Cyanotic Congenital Heart Disease_Effects of Iron Supplementation on Hematological Indices in Iron-Sufficient and Iron-Deficient Children

Abstract

Background: 

Cyanotic congenital heart disease (CCHD) children often have malnutrition and iron-deficiency anemia along with poor weight gain. Low arterial oxygen saturation due to CCHD affects hematological indices.

Objective: 

The objective of the study is to find iron status and hematological indices in children having CCHD and to study the impact of iron therapy in the sample population under study.

Materials and Methods: 

This hospital-based, prospective, cross-sectional, observational type of study evaluated 50 CCHD children aged more than 1 year with informed written consent from the parents. Sample size is calculated at 95% confidence level and alpha error 4.005 assuming 52.2% iron deficiency in patient with CCHD with hematocrit value <60%.

Results: 

Tetralogy of Fallot was the most common CCHD followed by transposition of great arteries and tricuspid atresia. Most common age of presentation is <50 months with cyanosis (50%) and congestive cardiac failure (16%) with male preponderance (M:F = 3:1). 60% CCHD patients were iron deficient. Iron-deficient group shows significant improvement in all hematological parameters after iron supplementation compared with iron-sufficient group.

Results and Discussions: 

Serum iron levels, serum ferritin levels, mean hemoglobin levels, total red blood cell count, hematocrit, and red cell distribution width along with red cell indices (mean corpuscular volume, mean corpuscular hemoglobin, and MCHC) should be used as diagnostic tool for the evaluation of iron status in patients as well as for monitoring improvement. This emphasizes that iron therapy iron must be supplemented with special focus on iron status of children.

INTRODUCTION

Congenital Heart Diseases (CHD) are structural or functional heart diseases which present since birth. The worldwide reported incidence of CHD is 8–10/1000 live births. In India, the prevalence of CHD is high due to high birth rate.[¹²] CHD contributes in approximately 10% of present infant mortality in India.[³]

Poor nutritional status in children with CHD may be due to genetic predisposition, prenatal factors, increased metabolic demands in the presence of heart failure, poor oxygenation and reduced availability, intake and absorption of nutrients.[³] Malnutrition is a major burden among children in developing countries due to prevailing food insecurity, poverty, large family size, ignorance, and prevalent preventable infectious diseases.[⁴] Iron deficiency is an important problem in patients with cyanotic congenital heart disease (CCHD).[⁵] In CCHD, arterial oxygen saturation decreases and red blood cell (RBC) count may reach to high level and hyperviscosity develops resulting in compensatory increase in hemoglobin and hematocrit levels.[⁶] Iron deficiency causes discrepant values for arterial oxygen saturation and hemoglobin/hematocrit and that “normal” hemoglobin/hematocrit levels in such children may constitute anemia.[⁷⁸]

In CCHD, normal hemoglobin represents relative anemia and physiological nadir of hemoglobin is impaired if there is marked arterial desaturation since birth, although relative anemia in this situation develops by the 3^rd or 4^th month of life. The consequences of iron-deficiency anemia in cyanotic heart disease are metabolic acidosis, cyanotic attacks, high RBC counts increase blood viscosity, and tendency to cerebrovascular accidents. When the hematocrit is above 60%, further small increases produce large increments in viscosity.[⁹¹⁰] At a hematocrit level of 70%, blood viscosity is so high that fluidity in small vessel becomes critical.

Pediatric cardiac programs are not fully established in India and lot of children have unoperated congenital heart defect. The epidemiological data on CHD-related malnutrition and associated micronutrient deficiency are lacking. Therefore, this study aimed to assess hematological indices in children with CCHD and to see the impact of iron therapy on children who are having iron deficiency or iron sufficiency.

MATERIALS AND METHODS

This hospital-based, prospective, cross-sectional, observational type of study aimed to assess iron status and hematological indices in children having cyanotic CHD and the impact of iron therapy in the sample population under study was conducted by department of pediatrics S.M.S medical college Jaipur, Rajasthan, after getting the requisite clearance from the Institute Research Review Board. Informed written consent was taken from the parents. Children having cyanotic CHD aged more than 1 year were included in the study as hemodynamic deterioration is expected in this generally low-weight population. Patient/parents with negative consent and those with some known chronic disease such as asthma, chronic kidney disease, known genetic syndrome, and in critically ill state were excluded from the study. Sample size is calculated at 95% confidence level and alpha error 4.005 assuming 52.2% iron deficiency in patient with CCHD with hematocrit value <60%. At 16% absolute allowable error in the occurrence of iron deficiency, required sample size was 39, considering up to 20% dropout in the study, 50 CCHD patients were enrolled in the study.

RESULTS

Age-wise distribution – 37 children with tetralogy of Fallot (TOF) (74%), 12 children with transposition of great arteries (TGA) (24%), and 1 child with tricuspid atresia (2%) were studied. Forty one (82%) of cyanotic CHD patients were <50 months old and 9 (18%) were >50 months old. Twenty-three (46%) males and 14 (28%) females had TOF, 10 (20%) males and 2 (4%) females had TGA, and 1 male (2%) and 1 female (2%) had tricuspid atresia.

Presenting features – above 50 children were divided into 2 groups on the basis of serum ferritin levels. Thirty children having serum ferritin level below 10 ng/ml were considered iron deficient and 20 with >10 ng/ml levels were considered iron sufficient; 40% were in iron-sufficient group and 60% were in iron-deficient group. In iron-deficient group, 15 patients out of 30 presented with cyanosis and 10 patients out of 20 in iron-sufficient group presented with cyanosis. Seven patients in iron-deficient group had congestive heart failure and one patient in iron-sufficient group had CHF.

In iron-deficient group, 24 children out of 30 (19 males and 11 females) were below 50 months of age and in iron-sufficient group, 17 children out of 20 (14 males and 6 females) were below 50 months of age. Hematological profile – baseline hematological parameters in the study population in both groups before iron supplementation are depicted in Table 1. The baseline hematological parameters were compared between iron-sufficient and iron-deficient group. Among iron-deficient group, mean hemoglobin levels (15.78 ± 1.52) g/dl, total RBC (TRBC) count (5.59 ± 0.93) per cubic mm, hematocrit % (50.87 ± 3.88), red cell distribution width (RDW), mean corpuscular volume (MCV) (66.93 ± 3.29) fL, mean corpuscular hemoglobin (MCH) (28.57 ± 4.30) pg, and MCH concentration was (33.33 ± 5.84) g/dl.

Table 1: Baseline hematological parameters in the study population

Pretreatment mean hemoglobin in iron-sufficient group was 15.78 ± 1.52 g/dl which improved to a mean level of 15.98 g/dl after 1 month of iron supplementation. The mean hemoglobin levels of 13.70 g/dl in iron-deficient group improved to 15.20 after 1 month of iron therapy. Comparisons of hemoglobin levels in iron-sufficient group and iron-deficient group before and after iron therapy in CCHD patients revealed that Hb levels showed statistically significance improvement in iron-deficient group. Mean hematocrit levels were compared in both iron-deficient and sufficient groups and showed marked increase after 1 month of iron therapy in iron-deficient group with P < 0.001.

Pretreatment mean TRBC values among iron-sufficient group and iron-deficient group were 5.90 ± 1.05 million/cumm and 5.59 ± 0.09 million/cumm, respectively. After 1 month of iron therapy, mean TRBC values among iron-sufficient and iron-deficient groups were 6.53 ± 0.88 million/cumm and 6.31 ± 1.09 million/cumm, respectively; improvement in TRBC was significant in iron-deficient group (P = 0.008).

Pretreatment RDW% in iron-sufficient and iron-deficient group was 16.60% ± 2.60% and 15.77% ± 1.52%, respectively. After the 1 month of iron therapy, mean value of RDW% increased 17.65% ± 2.98% in iron-sufficient group and to 17.31% ± 2.76% in iron-deficient group which was statically significant (P = 0.009). MCV was compared before and after iron therapy in cyanotic CHD patient in above table. After 1 month of iron therapy, MCV increased significantly in iron-deficient group with P = 0.02. MCH levels were low in both iron-deficient and sufficient group. After iron therapy, MCH improved markedly in iron-deficient group than iron-sufficient group with P = 0.042.

MCH values were lower in iron-deficient group than iron-sufficient group before iron therapy with mean values of 35.95 g/dl in iron-sufficient group and 33.33 g/dl in iron-deficient group, respectively. With iron treatment, MCHC levels became equal in both groups (36.95 g/dl and 36.87 g/dl, respectively) with significant change in iron-deficient group due to more effect of iron therapy on MCHC levels in iron-deficient group.

(Mean Total platelet counts with a mean value of 241.80 × 10³/cumm) in iron-sufficient group were recorded as 243.60 × 10³/cumm after 1-month therapy. The values for iron-deficient group were 227.77 × 10³/cumm before and 269.87 × 10³/cumm, respectively.

Toatal leucocyte counts (TLC) values in iron-sufficient and iron-deficient groups were 7.72 ± 1.28 × 10³/cumm and 7.75 ± 1.52 × 10³/cumm, respectively. After 1 month of iron therapy, mean TLC values increased to 8.22 ± 1.38 × 10³/cumm in iron-sufficient group and to 8.92 ± 2.09 × 10³/cumm in iron-deficient group showing significant improvement in TLC counts in iron-deficient group.

Pretreatment iron levels in iron-sufficient and deficient group were 30.85 ± 4.31 and 30.50 ± 4.18 ug/dl, respectively. After 1 month of iron therapy, mean iron levels in iron-sufficient and deficient group were 31.55 ± 3.86 ug/dl and 33.13 ± 3.82 ug/dl, respectively, showing significant improvement in iron levels after iron therapy in iron-deficient group [Table 2].

Table 2: Iron status in iron-sufficient and deficient groups 1 month after iron therapy

Comparison of serum ferritin levels before and after iron therapy in iron-sufficient group suggested [Figure 1-Bar Graph] serum ferritin levels of 45.25 ng/dl in iron-sufficient group which after 1-month iron supplementation were 46.55 ng/dl with P = 0.777 and statistically nonsignificant. Serum ferritin levels improved markedly in iron-deficient group from baseline value of 7.90 ng/dl to 8.53 ng/dl with P = 1.22 and statistically significant and improving colinearly with serum iron levels (P = 0.02).

Figure 1: Bar graph effect of iron therapy on serum ferritin levels

DISCUSSION

CHD is a common entity in our country. The prevalence of CHD is 9.3/1,000 life birth in Asia which is found to be highest globally.[¹⁰] Male preponderance is noted in our study and male-to-female ratio was 3:1. Most of the studies had shown male preponderance in CHDs. Studies of Kumar et al.[¹⁰] and Hussain et al.[¹¹] also found M: F ratio as 2.08:1 and 1.78:1, respectively. Gender discrepancy is quite striking and might be because of early reporting of male progeny by the parents.

In our study, TOF was most common cyanotic CHD followed by TGA and tricuspid atresia. Hussain et al. and Khan found that infants constituted 64.10% and 71.00%, respectively, of all CHDs.[¹¹] It also documented age-wise distribution of CCHD in individual CCHD conditions. Among 37 of TOF patients, 78% were <50 months and 22% were more than 50 months. Ninety-one percent of TGA seen in the study were <50 months of age. One female patient of tricuspid atresia included in study was <50 months old. A prospective study done by Sharmin[¹²] reported 18% cases of TOF, which was comparatively lesser to our study. Occurrence of TGA as low as 0.6% in study done by Smitha et al.[¹³] to as high as 6% in a study by Sharmin. The disparity in incidence may be because of small sample size of our study.

Age group <50 months (82%) presented early with remaining 18% presenting after 50 months. This might be attributed to early presentation of CCHD because of cyanosis and complication such as congestive heart failure, edema, and failure to thrive leading to early diagnosis.[⁵¹⁴] The common clinical presentations of CCHD were cyanosis, failure to thrive, congestive cardiac failure, difficulty in breathing, feeding difficulty, and edema.[¹⁴¹⁵] The incidence of iron deficiency in CCHD patients in the study was 60%. The results are comparable with Olcay study in which 67 children with cyanotic CHD were studied. Patient with hematocrit <60% was considered as iron deficient, and prevalence of iron deficiency in the study was 52.2%.[¹⁶] The results of our study confirm previously published data, which demonstrated that iron deficiency is more common in young patients with CCHD.[¹⁶¹⁷] High incidence of iron deficiency among children with CCHD draws attention to the evaluation of iron deficiency in this population. We evaluated the incidence of iron deficiency in CCHD and compared various hematological parameters among iron-deficient and sufficient groups in the study population. Iron deficiency was evaluated by serum ferritin levels.[¹⁸¹⁹] This may be beneficial for the purpose of formulating guidelines in reference to supplementation of iron in these children.

Olcay studied a group of 67 children with CCHD whose hematocrit was <60%, the prevalence of iron deficiency was 52.2%. Out of this, iron treatment was given to 35 patients who had MCV <60 by 6 mg/kg/day. Posttreatment MCV, MCH, and MCHC values had significant correlation with iron therapy. In this study, cutoff values of RBC, Hb, Hct, RDW of 6 × 10¹²/L, 16.5 g/dl, 50%, 16%, respectively, were of acceptable sensitivity and MCV of 80fL was of good specificity.[¹⁶] Our study in support of other studies[¹⁶²⁰²¹] concluded that hemoglobin (Hb), hematocrit (Hct), MCH, and RBC count are useful measurements for diagnosis of iron-deficiency anemia in children with cyanotic CHD with values depicted in our study taking as cutoff.

To determine effect of iron on hematological parameters, iron was supplemented to study population in the study for 1 month, and results were evaluated both among iron-deficient and iron-sufficient group. Increment in MCV, MCH, and MCHC values in our study showed significant increase of the above parameters in iron-deficient group than the iron-sufficient one – suggesting that the iron-deficient group made better use of the treatment than did the iron-sufficient group. This study demonstrates that hemoglobin, hematocrit, RBC count, RDW, and red cell indices measurement are not only easy but also less expensive test that requires 2–3 ml of blood and when combined, they suffice for diagnosis of iron deficiency in CCHD patients and also for response of iron therapy. Iron supplementation in iron-sufficient group did not show any satisfactory significant improvement, therefore, iron must be supplemented with special focus on iron status of children. Soni et al.(2018) study shows similar results. Mean Hb levels, hematocrit levels, RDW%, total RBC, MCH, and MCHC values were increased in iron-deficient group which significantly improve with iron as suggest in study.[¹⁶¹⁸²¹]

Along with other parameters, total leukocyte count also improved more in iron-deficient group. No other study supports above finding. Above findings reveal improvement in serum iron levels, serum ferritin levels, mean hemoglobin levels, hematocrit, and RDW both among iron-deficient and sufficient group, but statistically significant improvement was seen in iron-deficient group.[⁸¹⁸]

CONCLUSIONS

The findings in our study narrate about sample population under study only; larger sample size may be studied for more precise results. Cyanotic CHD is common pediatric cardiac conditions encountered in day-to-day practice. High incidence of iron deficiency among children with CCHD draws attention to the evaluation of iron deficiency in this population. Serum iron levels, serum ferritin levels, mean hemoglobin levels, TRBC count, hematocrit, and RDW along with red cell indices (MCV, MCH, and MCHC) fairly evaluate iron deficiency in CCHD patients and therefore should be used as diagnostic tool for the evaluation of iron status in patients as well as for monitoring improvement. Iron-deficient group shows significant improvement in all hematological parameters after iron supplementation compared with iron-sufficient group. This emphasizes that iron therapy iron must be supplemented with special focus on iron status of children. Iron profile of children with CCHD alone is a good parameter to assess response to therapy before and after iron supplementation. Hemoglobin, hematocrit, and total red cell count done as CBCs is simple and feasible test to depict iron-deficiency status and effect of iron therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.