CHD (congenital heart disease) is one of the most commonly occurring congenital anomalies seen across the globe that results in nearly 28% of all the existing and reported congenital birth defects. The prevalence of congenital heart disease Worldwide is nearly in the range of 8-12 every 1000 live birth. Congenital heart diseases are conventionally divided into cyanotic and acyanotic lesions depending on the absence or presence of systemic hypoxemia and cyanotic congenital heart diseases constitute to nearly 20% of all cases of congenital heart disease cases. Cyanotic congenital heart disease constitutes a diverse range of defects including truncus arteriosus, tricuspid atresia, transposition of the great arteries (TGA), and Tetralogy of Fallot (TOF). Among these, Teratology of Fallot is the most common factor that result in >50% of cyanotic lesions. Children that have CCHD usually remain un diagnosed and unmanaged for long time in developing nations as India owing to infrastructural and economic barriers.¹   

These affected child subjects usually lead to chronic hypoxic state that pose complex systemic effects especially on nutritional status and hematologic physiology. Chronic hypoxia in subjects with CCHD stimulate production of erythropoietin by kidneys resulting in secondary erythrocytosis. The compensatory raise in mass of red cells aim to increase the oxygen-carrying capacity, however, it is dependent on the sufficient iron availability. This result in high iron demand that could exhaust iron stores in cases of malabsorption or poor dietary intake resulting in iron deficiency. However, this deficiency is usually masked owing to hematocrit (Hct), hemoglobin (Hb), and other erythrocytic indices that are considered as markers of excessive or adequate iron status. This result in blind diagnosis where child subjects at risk of developing iron deficiency anemia remain undiagnosed.²

Most common nutritional deficiency seen globally is iron deficiency and has shown to have high prevalence in the developing nations. In India, anemia prevalence, in child subjects aged 6 months to 5 years is considered as high with 55% and main cause attributed is iron deficiency. In CCHD, deficiency can exaggerate clinical symptoms and raise complications risk as cerebrovascular accidents, metabolic acidosis, cyanotic spells, and hyperviscosity syndrome. However, iron deficiency remains undiagnosed in child subjects with CCHD owing to raised values of mean corpuscular volume (MCV), Hct, HB, and other erythrocyte indices using traditional anemia screening. Transferrin saturation, total iron-binding capacity (TIBC), serum iron, and serum ferritin are more adequate indicators, however, these are not utilized in routine.³

The prevalence of iron deficiency in child subjects with CCHD shows high variation across the globe with reported incidence of 18-72% based on the assessed population and the use of the diagnostic criteria. However, existing literature data is scarce in Indian scenario concerning assessment of iron status utilizing the standard serum biomarkers in child subjects with unrepaired CCHD.⁴ Hence, the present study was aimed to assess the iron deficiency and serum iron parameters in pediatric subjects with cyanotic congenital heart disease.

The present cross-sectional clinical study was aimed to assess the iron deficiency and serum iron parameters in pediatric subjects with cyanotic congenital heart disease. The study was done at Department of Paediatrics, Gian Sagar Hospital & Medical College, Jhansla, Punjab. Verbal and written informed consent were taken from all the subjects before study participation.

The present study assessed 254 child subjects in the age range of 6 months to 18 years that had unrepaired CCHD (Cyanotic congenital heart disease) and visited the Institute within the defined study period. The study assessed subjects that had a confirmed diagnosis of unrepaired CCHD or the subjects that had underwent palliative procedures as Bidirectional Glenn shunts and Blalock-Taussig. The exclusion criteria for the study were subjects on iron supplements, repeated phlebotomy within the last 3 months, blood transfusion, partial exchange transfusion, history of surgical repair for CCHD, antacids, H2-receptor antagonists, and receiving long-term therapy with proton pump inhibitors (PPIs).

Confirmation of CCHD was done using Chest X-ray, ECG, and echocardiography. Routine investigations were done using iron profile (serum iron, serum ferritin), renal function tests (RFT), liver function tests (LFT), and complete blood count (CBC). Anthropometric data were also collected including mid-upper arm circumference, length, height, and weight utilizing WHO (World Health Organization) growth charts for classification of malnutrition.

Caloric and protein intake was assessed using a 24-hours dietary recall and deficits were categorized as low with <20% and high for >20%. Socioeconomic status was assessed utilizing the Modified Kuppuswamy Scale and cyanotic spells frequency was assessed. Iron deficiency anemia was diagnosed following WHO criteria. At baseline, demographic data, physical examination, and clinical history was recorded in a preformed structured proforma. Predictors of iron deficiency anemia were also assessed.

Statistical Analysis was performed for the study data collected from child subjects using the chi-square test, Fisher’s exact test, Mann Whitney U test, and SPSS (Statistical Package for the Social Sciences) software version 24.0 (IBM Corp., Armonk. NY, USA) using ANOVA, chi-square test, and student's t-test. The significance level was considered at a p-value of <0.05.

The present cross-sectional clinical study was aimed to assess the iron deficiency and serum iron parameters in pediatric subjects with cyanotic congenital heart disease. The present study assessed 254 child subjects in the age range of 6 months to 18 years that had unrepaired CCHD (Cyanotic congenital heart disease) and visited the Institute within the defined study period. In all subjects, erythrocyte indices, total blood count, serum ferritin, and serum iron levels were evaluated along with sociodemographic, anthropometric, and nutritional data. Comparison was done in various erythrocytic indices in iron-deficient and non-deficient subjects.

The mean age of the study subjects was 5.4±4.5 years. There were 41% (n=104) female and 59% (n=150) males in the study. There were 2.4% (n=6), 55% (n=140), 35% (n=88), and 8% (n=20) subjects from upper middle, upper lower, lower middle and lower socioeconomic status. There were 33% (n=84) educated and 67% (n=170) uneducated parents. For nutritional deficiency, mean protein and iron deficiency was 17.3±8.1 and 26.6±11.0 respectively. For HAZ, majority subjects had<-3 SD with 61% (n=154) followed by -2 to -3 SD in 29% (n=74) subjects. For WAZ, normal, -2 to -3 SD, and <-3 SD scores were seen in 15% (n=38), 43% (n=110), and 42% (n=106) subjects respectively (Table 1).

It was seen that for comparison of hematological indices in iron deficient and non-deficient study subjects, MCHC in iron deficient subjects was 28.2±3.9 and was 28.7±3.9 in non-deficient subjects which showed a non-significant difference with p=0.46. Similar non-significant difference was seen for MCH, MCV, hematocrit, and hemoglobin among iron deficient and non-deficient subjects with p=0.47, 0.24, 0.84, and 0.97 respectively (Table 2).

The study results showed that for association between nutrition predictors of iron deficiency and demographic data, a non-significant association was seen in iron deficiency anemia and age ≤5 years with p=0.57. Similar non-significant association was seen in iron deficiency anemia to low socioeconomic status, male gender, high protein diet, high calorie diet, stunting (HAZ), and undernutrition (WAZ) with the respective p-values of 0.51, 0.55, 0.35, 0.51, 0.27, and 0.25 (Table 3).

Table 1: Demographic and disease data in study subjects at baseline

Table 2: Comparison of hematological indices in iron deficient and non-deficient study subjects

Table 3: Association between nutrition predictors of iron deficiency and demographic data

The present study assessed 254 child subjects in the age range of 6 months to 18 years that had unrepaired CCHD (Cyanotic congenital heart disease) and visited the Institute within the defined study period. In all subjects, erythrocyte indices, total blood count, serum ferritin, and serum iron levels were evaluated along with sociodemographic, anthropometric, and nutritional data. Comparison was done in various erythrocytic indices in iron-deficient and non-deficient subjects. The study design was comparable to the previous studies by Agarwal S et al⁵ in 2025 and Shebl SS et al⁶ in 2018 where study design comparable to the present study were also reported by the authors in their studies.

For demographics, the mean age of the study subjects was 5.4±4.5 years. There were 41% (n=104) female and 59% (n=150) males in the study. There were 2.4% (n=6), 55% (n=140), 35% (n=88), and 8% (n=20) subjects from upper middle, upper lower, lower middle and lower socioeconomic status. There were 33% (n=84) educated and 67% (n=170) uneducated parents. For nutritional deficiency, mean protein and iron deficiency was 17.3±8.1 and 26.6±11.0 respectively. For HAZ, majority subjects had<-3 SD with 61% (n=154) followed by -2 to -3 SD in 29% (n=74) subjects. For WAZ, normal, -2 to -3 SD, and <-3 SD scores were seen in 15% (n=38), 43% (n=110), and 42% (n=106) subjects respectively. These results were consistent with the findings of González R et al⁷ in 2019 and Mohammed SH et al⁸ in 2019 where authors assessed subjects with demographic data in their studies as in the present study.

The study results showed that for comparison of hematological indices in iron deficient and non-deficient study subjects, MCHC in iron deficient subjects was 28.2±3.9 and was 28.7±3.9 in non-deficient subjects which showed a non-significant difference with p=0.46. Similar non-significant difference was seen for MCH, MCV, hematocrit, and hemoglobin among iron deficient and non-deficient subjects with p=0.47, 0.24, 0.84, and 0.97 respectively. These findings were in agreement with the results of Chinawa AT et al⁹ in 2021 and Hassan BA et al¹⁰ in 2015 where results for comparison of hematological indices in iron deficient and non-deficient subjects comparable to the present study was also reported by the authors.

It was seen that for association between nutrition predictors of iron deficiency and demographic data, a non-significant association was seen in iron deficiency anemia and age ≤5 years with p=0.57. Similar non-significant association was seen in iron deficiency anemia to low socioeconomic status, male gender, high protein diet, high calorie diet, stunting (HAZ), and undernutrition (WAZ) with the respective p-values of 0.51, 0.55, 0.35, 0.51, 0.27, and 0.25. These results were in line with the findings of Poventud-Fuentes I et al¹¹ in 2024 and Cheng W et al¹² in 2024 where results reported by the authors for association between nutrition predictors of iron deficiency and demographic data were comparable to the results of the present study.

Considering its limitations, the present study concludes that iron deficiency is seen in significant proportion of subjects that have Cyanotic congenital heart disease. However, no difference exists in erythrocytic parameters and clinical predictors of iron deficiency in subjects with and without iron deficiency which highlights the need for routine assessment of the iron status in subjects with CCHD.

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