Physiologically based ferritin thresholds for defining iron deficiency in US children aged 5 to 14 years

ABSTRACT Iron deficiency (ID) is the most predominant nutritional deficiency globally. The current CDC iron guideline for ID screening uses serum ferritin (Ft) ≤15 μg/L based on bone-marrow assessment. We aimed to evaluate physiologically based Ft thresholds for defining ID in children aged 5 to 14 years. Ferritin and hemoglobin (Hb) data were analyzed from 3765 apparently healthy (no inflammation, infection, risk of iron overload or potential liver disease) US children, and an indicator of iron-deficient erythropoiesis such as erythrocyte zinc protoporphyrin (ZPP). Nonlinear ferritin concentration curves (Hb-Ft, ZPP-Ft) and differential equations were applied to identify ferritin thresholds at ID onset with inflection minima and plateau for each iron analyte. Mean age was 10.3 years. The ferritin curve inflection for ID occurred at 23.9 μg/L (95% confidence interval, 21.7–27.3) with Hb and 25.0 μg/L (23.8–27.1) with ZPP. No inter-analyte ( P = 0.67), age ( P = 0.49 with Hb, P = 0.95 with ZPP), or sex ( P = 0.39) differences observed. ID prevalence was 9.0% (7.3–10.7), and ID anemia (IDA) 0.5% (0.3–0.8) using CDC thresholds, versus ID 30.0% (27.4–32.5) and IDA 1.0% (0.6–1.3) % using physiologically based thresholds. Physiologically based ferritin thresholds for ID onset were consistently higher than current CDC thresholds across iron analyte, age, and sex. IDA remained unchanged with physiologically based thresholds, suggesting that anemia is not an adequate proxy for ID screening, and clinicians should consider higher ferritin as a functional threshold for defining ID in children aged 5-14 years.