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.

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.

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.

Impact of daily-supervised administration of a package of iron and folic acid and vitamin B12 on hemoglobin levels among adolescent girls (12-19 years): a cluster randomized control trial.

OBJECTIVE: The prevalence of anemia has remained high among Indian adolescent girls over the past decade, despite the ongoing iron and folic acid (IFA) supplementation program. This study was conducted to assess the impact of daily supplementation of a package of IFA with vitamin B12 on hemoglobin levels among adolescent girls. METHODS: A community-based cluster-randomized trial was conducted in the rural block of Faridabad District, Haryana, India in the year 2017. A total of 760 adolescent girls in the age group of 12-19 years with mild and moderate anemia were selected from government schools. Daily-supervised administration of iron and folic acid was conducted for 90 days: experimental group-IFA (iron (60 mg), folic acid (500) mcg), and cyanocobalamin (1000 mcg), control group-IFA and placebo. Hemoglobin, serum ferritin, and vitamin B12 levels were assessed at baseline and endline. RESULTS: Two-hundred adolescent girls completed 90 doses of daily supplementation. The mean hemoglobin (experimental group: 1.3 ± 1.0 g/dL, control group: 1.6 ± 1.2 g/dL, P = 0.004) and ferritin levels (experimental group: 18.6 ± 31.5 ng/mL, control group: 18.8 ± 35.0 ng/mL, P = 0.188) increased in both the control and experiment groups. Serum vitamin B12 deficiency significantly reduced to 2.5% in the experimental group and ferritin deficiency alleviated in more than 96% of the girls post intervention. CONCLUSIONS: Daily supplementation of IFA with/without vitamin B12 for 90 days eliminated iron, vitamin B12 deficiency and reduced the overall proportion of anemia by 53.5%. However, addition of vitamin B12 to IFA supplementation had no impact on improving the hemoglobin levels among adolescent girls. The present study does not recommend provision of vitamin B12 for prevention and treatment of anemia in this population group.

Vitamin A deficiency among children younger than 5 y in India: an analysis of national data sets to reflect on the need for vitamin A supplementation.

BACKGROUND: Biochemical vitamin A deficiency (VAD) is believed to be a serious public health problem (low serum retinol prevalence >20%) in Indian children, justifying universal high-dose vitamin A supplementation (VAS). OBJECTIVE: To evaluate in Indian children younger than 5 y the risk of biochemical VAD from the Comprehensive National Nutrition Survey, as well as dietary vitamin A inadequacy and excess over the tolerable upper limit of intake (TUL) from national and subnational surveys, factoring in fortification and VAS. METHODS: Child serum retinol data, corrected for inflammation, were examined to evaluate national- and state-level prevalence of VAD. Simultaneously, dietary intakes from the National Sample Survey Office and the National Nutrition Monitoring Bureau were examined for risk of dietary vitamin A deficiency against its average requirement (AR) derived for Indian children. Theoretical estimates of risk reduction with oil and milk vitamin A fortification were evaluated along with the risk of exceeding the TUL, as well as when combined with intake from VAS. RESULTS: The national prevalence of biochemical VAD measured in 9563 children was 15.7% (95% CI: 15.2%, 16.3%), and only 3 states had prevalence significantly >20%. The AR of vitamin A was 198 and 191 µg/d for boys and girls; the risk of dietary inadequacy was ∼70%, which reduced to 25% with oil and milk fortification. Then, the risk of exceeding the TUL was 2% and 1% in 1- to 3-y-old and 4- to 5-y-old children, respectively, but when the VAS dose was added to this intake in a cumulative 6-mo framework, the risk of exceeding the TUL rose to 30% and 8%, respectively. CONCLUSION: The national prevalence of VAD risk is below 20% in Indian children. Because there is risk of excess intake with food fortification and VAS, serious consideration should be given to a targeted approach in place of the universal VAS program in India.

National Iron Plus Initiative: Current status & future strategy.

Anaemia is a severe public health problem amongst all vulnerable age groups in India. The National Nutritional Anaemia Prophylaxis Programme initiated in 1970, was revised and expanded to include beneficiaries from all age groups namely children aged 6-59 months, 5-10 yr, adolescents aged 10-19 yr, pregnant and lactating women and women in reproductive age group under the National Iron Plus Initiative (NIPI) programme in 2011. The dose of iron, frequency and duration of iron supplementation and roles and responsibilities of the functionaries were described. At present, the coverage of beneficiaries with iron and folic acid has been poor at the national level. The prevalence of anaemia has continued to remain high during the last 60 years, and there has been no significant change in the scenario due to various reasons. The constraints in implementation and measures to improve the NIPI programme are discussed in the current article.

Low-quality scientific evidence for the continuation of universal Vitamin A supplementation among under 5 children in India.

Vitamin A supplementation (VAS) is presently being undertaken in India among under 5 (U5) children for two possible benefits (i) to prevent nutritional blindness due to Vitamin A deficiency (VAD) and (ii) to reduce U5 mortality. The existing scientific evidence suggests that nutritional blindness due to VAD has been virtually eliminated and also the difference between U5 mortality rate and infant mortality rate is very low for VAS to have any meaningful impact. On the contrary, scientific evidence indicates that there could be side effects of the administration of mega dose of Vitamin A (MDVA). These side effects of MDVA have not been systematically investigated. The universal VAS should be discontinued immediately as there are no likely benefits to U5 children.

Controversies Continue: Universal Supplementation of Megadose of Vitamin A to Young Children in India.

The universal megadose of vitamin A (MDVA) supplementation program was started in the year 1970. The program is presently in continuation for the prevention of nutritional blindness and possibly reduction in under-five mortality rate (U5MR). Presently, blindness due to vitamin A deficiency (VAD) has disappeared and the difference between U5MR and infant mortality rate (IMR) is less than 10 thus MDVA is unlikely to have any impact on mortality. The continuation of universal MDVA needs to be modified based on the current scientific evidence.

Reappearance of Bitot's spots after complete resolution in children between 1 and 5 years of age.

There is limited data on proportion of Bitot's spots (BS), which could reappear after receiving mega dose of Vitamin A (MDVA), and their complete resolution. A prospective, community-based, cohort study with 12 months follow-up was conducted among children (1-5 years) with BS at a district from North India. On diagnosis, 200,000 IU of vitamin A was administered on the same day, then after 4 weeks and subsequently after 6 months. Out of 262 children with BS, 157 (59.9%, 95% CI: 54.1-65.9) children had shown resolution of BS after the MDVA supplementation. Out of 157 children, 97 (61.8%, 95% CI: 54.2-69.4) had reappearance of BS after complete resolution. Kaplan-Meir analysis found that median duration of reappearance of BS was 5 months (95% CI: 3.8-6.2) after their complete resolution. The reappearance of BS after administration of two MDVA within 12 months suggests that children with possibly adequate serum retinol level status may have reappearance of BS.

Prevalence of Folate, Ferritin and Cobalamin Deficiencies amongst Adolescent in India.

BACKGROUND: In India, 60-90% of adolescent suffer from anemia. Studies have documented folate, ferritin, and cobalamin deficiencies to be the major causes of nutritional anemia. However, limited data is available on the prevalence of folate, ferritin, and cobalamin deficiencies amongst adolescent from India. OBJECTIVES: The present study was carried out to find out the magnitude of folate, ferritin, and cobalamin deficiencies amongst adolescent of 11-18 years of age in National Capital Territory (NCT) of Delhi, India. MATERIALS AND METHODS: A cross-sectional, school-based study was conducted in NCT of Delhi, India in the year 2010-2011. About 347 adolescent belonging to low- (LIG), middle- (MIG), and high-income groups (HIG) were selected using the probability proportionate to size (PPS) sampling methodology. Serum ferritin, serum folate, and serum cobalamin levels were determined by the enzyme-linked immunosorbent assay (ELISA) method, radioimmunoassay (RIA) method, and radioisotopic method, respectively. Hemoglobin (Hb) estimation was done by cyanmethemoglobin method in all the blood samples collected. RESULTS: The prevalence of deficiency of ferritin in HIG, MIG, and LIG categories of adolescent was found to be 52.9, 67, and 58.8%, respectively. In the HIG, MIG, and LIG categories of adolescent, the prevalence of folate deficiency was 22.5, 40.4, and 52.2%, respectively. The prevalence of deficiency of cobalamin in HIG, MIG, and LIG categories of adolescent was 47.1, 80.7 and 87.5%, respectively. About 48, 66.1, and 68.4% of adolescent in the HIG, MIG, and LIG categories, respectively had Hb levels less than 12 g/dL and were found to be suffering from anemia. CONCLUSIONS: A high prevalence of anemia existed along with deficiency of ferritin, cobalamin, and folate amongst adolescent. The strategies for prevention of anemia amongst adolescent in India should also include cobalamin along with iron and folate supplementation for prevention and control of nutritional anemia. Primary care physicians should suspect all the three causes for anemia.

Resolution of Bitot's spots following mega-dose vitamin A supplementation in children between 1 and 5 years of age.

OBJECTIVE: The prevalence of Bitot's spots (BS) is often used to quantify vitamin A deficiency burden in India, both before and after mega-dose vitamin A supplementation (MVAS) programmes. However, the proportion of BS cured following this intervention is unclear in contemporary times. The current study evaluated the responsiveness of BS over 1 year to MVAS administered as per the national programme in rural India. DESIGN: Prospective, community-based, 1-year follow-up of a cohort. SETTING: Rural Uttar Pradesh, India. SUBJECTS: Two hundred and sixty-two children with BS, aged between 1 and 5 years, administered 60 mg (retinol equivalent) of vitamin A on diagnosis and after 1 month. Cure or resolution was defined if there was no discernible BS in either eye. RESULTS: During 1 year, only three children were lost to follow-up. At 6 months of follow-up (MVAS at baseline and 1 month later), 51·1 (95% CI 45·3, 57·3) % were classified as cured. The corresponding figure at 1 year (additional MVAS at 6 months) was 59·9 (95% CI 54·1, 65·9) %. Among those cured at 6 months, about half and three-quarters had resolved at 2 and 3 months, respectively. Apart from male gender, there were no significant sociodemographic or clinical predictors of response. CONCLUSIONS: Substantial non-response to MVAS at 6 months (49%) and 1 year (40%) of follow-up suggests that presently in the Indian subcontinent, BS is a relatively crude indicator of severe current vitamin A deficiency. For programmatic decisions and evaluation, the public health burden of vitamin A deficiency should not be assessed solely through BS.