MJAFI-887; No.

of Pages 6

medical journal armed forces india xxx (2017) xxx–xxx

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Original Article

Iron deficiency anemia in children with cyanotic

congenital heart disease and effect on cyanotic
spells

Maj Sweta Mukherjee a,*, Maj Gen Mukti Sharma b, Col Amit Devgan c,
Brig S.K. Jatana, (Retd)d
a
Graded Specialist (Paediatrics), Command Hospital (Eastern Command), Kolkata, India
b
MG Med, HQ Western Command, India
c
Associate Professor (Paediatrics), Armed Forces Medical College, Pune 40, India
d
Professor (Pediatrics), Melaka Manipal Medical College, Malaysia

article info abstract

Article history: Background: Iron deficiency anemia (IDA) in cyanotic congenital heart disease (CCHD) and its
Received 1 July 2016 association with cyanotic spells has been documented in literature. However, Indian data
Accepted 8 July 2017 especially in the pediatric age group is scarce. This study was conducted to find out the
Available online xxx prevalence of IDA in this population.
Methods: An observational study was conducted in a tertiary care hospital. Children with
Keywords: CCHD in the age group of birth–12 years were included in the study. Hematological
Iron deficiency anemia parameters of these patients were determined and compared. An assessment of the
Cyanotic spells incidence of cyanotic spells in the iron-deficient and iron non-deficient children was also
Cyanotic congenital heart disease done. Data analysis was done using Fischer's exact test.
Results: The prevalence of IDA was 47.06% in the study population. The study also showed
that hemoglobin and hematocrit levels were paradoxically higher in the iron-deficient group
as compared to the non-deficient, though the iron studies revealed the iron deficiency. The
incidence of cyanotic spells was higher in the iron-deficient group. The mean corpuscular
volume (MCV), red cell distribution width (RDW), serum ferritin, serum iron, total iron
binding capacity (TIBC), and transferrin saturation (TS) values were the parameters, which
were found to be statistically significant to differentiate the study groups.
Conclusion: The prevalence of IDA in children with CCHD was found to be high. Iron-deficient
group had an increased frequency of cyanotic spells as compared to the non-deficient group,
which was statistically significant.
© 2017 Published by Elsevier B.V. on behalf of Director General, Armed Forces Medical
Services.

* Corresponding author.
E-mail address: [email protected] (S. Mukherjee).
http://dx.doi.org/10.1016/j.mjafi.2017.07.003
0377-1237/© 2017 Published by Elsevier B.V. on behalf of Director General, Armed Forces Medical Services.

Please cite this article in press as: Mukherjee S, et al. Iron deficiency anemia in children with cyanotic congenital heart disease and effect
on cyanotic spells, Med J Armed Forces India. (2017), http://dx.doi.org/10.1016/j.mjafi.2017.07.003
MJAFI-887; No. of Pages 6

2 medical journal armed forces india xxx (2017) xxx–xxx

hours of collection. The CBC and red cell indices were done on
Introduction
Beckman Coulter five point differential automated hematolo-
gy analyzer. The values for Hemoglobin (Hb), Mean Corpuscu-
Cyanotic congenital heart disease (CCHD) is congenital heart lar Volume (MCV), and Total Iron-Binding Capacity (TIBC) are
defect with right to left shunting of desaturated blood. This directly derived and rest were calculated. 3 ml of blood was
results in decreased oxygen saturation in the systemic taken in sterile vacutainer for serum iron studies and the
circulation which acts as a trigger for increase in erythropoie- serum separated at room temperature. The sample was
tin production and secondary erythropoiesis in an effort to preserved at 10 8C till it was run. Serum ferritin was done
maintain tissue oxygenation.1 The resultant polycythemia by ELISA by the Bio Rad ELISA reader model 680. Serum Iron
and hyperviscosity manifests clinically as thromboembolic was done by Bathophenanthroline method and the transferrin
events in the children with CCHD.1,2 Iron deficiency anemia saturation (TS) was calculated.
(IDA) is commonly encountered in children of CCHD. IDA
aggravates hyperviscosity symptoms due to the presence of
Statistics
microcytic erythrocytes not amenable to deformation in the
microcirculation. Thus, presence of IDA in these children
further increases their chances of morbidity in the form of The data was recorded in a predecided format. This was fed
cerebrovascular events and cyanotic spells.3 Polycythemia into an excel sheet by the authors and verified by a co-author.
causes hemoglobin and hematocrit to rise and the otherwise The data was analysed using SPSS. The Fischer's exact test was
normal values for age are unable to reflect the iron-deficient used to find the various associations among the cases and a p-
status of these children. value of ≤0.05 was considered statistically significant.
This study is an attempt to look at the prevalence of iron
deficiency in Indian children with CCHD and to find out the
Results
prevalence of cyanotic spells in the subsets of iron-deficient
and iron non-deficient children with CCHD.
Fifty one children participated in the study with mean age of 4
years (Range 3 months–9 yrs). These included thirty four male
Material and methods (66.67%). The demographic details have been highlighted in
the table (Table 1). Thirty eight of fifty one children had
The study was an observational study conducted in pediatric tetrology of Fallot.
OPD of a tertiary care center in Western India over 18 months. Twenty four of fifty one children (47.06%) were iron
Informed consent from parents and institutional ethical deficient, 95% CI [34.05, 60.48] and 52.94% were non-deficient,
committee clearance was obtained. 95% CI [39.52, 65.95]. Seven out of fifty-one children (13.72%)
had a history of cyanotic spells, 95% CI [6.81, 25.72]. There was
Inclusion criteria a significant association between iron deficiency and cyanotic
spells ( p = 0.042) (Table 2). The iron deficient group had a
All children with CCHD were diagnosed on 2D-Echocardiography. higher prevalence (12%) of cyanotic spells, 95% CI [12.00, 44.90]
as compared to the non-deficient group (3.7%), 95% CI [0.66,
Exclusion criteria 18.28].
The hematological parameters of the iron-deficient and
The children were excluded if they had undergone definitive non-deficient groups were compared. The Hb and hematocrit
surgery, received iron supplements in the previous three were higher in the iron-deficient group as compared to the
months, had systemic involvement to explain the cause of non-iron deficient group. The mean serum ferritin was 7.63 ng/
anemia e.g. chronic kidney disease, hemolytic anaemia. A total mL (SD 3.4) in the iron-deficient group as compared to 33.53 ng/
of 51 children were included in study. mL (SD 10.51) in non-iron deficient group. The serum iron and
The demographic profile, clinical data including frequency TS were lower and the TIBC higher in the iron-deficient group.
of cyanotic spells and the results from 2-D Echocardiography The group with cyanotic spells and the group with no cyanotic
were chronicled. Thereafter, these children underwent com- spells were compared. Among the various haematological
plete blood count including red blood cell indices and parameters MCV, RDW, Serum Ferritin, TIBC, TS and Serum
reticulocyte count and serum iron studies including serum Iron were detected to be significantly associated with the
ferritin, total iron binding capacity (TIBC) and transferrin incidence of cyanotic spells. The mean serum ferritin in
saturation. Based on Serum Ferritin levels the children were
divided into iron deficient and non-deficient group. IDA was
diagnosed by a serum ferritin concentration of less than 12 ng/
mL in children less than 5 years and 15 ng/mL in children more Table 1 – Age-wise distribution of the study population.
than 5 years and 30 ng/mL in children with infection.4–7 Age No of cases Percent
Birth–6 months 16 31.37
Sample collection and estimation methods
6 months–1 year 15 29.41
1 year–6 years 18 35.29
Two ml of blood was collected in an EDTA vacutainer for CBC, 6 years–12 years 2 3.92
red cell indices and PBS and the sample was tested within four

Please cite this article in press as: Mukherjee S, et al. Iron deficiency anemia in children with cyanotic congenital heart disease and effect
on cyanotic spells, Med J Armed Forces India. (2017), http://dx.doi.org/10.1016/j.mjafi.2017.07.003
MJAFI-887; No. of Pages 6

medical journal armed forces india xxx (2017) xxx–xxx 3

Table 2 – Comparison of prevalence of cyanotic spells in population of adults with congenital heart diseases and the
iron-deficient and iron non-deficient group. attendant problems. In these defects, the right to left shunting
Cyanotic spells Total of blood results in systemic arterial desaturation. This hypoxia
is a stimulus to increased production of erythropoietin
Yes No
resulting in an increase in erythrocyte mass in an attempt
IDA to correct the hypoxia.8–12 However this causes hyperviscosity
Yes 6 18 24 symptoms to develop which include headache, dizziness,
No 1 26 27
cerebrovascular events. Hyperviscosity and polycythemia
Total 7 44 51 cause deformation of RBCs, cell aggregates form and emboli-
p = 0.042; odds ratio = 8.67. sation may be seen. Iron deficiency is an important determi-
nant of the quality of life of children with CCHD. IDA causes
further deformation of RBCs due to the rigidity of the
erythrocyte membrane and has been implicated in the
children with cyanotic spells was much lower (5.32 ng/mL) aggravation of hyperviscosity symptoms.13
than children who did not have spells (23.89 ng/mL) (Tables 3 There is a paucity of literature discussing iron deficiency
and 4). among children with CCHD and these studies have shown
varying results. In 1990, West et al, have demonstrated that
more than one-third of patients with CCHD had iron
Discussion
deficiency.14 In another study done by Olcay et al, the
prevalence of IDA was found to be 52.2%.15 In a study done
Cyanotic heart defects have generated interest due to the in India by Gaiha et al, a prevalence of 18.18% was reported,
special problems seen in these defects, the complex surgeries however the subjects of this study were adolescents and young
and their peri-operative care and recently for the growing adults.16 In this study, we demonstrate that nearly five of ten

Table 3 – Comparison of hematological parameters of iron-deficient and non-deficient group.

IDA N Mean SD p-value
Hb Present 24 14.13 1.97 0.012
Absent 27 12.87 1.34

PCV Present 24 43.08 6.45 0.004

Absent 27 38.41 4.02

TLC Present 24 9910.42 2890.25 0.616

Absent 27 9543.70 2190.29

Pl Count Present 24 2.60 0.83 0.739

Absent 27 2.53 0.68

TRBC Present 24 6.36 1.36 <0.001

Absent 27 4.86 0.53

Retics Present 24 1.01 0.15 0.404

Absent 27 1.07 0.37

MCV Present 24 68.50 5.92 <0.001

Absent 27 79.39 9.02

MCH Present 24 23.23 2.33 0.001

Absent 27 26.26 3.44

MCHC Present 24 33.03 1.71 0.018

Absent 27 34.22 1.74

RDW Present 24 18.38 2.08 <0.001

Absent 27 11.70 1.68

Serum ferritin Present 24 7.63 3.40 <0.001

Absent 27 33.53 10.61

Serum iron Present 24 68.17 10.91 <0.001

Absent 27 96.44 16.17

TIBC Present 24 371.50 51.61 <0.001

Absent 27 287.30 46.47

TS Present 24 18.92 4.77 <0.001

Absent 27 34.82 10.70
Values given in bold are statistically significant.

Please cite this article in press as: Mukherjee S, et al. Iron deficiency anemia in children with cyanotic congenital heart disease and effect
on cyanotic spells, Med J Armed Forces India. (2017), http://dx.doi.org/10.1016/j.mjafi.2017.07.003
MJAFI-887; No. of Pages 6

4 medical journal armed forces india xxx (2017) xxx–xxx

60

50

40

30

20

10

0
0 5 10 15 20 25

Fig. 1 – Correlation graph of hemoglobin and ferritin. X axis: hemoglobin values; Y-axis: serum ferritin values.

children with CCHD are iron deficient and these children with the population for the need for early intervention. Two-thirds
iron deficiency are more likely to have cyanotic spells. of the study population comprised of male children. Previous
The study population was dominated by infants who studies have not shown any sex predilection in Tetralogy of
comprised of half of the total. This is probably because of Fallot, Double Outlet Right Ventricle (DORV), Truncus Arter-
increasing frequency of ante-natal diagnosis and awareness in iosus (TA), Ebstein's anomaly, Supracardiac Total Anomalous

Table 4 – Comparison of hematological parameters in children with and without cyanotic spells.
Spells Number of children Mean SD p-value
Hb Present 7 15.37 3.20 0.118
Absent 44 13.16 1.23

PCV Present 7 46.00 10.55 0.17

Absent 44 39.75 4.17

TLC Present 7 10,977.14 4077.07 0.387

Absent 44 9515.68 2188.44

Pl Ct Present 7 2.52 1.03 0.916

Absent 44 2.57 0.71

TRBC Present 7 7.06 2.30 0.095

Absent 44 5.33 0.82

Retics Present 7 0.93 0.22 0.192

Absent 44 1.06 0.30

MCV Present 7 66.83 7.69 0.025

Absent 44 75.45 9.18

MCH Present 7 22.84 3.68 0.158

Absent 44 25.15 3.18

MCHC Present 7 33.30 1.97 0.61

Absent 44 33.72 1.81

RDW Present 7 19.29 3.25 0.004

Absent 44 14.14 3.46

Serum ferritin Present 7 5.32 4.00 <0.001

Absent 44 23.89 14.89

Serum iron Present 7 66.29 12.04 0.004

Absent 44 85.82 19.60

TIBC Present 7 406.14 54.10 0.003

Absent 44 314.32 56.86

TS Present 7 16.92 4.38 <0.001

Absent 44 29.00 11.53
Values given in bold are statistically significant.

Please cite this article in press as: Mukherjee S, et al. Iron deficiency anemia in children with cyanotic congenital heart disease and effect
on cyanotic spells, Med J Armed Forces India. (2017), http://dx.doi.org/10.1016/j.mjafi.2017.07.003
MJAFI-887; No. of Pages 6

medical journal armed forces india xxx (2017) xxx–xxx 5

Pulmonary Venous connection (TAPVC) but, males outnumber incidence of cyanotic spells. It is also associated with
females in Transposition of the Great Arteries and infracardiac hyperviscosity and its attendant problems. Serum ferritin
TAPVC by a high ratios.17–21 In this study a majority of cases should be done routinely in children with cyanotic congenital
were children with Tetrology of Fallot (74.51%). This is an heart disease for diagnosis of IDA.
observation similar to other studies on this subject.
Almost half (47.06%) of the children were found to have iron
Conflicts of interest
deficiency as determined by their serum ferritin levels. This is
similar to the study by Cemile Banu Onur et al and Olcay et al
done in children with CCHD but higher than that seen in The authors have none to declare.
studies of adults with CCHD.1,15,16 However one study in
children with CCHD done by West et al also showed much
references
lower prevalence of IDA as compared to the other studies on
children.14
The higher prevalence of IDA in our population was
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on cyanotic spells, Med J Armed Forces India. (2017), http://dx.doi.org/10.1016/j.mjafi.2017.07.003
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Please cite this article in press as: Mukherjee S, et al. Iron deficiency anemia in children with cyanotic congenital heart disease and effect
on cyanotic spells, Med J Armed Forces India. (2017), http://dx.doi.org/10.1016/j.mjafi.2017.07.003