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Clinical thresholds for diagnosing iron deficiency: comparison of functional assessment of serum ferritin to
Gorkem Sezgin1, Paul Monagle2,3,4, Tze Ping Loh5
1Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 6, 75 Talavera Road, Ryde, NSW, 2109, Australia. gorkem.sezgin@mq.edu.au.
Insights
Functional limits for serum ferritin in children are more reliable than percentile-based cut-offs for diagnosing iron deficiency anemia. This approach better reflects physiological iron status.
Area of Science:
- Pediatric Hematology
- Clinical Biochemistry
- Iron Metabolism
Background:
- Serum ferritin is a key indicator of iron deficiency, but established lower cut-off values vary significantly, especially in pediatric populations.
- Current lower limits are often based on the 2.5th percentile, which may not accurately reflect physiological iron status.
- Iron deficient erythropoiesis offers a functional approach to assess iron status.
Purpose of the Study:
- To evaluate a functional approach based on iron deficient erythropoiesis as an alternative to percentile-based cut-offs for pediatric serum ferritin.
- To determine a more clinically relevant lower limit for serum ferritin in children.
Main Methods:
- Analysis of 64,443 pediatric ferritin test results from electronic health records.
- Statistical derivation of 2.5th percentile lower limits.
- Derivation of functional reference limits by correlating ferritin with erythrocyte parameters (hemoglobin, MCV, MCHC, RDW).
Main Results:
- Centile-derived lower limits were found to be too low for reliable clinical interpretation.
- Functional limits suggest iron deficiency anemia onset around 10 µg/L ferritin.
- Functionally-derived limits showed consistency across genders and age groups, unlike percentile-based limits.
Conclusions:
- Functional reference limits for serum ferritin provide a more accurate reflection of a child's underlying iron physiology.
- A functional approach may offer a superior basis for establishing treatment thresholds for iron deficiency in pediatric patients.
- This method could be applied to other biomarkers with functional outcomes.
Abstract:
Low serum ferritin is diagnostic of iron deficiency, yet its published lower cut-off values are highly variable, particularly for pediatric populations. Lower cut-off values are commonly reported as 2.5th percentiles, and is based on the variation of ferritin values in the population. Our objective was to determine whether a functional approach based on iron deficient erythropoiesis could provide a better alternative. Utilizing 64,443 ferritin test results from pediatric electronic health records, we conducted various statistical techniques to derive 2.5th percentiles, and also derived functional reference limits through the association between ferritin and erythrocyte parameters: hemoglobin, mean corpuscular volume, mean cell hemoglobin concentration, and red cell distribution width. We find that lower limits of reference intervals derived as centiles are too low for clinical interpretation. Functional limits indicate iron deficiency anemia starts to occur when ferritin levels reach 10 µg/L, and are largely similar between genders and age groups. In comparison, centiles (2.5%) presented with lower limits overall, with varying levels depending on age and gender. Functionally-derived limits better reflects the underlying physiology of a patient, and may provide a basis for deriving a threshold related to treatment of iron deficiency and any other biomarker with functional outcomes.
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