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. 2025 Jan-Dec:62:469580251372827.
doi: 10.1177/00469580251372827. Epub 2025 Sep 22.

The New WHO Cut-off Point for Defining High-altitude Anemia may be Inadequate

Gustavo F Gonzales  1 , Cinthya Vásquez-Velásquez  1 , Sandra Yucra  2 , Vilma Tapia  3 , Manuel Gasco  3 , Parminder S Suchdev  4   5 , Chris A Rees  6   7 , Julio Aguilar  8
Affiliations

The New WHO Cut-off Point for Defining High-altitude Anemia may be Inadequate

Gustavo F Gonzales et al. Inquiry. 2025 Jan-Dec.

Abstract

Introduction: Peru carries a high burden of childhood anemia, particularly in high-altitude regions where hemoglobin (Hb) adjustment for altitude is recommended. This study aimed to evaluate whether the proportion of anemia attributable to iron deficiency (ID), inflammation, and red blood cell indices varies by altitude in children, using different diagnostic criteria.

Methods: We conducted a cross-sectional study of 280 children aged 6 to 72 months residing in Arequipa, Peru at altitudes ranging from 9 to 4310 m above sea level. Venous blood samples were collected to assess Hb, complete blood count, and serum biomarkers of iron status and inflammation. Spearman's rank correlation was used to examine relationships between altitude and hematologic or biochemical parameters. Logistic regression models evaluated associations between altitude, Hb concentration, and anemia prevalence, defined with and without altitude adjustment.

Results: Anemia prevalence increased from 12% to 31% after applying altitude-adjusted Hb thresholds. At mid-altitudes (1000-<3000 m), prevalence rose from 8.3% to 43.8% (P < .001), and at ≥3000 m, from 0% to 16.3% (P < .001). Overweight and obese children had a higher anemia prevalence using unadjusted Hb (28.6% vs 10.5%; P < .05), a difference that disappeared after adjustment. Iron deficiency was present in 5.6% of participants, while inflammation was detected up to 26.5%. Receiver operating characteristic (ROC) analysis indicated that unadjusted Hb thresholds had better diagnostic performance for identifying iron deficiency anemia (IDA) compared to altitude-adjusted definitions.

Conclusion: These findings suggest that altitude-adjusted Hb cutoffs may overestimate anemia prevalence and lead to misclassification of IDA in high-altitude pediatric populations.

Keywords: altitude; anemia; etiology; iron deficiency.

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Conflict of interest statement

Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

A bar chart compares the proportion of anemia in unadjusted and adjusted groups at different altitude levels, with significance levels indicated by asterisks. B bar chart shows the same trend by weight (overweight vs normal) for unadjusted and adjusted anemia, with a star indicating a high level of significance.
Figure 1.
A. Proportion of anemia in children aged 6 to 72 months residing at different altitudes without adjusting Hb for altitude (Blue) and after adjustment of Hb for altitude. B. Proportion of anemia with and without Hb adjustment for altitude and according to weight Chi square test. *P = .014; **P = .00001; ***P = .00025.
Plot shows the correlation of hemoglobin levels in children aged 6-72 months against their Z-score-weight-for-age, with a negative trend line equation.
Figure 2.
The relationship between Z-score-weight-for-age and hemoglobin in children aged 6–72 months.
Two ROC curves comparing TBC and Ferritin as diagnostic criteria for IDA, adjusted vs. unadjusted.
Figure 3.
Comparison of areas under the ROC curves considering TBI < 0 and low Ferritin as diagnosis of A. non-adjusted IDA (without adjusted hemoglobin) or B. adjusted IDA (adjusted hemoglobin). Model adjusted by age, sex, altitude of residence, and inflammation (IL-6).
See this image and copyright information in PMC

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