JUSTIFICATION OF UNIVERSAL IRON SUPPLEMENTATION FOR INFANTS 6-12 MONTHS IN REGIONS WITH A HIGH PREVALENCE OF THALASSEMIA Iron Supplementation for Infants 6-12 months in Regions with a High Prevalence of Thalassemia

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Phakatip Sinlapamongkolkul
Pacharapan Surapolchai
Vip Viprakasit


Thalassemia, Iron supplementation


Introduction: Many clinicians hesitate adopting a universal infant iron supplementation program due to the risk of increased iron absorption for those with thalassemia. We aimed to determine thalassemia prevalence in 6- to 12-month old infants, along with the iron status of those with and without thalassemia.

Methods: We performed a cross-sectional descriptive study of infants attending the Well Baby Clinic at Thammasat University Hospital for routine checkups. Complete blood count, hemoglobin electrophoresis, iron parameters, and molecular genetics for common a- and b-thalassemia were evaluated.

Results: Overall, 97 of 206 (47%) participants had thalassemia minor, the majority having Hb E traits. None had thalassemia intermedia or major. Familial history of anemia or thalassemia presented an increased risk of detecting thalassemia minor in offspring (OR 5.18; 95% CI 2.60-10.33, p=0.001). There were no statistical differences in transferrin saturation, serum ferritin and hepcidin between iron-replete infants with thalassemia minor and those without.  However, one-third of infants with thalassemia minor (31/97) also had iron deficiency anemia (IDA), with a similar risk of having iron deficiency to infants without thalassemia. There was no hepcidin suppression in our infants with thalassemia minor as compared to controls.

Conclusions: Both thalassemia and IDA are endemic to Southeast Asia. Infants with thalassemia minor, particularly with Hb E and a-thalassemia traits, are at risk of IDA. Our short-term universal iron supplementation program for 6 to 12-month old infants does not appear to increase the risk of those with thalassemia minor developing iron overload in the future.


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1. Guideline: Daily iron supplementation in infants and children. Geneva: World Health Organization; 2016.
2. Essential Nutrition Actions: Improving maternal, newborn, infant and young child health and nutrition. Geneva: World Health Organization; 2013.
3. Department of Health: Ministry of Public Health of Thailand. Guidelines for controlling and preventing anemia from iron deficiency. Available at: URL: http://hpc.go.th/director/data/mch/IDAControl.pdf. Accessed Mar 27, 2019.
4. Guideline: Intermittent iron supplementation in preschool and school-age children Geneva: World Health Organization; 2011.
5. De‐Regil LM, Jefferds MED, Sylvetsky AC, Dowswell T. Intermittent iron supplementation for improving nutrition and development in children under 12 years of age. Cochrane Database Syst Rev. 2011;2011(12):CD009085. https://doi.org/10.1002/14651858.CD009085.pub2. PMID: 22161444.
6. Lukowski AF, Koss M, Burden MJ, Jonides J, Nelson CA, Kaciroti N,et al. Iron deficiency in infancy and neurocognitive functioning at 19 years: evidence of long-term deficits in executive function and recognition memory. Nutritional Neuroscience. 2010;13:54-70. https://doi.org/10.1179/147683010X12611460763689. PMID: 20406573.
7. Surapolchai P, Sinlapamongkolkul P, Thaweekul P, Viprakasit V. Prevalence of iron deficiency in 6-12 month-old infants at the Well Baby Clinic. In: Navarawong W, editor. Proceedings of the 52th TSH Annual meeting; 2018 Mar 4-7; Bangkok, Thailand. Bangkok: TSH; 2018. p. 212.
8. Porter J, Viprakasit V. Iron overload and chelation. In: Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, eds. Guidelines for the management of transfusion dependent thalassaemia, 3rd ed. Thalassaemia international federation; 2014. p. 42-97.
9. Taher A, Vichinsky E, Musallam K, Cappellini MD, Viprakasit V. Iron overload and chelation. In: Taher A, Vichinsky E, Musallam K, Cappellini MD, Viprakasit V, editors. Guidelines for the management of non transfusion dependent thalassaemia, 1st ed. Thalassaemia international federation; 2013. p. 35-50.
10. Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008;86:480–487. https://doi.org/10.2471/blt.06.036673. PMID: 18568278.
11. Weatherall DJ, Clegg JB, eds. The Thalassaemia Syndromes. 4th ed. Oxford: Blackwell Science; 2001.
12. Globin gene server home page. Available at: URL: http://globin.cse.psu.edu/. Accessed Mar 1, 2019.
13. Panich V, Pornpatkul M, Sriroongrueng W. The problem of thalassemia in Thailand. Southeast Asian J Trop Med Public Health 1992;23 Suppl 2:1-6. PMID: 1298980.
14. Fucharoen S, Winichagoon P. Hemoglobinopathies in Southeast Asia: molecular biology and clinical medicine. Hemoglobin. 1997;21:299-319. https://doi.org/10.3109/03630269709000664. PMID: 9255610.
15. Fucharoen S, Winichagoon P, Wisedpanichkij R, Sae-Ngow B, Sriphanich R, Oncoung W, et al. Prenatal and postnatal diagnoses of thalassemias and hemoglobinopathies by HPLC. Clin Chem. 1998;44:740–748. PMID: 9554484.
16. Viprakasit V, Limwongse C, Sukpanichnant S, Ruangvutilert P, Kanjanakorn C, Glomglao W, et al. Problems in determining thalassemia carrier status in a program for prevention and control of severe thalassemia syndromes: a lesson from Thailand. Clin Chem Lab Med. 2013; 51:1605–1614. https://doi.org/10.1515/cclm-2013-0098. PMID: 23525874.
17. Tachavanich K, Viprakasit V, Chinchang W, Glomglao W, Pung-Amritt P, Tanphaichitr VS. Clinical and hematological phenotype of homozygous hemoglobin E: revisit of a benign condition with hidden reproductive risk. Southeast Asian J Trop Med Public Health. 2009;40:306-316. PMID: 19323016.
18. Taher A, Hershko C, Cappellini MD. Iron overload in thalassaemia intermedia: reassessment of iron chelation strategies. Br J Haematol. 2009;147:634-640. https://doi.org/10.1111/j.1365-2141.2009.07848.x. PMID: 19681884.
19. Winichakoon P, Tantiworawit A, Rattanathammethee T, Hantrakool S, Chai-adisaksopha C, Rattarittamrong E, et al. Prevalence and risk factors for complications in patients with nontransfusion dependent alpha- and beta-thalassemia. Anemia. 2015;2015:1-7. https://doi.org/10.1155/2015/793025. PMID: 26664743
20. Aydinok Y, Porter JB, Piga A, Elalfy M, Beshlawy AE, Kilinc Y, et al. Prevalence and distribution of iron overload in patients with transfusion-dependent anemias differs across geographic regions: results from the CORDELIA study. Eur J Haematol. 2015;95:244-253. https://doi.org/10.1111/ejh.12487. PMID: 25418187.
21. Krittayaphonga R, Viprakasit V, Saiviroonpornc P, Siritanaratkuld N, Siripornpitake S, Meekaewkunchornf A, et al. Prevalence and predictors of cardiac and liver iron overload in patients with thalassemia: A multicenter study based on real-world data. Blood Cells Mol Dis. 2017;66:24–30. 10.1016/j.bcmd.2017.08.002. PMID: 28806577.
22. Zimmermann MB, Fucharoen S, Winichagoon P, Sirankapracha P, Zeder C, Gowachirapant S, et al. Iron metabolism in heterozygotes for hemoglobin E (HbE), α-thalassemia 1, or β-thalassemia and in compound heterozygotes for HbE/ β –thalassemia. Am J Clin Nutr. 2008;88:1026–1031. https://doi.org/10.1093/ajcn/88.4.1026. PMID: 18842790.
23. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT, et al .High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med. 2007;13:1096–1101. https://doi.org/10.1038/nm1629. PMID: 17721544.
24. Kim A, Nemeth E. New insights into iron regulation and erythropoiesis. Curr Opin Hematol. 2015;22:199–205. https://doi.org/10.1097/MOH.0000000000000132. PMID: 25710710.
25. Gupta R, Musallam KM, Taher AT, Rivella S. Ineffective erythropoiesis: anemia and iron overload. Hematol Oncol Clin N Am. 2018;32:213–21. https://doi.org/ 10.1016/j.hoc.2017.11.009. PMID: 29458727.
26. Gardenghi S, Marongiu MF, Ramos P, Guy E, Breda L, Chadburn A, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood. 2007;109:5027-5035. https://doi.org/10.1182/blood-2006-09-048868. PMID: 17299088.
27. Camberlein E, Zanninelli G, Détivaud L, Lizzi AR, Sorrentino F, Vacquer S, et al. Anemia in β-thalassemia patients targets hepatic hepcidin transcript levels independently of iron metabolism genes controlling hepcidin expression. Haematologica. 2008;93:111-115. https://doi.org/10.3324/haematol.11656. PMID: 18166793.
28. Jones E, Pasricha SR, Allen A, Evans P, Fisher CA, Wray K. Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait. Blood. 2015;125:873-880. https://doi.org/ 10.1182/blood-2014-10-606491. PMID: 25519750.
29. WHO Anthro for personal computers, version 3.2.2, 2011: Software for assessing growth and development of the world's children. Geneva: WHO, 2010. (http://www.who.int/childgrowth/software/en/)
30. Schlosnagle DC, Hutton PS, Conn RB. Ferrozine assay of serum iron and total iron-binding capacity adapted to the COBAS BIO centrifugal analyzer. Clin Chem. 1982;28:1730-1732. PMID: 7083590.
31. Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M. Immunoassay for human serum hepcidin. Blood. 2008;112:4292-4297. https://doi.org/10.1182/blood-2008-02-139915. PMID: 18689548.
32. Zipperer E, Post JG, Herkert M, Kündgen A, Fox F, Haas R, et al. Serum hepcidin measured with an improved ELISA correlates with parameters of iron metabolism in patients with myelodysplastic syndrome. Ann Hematol. 2013;92:1617–1623. https://doi.org/10.1007/s00277-013-1839-5. PMID: 23842708.
33. Troutt JS, Rudling M, Persson L, Ståhle L, Angelin B, Butterfield AM, et al. Circulating human hepcidin-25 concentrations display a diurnal rhythm, increase with prolonged fasting, and are reduced by growth hormone administration. Clin Chem. 2012;58:1225-1232. https://doi.org/10.1373/clinchem.2012.186866. PMID: 22679180.
34. Eng B PM, Walker L, Chui DHK, Waye JS. Detection of severe nondeletional α-thalassemia mutations using a single-tube multiplex ARMS assay. Genet Test. 2001;5:327-329. https://doi.org/10.1089/109065701753617471. PMID: 11960579.
35. Newton CR, Graham A, Heptinstall LE, Powell J, Summers C, Kalsheker N, et al. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Research. 1989;17:2503–2516. https://doi.org/10.1093/nar/17.7.2503. PMID: 2785681.
36. Tritipsombut J, Phylipsen M, Viprakasit V, Chalaow N, Fucharoen S, Harteveld CL, et al. A single-tube multiplex gap-polymerase chain reaction for the detection of eight beta-globin gene cluster deletions common in Southeast Asia. Hemoglobin. 2012;3:571-580. https://doi.org/10.3109/03630269.2012.747441. PMID: 23181748.
37. Craig JE, Barnetson RA, Prior J, Raven JL, Thein SL. Rapid detection of deletions caused β-thalassemia and hereditary persistence of fetal hemoglobin by enzymatic amplification. Blood. 1994;83:1673-1682. PMID: 7510147.
38. Ekwattanakit S MY, Riolueang S, Tachavanich K, Viprakasit V. Association of XmnI polymorphism and hemoglobin E haplotypes on postnatal gamma globin gene expression in homozygous hemoglobin E. Adv Hematol. 2012;2012:1-5. https://doi.org/10.1155/2012/528075. PMID: 23049556.
39. Iron deficiency anemia: assessment, prevention and control. A guide for programme managers. Geneva, World Health Organization, 2001 (WHO/NHD/01.3).
40. Camaschella C. Iron deficiency: new insights into diagnosis and treatment. Hematology Am Soc Hematol Educ Program. 2015;2015:8-13. https://doi.org/10.1182/asheducation-2015.1.8. PMID: 26637694.
41. Galanello R. Screening and diagnosis for haemoglobin disorders. In: Old J, editor. Prevention of thalassaemias and other haemoglobin disorders: volume 1, 2nd ed. Nicosia, Cyprus: Thalassaemia international federation; 2013.
42. Tachavanich K, Viprakasit V, Chinchang W, Glomglao W, Pung-Amritt P, Tanphaichitr VS. Clinical and hematological phenotype of homozygous hemoglobin E: revisit of a benign condition with hidden reproductive risk. Southeast Asian J Trop Med Public Health. 2009;40:306-316. PMID: 19323016.
43. Vrettou C, Kanavakis E, Traeger-Synodinos J, Metaxotou-Mavrommati A, Basiakos I, Maragoudaki E, et al. Molecular studies of beta-thalassemia heterozygotes with raised Hb F levels. Hemoglobin. 2000;24:203-220. https://doi.org/10.1016/j.bcmd.2017.06.001. PMID: 28651846.
44. Viprakasit V, Lee-Lee C, Chong QT, Lin KH, Khuhapinant A. Iron chelation therapy in the management of thalassemia: the Asian perspectives. Int J Hematol. 2009;90:435-445. https://doi.org/10.1007/s12185-009-0432-0.
45. Tassiopoulos T, Konstantopoulos K, Tassiopoulos S, Rombos Y, Alevizou-Terzaki V, Kyriaki P, et al. Erythropoietin levels and microcytosis in heterozygous beta-thalassaemia. Acta Haematol. 1997;98:147-149. https://doi.org/10.1159/000203609. PMID: 9352745.
46. Mehta BC, Pandya BG. Iron status of beta thalassemia carriers. Am J Hematol. 1987;24:137-141. https://doi.org/10.1002/ajh.2830240204. PMID: 3812467.
47. Hoorfar H, Sadrarhami S, Keshteli AH, Ardestani SK, Ataei M, Moafi A. Evaluation of iron status by serum ferritin level in Iranian carriers of beta thalassemia minor. Int J Vitam Nutr Res. 2008;78:204-207. https://doi.org/10.1024/0300-9831.78.45.204. PMID: 19326343.
48. Dolai TK, Nataraj KS, Sinha N, Mishra S, Bhattacharya M, Ghosh MK. Prevalance of iron deficiency in thalassemia minor: a study from tertiary hospital. Indian J Hematol Blood Transfus. 2012;28:7–9. https://doi.org/10.1007/s12288-011-0088-9. PMID: 23449336.
49. Hinchliffe RF, Lilleyman JS. Frequency of coincident iron deficiency and beta-thalassaemia trait in British Asian children. J Clin Pathol. 1995;48:594-595. https://doi.org/10.1136/jcp.48.6.594. PMID: 7665713.
50. Wray K, Allen A, Evans E, Fisher C, Premawardhena A, Perera L, et al. Hepcidin detects iron deficiency in Sri Lankan adolescents witha high burden of hemoglobinopathy: A diagnostic test accuracy study. Am J Hematol. 2017;92:196–203. https://doi.org/10.1002/ajh.24617. PMID: 27883199.
51. Uijterschout L, Domellöf M, Berglund SK, Abbink M, Vos P, Rövekamp L, et al. Serum hepcidin in infants born after 32 to 37 wk of gestational age. Pediatr Res. 2016;79:608-613. https://doi.org/10.1038/pr.2015.258. PMID: 26672736.
52. Aranda N, Bedmar C, Arija V, Jardí C, Jimenez-Feijoo R, Ferré N, et al. Serum hepcidin levels, iron status, and HFE gene alterations during the first year of life in healthy Spanish infants. Ann Hematol. 2018;97:1071-1080. https://doi.org/10.1007/s00277-018-3256-2. PMID: 29404719.

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