Publications

Abstract

The World Health Organization has recently lowered the hemoglobin (Hb) diagnostic cutoff for anemia in 6–23-month-old children by 0.5 g/dL and specifies the use of venous blood. The national prevalence of anemia defined from venous blood in children 6–23 months reduced by ~10% points when using the new Hb cutoff.

The diagnosis of anemia was recently revised by the World Health Organization (WHO)[1] in two important ways. First, the general principle of diagnosis was that anemia should only be diagnosed in individuals and population using venous blood hemoglobin (Hb) concentrations, measured by automated hematology analyzers along with high-quality control measures.[1] The Hb diagnostic cutoff was defined statistically, as the 5th percentile of the distribution of Hb concentrations in healthy populations at any age. Second, the Hb diagnostic cutoff for anemia was changed, from a single value for children aged 6–59 months (at 11 g/dL) to different values for children aged 6–23 months and 24–59 months.[1] This was because continuous analyses of the Hb diagnostic thresholds over ages showed an increase in the threshold till about 24 months of age, after which these values gently plateaued,[2] necessitating this age grouping. For the 6–23-month group, the diagnostic Hb cutoff in the 6–23-month group came from 924 children[2] and was found to be 10.4 g/dL (90% confidence interval 10.4–10.5) but was set at 10.5 g/dL in the WHO guideline.[1]

The change in anemia prevalence in children aged 6–59 months in India, due to this new WHO Hb cutoff in a subgroup of children, is important to analyze. Anemia has been perceived to be a persistent public health problem in India for many decades and is thought to be worsening, as chronicled by the periodic National Family Health Surveys (NFHSs), which gather essential health data and are conducted every 5–10 years.[3-5] The most recent NFHS-5 conducted in 2019–2021[5] revealed that the national anemia prevalence in Indian children had risen from 58.6% to 67.1%, compared to the previous NFHS-4 conducted in 2015–2016,[4] and that it was particularly high in 6–23-month-old children [Table 1]. The NFHSs classified anemia from capillary blood-based Hb measurements by HemoCue point-of-care testing. However, when Hb was measured from venous blood using automated Hb analyzers[1] as was done in the Comprehensive National Nutrition Survey (CNNS),[6] the prevalence in Indian 6–59 and 6–23-month-old children was lower

When the new Hb diagnostic cutoff was applied to these survey data, it had a significant impact on reducing (~10% point) the prevalence of anemia in 6–23-month-old children in both NFHS-5 and CNNS. The reduction in overall prevalence in 6–59-month-old children was lower by 2% points in the 6–59-month age group in the CNNS which used venous blood and by 4% points in the NFHS-5 which used capillary blood and had higher prevalence estimates (68%) than CNNS (41%). The reduction of the prevalence of anemia in 6–59-month-old children, diagnosed by venous blood as in the CNNS, appears small but changes the public health significance of anemia in this age group from severe to moderate;[1,7] however, for children aged 6–23 months, the prevalence remained in the severe public health significance category.

The WHO guideline states that Hb cutoffs should not be adjusted for the effect of genetic ancestry/ethnicity/race due to insufficient evidence and the complexity of operationalization (although this latter should not be an excuse). Although additional data collected in lower-income settings were available[8] and reported heterogeneous but generally lower values for the 5th Hb percentiles in children without biochemical evidence of iron and/or Vitamin A deficiencies or inflammation (C-reactive protein or α-1-acid glycoprotein), these data were not considered in the pooled analysis to derive the final Hb cutoff because of the backdrop of the high burden of infections and inflammation in these settings, as also with no definitive evidence to exclude their residual effects on Hb concentrations. While the WHO has taken a step toward reviewing its recommendations for anemia cutoff globally, it is important that rigorous studies are undertaken in such settings to review the applicability of these global cutoffs for the Indian population and take necessary steps to develop nation-specific cutoffs, if deemed necessary.