European Journal of Pediatrics

, Volume 178, Issue 1, pp 41–49 | Cite as

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

  • María A. Vázquez-López
  • Encarnación López-RuzafaEmail author
  • Mercedes Ibáñez-Alcalde
  • Manuel Martín-González
  • Antonio Bonillo-Perales
  • Francisco Lendínez-Molinos
Original Article


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).

Conclusions: CHr, sTfR and the sTfR-F index are useful parameters to discriminate ID without anaemia in children and adolescents, and specific cut-off values have been established. The combination of these new markers offers an alternative definition of ID with suitable discriminatory power.

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.


Iron deficiency Reticulocyte haemoglobin content Serum transferrin receptor sTfR-F index 



Anaemia of chronic disease


Area under the curve


reticulocyte haemoglobin content


confidence interval


C-reactive protein


erythrocyte protoporphyrin


iron deficiency


iron-deficiency anaemia


iron-deficient erythropoiesis


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 erythropoietin


serum transferrin receptor


sTfR/log ferritin


total iron binding capacity


transferrin saturation



We want to thank all the children and parents involved in the research for their disinterested collaboration.

Authors’ contributions

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

Ethical approval

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 consent

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • María A. Vázquez-López
    • 1
  • Encarnación López-Ruzafa
    • 1
    Email author
  • Mercedes Ibáñez-Alcalde
    • 2
  • Manuel Martín-González
    • 1
  • Antonio Bonillo-Perales
    • 1
  • Francisco Lendínez-Molinos
    • 1
  1. 1.Department of PediatricsTorrecárdenas HospitalAlmeríaSpain
  2. 2.Department of PediatricsPoniente HospitalEl EjidoSpain

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