: Children (18-24 months, n = 69) were classified into non-stunted (LAZ ≥ -2) and stunted (LAZ < -2), and no-EED (lactulose rhamnose ratio, LRR < 0.068) and EED (LRR ≥ 0.068) groups. Associations between MR and TEE (kcal per kg bodyweight [BW] or fat free mass [FFM]) with stunting and EED were examined using logistic regression., Results: Median TEE was significantly higher in the stunted compared to non-stunted group (76.8 versus 92.0 kcal/kg BW/day, p = <0.01). The adjusted (for sex, FFM, EED) odds ratio (AOR) for stunting with TEE (kcal/day) was 1.01 (95% CI: 1.00, 1.01), but importantly, there was no interaction between EED and TEE. The median TEE was also significantly higher in the EED compared to the no-EED group (89.1 vs 76.8 kcal/kg BW/day, p = 0.02), and the AOR (adjusted for sex and TEE) for stunting with EED was 3.56 (95% CI:1.09, 11.63). MR (per kg BW or FFM) was not associated with stunting or EED., Conclusion: Higher TEE and presence of EED were independently and positively associated with stunting. Children with EED also had higher TEE but not MR. Energetically, the higher TEE in stunted children may not specifically be linked to the presence of EED, although the latter independently had higher odds of stunting., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

In 2006, the WHO published a framework for calculating the desired level of fortification of any micronutrient in any staple food vehicle, to reduce micronutrient malnutrition. This framework set the target median nutrient intake, of the population consuming the fortified food, at the 97.5th percentile of their nutrient requirement distribution; the Probability of Inadequacy (PIA) of the nutrient would then be 2.5%. We argue here that the targeted median nutrient intake should be at Estimated Average Requirement (50 th percentile), since the intake distribution will then overlap the requirement distribution in a population that is in homeostasis, resulting in a PIA of 50%. It is also important to recognize that setting the target PIA at 2.5% may put a sizable proportion at risk of adverse consequences associated with exceeding the tolerable upper limit (TUL) of intake. This is a critical departure from the WHO framework. For a population with different age- and sex-groups, the pragmatic way to fix the fortification level for a staple food vehicle is by achieving a target PIA of 50% in the most deprived age- or sex-group of that population, subject to the condition that only a very small proportion of intakes exceed the TUL. The methods described here will aid precision in public health nutrition, to pragmatically determine the precise fortification level of a nutrient in a food vehicle, while balancing risks of inadequacy and excess intake., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Human milk provides essential nutrition for infants, and its benefits are well established. We lack data on the influence of maternal nutritional status on milk volume and composition in low-middle income countries., Objective: We aimed to 1) assess lactation performance (human milk volume, macronutrient composition, and infant energy intake) in Indian females and 2) examine the associations between maternal anthropometry (BMI, percentage body fat) and lactation performance., Methods: We conducted an observational study among 232 mother-infant dyads, 2 to 4 mo postpartum in Haryana, India. We used deuterium oxide dose-to-mother technique to measure milk volume and maternal percentage body fat and collected human milk samples to determine macronutrient and energy concentrations. Adjusted multiple linear regression models were used to examine the associations between maternal anthropometry and lactation performance., Results: The mean BMI and percentage body fat of mothers were 21.7 ± 3.6 kg/m 2 and 29.5 ± 7.7, respectively. Milk volume and macronutrient composition were similar to the reference values (means ± standard deviations: milk volume, 724 ± 184 mL/d; median (25th, 75th percentile); protein, 9.9 (8.3, 11.7) g/L; fat, 41.0 ± 15.2 g/L; energy density, 0.71 ± 0.14 kcal/g; lactose, 65.5 (55.3, 71.3) g/L). Maternal BMI and percentage body fat were not significantly associated with macronutrient composition. Both maternal BMI and percentage body fat were negatively associated with milk volume (-7.0, 95% CI: -12.4, -1.6 mL/d; -3.5, 95% CI: -6.0, -1.1mL/d, respectively) but there were no effects on the total energy intake of infants after adjusting for covariates., Conclusion: Most mothers had a normal BMI and milk of similar composition and volume to reference values. Future work in populations with a greater burden of underweight and/or obesity are needed to examine the underlying mechanisms between maternal body composition and milk volume. This trial was registered at The Clinical Trials Registry- India as CTRI/2017/01/007636., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Indian people are at high risk for type 2 diabetes (T2DM) even at younger ages and lower body weights. Already 74 million people in India have the disease, and the proportion of those with T2DM is increasing across all strata of society. Unique aspects, related to lower insulin secretion or function, and higher hepatic fat deposition, accompanied by the rise in overweight (related to lifestyle changes) may all be responsible for this unrelenting epidemic of T2DM. Yet, research to understand the causes, pathophysiology, phenotypes, prevention, treatment, and healthcare delivery of T2DM in India seriously lags behind. There are major opportunities for scientific discovery and technological innovation, which if tapped can generate solutions for T2DM relevant to the country's context and make leading contributions to global science. We analyze the situation of T2DM in India, and present a four-pillar (etiology, precision medicine, implementation research, and health policy) strategic research framework to tackle the challenge. We offer key research questions for each pillar, and identify infrastructure needs. India offers a fertile environment for shifting the paradigm from imprecise late-stage diabetes treatment toward early-stage precision prevention and care. Investing in and leveraging academic and technological infrastructures, across the disciplines of science, engineering, and medicine, can accelerate progress toward a diabetes-free nation., (© Indian Institute of Science 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

This study aimed to develop a regression equation to predict physical activity energy expenditure (PAEE) using accelerometry. Children aged 11-13 years were recruited and randomly assigned to validation ( n = 54) and cross-validation ( n = 25) groups. The doubly labelled water (DLW) technique was used to assess energy expenditure and accelerometers were worn by participants across the same period. A preliminary equation was developed using stepwise multiple regression analysis with sex, height, weight, body mass index, fat-free mass, fat mass and counts per minute (CPM) as independent variables. Goodness-of-fit statistics were used to select the best prediction variables. The PRESS (predicted residual error sum of squares) statistical method was used to validate the final prediction equation. The preliminary equation was cross-validated on an independent group and no significant ( p > 0.05) difference was observed in the PAEE estimated from the two methods. Independent variables of the final prediction equation (PAEE = [0.001CPM] - 0.112) accounted for 70.6% of the variance. The new equation developed to predict PAEE from accelerometry was found to be valid for use in Sri Lankan children.

Background: Accurate methods are needed to measure body fat mass (FM), particularly in South Asian children who are thought to have greater adiposity for a given body size. The accuracy of simple 2-compartment (2C) models of measuring FM depends on the primary measurement of the fat free mass (FFM) and the validity of assumed constants for FFM hydration and density. These have not been measured in this particular ethnic group., Objectives: To measure FFM hydration and density in South Indian children using a 4-compartment (4C) model and to compare FM estimates from this 4C-model with 2C-model-based estimates from hydrometry and densitometry, using literature-reported FFM hydration and density in children., Methods: This study included 299 children (45% boys), aged 6-16 y from Bengaluru, India. Total body water (TBW), bone mineral content (BMC), and body volume were measured using deuterium dilution, dual-energy X-ray absorptiometry, and air displacement plethysmography, respectively, to calculate the FFM hydration and density, and the FM using 4C and 2C models. The agreement between FM estimates from 2C and 4C models was also evaluated., Results: Mean FFM hydration and density were 74.2% ± 2.1% and 71.4% ± 2.0% and 1.095 ± 0.008 kg/L and 1.105 ± 0.008 kg/L in boys and girls respectively, which were significantly different from published values. Using the presently estimated constants, the mean hydrometry-based FM (as % body weight) estimates decreased by 3.5% but increased by 5.2% for densitometry-based 2C methods. When 2C-FM (using previously reported FFM hydration and density) were compared with 4C-FM estimates, the mean difference was -1.1 ± 0.9 kg for hydrometry and 1.6 ± 1.1 kg for densitometry., Conclusions: Previously published constants of hydration and density of FFM may induce errors of -12% to +17% in FM (kg) when using different 2C models in comparison to the 4C models in Indian children. J Nutr 20xx;x:xx., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Inadequate intake of fruits and vegetables is prevalent in rural areas of India, where around 65% of the population reside. Financial incentives have been shown to increase the purchase of fruits and vegetables in urban supermarkets, but their feasibility and effectiveness with unorganised retailers in rural India is unclear., Methods: A cluster-randomised controlled trial of a financial incentive scheme involving ∼20% cashback on purchase of fruits and vegetables from local retailers was conducted in six villages (3535 households). All households in three intervention villages were invited to participate in the scheme which ran for three months (February-April 2021), while no intervention was offered in control villages. Self-reported (pre-intervention and post-intervention) data on purchase of fruits and vegetables were collected from a random sub-sample of households in control and intervention villages., Findings: A total of 1109 households (88% of those invited) provided data. After the intervention, the weekly quantity of self-reported fruits and vegetables purchased were (i) 18.6 kg (intervention) and 14.2 kg (control), baseline-adjusted mean difference 4 kg (95% CI: -6.4 to 14.4) from any retailer (primary outcome); and (ii) 13.1 kg (intervention) and 7.1 kg (control), baseline-adjusted mean difference 7.4 kg (95% CI: 3.8-10.9) from local retailers participating in the scheme (secondary outcome). There was no evidence of differential effects of the intervention by household food security or by socioeconomic position, and no unintended adverse consequences were noted., Interpretation: Financial incentive schemes are feasible in unorganised food retail environments. Effectiveness in improving diet quality of the household likely hinges on the percentage of retailers willing to participate in such a scheme., Funding: This research has been funded by the Drivers of Food Choice (DFC) Competitive Grants Program, which is funded by the UK Government's Department for International Development and the Bill & Melinda Gates Foundation, and managed by the University of South Carolina, Arnold School of Public Health, USA; however, the views expressed do not necessarily reflect the UK Government's official policies., Competing Interests: SK receives research funding from 10.13039/501100000265Medical Research Council UK, University of Chiang Mai Thailand, and Ministry of AYUSH Gov of India. PM receives research funding from 10.13039/501100000265Medical Research Council UK and Ministry of AYUSH Gov of India. JL receives research funding from 10.13039/501100000265Medical Research Council, UK. HW receives research funding from 10.13039/501100002141Public Health England, the Health Services Research Initiative, and Helen Keller International, and has received honoraria from 10.13039/501100003504University of the Western Cape and ANH (Agriculture, Nutrition, & Health) Academy., (© 2023 The Authors.)