Vitamin D, insulin-like growth factor-1, and stunting in children with transfusion-dependent thalassemia

  • I Gusti Ayu Putu Eka Pratiwi Department of Child Health, Faculty of Medicine, Udayana University/Sanglah Hospital, Denpasar, Bali, Indonesia
  • Roedi Irawan Department of Child Health, Faculty of Medicine, Airlangga University/Dr. Soetomo Hospital, Surabaya, East Java, Indonesia
  • I Dewa Gede Ugrasena Department of Child Health, Faculty of Medicine, Airlangga University/Dr. Soetomo Hospital, Surabaya, East Java, Indonesia
  • Muhammad Faizi Department of Child Health, Faculty of Medicine, Airlangga University/Dr. Soetomo Hospital, Surabaya, East Java, Indonesia
Keywords: transfusion-dependent thalassemia; stunting, IGF-1; vitamin D


Background Transfusion-dependent thalassemia (TDT) has a major impact on a child's growth and is associated with stunting, risk of vitamin D deficiency, and decreased insulin-like growth factor-1 (IGF-1). To date, the relationship between vitamin D levels and stunting in TDT remains unclear. Futhermore, the role of vitamin D and IGF-1 in mediating stunting in TDT patients is still unknown. 

Objective To investigate the relationship between stunting and vitamin D as well as IGF-1 levels in children with TDT.

Methods This cross-sectional study involved 50 TDT children aged 5 to 18 years, included consecutively from the Pediatric Hemato-oncology Outpatient Clinic, Dr. Soetomo Hospital, Surabaya, East Java. Subjects were divided into two groups: stunted (S) and not stunted (NS). Vitamin D and IGF-1 were evaluated by antibody competitive immunoassay and sandwich-enzyme-linked immunosorbent assay (ELISA), respectively. Age, sex, and duration of repeated transfusion were analyzed as confounding factors.

Results Median IGF-1 levels were 91.43 (13.67-192.86) ng/mL and 161.53 (17.99-363.01) ng/mL in the S and NS groups, respectively (P=0.011). Mean vitamin D levels were 20 (+ 5.71) ng/mL and 20.46 (5.25) ng/mL in the S and NS groups, respectively (P=0.765). The correlation coefficient (r) of vitamin D and IGF-I levels was not significant. Multivariate analysis showed that low IGF-1 levels, male, and longer duration of repeated transfusions were associated with stunting in children with TDT. 

Conclusion Low IGF-1 level is associated with stunting in children with TDT. Vitamin D is not significantly associated with either stunting or IGF-1 in children with TDT.


1. Vibrakasit V, Origa R. Genetic basis, pathophysiology and diagnosis. In: Cappellini MD, Cohen A, Porter J, Taher A, Vibrakasit V, editors. Guidelines for the management of transfusion dependent thalassemia (TDT). 3rd ed. Nicosia: Thalassaemia International Federation; 2014. p. 14-27.
2. Jahagirdar R, Parikh S, Deshpande R, Lalwani S. Growth profile of children with thalassemia major. IJAR. 2017;7:724-6.
3. Vogiatzi MG, Macklin EA, Trachtenberg FL, Fung EB, Cheung AM, Vichinsky E, et al. Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. Br J Haematol. 2009;146:546-56. DOI: 10.1111/j.1365-2141.2009.07793.x
4. Uda R, Idjradinata PS, Djais JTB. Risk factors to growth retardation in major thalassemia. MKB. 2011;43:21-5. DOI: 10.15395/mkb.v43n1.40
5. Joseph N, Pai S, Sengupta S, Bharadwaj S, Dhawan S, Khare K. A clinico-epidemiological study of thalassemia cases in India. J Nat Sc Biol Med. 2018;9:236-41. DOI: 10.4103/jnsbm.JNSBM_224_17
6. Fung EB, Aguilar C, Micaily I, Haines D, Lal A. Treatment of vitamin D deficiency in transfusion-dependent thalassemia. Am J Hematol. 2011;86:871–3. DOI: 10.1002/ajh.22117
7. Shamshirsaz AA, Bekheirnia MR, Kamgar M, Pourzahedgilani N, Bouzari N, Habibzadeh M, et al. Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran. BMC Endocr Disord. 2003;3:4. DOI: 10.1186/1472-6823-3-4
8. Singh K, Kumar R, Shukla A, Phadke SR, Agarwal S. Status of 25-hydroxyvitamin D deficiency and effect of vitamin D receptor gene polymorphisms on bone mineral density in thalassemia patients of North India. Hematology. 2012;17:291-6. DOI: 10.1179/1607845412Y.0000000017
9. Nakavachara P, Viprakasit V. Children with hemoglobin E/?-thalassemia have a high risk of being vitamin D deficient even if they get abundant sun exposure: A study from Thailand. Pediatr Blood Cancer. 2013;60:1683-8. DOI: 10.1002/pbc.24614
10. Singh SK. Study of growth promoting effect of vitamin D supplementation in vitamin D deficient hypothyroid children. Thyroid Res Pract. 2014;11:81-2. DOI: 10.4103/0973-0354.129737
11. Borgna-Pignatti C, Gamberini MR. Complications of thalassemia major and their treatment. Expert Rev Hematol. 2011;4:353–66. DOI: 10.1586/ehm.11.29
12. Hendarto A, Sjarif DR. Antropometri anak dan remaja. In: Sjarif DR, Lestari ED, Mexitalia M, Nasar SS, editors. Buku ajar nutrisi pediatrik dan penyakit metabolik jilid I. Jakarta: Badan Penerbit IDAI;2014. p. 25-37.
13. Anggraeni AC. Antropometri. Asuhan Gizi: Nutritional Care Process. Yogyakarta: Graha Ilmu; 2012. p:1-33.
14. Elizabeth M, Fadlyana E, Reniarti L, Faisal, Sukandar H, Rusmil K. Serum IGF-1 and short stature in adolescents with ß-thalassemia major. Paediatr Indones. 2018;58:151-8. DOI: 10.14238/pi58.4.2018.151-8
15. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122:398–417. DOI: 10.1542/peds.2007-1894
16. Cachat F, Combescure C, Cauderay M, Girardin E dan Chehade H. A systematic review of glomerular hyperfiltration assessment and definition in the medical literature. Clin J Am Soc Nephrol. 2015;10:1-8. DOI: 10.2215/CJN.03080314
17. Moiz B, Habib A, Sawani S, Raheem A, Hasan B, Gangwani M. Anthropometric measurements in children having transfusion-dependent beta thalassemia. Hematology. 2018;23:248-52. DOI: 10.1080/10245332.2017.1396044
18. Rathaur VK, Imran A, Pathania M. Growth pattern in thalassemic children and their correlation with serum ferritin. J Family Med Prim Care. 2020;9:1166-9. DOI: 10.4103/jfmpc.jfmpc_951_19
19. Ramadan M, Ebrahim NA, Ramadan MS, Salahedin O. Growth pattern in children with beta-thalassemia major and its relation with serum ferritin, IGF1 and IGFBP3. J Clin Exp Invest. 2012;3:157-63. DOI: 10.5799/ahinjs.01.2012.02.0135
20. Skordis N, Kyriakou A. The multifactorial origin of growth failure in thalassaemia. Pediatr Endocrinol Rev. 2011;8:271-7.
21. Saxena A. Growth retardation in thalassemia major patients. Int J Hum Genet. 2003;3:237-46. DOI: 10.1080/09723757.2003.11885858
22. Prabhu R, Prabhu V, Prabhu RS. Iron overload in beta thalassemia – a review. J Biosci Tech. 2009;1:20-31.
23. Golden MHN. Specific deficiencies versus growth failure: type I and type I1 nutrients. J Nutritional & Environmental Medicine. 1996;6:301-8. DOI: 10.3109/13590849609007256
24. Ameri P, Giusti A, Boschetti M, Murialdo G, Minuto F, Ferone D. Interactions between vitamin D and IGF-I: from physiology to clinical practice. Clinical Endocrinology. 2013;79(4):457–63. DOI:10.1111/cen.12268
25. Gannagé-Yared MH, Chahine E, Farah V, Ibrahim T, Asmar N, Halaby G. Serum insulin-like growth factor 1 in Lebanese school children and its relation to vitamin D and ferritin levels. Endocr Pract. 2017;23:391-8. DOI: 10.4158/EP161623.OR
How to Cite
Pratiwi IGAPE, Irawan R, Ugrasena IDG, Faizi M. Vitamin D, insulin-like growth factor-1, and stunting in children with transfusion-dependent thalassemia. PI [Internet]. 7Mar.2022 [cited 14Jun.2024];62(2):98-03. Available from:
Pediatric Hemato-Oncology
Received 2021-05-11
Accepted 2022-03-07
Published 2022-03-07