Hemoglobin Thresholds to Define Anemia in a National Sample of Healthy 1-19 Years Old Children and Adolescents in India: A Population-Based Study

Abstract

Background: The original World Health Organization (WHO) thresholds to define anemia were based on five studies of predominantly white adult populations. In 2000, the threshold was lowered for 5-11 years based on National Health and Nutrition Examination Survey II data. A re-examination of the existing thresholds is now recommended, including through defining anemia by hemoglobin levels below the reference range in a representative and healthy population, employing stringent exclusion criteria. Such data are scarce, especially for children residing in Low- and Middle-Income-Countries. Methods: Age- and sex-specific hemoglobin percentiles were constructed from a nationally representative sample of 1-19 years old participants in India, employing “best practice” laboratory methods and rigorous quality control. The primary “healthy population” (n=8087) excluded iron, folate, vitamin B 12 and retinol deficiencies, inflammation (C-reactive protein), variant hemoglobins (HbA2 and HbS), and smokers. Sensitivity analyses filtered further for high total cholesterol, glycosylated haemoglobin and serum creatinine, zinc deficiency, stool parasitosis, and hypoalbuminemia. These Indian (<5 th percentile) and WHO thresholds were compared. Findings: Compared to WHO thresholds, these hemoglobin cut-offs were lower throughout 1-19 years, usually by 1-2 g/dl, and more so in 1-2 years old and in girls after 9 years age. The overall anemia prevalence was lower (10.8% vs 30.0%; gap 19.2) with marked differences for 1-4 and 15-19 years. The anemia prevalence gap was higher for 1-4 years old boys (28.3 vs 22.2), and for girls >10 years old (22.6 vs 8.9 for 10-14 years and 32.6 vs 11.5 for 15-19 years). Interpretation: These contemporary hemoglobin reference centiles are suitable for national use in India. Substantial variations argue against pooling thresholds across ages and sexes for convenience. The lower anemia burden may better reflect the responsiveness to programmatic interventions. These findings support an urgent re-examination of WHO thresholds for anemia. Funding: The survey was funded by the Mittal Foundation. For this analysis no funding was available. Declaration of Interests: HSS designed the draft protocol of the CNNS with consultancy support from the UNICEF, India. HSS, AS, UK and AVK were members of the Technical Advisory Committee of the CNNS, constituted by the Ministry of Health and Family Welfare of the Government of India, to oversee its conduct and analysis. HSS is a member of the World Health Organization Nutrition Guidance Expert Advisory Subgroup on Diet and Health and Guideline Development Group on Use and interpretation of haemoglobin concentrations for assessing anaemia status in individuals and populations, and member of the National Technical Board on Nutrition of NITI Aayog, and Expert Groups of the Ministry of Health and Family Welfare on Nutrition and Child Health. AVK is a Nutrition Advisor to the Tata Trusts. AS, RA, SR, NK and AP were involved in the CNNS study implementation and main analyses. There were no other conflicts to declare. Ethics Approval Statement: Ethics approvals were obtained from the Ethics Committee of the Postgraduate Institute for Medical Education and Research in Chandigarh, India, and the Institutional Review Board of the Population Council, Zone 5A, Ground Floor India Habitat Centre, Lodi Road, New Delhi, Delhi 110003, India, New York. Written, informed consent was obtained from caregivers of children aged 0–10 years. For adolescents aged 11–17 years, written informed consent was obtained from their caregivers and written informed assent obtained from the adolescents. Adolescents aged 18–19 years provided their own consent.