The effect of therapy on electrocardiography parameters in children with iron deficiency anemia and minor thalassemia compared with the healthy children

Б  том ХXXI, 2025, № 3 ДРУЖЕСТВО НА КАРДИОЛОЗИТЕ В БЪЛГАРИЯ АВТОРСКИ СТАТИИ ORIGINAL ARTICLES THE EFFECT OF THERAPY ON ELECTROCARDIOGRAPHY PARAMETERS THE EFFECT OF THERAPY ON ELECTROCARDIOGRAPHY PARAMETERS IN CHILDREN WITH IRON DEFICIENCY ANEMIA AND MINOR THALASSEMIA IN CHILDREN WITH IRON DEFICIENCY ANEMIA AND MINOR THALASSEMIA COMPARED WITH THE HEALTHY CHILDREN COMPARED WITH THE HEALTHY CHILDREN N. M. Noori1, G. M. Aliabad2, T. Boryri3, A. Teimouri4 1Children and Adolescents Health Research Center, Research Institute of Cellular and Molecular Science in Infectious Diseases, Zahedan University of Medical Science’s – Zahedan, Iran 2Pediatric ward, School of Medicine, Iran University of Medical Sciences – Tehran, Iran 3Department of Midwifery, School of Nursing and Midwifery, Pregnancy Health Research Center, Zahedan University of Medical Sciences – Zahedan, Iran 4Children and Adolescents Health Research Center, Research Institute of cellular and Molecular Science in Infectious Diseases, Zahedan University of Medical Science’s – Zahedan, Iran ЕФЕКТЪТ НА ТЕРАПИЯТА ВЪРХУ ЕЛЕКТРОКАРДИОГРАФСКИТЕ ПАРАМЕТРИ ЕФЕКТЪТ НА ТЕРАПИЯТА ВЪРХУ ЕЛЕКТРОКАРДИОГРАФСКИТЕ ПАРАМЕТРИ ПРИ ДЕЦА С ЖЕЛЯЗОДЕФИЦИТНА АНЕМИЯ И ЛЕКА ТАЛАСЕМИЯ ПРИ ДЕЦА С ЖЕЛЯЗОДЕФИЦИТНА АНЕМИЯ И ЛЕКА ТАЛАСЕМИЯ В СРАВНЕНИЕ СЪС ЗДРАВИ ДЕЦА В СРАВНЕНИЕ СЪС ЗДРАВИ ДЕЦА Н. М. Нури1, Г. М. Алиабад2, Т. Борири3, А. Теймури4 1Изследователски център за здравето на деца и юноши, Изследователски институт по клетъчна и молекулярна наука в областта на инфекциозните болести, Медицински университет в Захедан – Захедан, Иран 2Педиатрично отделение, Медицински факултет, Ирански университет по медицински науки – Техеран, Иран 3Катедра по акушерство, Факултет по медицински сестрински грижи и акушерство, Изследователски център по здравето на бременните жени, Медицински университет в Захедан – Захедан, Иран 4Изследователски център за здравето на деца и юноши, Изследователски институт по клетъчни и молекулярни науки в областта на инфекциозните болести, Медицински университет в Захедан – Захедан, Иран Abstract. Introduction: Iron defi ciency anemia (IDA) and minor thalassemia (MT) are common hematologic disorders in children that may affect cardiovascular function. Objectives: The goal of the study was to determine whether ECG abnormalities in these populations are clinically signifi cant and potentially reversible. Material and methods: This prospective, randomized clinical trial aimed to evaluate electrocardiographic (ECG) changes in 135 children aged 5-18 years, equally divided into IDA, minor thalassemia, and healthy control groups. ECG parameters such as QT interval, corrected QT interval (QTc), P-wave dispersion (PWd), Tpe interval, and Tpe/QTc ratio were assessed before and after Iron supplementation in the IDA group. Results: Pre-treatment, the IDA group showed signifi cantly lower hemoglobin, ferritin, and serum Iron levels, along with elevated TIBC and marked ECG abnormalities including prolonged QTc, P-wave dispersion, Tpe interval, and increased Tpe/QTc ratio, indicating higher arrhythmogenic risk. Following Iron supplementation, the IDA group demonstrated signifi cant improvements in hematological parameters and normalization of ECG indices. In contrast, the MT and control groups exhibited stable hematologic and ECG profi les throughout the study. Statistical analysis confi rmed signifi cant preto post-treatment improvements in IDA patients, while no signifi cant ECG changes were observed in MT or control groups. These fi ndings suggest that ECG abnormalities in IDA are reversible with appropriate treatment, highlighting the importance of early diagnosis and intervention to prevent cardiac complications in pediatric populations. Conclusion: These fi ndings highlight the importance of early detection and treatment of IDA to mitigate cardiac complications in pediatric populations. Key words: electrocardiography, iron defi ciency anemia, minor thalassemia, children This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. doi: 10.3897/bgcardio.31.e170466 81 The eff ect of therapy on electrocardiography parameters... I Electrocardiography (ECG) is a simple, non-invasive, and highly informative tool that allows clinicians to evaluate how the heart’s electrical system is functioning. In children, even small ECG changes can provide early clues about hidden health issues, including blood-related disorders such as iron defi ciency anemia (IDA) and minor thalassemia (MT). Although these conditions primarily aff ect the blood, growing evidence shows that they can also infl uence heart function [1, 2]. IDA is the most common nutritional disorder among children. It typically develops when the body does not receive enough iron from the diet, has diffi culty absorbing it, or requires more iron during periods of rapid growth. When iron levels drop, the production of hemoglobin the molecule in red blood cells that carries oxygen also decreases. Consequently, tissues receive less oxygen, leading to symptoms such as fatigue, pale skin, and an increased heart rate. Over time, as anemia becomes more severe, the heart must work harder to meet the body’s oxygen needs, which may cause subtle but important cardiovascular changes [3, 4]. On an ECG, children with IDA may present with a faster heart rate or a prolonged QT interval, indicating that the heart takes longer to recharge between beats. This delay can raise the risk of developing irregular heart rhythms, such as Torsades de Pointes. Other ECG fi ndings, including ST-segment depression, T-wave inversion, or mild alterations in PR or QRS intervals, may represent early eff ects of chronic anemia on heart muscle performance [5]. Minor thalassemia, on the other hand, is an inherited blood disorder that causes the body to produce abnormal hemoglobin. Most aff ected children appear healthy, yet persistent anemia forces the heart to work harder to ensure suffi cient oxygen delivery. Some studies have noted mild ECG abnormalities in these children, such as QT prolongation and T-wave changes. These alterations may arise from a combination of anemia, oxidative stress, and in cases involving transfusions mild iron overload [6-8]. Despite increasing awareness of these cardiac effects, few studies have specifi cally examined ventricular repolarization parameters such as QT and QTcd, Tpe interval, and Tpe dispersion in children with IDA or MT compared to healthy peers. Understanding these Address for correspondence: Prof. Noor Mohammad Noori, Professor Pediatric Cardiology, e-mail: [email protected], ORCID: 0000-0002-07326412; Prof. Ghasem Miri Aliabad, Professor Pediatric Hematology and Oncologist, e-mail: [email protected], ORCID: 00000002-9112-5567; Tahereh Boryri, Instructor of Midwifery, e-mail: [email protected], ORCID: 0000-0001-7897-1884; Alireza Teimouri, Assoc. Prof. in Demography, e-mail: [email protected], ORCID: 0000-0002-8356-4260 Резюме.Въведение: Желязодефицитната анемия (ЖДA) и леката таласемия (ЛT) са често срещани хематологични заболявания при деца, които могат да повлияят на сърдечно-съдовата функция. Цел: Целта на проучването беше да се определи дали ЕКГ аномалиите при тези популации са клинично значими и потенциално обратими. Материал и методи: Това проспективно, рандомизирано клинично проучване имаше за цел да оцени електрокардиографските (ЕКГ) промени при 135 деца на възраст 5-18 години, разделени поравно в групи с ЖДA, лека таласемия и здрави контроли. ЕКГ параметри като QT-интервал, коригиран QT-интервал (QTc), дисперсия на P-вълната (PWd), Tpe-интервал и съотношение Tpe/QTc бяха оценени преди и след приема на железни добавки в групата с ЖДА. Резултати: Преди лечението групата с ЖДA показа значително по-ниски нива на хемоглобин, феритин и серумно желязо, заедно с повишени нива на TIBC и отчетливи ЕКГ аномалии, включително удължен QTc, дисперсия на P-вълната, Tpe-интервал и повишено съотношение Tpe/QTc, което показва по-висок риск от аритмия. След приема на железни добавки групата с IDA показа значително подобрение в хематологичните параметри и нормализиране на ЕКГ индексите. За разлика от това групата с ЛT и контролната група показаха стабилни хематологични и ЕКГ профили през целия период на проучването. Статистическият анализ потвърди значително подобрение при пациентите с ЖДA преди и след лечението, докато при ЛT или контролната група не бяха наблюдавани значителни промени в ЕКГ. Тези резултати демонстрират, че аномалиите в ЕКГ при ЖДA са обратими с подходящо лечение, което подчертава важността на ранната диагностика и интервенция за предотвратяване на сърдечни усложнения при педиатричната популация. Заключение: Получените резултати подчертават важността на ранното откриване и лечение на ЖДA за намаляване на сърдечните усложнения при педиатричната популация. Ключови думи:електрокардиография, желязодефицитна анемия, лека таласемия, деца Адрес за кореспонденция: Проф. Нур Мохамад Нури, професор по детска кардиология, e-mail: [email protected], ORCID: 0000-0002-07326412; Проф. Гасем Мири Алиабад, професор по педиатрична хематология и онкология, e-mail: [email protected], ORCID: 0000-0002-9112-5567; Тахерех Борири, инструктор по акушерство, e-mail: [email protected], ORCID: 00000001-7897-1884; Алиреза Теймури, доцент по демография, e-mail: [email protected], ORCID: 00000002-8356-4260 N. M. Noori, G. M. Aliabad, T. Boryri, A. Teimouri 82 diff erences could help identify early electrical changes in the heart before more serious complications develop [9, 10]. Researchers have emphasized the need for larger, well-designed studies to clarify how these ECG changes relate to the risk of future cardiac events [11]. If left untreated, IDA may progressively impair heart function and elevate the risk of arrhythmias [12]. Encouragingly, eff ective treatment and correction of anemia can help the heart recover and reduce these risks. Establishing reliable ECG reference values for healthy children can also assist clinicians in recognizing early warning signs in those with anemia. The present study aims to determine whether the ECG abnormalities observed in children with IDA and MT are clinically meaningful and whether they improve with appropriate treatment. These fi ndings may contribute to a more comprehensive and preventive approach to managing pediatric anemia and its potential cardiovascular consequences. M Study Design and Population This prospective, randomized, and blinded clinical trial was conducted on children with blood disorders of Iron Defi ciency Anemia (IDA) and Minor thalassemia (MT) to evaluate the electrocardiographic (ECG) changes in pediatric patients both before and after treatment, compared to healthy controls. The study run on patients who referred to Ali Asghar pediatric hospital affi liated to the Zahedan University of medical sciences between 2020 and 2021. A total of 135 children aged 5-18 years were equally shared and enrolled into three groups of: (1) IDA, (2) MT, and (3) healthy controls after considering the exclusion criteria. Inclusion and Exclusion Criteria Participants in this study were pediatric patients aged 5 to 18 years who had been diagnosed with either IDA or MT. Diagnosis of IDA was based on hemoglobin levels below 13 g/dL in boys and below 12 g/dL in girls, while children with MT were identifi ed through hemoglobin electrophoresis showing HbA2 levels greater than 3.5%. Exclusion criteria were carefully defi ned to eliminate confounding factors and included patients with other types of anemia, hematologic disorders, cardiac, renal, gastrointestinal, or endocrine diseases, as well as infections or malignancies. Children who had used medications aff ecting iron absorption, received iron or anti-infl ammatory treatments prior to enrollment, or demonstrated poor adherence to prescribed iron therapy were also excluded. The control group consisted of healthy children with no history of anemia or chronic illness. For all study groups, additional exclusion criteria included known cardiovascular disease or congenital heart defects, ongoing infections or infl ammatory conditions, iron or folate supplementation within the past three months, a history of blood transfusion in the previous six months, and any electrolyte imbalances or metabolic disorders. Treatment The typical dosage of ferrous sulfate, Tablet 200 mg with the 50mg elemental Iron (Made in Iran, DaruPakhsh) that used 4-6 mg of elemental Iron per kilogram of body weight per day, divided into 2 doses in 3 months. Ferrous sulfate is best to be taken with empty stomach to optimize absorption, but if gastrointestinal discomfort arises, it can be consumed with a small amount of food. It is important to avoid taking it alongside dairy products, calcium supplements, or anti-acids, as these can hinder Iron absorption. Hemoglobin levels and serum ferritin checked monthly to monitor the treatment’s eff ectiveness. Additionally, potential side eff ects, such as gastrointestinal issues like constipation or nausea, monitored and managed through dietary adjustments or alternative formulations if was necessary. The treatment for children with minor thalassemia primarily focused on supportive care, as these patients usually do not require specifi c medical therapy. The mainstay of management include folic acid supplementation) Iran Daru( (1 mg daily) to support red blood cell production and prevent megaloblastic changes. Blood Sample Collection and Measurements To diagnose and monitor IDA in children, hematological parameters including hemoglobin (Hb), ferritin, serum Iron, and total Iron-binding capacity (TIBC) were measured before treatment and after 3 months of therapy. A total of 5 mL of venous blood was collected from each participant to perform all required tests. For Hb measurement, whole blood was collected in an EDTA tube and analyzed using an automated hematology analyzer. Ferritin, serum iron, and TIBC were determined from serum samples obtained after clotting and centrifugation, using standard assay kits or automated analyzers according to the manufacturers’ instructions. All results were recorded in appropriate units (Hb in g/dL, ferritin in ng/mL, serum Iron in μg/dL). Electrocardiography At the time of diagnosis and at the end of Iron treatment, every child underwent electrocardiography (ECG). The 12-lead ECG was recorded at a paper speed of 50 mm/second and a gain of 10 mm/mV using a Cardiofax V device (Nihon Kohden Corporation, Tokyo, Japan) while the patient was in a supine position. During the recording, patients were allowed to breathe normally but were instructed not to speak. All measurements were taken manually using a magnifying glass, 83 The eff ect of therapy on electrocardiography parameters... and the mean values were obtained by averaging the results of three consecutive measurements. P-wave duration was measured in lead II from the beginning to the end of the P wave. P wave dispersion was calculated by subtracting the minimum P wave duration from the maximum P-wave duration. QT interval measurement started from the onset of the Q wave to the end of the T wave. The QTc was calculated using Bazett’s formula. QTd was calculated as the diff erence between the longest and shortest QT intervals. QTcd was found by subtracting the minimum QTc interval from the maximum QTc interval (Fig. 1). The Tpe interval, measured from the peak of the T wave (highest point) to the end of the T wave, was defi ned as the intersection between the tangent of the downward slope of the T wave and the isoelectric line (Fig. 2). The Tpe/QTc ratio was calculated based on these measurements, with all Tpe measurements taken from the precordial leads. Ethical Approval This study approved by the ethical committee of the University of Medical Science, Zahedan, Iran, coded as IR.ZAUMS.REC.1399.373 and coded IRCT20250416065355N1 as a clinical trails. Statistical Analysis Continuous variables were summarized using mean ± standard deviation (SD), while categorical variables were reported as frequencies and percentages. The Shapiro-Wilk test was used to assess the normality of continuous data. Hematological and electrocardiographic parameters were compared among the IDA, MT and control groups both before and after treatment. For comparisons across the three groups, the Kruskal-Wallis test was applied. When signifi cant diff erences were observed, pairwise comparisons were performed using Dunn’s post hoc test with adjustment for multiple comparisons. A p value <0.05 was considered statistically signifi cant. R The mean age of participants was 11.69 years (SD = 4.27) in the IDA group, 11.24 years (SD = 3.73) in the MT group, and 11.64 years (SD = 3.65) in the control group. The overall mean age across all groups was 11.53 years (SD = 3.87) with no statistically signifi cant diff erences (F = 0.178, p = 0.837). The sex distribution among participants was relatively balanced across all groups. In the IDA group, 51.1% were girls. The MT group included 48.9% girls, identical to the control group, which also had 48.9% girls. Overall, the total sample consisted of 49.6% girls. The comparison of sex distribution among the groups revealed no statistically signifi cant diff erence (Contingency Coeffi cient = 0.021, p = 0.971). Figure 3 illustrated that prior to treatment, children with IDA had the lowest mean (SD) hemoglobin (HB) Fig. 1. Schematic Representation of ECG Waves and Intervals (PR, QRS, ST, QT, and RR) on a Standard Electrocardiogram Fig. 2. Measurement of the TPe Interval on a Standard Electrocardiogram (ECG) Trace N. M. Noori, G. M. Aliabad, T. Boryri, A. Teimouri 84 levels 9.27 (0.91), ferritin 10.38(2.12), and serum Iron 21.42 (3.63), alongside the highest TIBC 449.78 (25.12), compared to the minor thalassemia and control groups. ECG parameters in the IDA group also showed marked abnormalities, including elevated QTc of 455.28 (11.57), QTcd of 59.60 (6.69), Tpe of 98.76 (4.57), Tped of 36.8 (3.95), P wave duration of 98.13 (5.29), PDIS 34.16(3.20), and Tpe/QTc ratio of 0.22 (0.01), suggesting greater electrical instability. After treatment, the IDA group showed signifi cant improvement: HB rose to 11.12 (1.36), serum Iron increased to 58.98 μg/dL (13.38), ferritin improved to 79.47 (31.93), and TIBC declined. Concurrently, ECG indices improved, with reductions in QTc of 425.14 (10.81), QTcd of 36.02 (7.75), Tpe of 77.11 (10.56), Tped of 26.19 (8.29), and Tpe/QTc of 0.18 (0.02). In contrast, the minor thalassemia and control groups showed stable hematological and ECG values across both time points. Kruskal-Wallis test results between the three groups before treatment in the Table 1 showed signifi cant diff erences (p < 0.001) among the three groups of participants across all hematological and ECG parameters. The IDA group had the lowest mean ranks for hemoglobin (30.94), ferritin (23.00), and serum Iron (23.09), and the highest for TIBC (109.62), P wave (94.37), P wave dispersion (108.52), QTc (106.69), QTcd (112.42), Tpe (110.08), Tpedb (108.20), and Tpe/QTc (105.31), refl ecting more severe hematological defi cits and cardiac electrical abnormalities. After treatment, while diff erences in hemoglobin, ferritin, and serum Iron remained signifi cant (p < 0.001), the IDA group’s mean ranks notably improved (e.g., hemoglobin = 46.47), and TIBC no longer diff ered signifi cantly (p = 0.220), indicating recovery in Iron status. Importantly, all ECG parameters showed no signifi cant diff erences post-treatment (p = 0.251-0.801), suggesting that the cardiac electrical abnormalities observed in IDA children were largely resolved with therapy. Table 2 showed that before treatment, children with IDA had signifi cantly worse hematological and electrocardiographic parameters compared to both the MT and control groups. Hemoglobin levels diff ered across all three groups, with the most pronounced diff erence between IDA and control (Adj. p < 0.001). Ferritin, serum Iron, and TIBC were signifi cantly worse in the IDA group versus both MT and control (Adj. p < 0.001), while no diff erences were found between MT and control. Similarly, all ECG parameters – including P wave, PDIS, QTc, QTcd, Tpe, Tpedb, and Tpe/QTc were signifi cantly elevated in IDA compared to both MT and control (Adj. p < 0.001), but not between MT and control (Adj. p = 0.281 to 1.00), indicating a unique cardiac burden in IDA. After treatment, hemoglobin improved in the IDA group, as reFig. 3. Comparison of Hematological and Electrocardiographic Parameters in Iron Defi ciency and Minor Thalassemia Before (B) and After (A) Intervention/Time 85 The eff ect of therapy on electrocardiography parameters... fl ected by the lack of signifi cant diff erence between IDA and MT (Adj. p = 0.609), though IDA vs. control and MT vs. control remained signifi cant (Adj. p < 0.001). Ferritin and serum Iron remained signifi cantly lower in the IDA group compared to both MT and control (Adj. p < 0.001 to 0.034), while MT and control diff erences stayed non-signifi cant. These fi ndings highlight marked baseline impairments in IDA patients, with post-treatment recovery most evident in hemoglobin levels, while Iron stores and serum Iron remained suboptimal. Table 3 showed that treatment led to markedly different responses between the IDA and MT groups. In the IDA group, Wilcoxon signed-rank analysis revealed strong and consistent improvements in all hematologic parameters, with signifi cant increases in hemoglobin, ferritin, and serum Iron (Z = -6.09 to -6.56, p < 0.001), and a signifi cant reduction in TIBC (Z = -6.26, p < 0.001). Electrocardiographic parameters also improved signifi cantly, including reductions in P wave duration, PDIS, QTc, QTcd, Tpe, Tped, and Tpe/QTc ratio (Z = -3.17 to -6.56, p ≤ 0.002), indicating enhanced cardiac conduction and reduced arrhythmogenic risk. In contrast, the MT group showed modest but signifi cant hematologic gains (Z = -4.399 to -5.841, p < 0.001), particularly in ferritin and serum Iron, while TIBC also declined favorably. However, ECG parameters in MT patients remained unchanged, with all p-values > 0.05, suggesting limited or no cardiac electrical impact. Overall, the IDA group exhibited both hematologic recovery and substantial ECG improvement post-treatment, while the MT group demonstrated hematologic gains without notable cardiac changes. Table 1. Comparison of hematological and electrocardiographic parameters among iron defi ciency anemia, minor thalassemia, and control groups using the Kruskal-Wallis Test before and after Variables Groups of participants Before Treatment After Treatment Mean Rank x2p value Mean Rank x2p Hemoglobin Iron defi ciency 30.94 102.02 < 0.001 46.47 48.78 < 0.001Minor Thalassemia 60.50 56.93 control 112.56 100.60 Ferritin Iron defi ciency 23.00 90.51 < 0.001 49.47 17.96 < 0.001Minor Thalassemia 94.80 84.18 control 86.20 70.36 Serum Iron Iron defi ciency 23.09 91.65 < 0.001 33.76 54.14 < 0.001 Minor Thalassemia 97.16 91.51 control 83.76 78.73 TIBC Iron defi ciency 109.62 76.49 < 0.001 59.78 3.02 0.220Minor Thalassemia 47.84 72.96 control 46.53 71.27 PWAVE Iron defi ciency 94.37 30.93 < 0.001 61.49 2.30 0.316Minor Thalassemia 56.74 73.97 control 52.89 68.54 PDIS Iron defi ciency 108.52 73.17 < 0.001 73.29 1.28 0.527Minor Thalassemia 44.42 64.49 control 51.06 66.22 QTC Iron defi ciency 106.69 66.04 < 0.001 70.44 0.49 0.783Minor Thalassemia 48.60 68.73 control 48.71 64.82 QTcd Iron defi ciency 112.42 87.87 < 0.001 70.07 2.39 0.302Minor Thalassemia 49.42 73.09 control 42.16 60.84 Tpe Iron defi ciency 110.08 78.19 < 0.001 75.36 2.66 0.265Minor Thalassemia 47.56 66.47 control 46.37 62.18 Tpedb Iron defi ciency 108.20 71.81 < 0.001 69.98 0.44 0.801Minor Thalassemia 45.11 64.87 control 50.69 69.16 TPe / QTC Iron defi ciency 105.31 61.54 < 0.001 75.33 2.76 0.251Minor Thalassemia 47.91 66.91 control 50.78 61.76 TIBC – Total Iron Binding Capacity, P-wave – duration from the beginning to the end of the P-wave, P wave d – maximum P-wave duration– minimum P-wave duration, QT interval – started from the onset of the Q wave to the end of the T wave, QTc – was calculated using Bazett’s formula ,QTd – Diff erence between the longest and shortest QT intervals ,QTCd – maximum QTc interval–minimum QTc interval, Tpe interval – measured from the peak of the T wave (highest point) to the end of the T wave, Tped – maximum Tpe interval–minimum Tpe interval N. M. Noori, G. M. Aliabad, T. Boryri, A. Teimouri 86 Table 2. Pairwise Comparisons of Hematological and Electrocardiographic Parameters Between Iron Defi ciency Anemia, Minor Thalassemia, and Control Groups Before and After Treatment Using Dunn’s Post Hoc Test Variables Sample1-Sample2 Dunn Statistics p value Adj. p value Before treatments Hemoglobin IDA-MT 29.556 < 0.001 0.001 IDA-Control 81.611 < 0.001 < 0.001 MT-Control 52.056 < 0.001 < 0.001 Ferritin IDA-MT 71.800 < 0.001 < 0.001 IDA-Control 63.200 < 0.001 < 0.001 MT-Control 8.600 0.297 0.890 Serum Iron IDA-MT 74.67 < 0.001 < 0.001 IDA-Control 60.667 <0.001 < 0.001 MT-Control 13.400 0.104 0.312 TIBC IDA-MT 61.778 < 0.001 < 0.001 IDA-Control 63.089 < 0.001 < 0.001 MT-Control 1.311 0.874 1.00 PWAVE IDA-MT 36.422 < 0.001 < 0.001 IDA-Control 41.378 < 0.001 < 0.001 MT-Control 4.956 0.548 1.00 PDIS IDA-MT 64.100 < 0.001 < 0.001 IDA-Control 57.467 < 0.001 < 0.001 MT-Control 6.633 0.421 1.00 QTC IDA-MT 59.267 < 0.001 < 0.001 IDA-Control 58.067 < 0.001 < 0.001 MT-Control 1.200 0.884 1.00 QTcd IDA-MT 61.778 < 0.001 < 0.001 IDA-Control 71.489 < 0.001 < 0.001 MT-Control 9.711 0.238 0.716 Tpe IDA-MT 62.522 < 0.001 < 0.001 IDA-Control 63.711 < 0.001 < 0.001 MT-Control 1.189 0.885 1.00 Tped IDA-MT 63.089 < 0.001 < 0.001 IDA-Control 57.511 < 0.001 < 0.001 MT-Control 5.578 0.499 1.00 TPe / QTc IDA-MT 57.166 < 0.001 < 0.001 IDA-Control 54.378 < 0.001 < 0.001 MT-Control 2.778 0.736 1.00 After Treatments HB IDA-MT 10.467 0.203 0.609 IDA-Control 54.133 < 0.001 < 0.001 MT-Control 43.667 < 0.001 < 0.001 Ferritin IDA-MT 34.711 < 0.001 < 0.001 IDA-Control 20.889 0.011 0.034 MT-Control 12.822 0.094 0.281 Serum Iron IDA-MT 57.756 < 0.001 < 0.001 IDA-Control 44.978 < 0.001 < 0.001 MT-Control 12.778 0.121 0.364 TIBC – Total Iron Binding Capacity, P-wave – duration from the beginning to the end of the P-wave , P wave d – maximum P-wave duration– minimum P-wave duration, QT interval – started from the onset of the Q wave to the end of the T wave, QTc – was calculated using Bazett’s formula ,QTd – Diff erence between the longest and shortest QT intervals ,QTCd – maximum QTc interval–minimum QTc interval, Tpe interval – measured from the peak of the T wave (highest point) to the end of the T wave, Tped – maximum Tpe interval – minimum Tpe interval 87 The eff ect of therapy on electrocardiography parameters... Table 3. Thalassemia: A Wilcoxon Signed-Rank Analysis Variables changes Iron Defi ciency Anemia Major thalassemia NZPNZ P HB Negative 0 -6.09 < 0.001 10 -4.399 < 0.001Positive 39 35 Ties 6 0 Ferritin Negative 0 -6.56 < 0.001 0 -5.841 < 0.001Positive 45 45 Ties 0 0 Serum Iron Negative 0 -6.56 < 0.001 0 -5.842 < 0.001Positive 45 45 Ties 0 0 TIBC Negative 44 -6.26 < 0.001 0 -5.841 < 0.001Positive 1 45 Ties 0 0 PWAVE Negative 33 -3.17 0.002 20 -0.863 0.388Positive 11 18 Ties 1 7 PDIS Negative 41 -5.37 < 0.001 28 -0.073 0.942Positive 4 17 Ties 0 0 QTC Negative 45 -6.56 < 0.001 15 -1.884 0.060Positive 0 10 Ties 0 20 QTcd Negative 45 -6.56 < 0.001 20 -1.867 0.062Positive 0 15 Ties 0 10 TPe Negative 45 -6.56 < 0.001 2 -0.271 0.786Positive 0 3 Ties 0 40 Tped Negative 42 -5.66 < 0.001 21 -0.231 0.817Positive 3 24 Ties 0 0 TPe./ QTc Negative 45 -6.56 < 0.001 11 -1.706 0.088Positive 0 16 Ties 0 18 TIBC – Total Iron Binding Capacity, P-wave – duration from the beginning to the end of the P-wave, P wave d – maximum P-wave duration– minimum P-wave duration, QT interval – started from the onset of the Q wave to the end of the T wave, QTc – was calculated using Bazett’s formula ,QTd – Diff erence between the longest and shortest QT intervals ,QTCd – maximum QTc interval – minimum QTc interval, Tpe interval – measured from the peak of the T wave (highest point) to the end of the T wave, Tped – maximum Tpe interval–minimum Tpe interval D The study explored electrocardiographic (ECG) alterations in children with iron defi ciency anemia (IDA) and thalassemia minor (MT) compared to healthy controls, assessing changes before and after treatment. Signifi cant diff erences were observed in both hematological and ECG parameters, especially among untreated IDA patients, highlighting the broader cardiovascular eff ects of anemia. IDA, the most prevalent nutritional defi ciency globally, can cause myocardial hypoxia and altered ventricular repolarization, which may normalize after Iron supplementation [11]. In contrast, MT, a genetic condition, typically presents with milder and less reversible ECG changes managed through regular monitoring and folic acid supplementation. Previous studies have shown that parameters like P wave dispersion, QTd, and Tpe interval can serve as predictors of atrial and ventricular arrhythmias in anemic patients, linking anemia severity to electrical instability of the heart [10, 12]. In children, Iron defi ciency impairs hemoglobin synthesis, leading to systemic hypoxia. This hypoxia exerts stress on the cardiovascular system, manifest- N. M. Noori, G. M. Aliabad, T. Boryri, A. Teimouri 88 ing through sympathetic nervous system activation, increased cardiac output, and subsequent electrophysiological alterations detectable on ECG [13, 14]. Patil et al. [15], and Kumar et al. [10] emphasized that hypoxia from chronic anemia enhances sympathetic drive, which can lead to changes in ventricular repolarization such as QT prolongation, T-wave inversion, and reduced QRS voltage. Our study corroborated these physiological mechanisms. Children with untreated IDA demonstrated statistically signifi cant prolongation of the QTc interval, QTcd, and Tpe, as well as increased Tpe/QTc ratio and P wave dispersion (PDIS). These parameters refl ect increased heterogeneity in atrial and ventricular repolarization and are known to predict a higher risk of arrhythmias. Kumar et al. [10] similarly reported that lower hemoglobin levels were associated with more pronounced ECG changes, particularly in patients with cardiomegaly or increased cardiothoracic ratios. The association between systemic hypoxia and repolarization heterogeneity highlights the potential arrhythmogenic risk in pediatric IDA, even in the absence of overt cardiac pathology. Biochemically, our IDA cohort exhibited signifi cantly reduced levels of hemoglobin, ferritin, and serum Iron, alongside elevated TIBC, consistent with a classic profi le of Iron depletion. Bouri et al. [16] highlighted TIBC as a sensitive marker refl ecting the body’s attempt to enhance Iron transport under defi cient states, thereby reconfi rming our fi ndings. Importantly, our post-treatment analysis revealed notable improvements in both hematological and ECG parameters in the IDA group. In this regard, QTc and QTcd values normalized signifi - cantly, as did indices like Tpe and Tpe/QTc ratio. These results support the reversibility of electrophysiological alterations following Iron repletion. Savarese et al. [17], Singer et al. [18], and Moscheo et al. [13] have all emphasized that correction of Iron defi ciency not only restores hematologic values but also stabilizes myocardial electrophysiology. Notably, Findikli and Tutak [19] and Kwon et al. [20] observed that children with the lowest baseline ferritin and hemoglobin levels exhibited the most signifi cant ECG abnormalities and demonstrated the most marked improvements following Iron therapy. These fi ndings align closely with our observations and suggest that early detection and prompt treatment are crucial in preventing potential long-term cardiac remodeling. Furthermore, our fi ndings reinforce the argument by Triphaus et al. [21] who stressed that maintaining adequate hemoglobin levels is essential for optimal myocardial oxygenation and electrical stability. The improvement seen in dispersion indices following treatment underscores the value of integrating cardiovascular monitoring in the routine care of pediatric IDA patients. Falahati et al. [22] also advocated for the use of bioavailable Iron formulations like ferrous gluconate to accelerate recovery, which is relevant in the context of clinical decision-making regarding Iron supplementation. Thalassemia minor, characterized by chronic microcytic hypochromic anemia due to defective β-globin synthesis, is generally considered a clinically benign condition [23]. Our study supports this understanding, showing that although hemoglobin levels were signifi cantly lower in thalassemia minor children compared to healthy controls, serum Iron, ferritin, and TIBC did not diff er signifi - cantly, indicating that anemia in thalassemia minor is genetically mediated rather than driven by Iron defi ciency [24]. Correspondingly, pre-treatment ECG parameters including QTc, QTcd, Tpe, Tped, and PDIS showed no signifi cant diff erences between MT patients and healthy controls, suggesting no increased risk of repolarization abnormalities or arrhythmogenicity in this population. Kolios et al. [25] conducted a study on the EKG abnormalities and arrhythmic risk markers in adult patients with beta thalassemia major and found that the majority of patients, had prolonged QT and QTc intervals, as well as increased QTd and QTcd despite the absence of overt systolic dysfunction. Akarsu et al. [26] reported that MT patients exhibited electrocardiographic changes similar to those in IDA, especially in QT and QTc intervals, despite normal Iron levels. This suggests that factors beyond Iron defi ciency, such as genetic or structural infl uences, may aff ect cardiac repolarization in MT. Elevated QT dispersion in MT further indicates subtle ventricular repolarization disturbances, even in clinically mild anemia, challenging the notion that MT is entirely electrophysiologically benign and implying that cardiac monitoring might be warranted in some cases. Similarly, Karadeniz et al. [9] reported that otherwise healthy children with low serum ferritin (<15 ng/mL) showed signifi cantly increased P wave duration, QT and Tpe intervals, as well as increased dispersions of PW, QT, QTc, and Tpe compared to children with higher ferritin levels. These fi ndings underscore that low Iron stores, even without overt anemia, are associated with changes in ECG parameters that refl ect ventricular repolarization heterogeneity and may increase arrhythmia risk. Given these distinctions, routine ECG screening appears particularly important in children with IDA especially in moderate to severe cases or when treatment is delayed while in children with thalassemia trait, cardiovascular surveillance may be best reserved for those with additional risk factors or clinical symptoms. Future studies with larger cohorts and extended follow-up are needed to clarify any potential long-term cardiac risks associated with Beta Thalassemia Trait and to investigate the infl uence of specifi c genetic variants on cardiac outcomes. S  The main limitation of this study was the relatively small sample size, which may have limited the ability to