Etiology of Mild and Moderate Anaemia Among Rural Adolescent Girls in India.

A cluster randomized control trial study was conducted in Ballabgarh block of Faridabad District, Haryana, India. Baseline data of a total of 198 non-anemic and 202 anemic adolescent girls (12-19 years) was analyzed for hemoglobin and serum level of hepcidin, ferritin, folate acid, soluble transferrin receptor, vitamin B12 and CRP. Deficiency of iron (p < 0.001), folate (p < 0.01) and their mixed deficiency (p < 0.001) significantly increased with increasing severity of anaemia and contributed to 48.7% mild anaemia and 66.9% moderate anaemia. Anaemia of inflammation contributed to 16.2% of mild anaemia and 11.7% of moderate anaemia. More than one third of mild anaemia is caused by other causes. Current iron and folic acid program can alleviate around more than 2/3rd moderate anaemia and around half of mild anaemia among adolescent girls. Unknown causes of anaemia need further investigation.

Development and Validation of a Weight Estimation Tool for Acutely Ill Children Who Cannot be Weighed.

OBJECTIVES: To develop and validate weight estimation tools using mid upper arm circumference (MUAC) and body length, and determine accuracy and precision of Broselow tape in children 6 mo to 15 y of age. METHODS: Data of 18,456 children aged 6 mo to 5 y and 1420 children aged 5 to 15 y were used to develop linear regression equations using length and MUAC to estimate weight. These were validated on prospectively enrolled populations of 276 and 312 children, respectively. Accuracy was measured by Bland-Altman bias, median percentage errors, and percentage of predicted weight within 10% of true weight. Broselow tape was tested on the validation population. RESULTS: Gender specific equations were developed which estimated weight within 10% of true weight in 69.9% (64.1-75.2%) and 65.7% (60.1-70.9%) of children aged 6 mo to 5 y, and 5 to 15 y, respectively. Broselow tape predicted weight within 10% of the true weight in 40.5% (34.7-46.6%) and 32.5% (26.7-38.7%) of children aged 6 mo to 5 y and 5 to 15 y, respectively. CONCLUSIONS: The model developed from MUAC and length accurately estimated weight in children aged 6 mo to 15 y, and is potentially useful during emergencies. The Broselow tape frequently overestimated weight in authors' setting.

Diagnostic performance of non-invasive liver fibrosis risk scores in biopsy-proven non-alcoholic fatty liver disease patients in India.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. India and other developing countries are witnessing an unprecedented rise in the prevalence of NAFLD. As part of population-level strategy, at primary healthcare, an efficient risk stratification is crucial to ensure appropriate and timely referral of individuals who require care at secondary and tertiary levels. The present study was conducted to assess the diagnostic performance of two non-invasive risk scores, fibrosis-4 (FIB-4), and NAFLD fibrosis score (NFS), in Indian patients of biopsy-proven NAFLD. METHODS: We conducted a retrospective analysis of biopsy-proven NAFLD patients that reported to our center between 2009 and 2015. Clinical and laboratory data were collected and two non-invasive fibrosis scores, NFS and FIB-4 score, were calculated using the original formulas. Liver biopsy was utilized as gold standard for diagnosis of NAFLD, diagnostic performance was determined by plotting receiver operator characteristic (ROC) curves and area under the ROC curve (AUROC) was calculated for each score. RESULTS: The mean age of 272 patients included was 40 (11.85) years and 187 (79.24%) were men. We found that the AUROCs for FIB-4 score (0.634) was higher for any degree of fibrosis as compared to NFS (0.566). The AUROC for FIB-4 for advanced liver fibrosis was 0.640 (.550-.730). The performance of the scores for advanced liver fibrosis was comparable with overlapping confidence intervals for both scores. CONCLUSION: The present study found an average performance of FIB-4 and NFS risk scores for detecting advanced liver fibrosis in Indian population. This study highlights the need for devising novel context-specific risk scores for efficient risk stratification of NAFLD patients in India.

Reference cut-offs to define low serum zinc concentrations in healthy 1-19 year old Indian children and adolescents.

BACKGROUND/OBJECTIVES: Population zinc (Zn) status assessment is based on serum zinc concentration (SZC) cut-offs defined by the International Zinc Nutrition Consultative Group (IZiNCG). The objective of this study is to derive reference SZC cut-offs in apparently healthy 1-19 year Indian children and adolescents using comprehensive national nutrition survey (CNNS) data, and to measure the prevalence of Zn deficiency. SUBJECTS/METHODS: Apparently healthy children (n = 12,473) were selected from the CNNS, by including the highest 2 wealth quintiles, and excluding stunted, thin and obese children, and those with CRP > 5 mg/L, anaemia, hypo-albuminemia, diabetes, recent diarrhoea and history of smoking. The 2.5th centile of age-based distributions defined the SZC cut-offs, used to measure the prevalence of Zn deficiency in India, as against the IZiNCG cut-offs. RESULTS: The present study SZC cut-offs were significantly lower, by 10-18 µg/dL, than the IZiNCG cut-offs; more in adolescents. Prevalence of Zn deficiency in the entire CNNS, with these cut-offs, was 2.7 (<10 years) to 5.5 (10-19 years) times lower than with the IZiNCG cut-offs. No geographical state, nor any age group, had Zn deficiency as a serious public health problem (≥20%). In contrast, with IZiNCG cut-offs, 9-27 states (depending on age group) had a public health problem. CONCLUSIONS: The present study reference SZC cut-offs for Zn deficiency are lower than the IZiNCG cut-offs, and their rigorous selection from a national sample makes them more appropriate for use in India. A re-examination of the global applicability of IZiNCG recommended cut-offs in other LMICs appears appropriate.

Characterisation of anaemia amongst school going adolescent girls in rural Haryana, India.

OBJECTIVE: High burden of anaemia exists amongst rural adolescent girls in India. The objective of this study was to characterise anaemia in school going adolescent girls in rural Haryana, India. DESIGN: Linear and multiple logistic regression analysis of data collected prior to an intervention trial was conducted. Participants were classified into anaemic (haemoglobin <12 g/dl) and non-anaemic group and were further classified into deficiencies of Fe, folate or vitamin B12, mixed, anaemia of other causes and inflammation. SETTING: Three schools in Ballabgarh block of Faridabad District, Haryana, India. PARTICIPANTS: One hundered and ninety-eight non-anaemic and 202 anaemic adolescent girls (12-19 years). RESULTS: Anaemic girls had 29·6 % Fe deficiency, 28·1 % folate or vitamin B12 deficiency, 15·8 % mixed deficiency and 9·7 % acute inflammation. Anaemia of other causes was found in 16·8 % of the anaemic participants. Girls with Fe and isolated folate deficiency had 2·5 times and four times higher odds of developing anaemia, respectively, as compared with non-anaemic girls. Fe deficiency with no anaemia was found amongst 11 % non-anaemic girls. Non-anaemic girls had a high prevalence of combined deficiency of folate or vitamin B12 (29·5 %) and acute inflammation (14·4 %). CONCLUSIONS: The current strategy of Fe and folic acid supplementation alone will not suffice for achieving the desired reduction in the prevalence of anaemia as unknown causes and anaemia of inflammation contribute to a substantial proportion of anaemia. Integrating other nutrition-specific components like improving water, sanitation and hygiene practices with the ongoing micronutrient supplementation program will comprehensively tackle anaemia. Unknown causes of anaemia warrant further research.

Association of Vitamin A Status With Under-Five Mortality in India.

OBJECTIVE: To re-estimate the survival benefit from Vitamin A supplementation (VAS) in India using meta-analysis and to correlate mortality and vitamin A deficiency (VAD) in children aged 6 month to 5 year. METHODS: Pooled risk ratio (fixed effects model) for mortality reduction with VAS was calculated from available Indian studies. Computed mortality rates in 6 months to 5 years children in Indian states were regressed on VAD prevalence estimates of the states. RESULTS: There was no reduction in risk of all-cause mortality with VAS (RR=0.96; 95% CI: 0.89, 1.03). When regressing mortality on VAD in high or low VAD prevalence states, the regression coefficients were discordant. CONCLUSION: No survival benefit was observed for VAS in India from the available literature. The targeting of VAS programs should be given serious consideration.

Prevalence of vitamin A deficiency and dietary inadequacy in Indian school-age children and adolescents.

PURPOSE: There are no representative estimates of vitamin A deficiency (VAD) and risk of vitamin A (VA) dietary inadequacy in Indian children and adolescents. To evaluate, from national surveys, the prevalence of VAD measured by serum retinol concentrations (< 0.7 µmol/L or < 20 µg/dL), and the risk of VA dietary inadequacy and excess intake beyond the tolerable upper limit (TUL). METHODS: National and state-level VAD prevalence adjusted for inflammation was estimated in school-age children (5-9 years: 10,298) and adolescents (10-19 years: 9824) from the Comprehensive National Nutrition Survey (CNNS 2016-18). The risk of dietary inadequacy against age-specific average VA requirements, and excess intake against the TUL, was assessed from the National Sample Survey Office (NSSO 2014) data. RESULTS: Serum retinol concentrations increased with age (5-19 years) in both genders and were significantly lower in school-age children (1.02 µmol/L, CI: 1.01-1.03) compared to adolescents (1.13 µmol/L, CI 1.12-1.15). The inflammation-adjusted prevalence of VAD in school-age children and adolescents was 19.3% (CI 18.8-19.9) and 14.4% (CI 13.9-14.9) respectively, and this was > 20% in seven and four states for children and adolescents, respectively. The prevalence of VAD was significantly higher among children with lower socio-economic status. The risk of dietary VA inadequacy, from the NSSO survey, was 69 and 78% in children and adolescents, respectively. This risk reduced to 6 and 17% with VA fortified oil and milk intake, while the proportion of intakes exceeding the TUL became 6 and 0.5% in children and adolescents, respectively. CONCLUSIONS: The national prevalence of VAD in school-age children and adolescents in India was just less than 20%. The risk of dietary VA deficiency is likely to decline substantially with VA fortified food intake, but a risk of excessive intake also begins to appear; therefore, a careful assessment of the risk of hypervitaminosis A is required at these ages.

Perspective: When the cure might become the malady: the layering of multiple interventions with mandatory micronutrient fortification of foods in India.

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 Effects of a Single Freeze-Thaw Cycle on Concentrations of Nutritional, Noncommunicable Disease, and Inflammatory Biomarkers in Serum Samples.

Background The stability of biological samples is vital for reliable measurements of biomarkers in large-scale survey settings, which may be affected by freeze-thaw procedures. We examined the effect of a single freeze-thaw cycle on 13 nutritional, noncommunicable diseases (NCD), and inflammatory bioanalytes in serum samples. Method Blood samples were collected from 70 subjects centrifuged after 30 minutes and aliquoted immediately. After a baseline analysis of the analytes, the samples were stored at - 70°C for 1 month and reanalyzed for all the parameters. Mean percentage differences between baseline (fresh blood) and freeze-thaw concentrations were calculated using paired sample t -tests and evaluated according to total allowable error (TEa) limits (desirable bias). Results Freeze-thaw concentrations differed significantly ( p < 0.05) from baseline concentrations for soluble transferrin receptor (sTfR) (- 5.49%), vitamin D (- 12.51%), vitamin B12 (- 3.74%), plasma glucose (1.93%), C-reactive protein (CRP) (3.45%), high-density lipoprotein (HDL) (7.98%), and cholesterol (9.76%), but they were within respective TEa limits. Low-density lipoprotein (LDL) (- 0.67%), creatinine (0.94%), albumin (0.87%), total protein (1.00%), ferritin (- 0.58%), and triglycerides (TAG) (2.82%) concentrations remained stable following the freeze-thaw cycle. In conclusion, single freeze-thaw cycle of the biomarkers in serum/plasma samples after storage at - 70°C for 1 month had minimal effect on stability of the studied analytes, and the changes in concentration were within acceptable limit for all analytes.

Prevalence of Iron Deficiency and its Sociodemographic Patterning in Indian Children and Adolescents: Findings from the Comprehensive National Nutrition Survey 2016-18.

BACKGROUND: Anemia control programs in India focus mainly on the measurement of hemoglobin in response to iron-folic acid supplementation. However, representative national estimates of iron deficiency (ID) are not available. OBJECTIVES: The objective of the present study was to evaluate ID prevalence among children and adolescents (1-19 y) using nationally representative data and to examine the sociodemographic patterning of ID. METHODS: Cross-sectional data from the Comprehensive National Nutrition Survey in children (1-4 y: n = 9635; 5-9 y: n = 11,938) and adolescents (10-19 y; n = 11,507) on serum ferritin (SF) and other biomarkers were analyzed to determine inflammation-adjusted ID prevalence [SF (µg/L): <12 in 1-4 y and <15 in 5-19 y] and its relation to sociodemographic indicators. Multiple-regression analyses were conducted to identify the exposure associations of iron status. In addition, the relation between SF and hemoglobin was assessed as an indicator of iron utilization in different wealth quintiles. RESULTS: ID prevalence was higher in 1- to 4-y-old children (31.9%; 95% CI: 31.0%, 32.8%) and adolescent girls (30.4%; 95% CI: 29.3%, 31.5%) but lower in adolescent boys and 5- to 9-y-old children (11%-15%). In all age groups, ID prevalence was higher in urban than in rural participants (1-4 y: 41% compared with 29%) and in those from richer quintiles (1-4 y: 44% in richest compared with 22% in poorest), despite adjustment for relevant confounders. SF significantly interacted with the wealth index, with declining trends in the strength of association between hemoglobin and SF from the richest to the poorest groups suggesting impaired iron utilization for hemoglobin synthesis in poorer wealth quintiles. CONCLUSIONS: ID prevalence was indicative of moderate (in preschool children and adolescent girls) or mild (in 5- to 9-y-old children and adolescent boys) public health problem with significant variation by state and age. Focusing on increasing iron intake alone, without addressing the multiple environmental constraints related to poverty, may not result in intended benefits.

Haemoglobin thresholds to define anaemia in a national sample of healthy children and adolescents aged 1-19 years in India: a population-based study.

BACKGROUND: WHO's haemoglobin cutoffs to define anemia were based on five studies of predominantly White adult populations, done over 50 years ago. Therefore, a general re-examination of the existing haemoglobin cutoffs is warranted for global application, in representative healthy populations of children and adults. Such data are scarce in low-income and middle-income countries; however, a 2019, large-scale, nationally representative survey of children and adolescents aged 0-19 years in India (Comprehensive National Nutrition Survey [CNNS]) offered an opportunity for this re-examination. Using this survey, we aimed to assess the age-specific and sex-specific percentiles of haemoglobin and cutoffs to define anaemia in the CNNS population. METHODS: For this population-based study, we constructed age-specific and sex-specific haemoglobin percentiles from values reported for a defined healthy population in the CNNS, which used rigorous quality control measures during sample collection and in the laboratory analyses. To obtain a healthy population, we excluded participants with iron, folate, vitamin B12, and retinol deficiencies; inflammation; variant haemoglobins (haemoglobin A2 and haemoglobin S); and history of smoking. We considered age-specific and sex-specific 5th percentiles of haemoglobin derived for this healthy population as the study cutoff to define anaemia. We compared these with existing WHO cutoffs to assess significant differences between them at each year of age and sex for quantifying the prevalence of anaemia in the entire CNNS sample. FINDINGS: Between Feb 24, 2016, and Oct 26, 2018, the CNNS survey collected blood samples from 49 486 individuals. 41 210 participants had a haemoglobin value, 8087 of whom were included in our study and comprised the primary analytical sample. Compared with existing WHO cutoffs, the study cutoffs for haemoglobin were lower at all ages, usually by 1-2 g/dL, but more so in children of both sexes aged 1-2 years and in girls aged 10 years or older. Aanemia prevalence with the study cutoffs was 19·2 percentage points lower than with WHO cutoffs in the entire CNNS sample with valid haemoglobin values across all ages and sexes (10·8% with study cutoffs vs 30·0% with WHO cutoffs). INTERPRETATION: These findings support the re-examination of WHO haemoglobin cutoffs to define anaemia. Our haemoglobin reference percentiles, derived from healthy participants in a large representative Indian survey, are suitable for national use in India. Substantial variations in the 5th percentile of haemoglobin values across the 1-19 years age range and between sexes argue against constructing common cutoffs in stratified age groups for convenience. FUNDING: None. TRANSLATIONS: For the Hindi, Punjabi, Tamil and Kannada translations of the abstract see Supplementary Materials section.

Intraindividual double-burden of anthropometric undernutrition and "metabolic obesity" in Indian children: a paradox that needs action.

BACKGROUND: Intra-individual coexistence of anthropometrically defined undernutrition and 'metabolic obesity', characterised by presence of at least one abnormal cardiometabolic risk factor, is rarely investigated in young children and adolescents, particularly in Low-and-Middle-Income-Countries undergoing rapid nutrition transition. METHODS: Prevalence of biomarkers of metabolic obesity was related to anthropometric and socio-demographic characteristics in 5-19 years old participants from the population-based Comprehensive National Nutrition Survey in India (2016-2018). The biomarkers, serum lipid-profile (total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides), fasting glucose, and glycosylated hemoglobin (HbA1C), and all jointly were analysed in 22567, 23192, 25962 and 19143 participants, respectively. RESULTS: Overall (entire dataset), the prevalence of abnormalities was low (4.3-4.5%) for LDL and TC, intermediate for dysglycemia (10.9-16.1%), and high for HDL and triglycerides (21.7-25.8%). Proportions with ≥1 abnormal metabolic obesity biomarker(s) were 56.2% overall, 54.2% in thin (BMI-for-age < -2 SD) and 59.3% in stunted (height-for-age < -2 SD) participants. Comparable prevalence was evident in mild undernutrition (-1 to -2 SD). Clustering of two borderline abnormalities occurred in one-third, warranting active life-style interventions. Metabolic obesity prevalence increased with BMI-for-age. Among those with metabolic obesity, only 9% were overweight/obese (>1 SD BMI-for-age). Among poor participants, triglyceride, glucose and HDL abnormalities were higher. CONCLUSIONS: A paradoxical, counter-intuitive prevalence of metabolic obesity biomarker(s) exists in over half of anthropometrically undernourished and normal-weight Indian children and adolescents. There is a crucial need for commensurate investments to address overnutrition along with undernutrition. Nutritional status should be characterized through additional reliable biomarkers, instead of anthropometry alone.