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The WHO's long-standing hemoglobin cutoffs for anemia do not match reality for people around the world, a cross-sectional study found.

Pooled fifth percentile estimates of hemoglobin were 9.65 g/dL for children and 10.81 g/dL for women across 27 nutrition surveys from 25 countries, with low inter-survey variance around these estimates, reported O. Yaw Addo, PhD, of the CDC and Emory University in Atlanta, and colleagues.

In line with this finding, hemoglobin concentrations plotted against soluble transferrin receptor (a biomarker of tissue iron deficiency and a physiological indicator of erythropoiesis) reveal compensatory increased erythropoiesis when hemoglobin dips below 9.61 g/dL among children and 11.01 g/dL among women, they noted in .

Thus, the newly calculated multinational fifth percentile estimates of hemoglobin are more than 1.0 g/dL lower than current WHO cutoffs for defining anemia in apparently healthy people: .

The study authors said that this change is supported by that also called for a decrease of approximately 1.0 g/dL in hemoglobin cutoffs.

Moreover, they said their results "support the use of a pooled multinational Hb [hemoglobin] fifth percentile for defining anemia, as opposed to adopting Hb estimates that are specific to a survey, country, or race/ethnicity, which could lead to proliferation of multiple different Hb cutoffs and, thus, complicate their clinical application and global disease burden quantification, among other factors."

Released in 1968, the WHO cutoffs had been based on smaller studies of Europeans and Canadians and later validated using a U.S. population.

"Evaluation of the WHO Hb cutoffs has been a subject of active research for decades. These cutoffs were derived from statistical cutoffs not linked with physiological or health outcomes. Furthermore, the appropriateness of these cutoffs for defining anemia among certain population groups, age groups, and ethnicities has been questioned repeatedly," Addo and colleagues wrote.

Anemia is defined as having hemoglobin levels too low to meet an individual's physiological needs.

However, evaluating other factors associated with anemia (e.g., malaria, vitamin A, vitamin B12, folate, and inherited blood disorders) is also crucial to guiding anemia management, Addo's group cautioned.

The cross-sectional study was based on a healthy sample of 13,445 children (mean age 32.9 months, 50.2% boys) and 25,880 nonpregnant women (mean age 31.0 years), after excluding those with iron deficiency, vitamin A deficiency, inflammation, or malaria.

Survey-specific hemoglobin fifth percentile estimates ranged from 7.90 g/dL (in Pakistan) to 11.23 g/dL (in the U.S.) for children, and from 8.83 g/dL (in Gujarat, India) to 12.09 g/dL (in the U.S.) for women.

Study results persisted when using higher ferritin cutoffs to define iron deficiency.

The lack of uniformity in laboratory assessment of hemoglobin was a major caveat of the study, the authors acknowledged.

In addition, hemoglobin cutoffs were derived without input from medical records, precluding analysis linking hemoglobin with clinical outcomes.

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