220 J Contemp Med Sci | Vol. 8, No. 4, July-August 2022: 220–223 Original The Association Between Iron Deficiency Anemia and Obesity in Children Akrem M. Atrushi1, Farhad Shaker Armishty2*, Sirwan A. Saleh2, Mehvan Sh. Abdulrahman3 1Department of Pediatric, College of Medicine, University of Duhok, Kurdistan Region, Iraq. 2*Department of Clinical Sciences, College of Medicine, University of Zakho, Kurdistan Region, Iraq. 3Department of Pediatric, Directorate of Health, Duhok, Kurdistan Region, Iraq. *Correspondence to: Dr. Farhad Shaker Armishty (E-mail: farhad.shaker@uoz.edu.krd) (Submitted: 02 May 2022 – Revised version received: 21 May 2022 – Accepted: 15 June 2022 – Published online: 26 August 2022) Abstract Background: Obesity is a growing health problem all over the world. Approximately 18–38% of under 5 years old children have iron deficiency anemia. Obese people are more likely to be have iron deficiency. Studies that dealt with the relationship between iron deficiency and obesity are not homogeneous. Aim: To examine the association between obesity and iron status and the presence of iron deficiency anemia in children. Methods: This case-control study included 100 children between 2–14 years of age who were divided into two age- and sex-matched equal groups of 50 children each. Children with a body mass index (BMI) greater than or equal to 95th centile were categorized as obese while the other 50 children with a BMI greater than or equal to 5th centile but less than 95th centile were considered the normal weight group. Children with cardiac disease, liver disease, chronic gastrointestinal disease and chronic hematologic disorders except iron deficiency (with or without anemia) and those taking Vitamin or mineral supplements regularly during the previous year were excluded. Each participant was sent for serum iron, ferritin, total iron binding capacity (TIBC), transferrin saturation TS and complete blood count. Iron deficiency is defined as Transferrin Saturation (TS) lower than 16% and IDA is defined as TS lower than 16% and hemoglobin (Hb) concentration lower than 120 g/l or 12 mg/dl for children. The data were analyzed using SPSS-23 software and for all data normal distribution was tested so that P-value <0.05 is the level of threshold for statistical significance. Results: The gender distribution between the both group is reversed with male being more common in obese group but no statistical difference. The age distribution shows dominance of the age group 5–10 years in the both group with some differences which are of no statistical significance (P = 0.294). The values of Hemoglobin, serum iron, serum ferritin, total iron binding capacity and transferrin saturation are obviously similar between the both genders of the whole study population with no statistically significant differences (P = 0.084, 0.469, 0.48, 0.4, 0.571 respectively). Obese children have higher level of Hemoglobin (P = 0.069), Ferritin (P = 0.5) and total iron binding capacity (P = 0.449) but lower levels of serum iron (P = 0.234) and transferrin saturation(P = 0.45) but with no statistical significance. Conclusion: There is no significant association between obesity and iron status and the presence of iron deficiency anemia despite a lower level of serum iron and lower transferrin saturation in obese than normal weight children. ISSN 2413-0516 Introduction Obesity is a growing health problem all over the world. Its prevalence has increased apparently in recent years.1,2 Up to 16–31% of children suffer from obesity nowadays.2,3 According to the World Health Organization (WHO) classification, the prevalence of iron deficiency anemia (IDA) is in the medium level.4 Approximately 18–38% of under 5 years old children have iron deficiency anemia.5 The rapid changes in lifestyles and dietary patterns with large amounts of fat, sugar and oil are of the most important causes of obesity.6-8 It has been found that obese people are more likely to be have iron deficiency. Iron deficiency anemia is significantly more prevalent among obese than normal weight people.9-11 Foods high in calorie are low in nutrients leading to poor diet. Obese children are susceptible to a variety of micronu- trient deficiencies.12 Obesity is considered a low-grade inflammatory disease. Adipose tissue is considered an endocrine organ that secret pro-inflammatory cytokines named adipokines that con- tribute to the inflammatory process that may have an impor- tant pathogenic role in some obesity-related comorbidities.13 It has been suggested that expansion of tissue mass and adipocyte size in obesity makes white adipose tissue hypoxic leading to inflammation and cellular dysfunction.14 Moreover, when hypertrophied adipose tissue is unable to satisfy its storage function, there will be excess free fatty acids exposed to organs which are lipid intolerant leading to lipotoxicity and thereby low-grade inflammation in the adipose tissue. There- fore, hypertrophy of adipocytes and local tissue hypoxia, trig- gers overproduction of adipokine that enhances macrophage infiltration in obesity.15 This inflammation can cause transformation of iron metabolism leading to overload of iron in tissues with decreased mobility and as a result reduction of the breakdown of myoglobin. This will decrease the serum iron needed for hematopoiesis.16 Studies that dealt with the relationship between iron defi- ciency and obesity are not homogeneous.17-20 They are gener- ally case/control or cross-sectional studies, in many cases, not population-based, but rather they considered many variables related to iron deficiency and obesity21,22 and used different criteria for defining iron deficiency. A frequently used iron parameter is serum ferritin23-25 which is an acute-phase reac- tant that is positively related to adiposity and thus reducing its sensitivity. To the best of our knowledge, no studies have been done locally to study the relation between obesity and each of iron status and the presence of iron deficiency anemia. The aim of study is to examine the association between obesity and iron status and the presence of iron deficiency anemia in children. Methods This case-control study was out at Zakho General Hospital in the period from May 1st 2021 to May 1st 2022. A total of 100 mailto:farhad.shaker@uoz.edu.krd 221J Contemp Med Sci | Vol. 8, No. 4, July-August 2022: 220–223 A.M. Atrushi et al. Original The Association Between Iron Deficiency Anemia and Obesity in Children children between 2–14 years of age were included in the study. The participants were divided into two equal groups of 50 chil- dren each. Both groups were age- and sex- matched. Children with a body mass index (BMI) greater than or equal to 95th centile were categorized as obese and termed as cases while the other 50 children with a BMI greater than or equal to 5th cen- tile but less than 95th centile (as per the World Health Organ- ization [WHO] standards) were the normal weight group and termed controls. The exclusion criteria were: 1- Any disorder, such as car- diac disease, liver disease, chronic gastrointestinal disease and chronic hematologic disorders except iron deficiency (with or without anemia). 2- Vitamin or mineral supplements taken regularly during the previous year. From each participant, about 5 cc of fasting blood were taken to evaluate the serum iron, ferritin, total iron binding capacity (TIBC) and transferrin saturation TS, and about 2 cc citrated fasting blood sample were evaluated for complete blood count (CBC) and analyzed according to standard protocols. Iron deficiency is defined as Transferrin Saturation (TS) lower than 16% and IDA is defined as TS lower than 16% and hemoglobin (Hb) concentration lower than 120 g/l or 12 mg/dl for children. The data were analyzed using SPSS-23 software and for all data normal distribution was tested so that P-value <0.05 is the level of threshold for statistical significance. Results As shown in Table 1, the gender distribution between the both group is reversed but no statistical difference has been found. The age distribution shows dominance of the age group 5–10 years in the both group with some differences which are of no statistical significance. So, the obese and normal weight chil- dren are age and gender matched. The laboratory findings of the whole participants are shown in Table 2. The values of Hemoglobin, serum iron, serum ferritin, total iron binding capacity and transferrin saturation are obviously similar between the both genders of the whole study population with no statistically significant differences. Comparison between obese and normal weight children laboratory values shows the obese children have higher level of Hemoglobin, Ferritin and TIBC but lower levels of serum iron and transferrin saturation but with no statistical significance as shown in Table 3. Discussion The sociodemographic characteristics show males are more commonly obese and that age group of 5–10 years are the most prevalent but no significant differences were noticed between the both groups. Numerous previous studies have found higher prevalence of iron deficiency in obese children.28-35 Our findings show a lower level of serum iron and lower transferrin saturation in obese children than normal weight but do not reveal a signifi- cant deficiency of iron in obese children. These results corroborate the results of Perez et al.29 that found the prevalence of iron deficiency in otherwise healthy obese was not higher than in normal weight children so the effect of obesity on iron status was low. They suggested that Table 1. The sociodemographic characteristics of cases and controls Normal Obese P-value Gender Male 24 (48%) 26 (52%) 0.689 Female 26 (52%) 24 (48%) Age Under 5 years 12 (24%) 6 (12%) 0.2945–10 years 22 (44%) 25 (50%) Above 10 years 16 (32%) 19 (38%) Table 2. Laboratory values of the study population Mean ± SD Male Female Total P-value Hb 12.5380 ± .94694 12.5180 ± 1.07489 12.5280 ± 1.00786 0.084 Iron 62.9948 ± 30.31192 59.0934 ± 28.53107 61.0441 ± 29.35148 0.469 Ferritin 35.7664 ± 26.75804 30.3876 ± 23.27093 33.0770 ± 25.09420 0.480 TIBC 378.0280 ± 82.31149 390.4890 ± 81.36954 384.2585 ± 81.66790 0.541 TS 19.6440 ± 22.87591 16.9146 ± 9.8158 18.2793 ± 17.566 0.571 Table 3. Relation between weight status and laboratory values Normal Obese P-value Hb 12.4960 ± 1.12847 12.5600 ± .88133 0.069 Iron 63.1104 ± 35.55115 58.9778 ± 21.63337 0.234 Ferritin 30.0546 ± 21.68217 36.0994 ± 27.99161 0.5 TIBC 368.0170 ± 72.77616 400.5000 ± 87.41108 0.449 TS 18.7760 ± 10.94805 17.7826 ± 22.42977 0.450 222 J Contemp Med Sci | Vol. 8, No. 4, July-August 2022: 220–223 The Association Between Iron Deficiency Anemia and Obesity in Children Original A.M. Atrushi et al. specific cutoff values for iron deficiency in overweight adoles- cents need to be defined. This is in agreement with Ferrari et al.36 who revealed that adiposity of the European adolescents was sufficient to cause chronic inflammation but not sufficient to impair iron status and cause iron deficiency. In line with our findings, Demircioglu et al.37 found that serum iron and ferritin level were comparable between obese and normal weight children and stressed a significant role of hepcidin in obesity. Cheng et al.38 did a study on obese adult women and found that obesity alone may not be sufficient to cause distur- bances to iron metabolism which are clinically significant as previously described and Qin39 [IDA similar 9] found anemia to be even less prevalent in obese women and this is in agree- ment with our study on pediatric population. Gajewska40 found that in obese children with sufficient iron intake, the altered ferroportin-hepcidin axis may occur without signs of iron deficiency or iron deficiency anemia. They suggested that the role of other micronutrients, besides dietary iron, may also be considered in the iron status of obese children while Huang22 concluded that being over- weight or obese would not be a risk factor of iron deficiency in adolescents, if it were defined by ferritin rather than iron level. In total, the paradoxical results of the studies regarding association between obesity and iron deficiency might be attributed to the differences in the definition of obesity or using different techniques to assess laboratory parameters.41 One of the limitations of this study is that we did not include the dietary intake of iron which if sufficient can over- come the effects of obesity on causing iron deficiency and anemia. Also, it would have been much better if we studied the role of hepcidin in iron status in obesity as proved in many studies.37 Conclusion There is no significant association between obesity and iron status and the presence of iron deficiency anemia despite a lower level of serum iron and lower transferrin saturation in obese than normal weight children. Conflict of Interest None.  References 1. Ghadimi R, Asgharzadeh E, Sajjadi P. Obesity among Elementary Schoolchildren: A Growing Concern in the North of Iran, 2012. Int J Prev Med 2015; 6: 99. 2. Gahagan S. Overweight and obesity. In: Nelson text book of pediatrics, 19th ed. Philadelphia: Elsevier Saunders 2011: 179–211. 3. Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of high body mass index in US children and adolescents, 2007–2008. J Am Med Assoc 2010; 303(3):242–9. 4. Bahrami M. Malnutrition and its effects on development in Iranian children. Iran J Pediatr 2004; 14(2): 149–56. [in Persian] 5. World Health Organization. Worldwide prevalence of anemia 1993–2005. WHO, Global Database on Anaemia, Geneva, Switzerland, 2008. 6. Sajjadi P, Enayatzadeh H, Ghadimi R. Which food groups and macronutrients are more associated with central obesity in Iranian children? Caspian J Social Medicine 2015; 1(1): 24–30. 7. World Health Organization. Diet, Nutrition and prevention of chronic diseases, WHO technical report jointWHO/FAO expert consultation, Geneva 2003. Available at: http://www.who.int/dietphysicalactivity/publications/tr s916/en/gsfao_introduction.pdf 8. Daniels SR, Arnett DK, Eckel RH, et al. Overweight in children and adolescents: pathophysiology, consequences, prevention and treatment. Circulation 2005; 111(15): 1999–2012. 9. Nead KG., Halterman JS, Kaczorowski JM, et al. Overweight children and adolescents: a risk group for iron deficiency. Pediatr 2004; 114(1): 104–8. 10. Chambers EC, Heshka S, Gallagher D, et al. Serum iron and body fat distribution in a multiethnic cohort of adults living in New York City. J Am Diet Assoc 2006; 106(5): 680–4. 11. Keikhaei B, Askari R, Aminzadeh M. Adolescent with Unfeasible Body Mass Index: A Risk Factor for Iron Deficiency Anemia. J Health Med Informat 2012; 3(1). Available at: http://www.omicsonline.org/adolescentwith- unfeasible-body-mass-index-a-risk-factor-foriron-deficiency- anemia-2157-7420.1000109.pdf 12. Daniels SR, Arnett DK, Eckel RH, Gidding SS, Hayman LL, Kumanyika S, et al. Overweight in children and adolescents: pathophysiology, consequences, prevention and treatment. Circulation 2005; 111(15): 1999–2012. 13. Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci 2013;9(2): 191–200. 14. Sarmiento OL, Parra DC, Gonzalez SA, Gonzalez-Casanova I, Forero AY, Garcia J. The dual burden of malnutrition in Colombia. The American Journal of Clinical Nutrition 2014;100(6):1628s-35s. doi: 10.3945/ ajcn.114.083816. 15. Ramirez-Zea M, Kroker-Lobos MF, Close-Fernandez R, Kanter R. The double burden of malnutrition in indigenous and nonindigenous Guatemalan populations. The American Journal of Clinical Nutrition 2014;100(6):1644s-51s. doi: 10.3945/ajcn.114.083857. 16. Richardson MW, Ang L, Visintainer PF, Wittcopp CA. The abnormal measures of iron homeostasis in pediatric obesity are associated with the inflammation of obesity. Int J Pediatr Endocrinol 2009; 2009: 713269. doi: 10.1155/2009/713269. 17. Manios Y, Moschonis G, Chrousos GP, et al. The double burden of obesity and iron deficiency on children and adolescents in Greece: The Healthy Growth Study. J Hum Nutr Diet 2013; 26:470–478. 18. Tussing-Humphreys LM, Liang H, Nemeth E, et al. Excess adiposity, inflammation, and iron-deficiency in female adolescents. J Am Diet Assoc 2009; 109:297–302. 19. Frelut ML, Girardet P, Bocquet A, et al. Impact of obesity on biomarkers of iron and vitamin D status in children and adolescents: The risk of misinterpretation. Arch Pediatr 2018; 25:3–5. 20. Johnson K, Showell NN, Flessa S, et al. Do neighborhoods matter? A systematic review of modificable risk factors for obesity among low socioeconomic status black and Hispanic children. Chilhood Obesity 2019; 15:71–86. 21. Hutchinson C. A review of iron studies in overweight and obese children and adolescents: A double burden in the Young. Eur J Nutr 2016; 55: 2179–2197. 22. Huang YF, Tok TS, Lu CL, et al. Relationship between being overweight and iron deficiency in adolescents. Pediatr Neonatol 2015; 56:386–392. 23. Mattiello V, Schmugge M, Hengartner H, et al. Diagnosis and management of iron deficiency in children with or without aaemia: consensus recommendations of the SPOG Pediatric Hematology Group. Eur J Pediatr 2020; 179:527–545. 24. Thomas DW, Hinchliffe RF, Briggs C, et al. British Committee for Standards Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol 2013; 161:639–648. 25. Khan A, Khan WM, Maimoona A, et al. Ferritin is a marker of inflammation rather than iron deficiency in overweight and obese people. J Obes 2016; 2016:1937320. 26. Siyaram D, Bhatia P, Dayal D. Hypoferremic state in overweight and obese children. Indian Pediatr 2018; 55:72–73. 27. Pinhas-Hamiel O, Newfield RS, Koren I, et al. Greater prevalence of iron deficiency in overweight and obese children and adolescents. Int J Obes 2003; 27:416–418. http://www.omicsonline.org/adolescentwith-unfeasible-body-mass-index-a-risk-factor-foriron-deficiency-anemia-2157-7420.1000109.pdf http://www.omicsonline.org/adolescentwith-unfeasible-body-mass-index-a-risk-factor-foriron-deficiency-anemia-2157-7420.1000109.pdf http://www.omicsonline.org/adolescentwith-unfeasible-body-mass-index-a-risk-factor-foriron-deficiency-anemia-2157-7420.1000109.pdf 223J Contemp Med Sci | Vol. 8, No. 4, July-August 2022: 220–223 A.M. Atrushi et al. Original The Association Between Iron Deficiency Anemia and Obesity in Children 28. Aloufi ME, Aljaed NM, Aloufi RA, Jafri SA, Jafri Su A, Elnashar MA. Prevalence of Iron Deficiency anemia in Obese Children in Taif Area - Saudi Arabia. The Egyptian Journal of Hospital Medicine 2018;73(5): 6744–6752. 29. Ortíz-Pérez M, Vázquez-López MA, Ibáñez-Alcalde M, et al. Relationship Between Obesity and Iron Deficiency in Healthy Adolescents. Childhood Obesity. 2020;16(6):440–7. doi: 10.1089/chi.2019.0276 30. Cepeda-Lopez AC, Osendarp SJ, Melse-Boonstra A, Aeberli I, Gonzalez- Salazar F, Feskens E, Villalpando S, Zimmermann MB: Sharply higher rates of iron deficiency in obese mexican women and children are predicted by obesity-related inflammation rather than by differences in dietary iron intake. Am J Clin Nutr. 2011, 93 (5): 975–983. 10.3945/ajcn.110.005439. 31. Alshwaiyat N.M., Ahmad A., Hassan W.M.R.W., Al-Jamal H.A.N. Association between obesity and iron deficiency (Review) Exp. Ther. Med. 2021;22:1268. doi: 10.3892/etm.2021.10703. [PMC free article] [PubMed] [CrossRef ] [Google Scholar] 32. Khemphet R, Yupensuk N. Prevalence and Association between Obesity and Iron Deficiency in Children. J Med Assoc Thai 2022; 105:212–8. 33. Akca SO, Bostanci MO. The impact of anemia and body mass index (BMI) on neuromotor development of preschool children. Rev. Assoc. Med. Bras. 2017;63 (9) :779–786. 34. Malden S, Gillespie J, Hughes A, Gibson AM, Farooq A, Martin A, et al. Obesity in young children and its relationship with diagnosis of asthma, vitamin D deficiency, iron deficiency, specific allergies and flat-footedness: a systematic review and meta-analysis. Obes Rev 2020 Aug 18. [Ahead of print].10.1111/obr.13129 35. Ibrahim LS, Tayyem RF. Evaluation of Iron Deficiency and the Intake of Macro- and Micronutrients among Normal, Overweight, and Obese Children Under 5 Years in Amman. Iran J Ped Hematol Oncol. 2018; 8:21–36. 36. Ferrari M, Cuenca-García M, Valtueña J, et al. HELENA Study Group. Inflammation profile in over-weight/obese adolescents in Europe: An analysis in relation to iron status. Eur J Clin Nutr 2015; 69:247–255. 37. Demircioğlu F., Görünmez G., Dağıstan E, et al. Serum hepcidin levels and iron metabolism in obese children with and without fatty liver: case– control study. Eur J Pediatr 173, 947–951 (2014). https://doi.org/10.1007/ s00431-014-2268-8. 38. Cheng HL, Bryant CE, Roonkey KB, Steinbeck KS, Griffin HJ, Petocz P, et al. Iron, hepcidin and inflammatory status of young healthy overweight and obese women in Australia. PLoS One. 2013; 4; 8(7):e68675. 39. Qin Y., Melse-Boonstra A., Pan X, et al. Anemia in relation to body mass index and waist circumference among chinese women. Nutr J 12, 10 (2013). https://doi.org/10.1186/1475-2891-12-10. 40. Gajewska J, Ambroszkiewicz J, Klemarczyk W, Głąb-Jabłońska E, Weker H, Chełchowska M. Ferroportin-Hepcidin Axis in Prepubertal Obese Children with Sufficient Daily Iron Intake. International Journal of Environmental Research and Public Health. 2018; 15(10):2156. https://doi.org/10.3390/ ijerph15102156. 41. Arshad M, Jaberian F, Pazouki A, Riazi S, Rangraz MA, Mokhber S. Iron deficiency anemia and megaloblastic anemia in obese patients. Rom. J. Intern. 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