Evaluation of Hemoglobin Cutoffs for Defining Anemia in a Multinational Sample of Healthy Individuals: The BRINDA Project (OR07-07-19)

Abstract

Objectives Current WHO hemoglobin (Hb) cutoffs (< 110 g/L, 6–59mo; < 120 g/L, 15–49y non-pregnant women) to define anemia were established in 1967 and validated in 1980 s among iron replete USA survey participants. Our objective was to examine the consistency of Hb cutoffs from multiple countries and age-variations in Hb concentrations among apparently healthy people using contemporary data. Methods We analyzed altitude and smoking (women only)-adjusted Hb data from 25 countries for preschool children (PSC, 6–59mo, 24 surveys, n = 35,088) and women of reproductive age (WRA, 15–49y, 20 surveys, n = 50,846) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Healthy was defined as: [ferritin >12 µg/L (< 5y), >15 µg/L ( >5y)], RBP or retinol >0.7 µmol/L, CRP ≤ 5 mg/L or AGP ≤ g/L, and no malaria (if measured)]. We examined Hb levels, cut-offs at specified percentiles (%ile) and country variations with age-adjusted generalized mixed models using country as random intercept. Results The final analytic sample was 41,314; the healthy inclusion criteria resulted in 17–88% data loss of the original data depending on country. Age and country-adjusted mean (SE) of Hb was 116.9 (1.44)g/L for PSC, and 129.1 (1.49)g/L for WRA and was significantly (P < 0.001) associated with age in PSC but not in WRA, and varied by country (pheterogeniety < .001, in each target group). Country explained 22% of the total Hb variance for each group. The pooled countries’ Hb at the 5%ile was 94 g/L for PSC [range: 79 g/L (Pakistan) - 113 g/L (USA], and 110 g/L for WRA [92 g/L (Nigeria) - 121 g/L (USA)]. Conclusions The high heterogeneity in Hb cutoffs among healthy people from different countries suggests that a single Hb cutoff for anemia may not work for every country. This multinational analysis suggests that different approaches may be warranted to establish Hb cutoffs. Funding Sources Bill & Melinda Gates Foundation.

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

“…Subclinical malaria, though not formally examined by a peripheral smear examination, was effectively excluded through negative inflammatory biomarkers, and negligible (0·26%) history of malaria in the 2 weeks preceding the survey. We chose the 5th percentile cutoffs to define anaemia for comparability with published literature; 9 these cutoffs are marginally higher than the suggested 2·5th percentile. 4 The 5th percentile is also a more conservative cutoff; if the 2·5th percentile was chosen as the cutoff, the anaemia prevalence would also be lower than our estimates and further from prevalence estimates based on the WHO cutoff.…”

“…A 2019 conference abstract reported summary haemoglobin data from 25 countries for preschool children (aged 6—59 months, 24 surveys, n=35 088) and women of reproductive age from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anaemia (BRINDA) project. 9 Their definition of healthy was based on the exclusion of iron and vitamin A deficiency, inflammation detected through biomarkers, and malaria. In this study, we aimed to assess the age-specific and sex-specific percentiles of haemoglobin and cutoffs to diagnose anaemia in children and adolescents aged 1–19 years, including additional rigorous criteria to define a healthy population, using the 2019 quality controlled, nationally representative Comprehensive National Nutrition Survey (CNNS) in India.…”

Re-Defining the Population-Specific Cut-Off Mark for Vitamin A Deficiency in Pre-School Children of Malawi

“…Despite the lack of updating and proper validation of this threshold, it is still used globally to identify VAD in PSC through SR and sometimes RBP concentrations (when it’s used as a proxy), in national and sub-national MNS. This challenge is present with most thresholds of nutrition biomarkers [ 56 , 58 ], especially those where proper development and validation procedures were not followed. After close to 60 years, the cut-off value for SR needs to be reviewed through properly designed studies and updated methods, to determine its accuracy and relevance for different countries and age groups.…”

Anemia in preschool children from Angola: a review of the evidence

“…16 Furthermore, there are reports of high heterogeneity regarding the hemoglobin levels that should define anemia among different countries, particularly in tropical regions. 124 – 126 …”

“…16 Furthermore, there are reports of high heterogeneity regarding the hemoglobin levels that should define anemia among different countries, particularly in tropical regions. [124][125][126] Health determinants of anemia. The prevalence and distribution of anemia (particularly IDA) is considered to have (1) fundamental, (2) underlying, (3) intermediate, and (4) immediate determinants, involving a complex interplay of factors.…”