Evaluating reticulocyte hemoglobin as a marker of iron depletion in pediatric patients in Banda Aceh
Anemia in children remains a major public health problem worldwide and in Indonesia, where national data report a prevalence of 21.7% among children aged ≥1 year. Iron deficiency is the leading cause, with iron depletion representing the earliest subclinical stagewhich is often difficult to detect using conventional parameters. Reticulocyte hemoglobin (Ret-He) has been proposed as a marker of functional iron availability during erythropoiesis. This study aimed to evaluate the diagnostic performance of Ret-He in identifying iron depletion in pediatric patients. A cross-sectional analytical study was conducted at Dr. Zainoel Abidin General Hospital in Banda Aceh between July and September 2024. A total of 87 pediatric patients aged 1 month to 18 years were initially enrolled; after excluding subjects with anemia to focus on the iron depletion stage, 54 children were included in the final analysis. Iron depletion was identified in 12.6% of the subjects. Receiver operating characteristic (ROC) analysis showed an optimal Ret-He cut-off value of 29.5 pg, with an area under the curve (AUC) of 0.609, sensitivity of 70%, specificity of 63.6%, and a non-significant p-value (p = 0.398), indicating a limited diagnostic accuracy. Ret-He levels were significantly positively correlated with mean corpuscular volume (MCV) (r = 0.444; p = 0.001) and mean corpuscular hemoglobin (MCH) (r = 0.511; p < 0.001), but were not significantly associated with hemoglobin, ferritin, or transferrin saturation. In conclusion, Ret-He cannot be used as a standalone diagnostic marker of iron depletion in pediatric patients. However, its association with erythrocyte indices suggests that Ret-He may serve as a complementary parameter when interpreted alongside conventional iron status markers during the early evaluation of iron-related disorders.
Keywords : Iron Depletion, Reticulocyte Hemoglobin (Ret-He), Pediatric Patients
- Abbas, M., Gandy, K., Salas, R., Devaraj, S., & Calarge, C. A. (2023). Iron deficiency and internalizing symptom severity in unmedicated adolescents: A pilot study. Psychological Medicine, 53(6), 2274–2284. https://doi.org/10.1017/S0033291721004098
- Al-Numan, A. H., & Al-Obeidi, R. A. (2021). The value of the red cell distribution width index versus other parameters in the differentiation between iron deficiency anemia and beta thalassemia trait among children in Mosul, Iraq. Expert Review of Hematology, 14(4), 401–406. https://doi.org/10.1080/17474086.2021.1905514
- Andriastuti, M., Adiwidjaja, M., & Satari, H. I. (2019). Diagnosis of iron deficiency and iron deficiency anemia with reticulocyte hemoglobin content among children aged 6–18 years. Iranian Journal of Blood and Cancer, 11(4), 127–132.
- Andriastuti, M., Fathinasari, A. D., Fahriyani, A., Widiatmika, K. S., Salsabila, K., & Primacakti, F. (2024). The role of reticulocyte hemoglobin content in diagnosing iron deficiency in childhood cancer. Indian Journal of Medical and Paediatric Oncology, 45(5), 396–401. https://doi.org/10.1055/s-0044-1779047
- Auerbach, M., Staffa, S. J., & Brugnara, C. (2021). Using reticulocyte hemoglobin equivalent as a marker for iron deficiency and responsiveness to iron therapy. Mayo Clinic Proceedings, 96(6), 1510–1519. https://doi.org/10.1016/j.mayocp.2020.10.042
- Baker, R. D., Greer, F. R., Bhatia, J. J. S., Abrams, S. A., Daniels, S. R., Schneider, M. B., Silverstein, J., Stettler, N., Thomas, D. W., Grummer-Strawn, L., Hubbard, V. S., Marchand, V., Silverman, B. M., Soto, V., & Burrowes, D. L. (2010). Clinical report: Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0–3 years of age). Pediatrics, 126(5), 1040–1050. https://doi.org/10.1542/peds.2010-2576
- Barr, H., Kulkarni, K., Singh, B., Sandila, N., Morrison, L., Beach, L., & Ghotra, S. (2023). Accuracy of reticulocyte hemoglobin for diagnosing iron deficiency in former very preterm infants: A population-based cohort study. Frontiers in Pediatrics, 11, 1281513. https://doi.org/10.3389/fped.2023.1281513
- Bó, S. D., Fragoso, A. L. R., Farias, M. G., Hubner, D. P. G., & de Castro, S. M. (2023). Evaluation of RET-He values as an early indicator of iron deficiency anemia in pregnant women. Hematology, Transfusion and Cell Therapy, 45(1), 52–57. https://doi.org/10.1016/j.htct.2021.05.006
- Camaschella, C. (2015). Iron-deficiency anemia. New England Journal of Medicine, 372(19), 1832–1843. https://doi.org/10.55735/qybbh562
- Carman, N., Muir, R., & Lewindon, P. (2019). Ferric carboxymaltose in the treatment of iron deficiency in pediatric inflammatory bowel disease. Translational Pediatrics, 8(1), 28–34. https://doi.org/10.21037/tp.2019.01.01
- Fitriany, J., & Saputri, A. I. (2018). Anemia defisiensi besi. Averrous: Jurnal Kedokteran dan Kesehatan Malikussaleh, 4(2), 1. https://doi.org/10.29103/averrous.v4i2.1033
- Ganz, T., & Nemeth, E. (2015). Iron homeostasis in host defence and inflammation. Nature Reviews Immunology, 15(8), 500–510. https://doi.org/10.1038/nri3863
- Hwang, I., Cheong, J., & Subramonia, S. (2021). Hypochromia is an early marker of iron deficiency anaemia. British Journal of Surgery, 108(Suppl. 7). https://doi.org/10.1093/bjs/znab362.057
- Jahangiri, M., Rahim, F., Saki Malehi, A., Pezeshki, S. M. S., & Ebrahimi, M. (2020). Differential diagnosis of microcytic anemia, thalassemia or iron deficiency anemia: A diagnostic test accuracy meta-analysis. Modern Medical Laboratory Journal, 3(1), 16–29. https://doi.org/10.30699/mmlj17.3.1.16
- Kementerian Kesehatan Republik Indonesia. (2019). Prevalensi anemia menurut karakteristik: Riskesdas 2018. Kementerian Kesehatan Republik Indonesia, Jakarta.
- Kessy, J., Philemon, R., Lukambagire, A., Abdulrahmani, M., Urio, G., Beyanga, G., Musyoka, A., Ndaro, A., Mwitalemi, R., Maro, M., Majaliwa, E., Kinabo, G., & Mmbaga, B. (2019). Iron depletion, iron deficiency, and iron deficiency anaemia among children under 5 years old in Kilimanjaro, Northern Tanzania: A hospital-based cross-sectional study. East African Health Research Journal, 3(1), 42–47. https://doi.org/10.24248/eahrj.v3i1.597
- Kılıç, M., Özpınar, A., Serteser, M., Kilercik, M., & Serdar, M. (2022). The effect of reticulocyte hemoglobin content on the diagnosis of iron deficiency anemia: A meta-analysis study. Journal of Medical Biochemistry, 41(1), 1–13. https://doi.org/10.5937/JOMB0-31435
- Mantadakis, E., Chatzimichael, E., & Zikidou, P. (2020). Iron deficiency anemia in children residing in high and low-income countries: Risk factors, prevention, diagnosis and therapy. Mediterranean Journal of Hematology and Infectious Diseases, 12(1), e2020041. https://doi.org/10.4084/MJHID.2020.041
- Mathew, B. M., Santhakumar, R., Innah, S. J., Cherian, V. J., & Rafi, A. M. (2024). Evaluating RET-Hb vs Hb in predicting early response in oral iron therapy: A prospective interventional study. Journal of Clinical and Diagnostic Research, 18(11), 01–05. https://doi.org/10.7860/jcdr/2024/70908.20223
- Mohammed, S., Mousa, A., & Hashim, A. (2020). Role of hypochromia and microcytosis in the prediction of iron deficiency anemia. Minia Journal of Medical Research, 31(3), 262–268. https://doi.org/10.21608/mjmr.2022.220289
- Mouzaki, M., Bramlage, K., Arce-Clachar, A. C., & Xanthakos, S. A. (2018). Serum immunoglobulin A levels do not correlate with liver disease severity in pediatric nonalcoholic fatty liver disease. Journal of Pediatric Gastroenterology and Nutrition, 67(5), 631–634. https://doi.org/10.1097/MPG.0000000000002104
- Natekar, P., Deshmukh, C., Limaye, D., Ramanathan, V., & Pawar, A. (2022). A micro review of a nutritional public health challenge: Iron deficiency anemia in India. Clinical Epidemiology and Global Health, 14, 100992. https://doi.org/10.1016/j.cegh.2022.100992
- Neef, V., Schmitt, E., Bader, P., Zierfuß, F., Hintereder, G., Steinbicker, A. U., Zacharowski, K., & Piekarski, F. (2021). The reticulocyte hemoglobin equivalent as a screening marker for iron deficiency and iron deficiency anemia in children. Journal of Clinical Medicine, 10(16), 3506. https://doi.org/10.3390/jcm10163506
- Osei Bonsu, E., Addo, I. Y., Boadi, C., Boadu, E. F., & Okeke, S. R. (2024). Determinants of iron-rich food deficiency among children under 5 years in sub-Saharan Africa: A comprehensive analysis of Demographic and Health Surveys. BMJ Open, 14(3), e079856. https://doi.org/10.1136/bmjopen-2023-079856
- Pasricha, S.-R., Tye-Din, J., Muckenthaler, M. U., & Swinkels, D. W. (2021). Iron deficiency. The Lancet, 397(10270), 233–248. https://doi.org/10.1016/S0140-6736(20)32594-0
- Ringoringo, H. P., Purnamasari, L., Yunanto, A., Syahadatina, M., & Hidayah, N. (2023). Reference range of complete blood count, Ret-He, immature reticulocyte fraction, reticulocyte production index in healthy babies aged 1–4 months. Scientific Reports, 13(1), 423. https://doi.org/10.1038/s41598-023-27579-3
- Safiri, S., Kolahi, A. A., Noori, M., Nejadghaderi, S. A., Karamzad, N., Bragazzi, N. L., Sullman, M. J. M., Abdollahi, M., Collins, G. S., Kaufman, J. S., & Grieger, J. A. (2021). Burden of anemia and its underlying causes in 204 countries and territories, 1990–2019: Results from the Global Burden of Disease Study 2019. Journal of Hematology & Oncology, 14(1), 185. https://doi.org/10.1186/s13045-021-01202-2
- Sun, H., & Weaver, C. M. (2021). Decreased iron intake parallels rising iron deficiency anemia and related mortality rates in the US population. The Journal of Nutrition, 151(7), 1947–1955. https://doi.org/10.1093/jn/nxab064
- Sundararajan, S., & Rabe, H. (2021). Prevention of iron deficiency anemia in infants and toddlers. Pediatric Research, 89(1), 63–73. https://doi.org/10.1038/s41390-020-0907-5
- Thane, C. W., Walmsley, C. M., Bates, C. J., Prentice, A., & Cole, T. J. (2000). Risk factors for poor iron status in British toddlers: Further analysis of data from the National Diet and Nutrition Survey of children aged 1.5–4.5 years. Public Health Nutrition, 3(4), 433–440. https://doi.org/10.1017/S1368980000000501
- Yang, J., Li, Q., Feng, Y., & Zeng, Y. (2023). Iron deficiency and iron deficiency anemia: Potential risk factors in bone loss. International Journal of Molecular Sciences, 24(8), Article 6891. https://doi.org/10.3390/ijms24086891
- Zia, A., Stanek, J., Christian-Rancy, M., Savelli, S., & O’Brien, S. H. (2022). Iron deficiency and fatigue among adolescents with bleeding disorders. American Journal of Hematology, 97(1), 60–67. https://doi.org/10.1002/ajh.26389
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