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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).)

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: Limited information on the co-prevalence of undernutrition, micronutrient deficiencies, overnutrition, and abnormal levels of noncommunicable disease biomarkers at the same time in children and adolescents in India hinders efforts to comprehensively address their health., Objectives: This study aimed to examine the prevalence and correlates of double burden of malnutrition (DBM) and triple burden of malnutrition (TBM) among children and adolescents (5-19 y) to inform policies and programs., Methods: A total of 17,599 children (5-9 y) and 16,184 adolescents (10-19 y) with available biomarker data from the Comprehensive National Nutrition Survey were included. Malnutrition was defined based on either undernutrition based on anthropometry, overnutrition/abnormal metabolic markers, and anemia/micronutrient deficiency. DBM was defined as the coexistence of any 2 forms of malnutrition. DBM+ was defined as the coexistence of undernutrition and/or micronutrient deficiency along with overnutrition. TBM was defined as having the coexistence of all 3 forms of malnutrition. The prevalence of DBM, DBM+, and TBM was estimated accounting for probabilistic selection. We used mixed-effect binomial regression to determine correlates of DBM/TBM in children and adolescents separately., Results: The prevalence of DBM, DBM+, and TBM was 50.8%, 37.2%, and 14.4%, respectively, in children and 53.4%, 36.1%, and 12.7%, respectively, in adolescents. The prevalence of DBM+ was significantly higher in girls compared to in boys in the 5-9 y age group. In children, being in a disadvantaged caste group, having a lower wealth index, having inadequate diet diversity, having no maternal schooling, and having a recent history of acute illness were associated with DBM. In adolescents, being in a disadvantaged caste group, maternal occupation, and lower paternal age were correlated with DBM. A similar set of variables was associated with TBM in both age groups., Conclusions: The prevalence of DBM and TBM is substantial in children and adolescents in India and varies across states. Socioeconomic factors and acute illness were the main correlates for DBM and TBM., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Two initiatives are reshaping how we can approach and address the persistent and widely prevalent challenge of malnutrition, the leading global risk factor for morbidity and mortality. First is the focus on precision nutrition to identify inter- and intra-individual variation in our responses to diet, and its determinants. Second is the Food is Medicine (FIM) approach, an umbrella term for programs and services that link nutrition and health through the provision of food (e.g., tailored meals, produce prescriptions) and access to healthcare services. This article outlines how interventions and programs using FIM can synergize with precision nutrition approaches to make individual- or population-level tailored nutrition accessible and affordable, help to reduce the risk of metabolic diseases, and improve quality of life., Competing Interests: Declaration of interests S.M. has an equity interest in VitaScan, a startup seeking to commercialize technology for point-of-care assessment of micronutrient status partially based on his research as a faculty member at Cornell University. The other authors report no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Precision nutrition (PN) considers multiple individual-level and environmental characteristics or variables to better inform dietary strategies and interventions for optimizing health, including managing obesity and metabolic disorders. Here, we review the evidence on potential mechanisms-including ones to identify individuals most likely to respond-that can be leveraged in the development of PN interventions addressing obesity. We conducted a review of the literature and included laboratory, animal, and human studies evaluating biochemical and genetic data, completed and ongoing clinical trials, and public programs in this review. Our analysis describes the potential mechanisms related to 6 domains including genetic predisposition, circadian rhythms, physical activity and sedentary behavior, metabolomics, the gut microbiome, and behavioral and socioeconomic characteristics, i.e., the factors that can be leveraged to design PN-based interventions to prevent and treat obesity-related outcomes such as weight loss or metabolic health as laid out by the NIH 2030 Strategic Plan for Nutrition Research. For example, single nucleotide polymorphisms can modify responses to certain dietary interventions, and epigenetic modulation of obesity risk via physical activity patterns and macronutrient intake have also been demonstrated. Additionally, we identified limitations including questions of equitable implementation across a limited number of clinical trials. These include the limited ability of current PN interventions to address systemic influences such as supply chains and food distribution, healthcare systems, racial or cultural inequities, and economic disparities, particularly when designing and implementing PN interventions in low- and middle-income communities. PN has the potential to help manage obesity by addressing intra- and inter-individual variation as well as context, as opposed to "one-size fits all" approaches though there is limited clinical trial evidence to date., (Copyright © 2024. Published by Elsevier Inc.)

Background: Small for gestational age (SGA) neonates are prone to growth deficits in early life, which may be associated with later life metabolic abnormalities., Objectives: To compare anthropometry and body composition using air-displacement plethysmography (ADP) in term SGA and appropriate for gestational age (AGA) neonates, and assess if sexual dimorphism existed in estimates of body composition., Study Design: Cross-sectional analytical study., Participants: 413 term neonates (91 SGA and 322 AGA) at birth (≤7days)., Methods: Neonatal anthropometry and body composition were measured using ADP. Length corrected fat mass index (FMI) and fat free mass index (FFMI) were calculated., Outcome: Anthropometry and body composition estimates of SGA and AGA neonates, segregated by sex., Results: The mean (SD) birth weight of SGA and AGA neonates was 2.5 (0.2) kg and 3.1 (0.3) kg, respectively. SGA neonates had significantly lower % body fat (BF) (2.0%), fat mass (94.4 g), fat free mass (FFM) (349.7 g), FMI (0.34 kg/m2), and FFMI (0.76 kg/m2), but higher %FFM (2.0%) compared to AGA neonates (P<0.001). Males had significantly higher %FFM [91.2 (3.1) vs 90.2 (3.5); P=0.001], FFM [2604 (280) vs 2442 (233) g; P<0.001], and FFMI [11.1 (0.8) vs 10.8 (0.8) kg/m2; P=0.005], but lower % BF [8.8 (3.1) vs 9.8 (3.5); P=0.001] and FMI [1.1(0.4) vs 1.2 (0.5) kg/m2; P=0.008], compared to females., Conclusions: Accurate estimates of body composition in neonates at birth suggest significantly lower body fat and fat free mass in SGA compared to AGA, with sexual dimorphism.

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

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.)

Developmental adversities early in life are associated with later psychopathology. Clustering may be a useful approach to group multiple diverse risks together and study their relation with psychopathology. To generate risk clusters of children, adolescents, and young adults, based on adverse environmental exposure and developmental characteristics, and to examine the association of risk clusters with manifest psychopathology. Participants (n = 8300) between 6 and 23 years were recruited from seven sites in India. We administered questionnaires to elicit history of previous exposure to adverse childhood environments, family history of psychiatric disorders in first-degree relatives, and a range of antenatal and postnatal adversities. We used these variables to generate risk clusters. Mini-International Neuropsychiatric Interview-5 was administered to evaluate manifest psychopathology. Two-step cluster analysis revealed two clusters designated as high-risk cluster (HRC) and low-risk cluster (LRC), comprising 4197 (50.5%) and 4103 (49.5%) participants, respectively. HRC had higher frequencies of family history of mental illness, antenatal and neonatal risk factors, developmental delays, history of migration, and exposure to adverse childhood experiences than LRC. There were significantly higher risks of any psychiatric disorder [Relative Risk (RR) = 2.0, 95% CI 1.8-2.3], externalizing (RR = 4.8, 95% CI 3.6-6.4) and internalizing disorders (RR = 2.6, 95% CI 2.2-2.9), and suicidality (2.3, 95% CI 1.8-2.8) in HRC. Social-environmental and developmental factors could classify Indian children, adolescents and young adults into homogeneous clusters at high or low risk of psychopathology. These biopsychosocial determinants of mental health may have practice, policy and research implications for people in low- and middle-income countries.

Background: RBC folate concentrations are monitored at the population level, with a recommended threshold for optimal neural tube defect (NTD) prevention. A corresponding threshold for serum folate has not been established., Objectives: This study aimed to estimate the serum folate insufficiency threshold corresponding to the RBC folate threshold for NTD prevention and examine how this threshold is modified by vitamin B 12 status., Methods: Participants were women (15-40 y; not pregnant or lactating; n = 977) from a population-based biomarker survey in Southern India. RBC folate and serum folate were measured via microbiologic assay. RBC folate deficiency (<305 nmol/L) and insufficiency (<748 nmol/L), serum vitamin B 12 deficiency (<148 pmol/L) and vitamin B 12 insufficiency (<221 pmol/L), elevated plasma MMA (>0.26 μmol/L), elevated plasma homocysteine (>10.0 μmol/L), and elevated HbA1c (≥6.5%) were evaluated. Bayesian linear models were used to estimate unadjusted and adjusted thresholds., Results: Compared with adequate vitamin B 12 status, the estimated serum folate threshold was higher in participants with serum vitamin B 12 deficiency (72.5 vs. 28.1 nmol/L) or vitamin B 12 insufficiency (48.7 vs. 24.3 nmol/L) and elevated MMA (55.6 vs. 25.9 nmol/L). The threshold was lower in participants with elevated HbA1c (HbA1c ≥6.5% vs. <6.5%; 21.0 vs. 40.5 nmol/L)., Conclusions: The estimated serum folate threshold for optimal NTD prevention was similar to previous reports (24.3 vs. 25.6 nmol/L) among participants with sufficient vitamin B 12 status. However, this threshold was more than 2-fold higher in participants with vitamin B 12 deficiency and substantially higher across all indicators of insufficient vitamin B 12 status (<221 pmol/L, elevated MMA, combined B 12 , impaired vitamin B 12 status), and lower in participants with elevated HbA1c. Findings suggest a serum folate threshold for NTD prevention may be possible in some settings; however, it may not be appropriate in populations with high prevalence of vitamin B 12 insufficiency. Am J Clin Nutr 2023;xx:xx-xx. This trial was registered at https://clinicaltrials.gov as NCT04048330., (Copyright © 2023 American Society for Nutrition. All rights reserved.)

With the growth of decentralized/federated analysis approaches in neuroimaging, the opportunities to study brain disorders using data from multiple sites has grown multi-fold. One such initiative is the Neuromark, a fully automated spatially constrained independent component analysis (ICA) that is used to link brain network abnormalities among different datasets, studies, and disorders while leveraging subject-specific networks. In this study, we implement the neuromark pipeline in COINSTAC, an open-source neuroimaging framework for collaborative/decentralized analysis. Decentralized exploratory analysis of nearly 2000 resting-state functional magnetic resonance imaging datasets collected at different sites across two cohorts and co-located in different countries was performed to study the resting brain functional network connectivity changes in adolescents who smoke and consume alcohol. Results showed hypoconnectivity across the majority of networks including sensory, default mode, and subcortical domains, more for alcohol than smoking, and decreased low frequency power. These findings suggest that global reduced synchronization is associated with both tobacco and alcohol use. This proof-of-concept work demonstrates the utility and incentives associated with large-scale decentralized collaborations spanning multiple sites., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cognitive abilities are markers of brain development and psychopathology. Abilities, across executive, and social domains need better characterization over development, including factors that influence developmental change. This study is based on the cVEDA [Consortium on Vulnerability to Externalizing Disorders and Addictions] study, an Indian population based developmental cohort. Verbal working memory, visuo-spatial working memory, response inhibition, set-shifting, and social cognition (faux pas recognition and emotion recognition) were cross-sectionally assessed in > 8000 individuals over the ages 6-23 years. There was adequate representation across sex, urban-rural background, psychosocial risk (psychopathology, childhood adversity and wealth index, i.e. socio-economic status). Quantile regression was used to model developmental change. Age-based trajectories were generated, along with examination of the impact of determinants (sex, childhood adversity, and wealth index). Development in both executive and social cognitive abilities continued into adulthood. Maturation and stabilization occurred in increasing order of complexity, from working memory to inhibitory control to cognitive flexibility. Age related change was more pronounced for low quantiles in response inhibition (β∼4 versus  -1 versus -0.25 for lower quantiles). Wealth index had the largest influence on developmental change across cognitive abilities. Sex differences were prominent in response inhibition, set-shifting and emotion recognition. Childhood adversity had a negative influence on cognitive development. These findings add to the limited literature on patterns and determinants of cognitive development. They have implications for understanding developmental vulnerabilities in young persons, and the need for providing conducive socio-economic environments., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Women of reproductive age are at an increased risk of anemia and micronutrient deficiencies. Evidence supports the role of periconceptional nutrition in the development of neural tube defects (NTDs) and other pregnancy complications. Vitamin B 12 deficiency is a risk factor for NTDs and may modify folate biomarkers that predict NTD risk at the population level. There is an interest in mandatory fortification with vitamin B 12 and folic acid for anemia and birth defect prevention. However, there are limited population-representative data needed to inform policy and guidelines., Objectives: This randomized trial will be conducted to evaluate the efficacy of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B 12 ) in 1,000 households in Southern India., Methods: Women 18 to 49 y who are not pregnant or lactating and reside within the catchment area of our community-based research site in Southern India will be screened and invited to participate in the trial. After informed consent, women and their households will be randomized to receive one of the following 4 interventions: 1) double-fortified salt (DFS; iron, iodine), 2) DFS + folic acid (iron, iodine, folic acid), 3) DFS + vitamin B 12 (iron, iodine, vitamin B 12 ), or 4) DFS + folic acid and vitamin B 12 (QFS; iron, iodine, folic acid, vitamin B 12 ) for 12 mo. Structured interviews will be conducted by trained nurse enumerators to collect sociodemographic, anthropometric, dietary, health, and reproductive history data. Biological samples will be collected at baseline, midpoint, and endpoint. Whole blood will be analyzed for hemoglobin using Coulter Counter. Total vitamin B 12 will be measured by chemiluminescence; red blood cell folate and serum folate will be evaluated using the World Health Organization-recommended microbiologic assay., Conclusions: The results of this randomized trial will help to evaluate the efficacy of QFS to prevent anemia and micronutrient deficiencies. Clinical trial registration numbers: NCT03853304 and Clinical Trial Registry of India REF/2019/03/024479., Registration Number: NCT03853304 and REF/2019/03/024479., (© 2023 The Author(s).)

Background: The prevalence of childhood obesity is increasing in low-middle income countries like India. Built environment features such as walkability can influence weight-related outcomes but data from developing countries are scanty., Objective: To develop population level walkability index in urban Bengaluru, and examine its association with indices of childhood obesity in school children., Study Design: Nested cross-sectional study based on a cohort., Participants: Normal healthy children aged 6 to 15 years from urban schools in Bengaluru. The children were stratified into different land use classification such as residential, commercial and open space based on residential address., Methods: Anthropometric data, body composition data, measured using air displacement plethysmography., Outcomes: Walkability index derived using residential density, street connectivity and land-use mix environment variables., Results: The mean (SD) of age, body mass index (BMI), BMI z-score and percentage body fat (% Body fat) of 292 (50% boys) children were 10.8 (2.9) year, 17.4 (3.3) kg/m2, -0.27 (1.35) and 20.9% (8.8), respectively. The mean (SD) walkability index was 16.5, which was negatively associated with BMI (slope -0.25 and -0.08) and percentage body fat (slope -0.47 and -0.21) for age 5 and 10 years, respectively in children, but the effects decreased with increasing age., Conclusions: The findings of this pilot study suggest that the neighborhood walkability may be associated with the obesity indices in younger children. Future longitudinal studies are needed to understand how built environment affects health and body composition of children in India and other low-middle income countries.

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: Anemia is an important public health problem, and accurate estimates may inform policy and programs. Although hemoglobin (Hb) assessment of venous blood via automated hematology analyzers (AHAs) is recommended, most population-based surveys estimate anemia prevalence based on analysis of capillary blood via portable hemoglobinometers., Objectives: We aimed to evaluate screening methods for hemoglobin and anemia assessment using paired venous samples., Methods: Participants were women 15-40 y who were not pregnant or lactating. Paired venous whole blood samples (n = 896) were analyzed for hemoglobin (Hb) via portable hemoglobinometer (HemoCue 301) and Coulter Counter AHA. Anemia and severe anemia were defined as Hb <12.0g/dL and <8.0 g/dL, respectively. Bland-Altman methods were used to assess the level of agreement for Hb results (mean difference, SD of differences, limits of agreement). Diagnostic accuracy parameters (sensitivity, specificity, positive predictive value, negative predictive value, accuracy) were calculated to evaluate HemoCue performance compared to the AHA reference, overall and by sociodemographic, nutritional, and metabolic characteristics., Results: The estimated anemia prevalence was significantly lower via HemoCue vs. AHA (36.3% compared with 41.6%; P value < 0.0001). The HemoCue had 84.4% accuracy for anemia screening and 98.8% for severe anemia, compared to the AHA reference. The HemoCue had 74.8% sensitivity and 91.2% specificity, compared to AHA. HemoCue sensitivity was higher in women with iron deficiency [serum ferritin (SF) <15.0 μg/L: 81.6% compared with SF ≥15.0 μg/L: 41.3%], and lower in women with metabolic risk factors, including overweight [BMI ≥25.0 kg/m2: 63.9% vs. BMI <25.0 kg/m2: 78.8%], or elevated CRP (>1.0 mg/L: 67.2% vs. ≤1.0 mg/L: 82.9%), trunk fat (>35%: 62.7% vs. ≤35%: 80.1%), or whole-body fat (>35%: 63.9% vs. ≤35%: 80.3%)., Conclusions: Findings suggest that women with anemia may be incorrectly identified as not anemic via portable hemoglobinometer, and anemia prevalence may be underestimated at the population level.This study was registered at clinicaltrials.gov as NCT04048330., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Women of reproductive age (WRA) are at increased risk for anemia and iron deficiency. However, there is limited population-level data in India, which could help inform evidence-based recommendations and policy., Aims: To conduct a population-based biomarker survey of anemia, iron deficiency, and inflammation in WRA in Southern India., Methods: Participants were WRA (15-40 y) who were not pregnant or lactating. Blood samples (n = 979) were collected and analyzed for hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and alpha-1 acid glycoprotein (AGP). Anemia and severe anemia were defined as Hb < 12.0 and < 8.0 g/dL. Serum ferritin was adjusted for inflammation using BRINDA methods. Iron deficiency was defined as SF <15.0 μg/L, iron insufficiency was defined as SF < 20.0 and < 25.0 μg/L, and iron deficiency anemia was defined as Hb < 12.0 g/dL and SF < 15.0 μg/L. Inflammation was defined as CRP > 5.0 mg/L or AGP > 1.0 g/L. Restricted cubic spline regression models were also used to determine if alternative SF thresholds should be used t to classify iron deficiency., Results: A total of 41.5% of WRA had anemia, and 3.0% had severe anemia. Findings from spline analyses suggested a SF cut-off of < 15.0 μg/L, consistent with conventional cut-offs for iron deficiency. 46.3% of WRA had SF < 15.0 μg/L (BRINDA-adjusted: 61.5%), 55.0% had SF < 20.0 μg/L (72.7%), 61.8% had SF < 25.0 μg/L (81.0%), and 30.0% had IDA (34.5%). 17.3% of WRA had CRP > 5.0 mg/L and 22.2% had AGP > 1.0 g/L. The prevalence of ID (rural vs. urban: 49.1% vs. 34.9%; p = 0.0004), iron insufficiency (57.8% vs. 43.8%; p = 0.0005), and IDA (31.8% vs. 22.4%; p = 0.01) were significantly higher in rural areas, although CRP levels were lower and there were no differences in elevated CRP or AGP., Conclusions: The burden of anemia and iron deficiency in this population was substantial, and increased after adjusting for inflammation, suggesting potential to benefit from screening and interventions., Registration Number: NCT04048330., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose related to this manuscript. SM is an unpaid board member and holds equity in a startup commercializing point-of-care diagnostic technology partially developed in his research laboratory at Cornell University. Findings and conclusions in this report are those of the authors and do not necessarily represent the official positions of the Centers for Disease Control and Prevention, the DRDC, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), or the National Institutes of Health., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: South Asians are known to have excess adiposity at a lower body mass index, with truncal fat accumulation. Whether this confers higher risk to develop severe COVID-19 is not known. This study evaluated body mass index, body fat mass and waist circumference as risk factors for COVID-19 severity and its progression, in South Asian adults., Methods and Study Design: Details of COVID-19 patients (19-90 years) were obtained prospectively, along with weight, height, waist circumference and body fat mass assessed by bioelectrical impedance analysis. Binomial logistic and Poisson regression were performed to test associations between waist circumference, body fat mass and body mass index to evaluate the adjusted OR or relative risk for disease severity at admission and length of stay., Results: After adjusting for age, sex, height and co-morbidities, body mass index >23 kg/m2 (adjusted OR 2.758, 95% CI 1.025, 7.427), waist circumference (adjusted OR 1.047, 95% CI 1.002, 1.093) and body fat mass (adjusted OR 1.111, 95% CI 1.013, 1.219) were associated with a significant risk for disease severity at admission, while only waist circumference (adjusted relative risk 1.004, 95% CI 1.001, 1.008), and body fat mass (adjusted relative risk 1.011, 95% CI 1.003, 1.018), were associated with a significantly longer length of stay., Conclusions: Body mass index, at a lower cut-off of >23 kg/m2, is a significant risk factor for COVID-19 disease severity in the group of patients studied. The waist circumference and body fat mass are also good indicators for both severity at admission and length of stay.

When public health programs with single nutrients are perceived to have a poor impact on the target health outcome, the policy response can be to supply more, by layering additional mandatory programs upon the extant programs. However, we argue for extreme caution, because nutrients (like medicines) are beneficial in the right dose, but potentially harmful when ingested in excess. Unnecessary motivations for the reactionary layering of multiple intervention programs emerge from incorrect measurements of the risk of nutrient inadequacy in the population, or incorrect biomarker cutoffs to evaluate the extent of nutrient deficiencies. The financial and social costs of additional layered programs are not trivial when traded off with other vital programs in a resource-poor economy, and when public health ethical dilemmas of autonomy, equity, and stigma are not addressed. An example of this conundrum in India is the perception of stagnancy in the response of the prevalence of anemia to the ongoing pharmacological iron supplementation program. The reaction has been a policy proposal to further increase iron intake through mandatory iron fortification of the rice provided in supplementary feeding programs like the Integrated Child Development Services and the School Mid-Day Meal. This is in addition to the ongoing pharmacological iron supplementation as well as other voluntary iron fortifications, such as those of salt and manufactured food products. However, before supplying more, it is vital to consider why the existing program is apparently not working, along with consideration of the potential for excess intake and related harms. This is relevant globally, particularly for countries contemplating multiple interventions to address micronutrient deficiencies. Supplying more by layering multiple nutrient interventions, instead of doing it right, without thoughtful considerations of social, biological, and ethics frameworks could be counterproductive. The cure, then, might well become the malady., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

There has been an upward trend in developing frameworks that enable neuroimaging researchers to address challenging questions by leveraging data across multiple sites all over the world. One such open-source framework is the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC) that works on Windows, macOS, and Linux operating systems and leverages containerized analysis pipelines to analyze neuroimaging data stored locally across multiple physical locations without the need for pooling the data at any point during the analysis. In this paper, the COINSTAC team partnered with a data collection consortium to implement the first-ever decentralized voxelwise analysis of brain imaging data performed outside the COINSTAC development group. Decentralized voxel-based morphometry analysis of over 2000 structural magnetic resonance imaging data sets collected at 14 different sites across two cohorts and co-located in different countries was performed to study the structural changes in brain gray matter which linked to age, body mass index (BMI), and smoking. Results produced by the decentralized analysis were consistent with and extended previous findings in the literature. In particular, a widespread cortical gray matter reduction (resembling a 'default mode network' pattern) and hippocampal increase with age, bilateral increases in the hypothalamus and basal ganglia with BMI, and cingulate and thalamic decreases with smoking. This work provides a critical real-world test of the COINSTAC framework in a "Large-N" study. It showcases the potential benefits of performing multivoxel and multivariate analyses of large-scale neuroimaging data located at multiple sites., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background/objectives: Young Indian adults are at greater risk of overweight/obesity due to their high energy intake and sedentary lifestyle. Their energy requirement (ER) is based on their total energy expenditure (TEE) estimated from factorial method, which possibly overestimates their basal metabolic rate (BMR) and physical activity level (PAL). This study aimed to compare the accurately measured TEE with ER in young adults. Secondarily, to compare measured with predicted BMR and guideline PAL with that obtained from questionnaire and step counts., Subjects/methods: TEE was measured in 19 male adults (18-30 years), using the doubly labeled water technique, over 14 days. Indirect calorimetry was used to measure BMR, while the PAL was estimated by (a) the ratio of measured TEE and BMR, (b) step counts over 7 days measured using tri-axial accelerometers and (c) a physical activity questionnaire (PAQ)., Results: The measured TEE (9.11 ± 1.30 MJ/d) was significantly lower than the ER using either the Indian (15.2%) or the FAO/WHO/UNU (11.9%, both p < 0.01) recommendations. The measured BMR (6.90 ± 0.65 MJ/d) was significantly lower than that predicted using the FAO/WHO/UNU equation (6.5%, p < 0.01) but not for the Indian equation. The estimated PAL from measured TEE and BMR (1.35 ± 0.18), and from accelerometers (1.33 ± 0.11) was significantly lower than PAL obtained from PAQ (1.53 ± 0.17) or the guideline of 1.53 for Indians., Conclusions: The predicted BMR and PAL guideline value was higher than that measured in young Indian adults, resulting in a ~13% lower measured TEE. This emphasizes the need to revisit the guidelines for predicting ER for this population.

Background: Lysine rich foods such as milk and legumes serve as important food additions to the lysine deficient cereal-based diets of vegetarian populations in low- and middle-income countries (LMICs) to alleviate the risk of quality corrected dietary protein inadequacy. Dietary protein quality can be determined by estimating the metabolic availability (MA) of lysine., Objectives: The study aimed to estimate the MA of lysine in spray-dried cow milk powder (SMP), heat-treated spray-dried cow milk powder (HSMP), and a habitually consumed cereal-legume based vegetarian meal (VM), using the indicator amino acid oxidation (IAAO) slope-ratio method., Methods: The MA of lysine in SMP, HSMP, and VM was estimated in 7 healthy young men aged 19-24 y with BMI of 21.5 ± 0.5 kg/m2 in a repeated measures design. The IAAO response slopes with 2 graded lysine intakes (10.5 and 15.0 mg·kg-1·d-1) from the SMP and VM were compared with the response slope generated with 3 graded crystalline lysine intakes (6.0, 10.5, and 15.0 mg·kg-1·d-1) at the subrequirement level. To produce HSMP, pasteurized cow milk was heat treated and spray dried. The MA of lysine in HSMP was tested at a single level of lysine intake (15 mg·kg-1·d-1). A total of 8 IAAO experiments were conducted on each participant in randomized order. The IAAO slopes were estimated using a linear mixed-effect regression model., Results: The MA of lysine in SMP, HSMP, and VM was 91.9%, 69.9%, and 86.6% respectively., Conclusions: Heat treatment reduced the MA of lysine by 22% in HSMP compared with SMP in healthy Indian adults. The lysine MA estimates can be used to optimize lysine limited cereal-based diets, with the addition of appropriately processed legumes and milk powder, to meet the protein requirement. This trial was registered at Clinical Trials Registry of India (http://ctri.nic.in) as CTRI/2019/08/020568., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Low and middle-income countries like India with a large youth population experience a different environment from that of high-income countries. The Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), based in India, aims to examine environmental influences on genomic variations, neurodevelopmental trajectories and vulnerability to psychopathology, with a focus on externalizing disorders., Methods: cVEDA is a longitudinal cohort study, with planned missingness design for yearly follow-up. Participants have been recruited from multi-site tertiary care mental health settings, local communities, schools and colleges. 10,000 individuals between 6 and 23 years of age, of all genders, representing five geographically, ethnically, and socio-culturally distinct regions in India, and exposures to variations in early life adversity (psychosocial, nutritional, toxic exposures, slum-habitats, socio-political conflicts, urban/rural living, mental illness in the family) have been assessed using age-appropriate instruments to capture socio-demographic information, temperament, environmental exposures, parenting, psychiatric morbidity, and neuropsychological functioning. Blood/saliva and urine samples have been collected for genetic, epigenetic and toxicological (heavy metals, volatile organic compounds) studies. Structural (T1, T2, DTI) and functional (resting state fMRI) MRI brain scans have been performed on approximately 15% of the individuals. All data and biological samples are maintained in a databank and biobank, respectively., Discussion: The cVEDA has established the largest neurodevelopmental database in India, comparable to global datasets, with detailed environmental characterization. This should permit identification of environmental and genetic vulnerabilities to psychopathology within a developmental framework. Neuroimaging and neuropsychological data from this study are already yielding insights on brain growth and maturation patterns.

Background and Objectives: Childhood obesity is increasing in urban India. This study aimed to examine the associations of younger siblings abdominal adiposity with individual, familial and environmental factors, in urban school aged siblings., Methods and Study Design: Weight, height and waist circumference of 2906 siblings aged 3-16 years were measured along with details on demographics, diet, lifestyle, behavior and reported parental anthropometrics. Abdominal adiposity was classified as waist circumference above the age and sex specific 75th percentile value. The associations of various factors with abdominal adiposity in the younger siblings were examined through logistic regression analyses., Results: Sibling, familial factors and environmental factors had significant associations with abdominal adiposity. The odds of a younger sibling having abdominal adiposity was greatest (OR=3.16, 95% confidence interval (95% CI): 2.27 to 4.42), when the older sibling had abdominal adiposity, followed by the odds ratio of both parents being overweight (OR=1.63, 95% CI: 1.33 to 1.99) compared to neither being overweight. The influence of abdominal adiposity of the older sibling was greater when the siblings were of the same sex (OR=3.55, 95% CI: 2.24 to 5.65) than when they were of different sex (OR=2.73, 95% CI: 1.67 to 4.46); the odds ratio being highest when both siblings were males., Conclusions: The younger sibling's abdominal adiposity is associated with that of his/her sibling and parental obesity, in addition to other known risk factors in urban south Indian families. Interventions to prevent childhood obesity need to also consider the sibling effect along with the other known factors.

Background and Objectives: Indians are more prone to develop diabetes at a younger age, with normal BMI, and this might partly be due to their higher body fat content. Increase in fat mass in the body might be because of the reduction in fat oxidizing capability. Given the fact that Indians consume high carbohydrate diets, effective fat oxidation is likely to be delayed. Simple preventive weight loss strategies like exercise or change in diet regimen are needed to reduce their body fat. This study investigated the effect of exercise with a high protein dinner on overnight thermogenesis and fat oxidation., Methods and Study Design: Nine healthy normal subjects aged 18 - 30 years participated in randomised cross over study. They underwent 6 sessions of overnight whole body indirect calorimetry on separate nights with the following experimental conditions: (i) standard (habitual) meal (ii) standard meal with exercise (iii) 20% protein meal (iv) 20% protein meal with exercise (v) 50% protein meal and (vi) 50% protein meal with exercise. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured overnight, from which energy expenditure, non-protein respiratory quotient (RQ), and fat oxidation were estimated., Results: The estimated marginal means of fat oxidation and energy expenditure were significantly different for protocols with exercise compared to those without exercise (p=0.02). There was no acute effect of protein on nocturnal fat or carbohydrate oxidation, with or without exercise., Conclusions: Post-dinner exercise increase nocturnal fat oxidation and energy expenditure in young active Indian men.

Objective: To examine the joint association of birth weight and physical activity/sedentary time with childhood obesity in 12 countries., Methods: A cross-sectional study of 5,088 children aged 9 to 11 years was conducted. Birth weight was recalled by parents or guardians. Moderate-to-vigorous physical activity (MVPA) and sedentary behavior were objectively measured using accelerometry., Results: The association of birth weight with the odds of obesity, central obesity, and high body fat was significant among children with either low MVPA or high sedentary time but not among children with either high MVPA or low sedentary time. In comparison with children with normal birth weight and high MVPA, children with high birth weight and low MVPA showed 4.48- to 5.18-fold higher odds of obesity, central obesity, and high body fat; children with normal birth weight and low MVPA showed 3.00- to 3.30-fold higher odds of obesity, central obesity, and high body fat, and children with high birth weight and high MVPA showed 1.16- to 1.68-fold higher odds of obesity, central obesity, and high body fat., Conclusions: High MVPA is more important than high birth weight as a correlate of obesity in children., (© 2017 The Obesity Society.)

Background and Objectives: Strategies to prevent and treat overweight/obesity are urgently needed. This study assessed the effect of a short-term intake of ready-to-eat cereal on body weight and waist circumference of overweight/obese individuals in comparison to a control group., Methods and Study Design: A randomized, controlled 2-arm trial was carried out on 101 overweight/obese (Body Mass Index - 29.2±2.4 kg/m2) females aged 18 to 44 years, at St. John's Medical College Hospital. The intervention group received a low fat, ready to eat cereal, replacing two meals/day for two weeks. The control group was provided with standard dietary guidelines for weight loss and energy requirements for both groups were calculated similarly. Anthropometric, dietary, appetite and health status assessments were carried out at baseline and at the end of two weeks., Results: At the end of two weeks, the mean reductions in body weight and waist circumference were significantly greater in the intervention group, -0.53 kg; 95% CI (-0.86 to -0.19) for body weight and -1.39 cm; 95% CI (-1.78, -0.99) for waist circumference. The intervention group had a significantly higher increase in dietary intakes of certain vitamins, fiber and sugar, and significantly higher reductions in total and polyunsaturated fats and sodium intakes, as compared to the control group (p<=0.05). No significant differences were observed between the groups, in change of appetite, health and perception scales., Conclusions: Portion controlled, ready to eat cereal could be effective for short-term weight loss, with some improvements in the nutrient intake profile. However, studies of longer duration are needed.

Background: The quantity and type of dietary fat is known to affect plasma lipid concentration and hence the choice of cooking oil is important to lower the risk of coronary heart disease. Rice bran oil, which was not popular worldwide, is slowly being recognized as a 'healthy' oil in India. We assessed if rice bran oil had hypolipidaemic effects in subjects with elevated lipid levels., Methods: The study had a cross-over design with subjects (n = 14) randomly assigned to consume either rice bran oil or refined sunflower oil in their homes, for a period of 3 months (period 1). After a washout period of 3 weeks, they were crossed over to the other oil (period 2). The serum lipid values were estimated at the beginning, on day 45 and day 90 of each phase. Additional parameters assessed included anthropometry, dietary and physical activity patterns., Results: The use of rice bran oil significantly reduced plasma total cholesterol and triglyceride levels compared with sunflower oil. The reduction in plasma LDL-cholesterol with rice bran oil was just short of statistical significance (p = 0.06). HDL-cholesterol levels were unchanged., Conclusion: The use of rice bran oil as the main cooking oil significantly reduced serum cholesterol and triglyceride levels. The use of rice bran oil together with dietary and lifestyle modifications may have implications for reducing the risk of cardiovascular disease.

Background & Objectives: The total body skeletal muscle mass plays a significant role in both health and disease states. Accurate measurement or prediction of muscle mass is useful in physiology, nutrition and clinical medicine. There are many prediction equations derived in the Western populations to estimate skeletal muscle mass, however, regression equations best fit the population they are derived from. There is hence a need to generate predictive equations for the Indian population. The objective of this study was to derive predictive equations for muscle mass from simple anthropometric measurements such as mid-arm circumference (MAC) and triceps skinfolds in a young Indian male population., Methods: Anthropometric measurements of body weight, height, mid-arm circumference and skinfold measurements were carried out on 66 subjects with a wide range of body mass indices. Twenty four hour urine samples were collected over a 3 day period for estimating urinary creatinine excretion, from which the total body muscle mass was inferred. Linear regression was carried out between MAC and corrected arm muscle area (CAMA) with muscle mass obtained from urinary creatinine to derive a prediction equation for muscle mass., Results: The prediction equation obtained for muscle mass (kg) using MAC alone was (1.641xMAC)-15.580 [r=0.72, standard error of estimate (SEE) 2.91kg] while the equation derived from CAMA alone was (0.496xCAMA)+10.183, (r=0.62, SEE=3.29kg)., Interpretation & Conclusion: A new prediction equation for the measurement of muscle mass was derived in young Indian men using simple anthropometric measurements such as mid-arm circumference and triceps skinfolds.