Developing a data repository to support interdisciplinary research into childhood stunting: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: As a topic of inquiry in its own right, data management for interdisciplinary research projects is in its infancy. Key issues include the inability of researchers to effectively query diverse data outputs and to identify potentially important synergies between discipline-specific data. Equally problematic, few semantic ontologies exist to better support data organisation and discovery. Finally, while interdisciplinary research is widely regarded as beneficial to unpacking complex problems, non-researchers such as policy-makers and planners often struggle to use and interrogate the related datasets. To address these issues, the following article details the design and development of the UKRI GCRF Action Against Stunting Hub (AASH)'s All-Hub Data Repository (AHDR). METHODS AND ANALYSIS: The AHDR is a single application, single authentication web-based platform comprising a data warehouse to store data from across the AASH's three study countries and to support data querying. Four novel components of the AHDR are described in the following article: (1) a unique data discovery tool; (2) a metadata catalogue that provides researchers with an interface to explore the AASH's data outputs and engage with a new semantic ontology related to child stunting; (3) an interdisciplinary aid to support a directed approach to identifying synergies and interactions between AASH data and (4) a decision support tool that will support non-researchers in engaging with the wider evidence-based outputs of the AASH. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by institutional ethics committees in the UK, India, Indonesia and Senegal. Results will be disseminated via publications in peer-reviewed journals; presentations at international conferences and community-level public engagement events; key stakeholder meetings; and in public repositories with appropriate Creative Commons licences allowing for the widest possible use.

Epigenetic studies in children at risk of stunting and their parents in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: In 2020, an estimated 150 million children under the age of 5 years were stunted. Stunting results from early-life adversity and it is associated with significant physical and cognitive deficit, lifelong socioeconomic disadvantage and reduced life expectancy. There is a need to understand the causes of stunting and its effects in order to develop strategies to avoid it and to mitigate the consequences once stunting has occurred. Epigenetics is an important mechanism through which early-life factors are thought to influence biological function, with long-term consequences. We describe a series of epigenetic studies designed to understand how early-life adversity results in stunting and to inform the development of practical tools such as predictive markers and therapeutic targets. This work is part of the UKRI GCRF Action Against Stunting Hub. METHODS AND ANALYSIS: The project-in India, Indonesia and Senegal-comprises an observational study of mothers, fathers, and offspring (n=500) spanning the first 1000 days of life, and an intervention study in each country. Epigenetic status (DNA methylation) is determined in saliva from babies collected within 1 month of birth and again at 18 months of age, and from mothers and fathers around the time of birth. Epigenome-wide analysis is carried out using the Illumina EPIC array, augmented by high-definition sequencing approaches. Statistical analysis is carried out at the level of candidate genes/regions, higher dimensional epigenetic states and epigenome-wide association. Data analysis focuses on the determinants of stunting, the effectiveness of interventions, population comparisons and the link between epigenetics and other thematic areas, which include anthropometry, microbiome, gut health, parasitology, cognition, nutrition, food hygiene and water sanitation, food systems and the home environment. ETHICS AND DISSEMINATION: This study has been approved by the relevant Ethics Committees in Indonesia, India and Senegal, and the UK. Research data will be published and posted in public repositories.

Eggs for Improving Nutrition, cognitive development and reducing linear growth retardation among Infants and young Children (ENRICH): protocol of an egg supplementation trial among children aged 9-18 months in Hyderabad, India.

INTRODUCTION: Evidence on the impact of nutrient-rich animal source foods such as eggs for improving child growth and cognition is inconsistent. This study aims to examine the impact of an egg intervention in children, along with behaviour change communication (BCC) to the mother, on linear growth and cognition, and nutritional status in children aged 9-18 months. METHODS AND ANALYSIS: A 9-month open-labelled randomised controlled trial will be conducted in three urban slums in Hyderabad, India, as a substudy of an observational cohort study (n=350) following pregnant women and their children until 18 months of age in a population at risk of stunting. The children born to women enrolled during the third trimester of pregnancy will be block randomised in a 1:4 ratio into the intervention (n=70) and control (n=280) groups. Children in the intervention group will be supplemented with one egg per day starting from 9 months until 18 months of age. BCC designed to enhance adherence to the intervention will be used. The control group will be a part of the observational cohort and will not receive any intervention from the study team. The primary outcome will be length-for-age z-scores, and the secondary outcomes will include cognition, blood biomarkers of nutritional status including fatty acid profile and epigenetic signatures linked with linear growth and cognition. Multivariate intention-to-treat analyses will be conducted to assess the effect of the intervention. ETHICS AND DISSEMINATION: The study is approved by the Institutional ethics committees of ICMR-National Institute of Nutrition, Hyderabad, India and London School of Hygiene and Tropical Medicine, UK. The results will be published in peer-reviewed journals and disseminated to policy-makers. Findings will also be shared with study participants and community leaders. TRIAL REGISTRATION NUMBER: CTRI/2021/11/038208.

A Point-of-Care Method with Integrated Decision Support Tool to Estimate Anemia at Population Level.

Robust point-of-care methods are required to estimate anemia at the population level. The accurate methods are lab-based and cannot be used at the point of care. To address this caveat, a novel method based on pooled capillary blood and a portable autoanalyzer was developed for the estimation of Hb. Additionally, custom software was developed for near-real-time integration of the Hb values from the auto analyzer to the server. Moreover, a decision support tool that can immediately categorize the participants into different stages of anemia was developed. The decision support tool was designed based on the World Health Organization (WHO) cut-off for anemia at the population level and was available for all age and gender groups. This simple and user-friendly tool could easily be used by front-line health workers who have limited technical skills. Overall, the method developed could be used at the point of care and is accurate. This high-throughput method could be used for screening anemia at the population level for all age and gender groups.

Disruptions, restorations and adaptations to health and nutrition service delivery in multiple states across India over the course of the COVID-19 pandemic in 2020: An observational study.

BACKGROUND: Modeling studies estimated severe impacts of potential service delivery disruptions due to COVID-19 pandemic on maternal and child nutrition outcomes. Although anecdotal evidence exists on disruptions, little is known about the actual state of service delivery at scale. We studied disruptions and restorations, challenges and adaptations in health and nutrition service delivery by frontline workers (FLWs) in India during COVID-19 in 2020. METHODS: We conducted phone surveys with 5500 FLWs (among them 3118 Anganwadi Workers) in seven states between August-October 2020, asking about service delivery during April 2020 (T1) and in August-October (T2), and analyzed changes between T1 and T2. We also analyzed health systems administrative data from 704 districts on disruptions and restoration of services between pre-pandemic (December 2019, T0), T1 and T2. RESULTS: In April 2020 (T1), village centers, fixed day events, child growth monitoring, and immunization were provided by <50% of FLWs in several states. Food supplementation was least disrupted. In T2, center-based services were restored by over a third in most states. Administrative data highlights geographic variability in both disruptions and restorations. Most districts had restored service delivery for pregnant women and children by T2 but had not yet reached T0 levels. Adaptations included home delivery (60 to 96%), coordinating with other FLWs (7 to 49%), and use of phones for counseling (~2 to 65%). Personal fears, long distances, limited personal protective equipment, and antagonistic behavior of beneficiaries were reported challenges. CONCLUSIONS: Services to mothers and children were disrupted during stringent lockdown but restored thereafter, albeit not to pre-pandemic levels. Rapid policy guidance and adaptations by FLWs enabled restoration but little remains known about uptake by client populations. As COVID-19 continues to surge in India, focused attention to ensuring essential services is critical to mitigate these major indirect impacts of the pandemic.

Point-of-care Hb measurement in pooled capillary blood by a portable autoanalyser: comparison with venous blood Hb measured by reference methods in cross-sectional and longitudinal studies.

Population-based surveys commonly use point-of-care (POC) methods with capillary blood samples for estimating Hb concentrations; these estimates need to be validated by comparison with reference methods using venous blood. In a cross-sectional study in 748 participants (17-86 years, 708 women, Hb: 5·1 to 18·2 g/dl) from Hyderabad, India, we validated Hb measured from a pooled capillary blood sample by a POC autoanalyser (Horiba ABX Micros 60OT, Hb-C-AA) by comparison with venous blood Hb measured by two reference methods: POC autoanalyser (Hb-V-AA) and cyanmethemoglobin method (Hb-V-CM). These comparisons also allowed estimation of blood sample-related and equipment-related differences in the Hb estimates. We also conducted a longitudinal study in 426 participants (17-21 years) to measure differences in the Hb response to iron folate (IFA) treatment by the capillary blood POC method compared with the reference methods. In the cross-sectional study, Bland-Altman analyses showed trivial differences between source of blood (Hb-C-AA and Hb-V-AA; mean difference, limits of agreement: 0·1, -0·8 to 1·0 g/dl) and between analytical methods (Hb-V-AA and Hb-V-CM; mean difference, limits of agreement: < 0·1, -1·8 to 1·8 g/dl). Cross-sectional anaemia prevalence estimated using Hb-C-AA did not differ significantly from Hb-V-CM or Hb-V-AA. In the longitudinal study, the Hb increment in response to IFA intervention was not different when using Hb-C-AA (1·6 ± 1·7 g/dl) compared with Hb-V-AA (1·7 ± 1·7 g/dl) and Hb-V-CM (1·7 ± 1·7 g/dl). The pooled capillary blood-autoanalyzer method (Hb-C-AA) offers a practical and accurate way forward for POC screening of anaemia.

Sun exposure as a strategy for acquiring vitamin D in developing countries of tropical region: Challenges & way forward.

Adopting sun exposure as a low-cost sustainable strategy in tropical countries needs critical analysis for its feasibility and inclusion in national policy. This review explores the opportunities and challenges associated with sun exposure in tropical countries and discusses potential strategies that may be adopted for promoting sun exposure. For this, two strands of evidence were reviewed; trials on sun exposure, analysed for risk of bias and, the environmental factors that influence acquisition of vitamin D from sun exposure in the context of on-going ecological and nutritional transition. Compilation of data from available databases in terms of deficiency, per cent rural population, status of fortification, air pollution, ultraviolet index, skin reflectance and skin cancer prevalence were done. In the context of environmental and lifestyle-related challenges, opportunities go hand-in-hand in terms of built environment, variability in air pollution and personal factors such as skin pigmentation, precursor availability and general nutritional status. Contextual policy decisions should consider urban and rural development planning, control of air pollution, targeted guidelines for indigenous and immigrant population and use of space technology in educating general population for balanced sun exposure as essential components for a sustainable strategy. Important opportunities exist for tropical countries to develop sun exposure as a strategy for acquiring vitamin D and these need to be explored.

Point of Care Diagnosis of Anemia Using Portable Auto Analyzer.

We describe a method for capillary blood sample-based point-of care testing of hemoglobin in population-based surveys using an automated analyzer system. The accuracy and precision of this method was comparable to hemoglobin estimated from venous blood sample (mean difference (SD) =0.2 (-2.77, 3.2), Pearson correlation coefficient, (0.969).

Food synergies for improving bioavailability of micronutrients from plant foods.

Plant foods are endowed with micronutrients but an understanding of bioavailability is essential in countries primarily dependent on plant based foods. Bioavailability depends majorly on food synergies. This review examines the nature of certain food synergies and methods to screen and establish it as a strategy to control micronutrient deficiency in the populations. Strong evidence on the synergistic effect of inclusion of vitamin C rich fruits and non-vegetarian foods in enhancing the bioavailability of iron has been demonstrated. Fat is found to be synergistic for vitamin A absorption. Red wine and protein have been explored for zinc absorption and effect of fat has been studied for vitamin D. Methods for screening of bioavailability, and biomarkers to demonstrate the synergistic effects of foods are required. Translation of food synergy as a strategy requires adaptation to the context and popularization of intelligent food synergies.

Country-specific nutrient requirements & recommended dietary allowances for Indians: Current status & future directions.

Nutrient requirements and recommended dietary allowances (RDAs) are set and revised periodically by the Indian Council of Medical Research. These are meant to guide the population and provide policy directions regarding nutrient requirements corresponding to a healthy population. This review article provides an overview of the current recommendations (RDA, 2010) and the challenges faced by the committee to contextualize RDA to the Indian scenario which has a background of double burden of malnutrition, diverse dietary habits but predominantly home-based cereal-pulse vegetarian diet with low bioavailability of several nutrients and lower consumption of packaged fortified foods. The need for country-specific requirements and harmonization of methodologies related to nutrient requirements and RDA are also discussed. The recommendations fixed for iron have been provided in detail as an example. The measures to carry forward RDA revisions to ensure its sustainability have been emphasized.

Exploring the bio-behavioural link between stress, allostatic load & micronutrient status: A cross-sectional study among adolescent boys.

BACKGROUND & OBJECTIVES: Allostatic load (AL) is a cumulative measure of physiological deregulation and is influenced by multiple factors including nutrition. The objectives of the study were to assess AL among adolescent boys (15-19 yr) and delineate its association with psychological stress and micronutrient status. METHODS: A cross-sectional, school-based study was conducted among 370 adolescent boys of five higher secondary schools from Hyderabad, India. Perceived stress, adolescent life event stress (ALES), psychological morbidity and coping were measured. Biomarkers of AL included dehydroepiandrosterone sulphate, 12-h urinary cortisol, interleukin-6, C-reactive protein, lipid profile, body mass index and blood pressure. Micronutrient status with respect to iron (haemoglobin, ferritin, hepcidin, soluble transferrin receptor), folate, vitamins B12, C and A were analyzed in a sub-sample of 146 boys. AL score ≥3 was calculated from eight biomarkers. RESULTS: Fourteen per cent participants had no AL but 34.3 per cent had AL score of ≥ 3. Unadjusted means of ALES scores were significantly different (P = 0.045) among participants with low [mean, 95% confidence interval (CI): 580, 531-629] and high (663, 605-721) AL. After controlling for confounders, the means were significantly different for controllable life event sub-scale of ALES (P = 0.048). Adjusted hepcidin concentrations were significantly higher among participants with high AL (means, 95% CI, 27.2, 24.0-30.8 for high AL; 22.1, 20.2-24.2 µg/l for low AL, P = 0.014). INTERPRETATION & CONCLUSIONS: Build-up of AL was found in adolescent boys and was positively associated with life event stress. Iron nutrition and stress exhibited a positive association through hepcidin. The study provides a link between iron nutrition, physiological deregulation and stress.

Characterisation of anaemia and associated factors among infants and pre-schoolers from rural India.

OBJECTIVE: In India, national databases indicate anaemia prevalence of 80 % among 6-35-month-old children and 58 % among 36-59-month-old children. The present study aimed to characterise anaemia and the associated factors among infants and pre-schoolers living in rural India. DESIGN: Multivariate logistic regression analysis of data collected prior to an intervention trial. Fe-deficiency with anaemia (IDA), Fe deficiency with no anaemia (IDNA) and anaemia without Fe deficiency were defined. Serum ferritin, soluble transferrin receptor (sTfR) and sTfR/log ferritin index were used to indicate Fe status. SETTING: Twenty-six villages of Nalgonda district, Telangana, India. Data were collected in community sites. Participants Four hundred and seventy-six infants (aged 6-12 months), 316 pre-schoolers (aged 29-56 months) and their mothers. RESULTS: Prevalence of anaemia among infants and pre-schoolers was 66·4 and 47·8 %, prevalence of IDA was 52·2 and 42·1 %, prevalence of IDNA was 22·2 and 29·8 %, prevalence of anaemia without Fe deficiency was 14·2 and 5·7 %. Among infants, anaemia was positively associated with maternal anaemia (OR=3·31; 95 % CI 2·10, 5·23; P<0·001), and sTfR/log ferritin index (OR=2·21; 95 % CI 1·39, 3·54; P=0·001). Among pre-schoolers, anaemia was positively associated with maternal anaemia (OR=3·77; 95 % CI 1·94, 7·30; P<0·001), sTfR/log ferritin index (OR=5·29; 95 % CI 2·67, 10·50; P<0·001), high C-reactive protein (OR=4·39; 95 % CI 1·91, 10·06, P<0·001) and young age (29-35 months: OR=1·92; 05 % CI 1·18, 3·13, P=0·009). CONCLUSIONS: Anaemia prevalence continues to be high among infants and pre-schoolers in rural India. Based on sTfR/ferritin index, Fe deficiency is a major factor associated with anaemia. Anaemia is also associated with inflammation among pre-schoolers and with maternal anaemia among infants and pre-schoolers, illustrating the importance of understanding the aetiology of anaemia in designing effective control strategies.

Food-Based Interventions to Modify Diet Quality and Diversity to Address Multiple Micronutrient Deficiency.

Global data indicate a high prevalence of hidden hunger among population. Deficiencies of certain micronutrients such as folic acid, iodine, iron, and vitamin A have long lasting effects on growth and development and therefore have been a National priority from many decades. The strategy implemented so far limits to the use of supplemental sources or fortified foods in alleviating the burden of deficiencies. These approaches however undermine the food-based strategies involving dietary diversification as the long-term sustainable strategy. There is lack of understanding on the level of evidence needed to implement such strategies and the level of monitoring required for impact evaluation. Dietary diversity concerns how to ensure access for each individual to a quality and safe diet with adequate macro- and micronutrients. The key to success in using dietary diversity as a strategy to tackle hidden hunger is in integrating it with the principles of bioavailability, translated to efficient food synergies with due emphasis on food accessibility, affordability, and outdoor physical activity/life style modifications. Promoting enabling environment and sustainable agriculture is crucial for practicing dietary diversification with behavior change communication as an integral segment. It can be concluded that food-based strategies require careful understanding of the factors associated with it and moderate it to form an effective strategy for controlling multiple micronutrient deficiencies.

Adolescent life-event stress in boys is associated with elevated IL-6 and hepcidin but not hypoferremia.

OBJECTIVE: The link between stress-related increases in inflammatory markers, hepcidin, and iron status are poorly understood, especially in developing countries like India. The aim of the study was to examine the relationship between adolescent life-event stress (ALES), inflammatory markers, and its association with hepcidin and biomarkers of iron status among adolescent boys. METHODS: Data pertaining to a subsample of 145 participants from a cross-sectional, school-based study recruiting 370 adolescent boys aged 15-19 years, from 5 schools in Hyderabad, India, were analyzed. Stress was assessed using the ALES scale, psychological distress by the General Health Questionnaire-2 (GHQ-12), and approach and avoidance coping using the Coping Strategies Scale. Biomarkers of iron and concentrations of other micronutrients, hepcidin, IL-6 and C-reactive protein (CRP) in plasma were analyzed. Data were subjected to regression, path analyses, and analysis of covariance (ANCOVA). RESULTS: ALES was a significant predictor of interleukin (IL)-6 (ß = 0.196, p = 0.012), CRP (ß = 0.217, p = 0.010), and log hepcidin (ß = 0.228, p = 0.006). Hepcidin correlated significantly (p < 0.001) with IL-6 (r = 0.344) and CRP (r = 0.370) but not with the biomarkers of iron status. Path analysis showed that the model had an acceptable fit, with a root mean square error of approximation of 0.019, 90% confidence interval (CI) of 0.00-0.074, comparative fit index of 0.988, chi-square p = 0.393, and chi-square/df of 1.053. CONCLUSIONS: Adolescent life-event stress is associated with elevated IL-6 and hepcidin concentration but not hypoferremia. These findings may help in iron supplementation programs for tackling anemia.

Psychometric validation of a knowledge questionnaire on micronutrients among adolescents and its relationship to micronutrient status of 15-19-year-old adolescent boys, Hyderabad, India.

OBJECTIVE: To develop a psychometrically valid questionnaire for testing knowledge on micronutrients and to assess the relationship between knowledge and biomarkers of micronutrient status among adolescents. DESIGN: Cross-sectional, institution-based, validity and reliability study. SETTING: Seven higher secondary schools were covered in the limits of Greater Hyderabad Municipal Corporation, Hyderabad, India. SUBJECTS: Students aged 15-19 years, n 92 for the pre-test, n 108 for test-retest and n 109 for studying the relationship between knowledge and biomarkers of Fe, retinol, ascorbic acid, α-tocopherol, folic acid and vitamin B12 status. RESULTS: From an item pool of 106, thirty-one items were selected based on content validity. Statistical tools to obtain a valid and reliable questionnaire among adolescent boys and girls resulted in eighteen items with a difficulty index of 0·11-0·86, discrimination index of 0·20-0·72 and validity index (point bi-serial correlation) of 0·10-0·62. Reliability as measured by Cronbach's α was 0·71 and the intra-class correlation coefficient was 0·80. A Bland-Altman plot showed good agreement between test and retest scores. The mean response score to the eighteen-item questionnaire was 5·2 (sd 2·68). The mean values of serum retinol were significantly different (P = 0·022) between groups below (24·8 (sd 6·64) µg/dl) and above (28·0 (sd 7·67) µg/dl) the 50th percentile of knowledge score. The relationship persisted after controlling for economic status as a covariate using analysis of covariance (P = 0·018). Other micronutrients did not show any significant relationship. CONCLUSIONS: A valid and reliable eighteen-item knowledge questionnaire was constructed and found to have a significant positive relationship with plasma retinol status alone.

Perceived stress, life events & coping among higher secondary students of Hyderabad, India: a pilot study.

BACKGROUND & OBJECTIVES: Psychosocial stressors leading to allostatic load need to be explored further as these have great scope for early intervention. Stress studies done in India are mostly based on sources of stress and objective measures of stress. Therefore, the objective of the present study was to assess stress appraisal among students (16-17 yr) and to identify institution-specific differences (Private vs. Government) in stress appraisal and coping. METHODS: The study was carried out among 16-17 yr old apparently normal students. Eighty students were recruited from six schools ensuring equal representation from gender/category of schools (Government/Private). Validated and culturally adaptable behavioural scales for perceived stress (PSS), stressful life events (LES) and coping were administered. Psychological morbidity was assessed using GHQ-12. Data on 75 students were available for statistical analysis. RESULTS: The students of both Government and Private schools showed similar stress perception, though the former tend to have a higher mean score. The scores were significantly higher on avoidance coping (P<0.05). The stepwise regression model showed coping as the independent predictor of perceived stress (R2 = 10%). INTERPRETATION & CONCLUSIONS: Students from Government schools had significantly higher scores on avoidance coping and therefore, suitable for a systematic study on chronic stress for early intervention.