Global Prevalence of Iron Deficiency Utilizing Differing Ferritin Cut-Offs - 15, 30, and 50 μg/L

Introduction: Ferritin is arguably the most accurate and most utilized test for iron deficiency. The World Health Organization (WHO) uses a ferritin cutoff of below 15 μg/L to diagnose iron deficiency in most individuals while a 2021 Cochrane review suggests 30. Our institution uses a lower limit of 50 in the non-inflamed patient, as this level has been shown to correlate with iron deficiency in women of reproductive age. Ferritin data from the WHO was utilized in this study to examine distribution of ferritin values across the world and thus estimate the prevalence of iron deficiency. Methods: Data was obtained from the Vitamin and Mineral Nutrition Information System from the WHO, and included datapoints from 2010-2022 from 36 countries. Each datapoint represented the weighted average of (where sample size was provided) median (preferred) or mean ferritins from the particular population (eg, adult males from Canada in 2011). If multiple years for the same country and category were present, the latest year was chosen. Human development index (HDI) data came from the United Nations. Data was categorized by sex, age, and pregnancy status, with age groups being roughly defined as 0-18 years (child) and greater than 18 years (adult). Data was analyzed using Welch's t-test, and the correlation coefficient. Results: Children: 37 ferritin datapoints representing at least 68,091 individuals. Male and female children had similar ferritins (33.4 male vs 31.3 μg/L female, P = 0.59) and HDI of contributing countries was also similar (0.705 vs 0.708, P = 0.94). No males and 5.3% of females had ferritins over 50; 66.7% of males and 52.6% of females had ferritins over 30; 88.9% of males and 89.5% of females had ferritins over 15. Adults: 56 ferritin datapoints representing at least 133,149 individuals. Males had significantly higher ferritins than females (117.0 vs 46.2, P = 0.001), though HDI was slightly higher for men (0.835 vs 0.732, P = 0.09). Pregnant women had lower ferritins than non-pregnant women (24.2 pregnant vs 34.2 non-pregnant, P = 0.02) with similar HDI (0.647 vs 0.612, P = 0.52). All adult males, 40.0% adult females, 16.7% non-pregnant females, and no pregnant females had ferritins over 50; 75% of adult females, 61.1% of non-pregnant females, and 10% of pregnant females had ferritins over 30; 100% of adult females, 100% of non-pregnant females, and 100% of pregnant females had ferritins over 15. In general, as HDI increased so did ferritin for all categories, though strength of the association varied by category, ranging from 0.20 in female children to 0.57 in male adults. Discussion: With a ferritin cut-off of 50, almost all children and pregnant women sampled had ferritins consistent with iron deficiency, with that number dropping to near zero when using a lower cut-off of 15. Thus, the majority of iron deficient individuals would be missed by using a lower, and to the best of our knowledge physiologically inappropriate, ferritin cut-off. As expected, adult men had significantly higher ferritins than adult women, likely due to obligate iron loss through menses for most women. Interestingly, while a country's HDI showed some correlation with ferritin values the strength was at most moderate, suggesting socioeconomic status does not play as large as expected role in iron deficiency. Being an acute phase reactant, ferritin levels may not correlate with iron deficiency in the inflamed state. Additional limitations include limited number of ferritin values, countries, and years. This study shows that with using a ferritin cut-off of 50 iron deficiency is widespread among children and women, particularly pregnant women. Use of a higher and more physiologically appropriate ferritin cut-off helps illustrate the magnitude of the problem of iron deficiency and the work that needs to be done to both better define and combat this treatable and preventable disease.

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