The usefulness of reticulocyte haemoglobin content, serum transferrin receptor and the sTfR-ferritin index to identify iron deficiency in healthy children aged 1–16 years
This cross-sectional study, conducted on a population-based representative sample, evaluates the usefulness of reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) to recognise iron deficiency (ID) without anaemia, provides specific cut-off points for age and gender, and proposes a new definition of ID. A total of 1239 healthy children and adolescents aged 1–16 years were included. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, CHr, sTfR, and sTfR-F index were determined. ROC curves were obtained and sensitivity, specificity, predictive values, likelihood ratios, and accuracy for each specific cut-off points were calculated. Seventy-three had ID without anaemia. Area under the curve for sTfR-F index, sTfR and CHr were 0.97 (CI95% 0.95–0.99), 0.87 (CI95% 0.82–0.92) and 0.68 (CI95% 0.61–0.74), respectively. The following cut-off points defined ID: sTfR-F Index > 1.5 (1–5 years and 12–16 years boys) and > 1.4 (6–11 years and 12–16 years girls); sTfR (mg/L) > 1.9 (1–5 years), > 1.8 (6–11 years), > 1.75 (12–16 years girls) and > 1.95 (12–16 years boys); and CHr (pg) < 27 (1–5 years) and < 28.5 (6–16 years).
What is Known:
• In adults, reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin index (sTfR-F index) have been evaluated and recognised as reliable indicators of iron deficiency (ID).
• Clinical manifestations of ID may be present in stages prior to anaemia, and the diagnosis of ID without anaemia continues to pose problems.
What is New:
• CHr, sTfR and the sTfR-F index are useful parameters in diagnosis of ID in childhood and adolescence when anaemia is not present.
• We propose a new strategy for the diagnosis of ID in childhood and adolescence, based on the combination of these measures, which offer greater discriminatory power than the classical parameters.
KeywordsIron deficiency Reticulocyte haemoglobin content Serum transferrin receptor sTfR-F index
Anaemia of chronic disease
Area under the curve
reticulocyte haemoglobin content
iron stores depletion
negative likelihood ratio
positive likelihood ratio
mean corpuscular volume
maximum diagnostic discrimination
negative predictive value
positive predictive value
receiver operating characteristics
serum transferrin receptor
total iron binding capacity
We want to thank all the children and parents involved in the research for their disinterested collaboration.
María A. Vázquez-López contributed to conception and design, analysis and interpretation of the data and writing of the manuscript. Encarnación López-Ruzafa contributed to conception and design, analysis and interpretation of the data and writing of the manuscript; Mercedes Ibáñez-Alcalde and Manuel Martín-González contributed to the acquisition of data; Antonio Bonillo-Perales and Francisco Lendinez-Molinos critically revised the manuscript and contributed with their final suggestions. All the authors approved the final manuscript for publication.
Compliance with ethical standards
The Ethics and Research Committee of Torrecárdenas Hospital (Almería) approved the study.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Conflict of interest
The authors declare that they have no conflict of interest.
Informed written consent was obtained from parents or legal guardians as well as from the participants themselves if they were > 12 years.
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