Main Article Content

Panagiota Zikidou
Christina Tsigalou
Gregorios Trypsianis
Alexandros Karvelas
Aggelos Tsalkidis
Elpis Mantadakis


Anemia, Iron deficiency, Iron deficiency anemia, Ferritin, Sideropenia biomarkers


Background and Objectives: Iron deficiency (ID) is a major public health problem with high prevalence in early childhood. We assessed the prevalence of anemia, ID, and iron deficiency anemia (IDA) in healthy children of Thrace, Greece, its correlation with dietary factors, and evaluated the diagnostic performance of hematologic and biochemical markers of sideropenia.

Patients and Methods: For 202 healthy children 1-5 years old, a questionnaire was filled out describing their nutritional habits during infancy and early childhood. Venous hemograms along with serum ferritin, TIBC, %TS, and CRP were obtained from all studied children. In a subset of 156 children, the concentration of sTfR was also determined.

Results: Children with ID and IDA had significantly lower beef consumption than children without sideropenia (p=0.044). Using the WHO cut-off values of Hb <11g/dl and ferritin <12μg/l, the prevalence of anemia, ID, and IDA was 9.41%, 6.44%. and 3.47%, respectively. If Hb <12g/dl and ferritin<18μg/l were used as cut-offs, the prevalence of anemia, ID, and IDA was 26.73%, 16.33%, and 5.94%, respectively. ROC analysis revealed that at ferritin <12μg/l, sTfR had the highest specificity and PPV but the lowest sensitivity for ID (93%, 47.4%, and 69.2%, respectively), while sTfR/Fer index had the highest sensitivity and NPV (100%).

Conclusions: The prevalence of ID and IDA in children 1-5 years old in Thrace is like in other developed countries. sTfR and sTfR/Fer index have the highest accuracy to diagnose ID, with the sTfR/Fer index being superior irrespective of the ferritin cut-off value used to define ID.


Download data is not yet available.

Abstract 722
PDF Downloads 461
HTML Downloads 154


1.Mantadakis E, Chatzimichael E, Zikidou P. Iron Deficiency Anemia in Children Residing in High and Low-Income Countries: Risk Factors, Prevention, Diagnosis and Therapy. Mediterr J Hematol Infect Dis. 2020;12(1):e2020041. doi: 10.4084/MJHID.2020.041. Epub 2020 Jul 1.
2.Assessing the iron status of populations: including literature reviews. Report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level. Geneva, Switzerland. 6–8 April 2004. 2nd edition.
3.WHO (2000). Nutrition for health and development. A global agenda for combating malnutrition. Geneva.
4.ACC/SCN (2001). What Works? A Review of the Efficacy and Effectiveness of Nutrition Interventions, Allen LH and Gillespie SR. ACC/SCN: Geneva in collaboration with the Asian Development Bank, Manila.
5.Baker RD, Greer FR. Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics. 2010;126(5):1040-1050. doi: 10.1542/peds.2010-2576. Epub 2010 Oct 5.
6.Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med. 2020;287(2):153-170. doi: 10.1111/joim.13004. Epub 2019 Nov 12.
7.Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. MMWR Recomm Rep. 1998;47(RR-3):1-29.
8.Dupont C. Prevalence of iron deficiency. Arch Pediatr. 2017;24(5S):5S45-5S48. doi: 10.1016/S0929-693X(17)24009-3.
9.Kohli-Kumar M. Screening for anemia in children. Pediatrics. 2001;108(3):E56. doi: 10.1542/peds.108.3.e56.
10.Burke RM, Leon JS, Suchdev PS. Identification, prevention and treatment of iron deficiency during the first 1000 days. Nutrients. 2014;6(10):4093-4114. doi: 10.3390/nu6104093. Epub 2014 Oct 10. 
11.Cameron BM, Neufeld LM. Estimating the prevalence of iron deficiency in the first two years of life: technical and measurement issues. Nutr Rev. 2011;69(Suppl 1):S49–S56. doi: 10.1111/j.1753-4887.2011.00433.x.
12.Vázquez-López MA, López-Ruzafa E, Lendinez-Molinos F, Ortiz-Pérez M, Ruiz-Tudela L, Martín-González M. Reference values of serum transferrin receptor (sTfR) and sTfR/log ferritin index in healthy children. Pediatr Hematol Oncol. 2016;33(2):109-120. doi: 10.3109/08880018.2015.1138007. Epub 2016 Mar 7.
13.Malope BI, MacPhail AP, Alberts M, Hiss DC. The ratio of serum transferrin receptor and serum ferritin in the diagnosis of iron status. Br J Haematol. 2001;115(1):84-89. doi: 10.1046/j.1365-2141.2001.03063.x.
14.Vázquez-López MA, López-Ruzafa E, Ibáñez-Alcalde M, Martín-González M, Bonillo-Perales A, Lendínez-Molinos F. 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. Eur J Pediatr. 2019;178(1):41-49. doi: 10.1007/s00431-018-3257-0. Epub 2018 Sep 27. 
15.Ooi CL, Lepage N, Nieuwenhuys E, Sharma AP, Filler G. Pediatric reference intervals for soluble transferrin receptor and transferrin receptor-ferritin index. World J Pediatr. 2009;5(2):122-126. doi: 10.1007/s12519-009-0024-3. Epub 2009 Jul 9.
16.WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations. Geneva: World Health Organization. 2020. Licence: CC BY-NC-SA 3.0 IGO.
17.Punnonen K, Irjala K, Rajamäki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood. 1997;89(3):1052-1057.
18.Dimitriou H, Stiakaki E, Markaki EA, Bolonaki I, Giannakopoulou C, Kalmanti M. Soluble transferrin receptor levels and soluble transferrin receptor/log ferritin index in the evaluation of erythropoietic status in childhood infections and malignancy. Acta Paediatr. 2000;89(10):1169-1173. doi: 10.1080/080352500750027510.
19.Mantadakis E. Editorial: Serum Ferritin Threshold for Iron Deficiency Screening in One-Year-Old Children. J Pediatr. 2022. doi: j.jpeds.2022.02.050. Epub 2022 Feb 26.
20.Male C, Persson LA, Freeman V, Guerra A, van't Hof MA, Haschke F. Prevalence of iron deficiency in 12-mo-old infants from 11 European areas and influence of dietary factors on iron status (Euro-Growth Study). Acta Paediatr. 2001;90(5):492-498. doi: 10.1080/080352501750197601.
21.Eussen S, Alles M, Uijterschout L, Brus F, van der Horst-Graat J. Iron intake and status of children aged 6-36 months in Europe: a systematic review. Ann Nutr Metab. 2015;66(2-3):80-92. doi: 10.1159/000371357. Epub 2015 Jan 21.
22.Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CJ. Prevalence of Iron Deficiency in the United States. JAMA. 1997;277(12):973-976. doi: 10.1001/jama.1997.03540360041028.
23.Gupta PM, Perrine CG, Mei Z, Scanlon KS. Iron, anemia, and iron deficiency anemia among young children in the United States. Nutrients. 2016;8(6):330. doi: 10.3390/nu8060330.
24.Gompakis N, Economou M, Tsantali C, Kouloulias V, Keramida M, Athanasiou-Metaxa M. The effect of dietary habits and socioeconomic status on the prevalence of iron deficiency in children of northern Greece. Acta Haematol. 2007;117(4):200-204. doi: 10.1159/000098273. Epub 2007 Jan 3. 
25.Tympa-Psirropoulou E, Vagenas C, Dafni O, Matala A, Skopouli F. Environmental risk factors for iron deficiency anemia in children 12-24 months old in the area of Thessalia in Greece. Hippokratia. 2008;12(4):240-250.
26.Tympa-Psirropoulou E, Vagenas C, Psirropoulos D, Dafni O, Matala A, Skopouli F. Nutritional risk factors for iron-deficiency anaemia in children 12-24 months old in the area of Thessalia in Greece. Int J Food Sci Nutr. 2005;56(1):1-12. doi: 10.1080/09637480500081183.
27.Mukhtarova N, Ha B, Diamond CA, Plumb AJ, Kling PJ. Serum Ferritin Threshold for Iron Deficiency Screening in One-Year-Old Children. J Pediatr. 2022:S0022-3476(22)00081-6. doi: 10.1016/j.jpeds.2022.01.050. Online ahead of print.
28.Abdullah K, Birken CS, Maguire JL, Fehlings D, Hanley AJ, Thorpe KE, Parkin PC. Re-Evaluation of Serum Ferritin Cut-Off Values for the Diagnosis of Iron Deficiency in Children Aged 12-36 Months. J Pediatr. 2017;188:287-290. doi: 10.1016/j.jpeds.2017.03.028. Epub 2017 Apr 18.
29.Parkin PC, Koroshegyi C, Mamak E, Borkhoff CM, Birken CS, Maguire JL, Thorpe KE. Association between Serum Ferritin and Cognitive Function in Early Childhood. J Pediatr. 2020;217:189-191.e2. doi: 10.1016/j.jpeds.2019.09.051. Epub 2019 Nov 2.
30.Phiri KS, Calis JCJ, Siyasiya A, Bates I, Brabin B, Boele van Hensbroek M. New cut-off values for ferritin and soluble transferrin receptor for the assessment of iron deficiency in children in a high infection pressure area. J Clin Pathol. 2009;62(12):1103-1106. doi:10.1136/jcp.2009.066498.
31.Infusino I, Braga F, Dolci A, Panteghini M. Soluble Transferrin Receptor (sTfR) and sTfR/log Ferritin Index for the Diagnosis of Iron-Deficiency Anemia. A Meta-Analysis. Am J Clin Pathol. 2012;138(5):642-649. doi: 10.1309/AJCP16NTXZLZFAIB
32.Aguilar R, Moraleda C, Quintó L, Renom M, Mussacate L, Macete E, Aguilar JL, Alonso PL, Menéndez C. Challenges in the Diagnosis of Iron Deficiency in Children Exposed to High Prevalence of Infections. PLoS ONE. 2012;7(11):e50584. doi:10.1371/journal.pone.0050584. Epub 2012 Nov 27.
33.Krawiec P, Pac-Kozuchowska E. Soluble transferrin receptor and soluble transferrin receptor/log ferritin index in diagnosis of iron deficiency anemia in pediatric inflammatory bowel disease. Dig Liv Dis. 2019;51(3):352-357. doi: 10.1016/j.dld.2018.11.012. Epub 2018 Nov 22.
34.Krawiec P, Pac-Kozuchowska E. Biomarkers and Hematological Indices in the Diagnosis of Iron Deficiency in Children with Inflammatory Bowel Disease. Nutrients. 2020;12(5):1358. doi:10.3390/nu12051358.
35.Oustamanolakis P, Koutroubakis IE, Messaritakis I, Niniraki M, Kouroumalis EA. Soluble transferrin receptor-ferritin index in the evaluation of anemia in inflammatory bowel disease: a case-control study. Ann Gastroenterol. 2011;24(2):108-114.
36.Angeles Vázquez López M, Molinos FL, Carmona ML, Morales AC, Muñoz Vico FJ, Muñoz JL, Muñoz Hoyos A. Serum transferrin receptor in children: usefulness for determinating the nature of anemia in infection. J Pediatr Hematol Oncol. 2006;28(12):809-815. doi: 10.1097/MPH.0b013e31802d751a. 
37.Grant FK, Martorell R, Flores-Ayala R, Cole CR, Ruth LJ, Ramakrishnan U, Suchdev PS. Comparison of indicators of iron deficiency in Kenyan children. Am J Clin Nutr. 2012;95(5):1231-1237. doi: 10.3945/ajcn.111.029900. Epub 2012 Mar 28.
38.Jonker FA, Boele van Hensbroek M, Leenstra T, Vet RJ, Brabin BJ, Maseko N, Gushu MB, Emana M, Kraaijenhagen R, Tjalsma H, Swinkels DW, Calis JC. Conventional and novel peripheral blood iron markers compared against bone marrow in Malawian children. J Clin Pathol. 2014;67(8):717-723. doi: 10.1136/jclinpath-2014-202291. Epub 2014 Jun 10. 
39.Chen YC, Hung SC, Tarng DC. Association between transferrin receptor-ferritin index and conventional measures of iron responsiveness in hemodialysis patients. Am J Kidney Dis. 2006;47(6):1036-1044. doi: 10.1053/j.ajkd.2006.02.180. 
40.Holmlund-Suila EM, Hauta-Alus HH, Enlund-Cerullo M, Rosendahl J, Valkama SM, Andersson S, Mäkitie O. Iron status in early childhood is modified by diet, sex and growth: Secondary analysis of a randomized controlled vitamin D trial. Clin Nutr. 2022;41(2):279-287. doi: 10.1016/j.clnu.2021.12.013. Epub 2021 Dec 13. 
41.Moshe G, Amitai Y, Korchia G, Korchia L, Tenenbaum A, Rosenblum J, Schechter A. Anemia and iron deficiency in children: association with red meat and poultry consumption. J Pediatr Gastroenterol Nutr. 2013;57(6):722-727. doi: 10.1097/MPG.0b013e3182a80c42.
42.Szymlek-Gay EA, Ferguson EL, Heath AL, Gray AR, Gibson RS. Food-based strategies improve iron status in toddlers: a randomized controlled trial12. Am J Clin Nutr. 2009;90(6):1541-1551. doi: 10.3945/ajcn.2009.27588. Epub 2009 Oct 14.