BACKGROUND AND PURPOSE:

• The World Health Organization’s Hb anemia cutoffs, used internationally, are derived from “over 95% of normal individuals are believed to show Hb levels higher than the cutoffs given”
  • Based on a few studies of European and North American populations
  • 11.0 g/dL for children | 12.0 g/dL for nonpregnant women
• Yaw Addo et al. (JAMA Network Open, 2021) evaluated the current WHO Hb cutoffs for defining anemia and assessed threshold validity using tissue biomarkers along with multinational data

METHODS:

• Secondary cross-sectional study (2005 to 2016)
  • Data derived from Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project
    • Inclusion: Nonmissing Hb | Inflammation biomarkers | Nutritional biomarker of iron (ferritin or transferrin receptor) or vitamin A (retinol or retinol-binding protein [RBP])
  • 25 countries
  • Population-based nutrition surveys: Preschool children aged 6 to 59 months | Nonpregnant women aged 15 to 49 years
• Participants
  • Healthy members of the persons present in the above data sets
  • Exclusions
    • Iron deficiency: Ferritin <12 ng/mL for children or <15 ng/mL for women
    • Vitamin A deficiency: Retinol-binding protein or retinol <20.1 μg/dL
    • Inflammation: C-reactive protein >0.5 mg/dL or α-1-acid glycoprotein >1 g/L
    • Known malaria
• Exposure
  • Anemia according to WHO Hb cutoffs
• Study design
  • Survey-specific, pooled Hb fifth percentile cutoffs were estimated
  • Biomarker studies for tissue iron deficiency: Soluble transferrin receptor (sTfR), which reflects iron-deficient erythropoiesis
  • Among individuals with Hb and sTfR data, Hb-for-sTfR curve analysis was conducted to identify Hb inflection points that reflect tissue iron deficiency and increased erythropoiesis induced by anemia

RESULTS:

• Healthy children: 12,445 | Healthy women: 25,880
  • Children mean (SD) age: 32.9 (16.0) months | 50.2% boys
  • Women mean (SD) age: 31.0 (9.5) years
• Survey-specific Hb fifth percentile rages
  • Among children
    • Low: 7.90 g/dL (95% CI, 7.54 to 8.26 g/dL) in Pakistan
    • High: 11.23 g/dL (95% CI, 11.14 to 11.33 g/dL) in the US
  • Among women
    • Low: 8.83 g/dL (95% CI, 7.77 to 9.88 g/dL) in Gujarat, India
    • High: 12.09 g/dL (95% CI, 12.00 to 12.17 g/dL) in the US
• Intersurvey variance around the Hb fifth percentile was low, supporting use of pooled data
  • For children: 3.6%
  • For women: 3.5%
• Pooled fifth percentile estimates (low)
  • For children: 9.65 g/dL (95% CI, 9.26 to 10.04 g/dL)
  • For women: 10.81 g/dL (95% CI, 10.35 to 11.27 g/dL)
• The Hb-for-sTfR curve demonstrated curvilinear associations with sTfR inflection points occurring at
  • Among children: Hb of 9.61 g/dL (95% CI, 9.55 to 9.67 g/dL)
  • Among women: 11.01 g/dL (95% CI, 10.95 to 11.09 g/dL)

CONCLUSION:

• Current WHO cutoffs for determining anemia are higher than the pooled fifth percentile of Hb levels among healthy women and preschool children
• Multinational estimates of Hb fifth percentile were 1.35 and 1.19 g/dL lower than the current WHO Hb cutoffs
• Use of sTfR biomarker reinforced the fifth percentile data calculations
• The authors conclude

Future studies focusing on Hb thresholds associated with functional and clinical health outcomes will improve the understanding of overall disease burden

Until then, revising Hb cutoff level definitions according to pooled multinational data could be considered 

Learn More – Primary Sources:

Evaluation of Hemoglobin Cutoff Levels to Define Anemia Among Healthy Individuals

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