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Profile of Behavior and IQ
in Anemic Children
Ahmed Mubarak, MD, Wael Fadel, MD, Shibl Said, MD,
and Mohamed Abu Hammar, MD
Original Research
Dr. Mubarak and Dr. Fadel are professors of neuropsychiatry in the Department of Neuropsychiatry, and Dr. Said is professor of pediatrics in the Department
of Pediatrics, all at the College of Medicine at Tanta University in Tanta, Egypt. Dr. Hammar is a specialist (clinical psychiatrist) in the Department of General
Psychiatry at Al Ain Hospital in Al Ain, United Arab Emirates.
Faculty Disclosures: The authors report no affiliation with or financial interest in any organization that might pose a conflict of interest.
Submitted for publication: October 8, 2009; Accepted for publication: April 5, 2010;
Please direct all correspondence to:
Ahmed Mubarak, MD, Professor of Neuropsychiatry, College of Medicine, Tanta University, Tanta, Egypt; E-mail:
ahmed_mubarak@hotmail.com
ABSTRACT
Objectives: Study the profile of behavior
and intelligence of children with anemia and
their possible association to the hematological
parameters.
Methods: Fifty-eight children (42 anemic; 16
controls), matched by age, sex, and culture with
the patients, were subjected to both behavioral
and IQ testing using Revised Behavior Problem
Checklist (RBPCL) and Wechsler intelligence
scale for children-revised and hematological lab-
oratory evaluation
Results: After controlling for age, sex and cul-
ture, the mean IQ was lower in the iron deficiency
group than both thalassemic and control groups
(P<.000). The mean scores of conduct disorder,
socialized aggression, and anxiety withdrawal of
RBPCL were higher in thalassemic group while
the mean scores of motor excess and attention
problems score were higher in the iron deficiency
group. Regression analysis showed that hemo-
FOCUS POINTS
• The behavioral problems of anemic children
are significantly higher compared with children
of the same age, sex and culture.
• The main problems of iron deficiency anemia
are, inattention, hyperactivity and low IQ.
• The main problems of thalassemic children
are in conduct, socialized aggression and
anxiety withdrawal.
• The hemoglobin concentration show significant
predictive value for inattention and low IQ in
iron deficiency anemia.
• The hematological parameters did not show
significant predictive value in behavioral prob-
lems of thalassemic patients.
globin concentration in gram/dl was the predic-
tor of IQ in both anemic group and for attention
problems in iron deficiency group while the mean
corpuscular volume was the predictor of motor
excess score in iron deficiency group. Other asso-
ciations were not statistically significant.
Conclusion: Behavior problems and low
intelligence were significantly high among
anemic children. Their association with the
CNS Spectr 15:12 December 2010
doi: 10.1017/S1092852912000089
631
First published online: 201 1, 0.December
hematological parameters varies according to the
type of behavior and the type of anemia. These
results cannot exclude the role of other factors
in shaping the profile of behavior and IQ.
INTRODUCTION
Anemia is considered a worldwide problem,
affecting all age groups and socioeconomic levels
of society. Approximately 15% to 20% of the popu-
lation of the United States <18 years of age is iron
deficient.1 Adolescents are susceptible to iron defi-
ciency because of high requirements due to the
growth spurt, dietary deficiencies, and menstrual
blood loss. In several affluent countries, ~40%
of adolescent girls and 15% of boys have serum
ferritin levels <16% reflecting low bone marrow
iron stores.2 In the National Nutritional Survey
conducted for the general population in Egypt in
1978 and 1980, the prevalence of anemia in the
preschool age was 38% and 39%, respectively.3 In
spite of a large amount of information pointing to
a severe retardation of physical growth in patients
with thalassemia, very little has been said concern-
ing mental development.4 Since physical, mental,
emotional, and social growth and development
proceed simultaneously, physicians should realize
that a threat to any of these areas could indicate a
threat to others especially in the child with chronic
disease or disability.5
Abnormalities in emotional response, character
and behavior, such as anxiety, sense of inferiority,
and oversensitivity, were reported in thalasse-
mic patients. These manifestations are suggested
to be due to the chronicity of the disease and its
restrictive nature which interferes with successful
achievement of those children.6 Underachievement
was reported in 10% of school children due to fre-
quent and multiple absences from school.4 There is
now reason to believe that the degree of visibility
of the lesion forces the child to recognize himself
as “disabled“ compared to non-visible disorders
such as diabetes, this contribute to a great degree
of psychological maladjustment.7
Our objectives is to study the profile of behav-
ior and IQ in one group of children suffering from
iron deficiency anemia and another group suffer-
ing from β-thalassemia major and comparing both
groups with a group of healthy children matched
to both by age, gender, and cultural background
and to test for any possible relationship of the
profile of behavior and IQ to the hematological
parameters and consequently to anemia.
METHODS
The sample of this study was collected from
children between 6–12 years of age attended an
outpatient clinic of the Hematology Unit at the
Tanta University Hospital in Egypt (Table 1). The
objectives and procedures of the study were
explained to the children and relatives and written
consent was taken giving the child or the relative
the right to stop during any step of the study. The
sample was classified into three groups. Group
A had 22 children with iron deficiency anemia
according to the diagnostic criteria of iron defi-
Original Research
TABLE 1.
Sociodemographic Backgrounds
Iron Deficiency
N=22
Thalassemia
N=20
Control
N=16 Statistics
Age in years (Mean±SD) 8.00±1.60 7.75±1.51 8.06±0.92 df=2 F=0.26 P=.77
Gender (number) Male 11 12 10 df=2 χ2=0.71 P=.70
Female 11 8 6
Culture Urban 11 9 8 df=2 χ2=0.13 P=.94
Rural 11 11 8
Socioeconomic
condition
Poor 2 2 2 df=4 χ2=0.14 P=.99
Average 11 10 8
Above
Average
9 8 6
Mubarak A, Fadel W, Said S, Hammar MA. CNS Spectr. Vol 15, No 12. 2010.
CNS Spectr 15:12 December 2010
632
ciency anemia in children.8 Group B had 20 chil-
dren with β-thalassemia major.9 Group C was the
control group of 16 healthy children of matched
age, gender, and cultural background to both thal-
assemic and iron deficient anemic groups (they
were collected from the relatives and companions
of the sick children).
All children (patients and control) were sub-
jected to the Revised Behavior Problem Checklist
(RBPCL)10 which is composed of six scales which
measures the following patterns of behavior. Scale
I: conduct disorder (22 items). Scale II: socialized
aggression (16 items). Scale III: attention problem-
immaturity (16 items). Scale IV: anxiety-withdrawal
(11 items). Scale V: psychotic behavior (6 items).
Scale VI: motor excess (5 items). The Wechsler intel-
ligence scale for children-revised11 assessed the
IQ of all the studied groups. Complete blood pic-
ture was tested using automatic blood cell counter
K 1000, and hemoglobin electrophoresis. Serum
iron was tested using iron without deproteinization
test.12 Total iron binding capacity was tested using
test combination iron-binding capacity (Table 2).13
Statistical Analysis
The SPSS software package version 13 under
Windows14 was used for computer data analysis
and graphs, cross-tabulation, and one-way analy-
sis of variance (ANOVA) was used to compare mul-
tiple means using the post-hoc LSD component. To
test the relationship between the studied biochem-
ical parameters and both RBPCL and IQ results we
Original Research
TABLE 2.
Results of Hematological Evaluation
95% CI for ANOVA
Case Type NO Mean SD Min Max Lo Up Df* F P
Hemoglobin con-
centration (gm/dl)
Iron Deficiency 22 7.41 0.85 6.00 9.00 7.03 7.78 2; 55 213.59 0.000
Thalassemia 20 6.50 1.17 4.30 8.30 5.95 7.04
Control 16 13.48 1.24 12.30 17.30 12.81 14.14
Mean corpuscu-
lar hemoglobin
concentration (%)
Iron Deficiency 22 20.05 2.32 17.00 24.00 19.02 21.07 2; 55 86.14 0.000
Thalassemia 20 24.10 2.27 21.00 28.00 23.04 25.16
Control 16 28.67 0.81 27.50 30.00 28.24 29.10
Mean corpuscu-
lar volume (fl)
Iron Deficiency 22 63.64 2.57 60.00 68.00 62.50 64.78 2; 55 453.95 0.000
Thalassemia 20 68.10 1.86 66.00 72.00 67.23 68.97
Control 16 86.84 2.82 83.70 95.00 85.34 88.35
Serum ferretin
(ng/ml)
Iron Deficiency 22 8.27 1.78 6.00 12.00 7.48 9.06 2; 55 430.86 0.000
Thalassemia 20 777.20 152.62 570.00 1000.00 705.77 848.63
Control 16 103.88 21.35 71.00 138.00 92.50 115.25
Serum iron (ug/dl) Iron Deficiency 22 37.32 10.52 25.00 57.00 32.66 41.98 2; 55 450.71 0.000
Thalassemia 20 214.70 30.34 173.00 274.00 200.50 228.90
Control 16 89.50 8.33 70.00 101.00 85.06 93.94
Total iron binding
capacity (ug/dl)
Iron Deficiency 22 492.32 88.15 313.00 655.00 453.24 531.40 2; 55 93.81 0.000
Thalassemia 20 239.30 25.69 199.00 281.00 227.28 251.32
Control 16 316.13 45.79 251.00 402.00 291.73 340.52
Iron store Iron Deficiency 22 7.50 2.02 6.61 8.39 4.10 10.00 2; 55 835.03 0.000
Thalassemia 20 89.14 9.47 84.70 93.57 64.00 99.20
Control 16 27.04 6.59 23.52 30.55 13.70 37.90
*df (between groups; within groups)
Mubarak A, Fadel W, Said S, Hammar MA. CNS Spectr. Vol 15, No 12. 2010.
CNS Spectr 15:12 December 2010
633
used regression analysis with each component of
the RBPCL and IQ as dependent variables and all
hematological parameters together as indepen-
dent variables after controlling for age and sex.
RESULTS
Our results showed that the mean IQ of iron
deficiency group was lower than both thalasse-
mic and control groups (P<.001). No significant
difference was found between thalassemic group
and control group. In RBPCL mean scores; with
the exception of psychotic behavior; all the mean
test scores showed significant difference among
the three studied groups (Table 3). Post-hoc mul-
tiple comparison analysis (Table 4) showed that;
conduct disorder mean score was highest among
thalassemic children compared with those with
iron deficiency (P<.005) and control (P<.001), the
mean score of children with iron deficiency ane-
mia was still higher than the control (P<.0 01).
Socialized aggression mean score was higher
in children with thalassemia than both children
with iron deficiency anemia (P<.001) and control
cases (P<.01) but without significant difference
between children with iron deficiency anemia
and control cases (P>.05). Motor excess mean
score was higher in children with iron deficiency
anemia than thalassemia and control (P<.001),
thalassemic children mean score was lower than
control (P<.000). Attention problems mean score
was higher in both type of anemic children than
control (P<.001). However, the mean score of iron
deficiency anemia group was still higher than thal-
assemic (P<.001). Anxiety withdrawal mean score
was higher in thalassemic children than both iron
Original Research
TABLE 3.
The Results of RBPCL and IQ Tests Among the Three Studied Groups
95% CI for
RBPCL Scores Case Type N Mean SD SE Lo Up Df F Sig.
Conduct
disorder
Iron Deficiency 22 19.91 4.93 1.05 17.73 22.09 2 29.22 0.000
Thalassemia 20 25.90 7.97 1.78 22.17 29.63
Control 16 10.19 4.92 1.23 7.57 12.81
Socialized
aggression
Iron Deficiency 22 0.68 1.32 0.28 0.10 1.27 2 7.78 0.001
Thalassemia 20 2.75 2.47 0.55 1.60 3.91
Control 16 1.00 1.27 0.32 0.33 1.67
Attention
problems
Iron Deficiency 22 24.919 4.30 0.92 23.00 26.81 2 88.84 0.000
Thalassemia 20 17.15 5.79 1.29 14.44 19.86
Control 16 4.75 3.09 0.77 3.11 6.40
Anxiety
withdrawal
Iron Deficiency 22 5.89 3.75 0.80 4.16 7.48 2 51.15 0.000
Thalassemia 20 15.55 3.15 0.71 14.07 17.03
Control 16 5.50 3.67 0.92 3.55 7.46
Psychotic
behavior
Iron Deficiency 22 0.17 0.35 0.08 -0.02 0.29 2 2.00 0.145
Thalassemia 20 0.40 0.82 0.18 0.02 0.78
Control 16 0.06 0.25 0.06 -0.07 0.20
Motor
excess
Iron Deficiency 22 6.86 1.81 0.39 6.06 7.67 2 68.80 0.000
Thalassemia 20 0.35 0.67 0.15 0.07 0.66
Control 16 4.062 2.60 0.65 2.68 5.45
Intelligence
quotient
(WISC-R)
Iron Deficiency 22 78.23 4.85 1.04 76.08 80.38 2 18.81 0.000
Thalassemia 20 89.50 4.26 0.95 87.51 91.49
Control 16 95.44 15.24 3.81 87.32 103.56
Mubarak A, Fadel W, Said S, Hammar MA. CNS Spectr. Vol 15, No 12. 2010.
CNS Spectr 15:12 December 2010
634
deficiency group and control. On the other hand,
there was no significant difference between iron
deficiency group and control. Psychotic behavior
mean score was not significant among the three
groups children (P>.05).
In order to test if the hematological param-
eters have direct relationship to IQ and RBPCL
scores we carried out regression analyses with all
the seven hematological parameters (hemoglo-
bin concentration, mean corpuscular hemoglobin
concentration percentage, mean corpuscular vol-
ume, serum ferretin, total iron binding capacity,
serum iron, iron store) as independent variables
with IQ and each score of RBPCL as dependent
variable. Age, gender, and cultural background
were controlled in the model. This model tests
if any of these hematological parameters could
predict the changes in RBPCL scores. The result
of this analysis showed that in the iron deficiency
group hemoglobin concentration in gram/l was
the predictor of IQ (df=7, 14; F=11.94; P=.000,
β=0.61; t=2.19; P=.046) (Figure 1) and attention
problem score of the RBPCL (df=7, 14; F=10.55;
P=.000, β=−1.12; t=−3.84; P=.002) ie, negative cor-
relation (Figure 2). The mean corpuscular volume
was predictor of motor excess score (df=7,14;
F=3.56; P=.021 β=0.55; t=2.24 ; P=.042). No signifi-
cant association between the other RBPCL scores
and hematological parameters.
In the thalassemia group, hemoglobin concentra-
tion in gram/l was the predictor of IQ that was pre-
dicted by l (df=7, 13; F=9.617; P=.000 β=0.185; t=4.75;
P<.05). The blood parameters could not predict any
of the RBPCL sub items in thalassemia patients. The
control cases showed no correlation between these
factors and either IQ or RBPCL mean score.
Original Research
TABLE 4.
Post Hoc Multiple Comparisons Among the Three Studied Groups
RBPCL
Score (I) Case Type (J) Case Type Mean Difference (I-J) SE Sig. Lo Up
Conduct
disorder
Iron Deficiency Control 9.72 2.02 .000 5.67 13.77
Thalassemia Iron Deficiency 5.99 1.99 .003 2.19 9.80
Thalassemia Control 15.71 2.06 .000 11.58 19.84
Socialized
aggression
Thalassemia Iron Deficiency 2.07 0.55 .000 0.96 3.18
Thalassemia Control 1.75 0.60 .005 0.55 2.95
Control Iron Deficiency 0.328 0.59 .591 -0.86 1.50
Attention
problems
Iron Deficiency Thalassemia 7.76 1.42 .000 4.91 10.61
Iron Deficiency Control 20.16 1.51 .000 17.13 23.19
Thalassemia Control 12.40 1.55 .000 9.30 15.50
Anxiety
withdrawal
Iron Deficiency Control .318 1.16 .785 -2.01 2.64
Thalassemia Iron Deficiency 9.73 1.09 .000 7.55 11.92
Thalassemia Control 10.05 1.19 .000 7.68 12.42
Psychotic
behavior
Iron Deficiency Control 0.074 0.18 .682 -0.29 0.43
Thalassemia Iron Deficiency 0.26 0.17 .123 -0.07 0.60
Thalassemia Control 0.34 0.18 0.07 -0.03 0.70
Motor
mxcess
Iron deficiency Thalassemia 6.51 0.56 .000 5.40 7.63
Iron deficiency Control 2.80 0.59 .000 1.62 3.99
Control Thalassemia 3.71 0.60 .000 2.50 4.92
IQ Thalassemia Iron deficiency 11.27 2.74 .000 5.79 16.76
Control Iron deficiency 17.21 2.91 .000 11.37 23.05
Control Thalassemia 5.94 2.97 .051 -0.02 11.90
Mubarak A, Fadel W, Said S, Hammar MA. CNS Spectr. Vol 15, No 12. 2010.
CNS Spectr 15:12 December 2010
635
DISCUSSION
The results of RBPCL showed that anemic chil-
dren have more behavioral problems (except psy-
chotic behavior [P>.05]) than the control group.
The association between iron deficiency anemia
and cognitive function is reported in previous
studies.17
Our study showed that the mean IQ was lower
among iron deficiency children than both thalasse-
mic and control groups (P<.001). The IQ in thalas-
semic children was not significantly lower than the
control group (P=.051). This non-significant differ-
ence between the thalassemic and control groups
could be explained by the notion that the low
intelligence in thalassemic children is attributed
more to indirect effects related to social or envi-
ronmental disadvantages (eg, decreased learning
opportunities, increased physical limitations from
chronic illness).18,19 These factors do not usually
lead to severe mental retardation in the same way
that the biological factors do.20 The significant dif-
ference in IQ between the control and the iron
deficiency anemia children can be attributed to the
of biological effects of anemia as a cause of the
behavioral and cognitive impairment. This attri-
bution is well supported in the literature.21-25 An
interesting observation on the IQ of both patient
groups is the narrow standard deviation than the
control group, a possible explanation of this is
that no child could escape the effect of the illness
on IQ. This anecdotal explanation needs support
by future studies on a large samples.
In order to test the direct (biological) or indirect
(psychosocial) impact of the disease process on
the difference in behavior and IQ, we selected the
control sample to be matched for age, sex, cultural
background, and economic status. The data from a
meta-analysis on cognitive deficits of sickle cell
anemia26 indicate that studies using demographi-
cally matched peers as a control group showed
approximately a 2-point greater IQ discrepancy
than studies that used a sibling control group. The
difference has a little effect and did not reach sta-
tistical significance with a large number of cases
and controls. In their analysis; the authors found
no evidence that the choice of control groups
poses a meaningful bias in outcomes for general
cognitive functioning and either siblings or nonsi-
bling peers are appropriate choices. We acknowl-
edge the limitation of the small number of our
control sample compared with the patients groups
but the non significant difference was based on
nonparametric statistical analysis that considers
such types of discrepancies in sampling.
Studying the role of changes of the studied
hematological parameters on the behavior and
IQ in the two types of anemia we found different
associations.
In thalassemia cases, regression analysis
showed non-significant predictive value of the
studied hematological parameter for the mean
score of RBPC which supports the likelihood that
the behavioral changes are associated more to
social and psychological problems than the
Original Research
FIGURE 1.
Profile of behavior and IQ in anemic
children
Mubarak A, Fadel W, Said S, Hammar MA. CNS Spectr. Vol 15, No 12. 2010.
120
110
100
90
80
70
Intelligence Quotient
Iron Deficiency
Thalassemia
Control
Hemoglobin Concentration in Gram/dl
4 6 8 10 12 14 16 18
*
**
*
*
*
**
*
*
*
*
*
*
*
FIGURE 2.
Relationship between attention prob-
lems and hemoglobin concentration
Mubarak A, Fadel W, Said S, Hammar MA. CNS Spectr. Vol 15, No 12. 2010.
40
30
20
10
0
Intelligence Quotient
Iron Deficiency
Thalassemia
Control
Hemoglobin Concentration in Gram/dl
4 6 8 10 12 14 16 18
*
*
**
*
*
*
**
*****
*
*
CNS Spectr 15:12 December 2010
636
hematological changes of the disease. The chronic
disabling illness causes more stress due to both
actual and anticipated disability caused by more
hospitalization, more time in blood transfusion
and multiple school absences with consequent
academic and social backwardedness.27,28 Another
source of stress on the child and family is the
cost of treatment and loss of working days of the
caregivers (parents) that creates a more stressful
family environment.29-32 Our findings do not rule
out the effect of other disease related biological
changes such as focal cerebral infarcts that could
happen in some cases.33-35
Steen and colleagues3 6 found an association
between focal brain injury and cognitive impair-
ment, suggesting that diffuse brain injury may
also contribute to impairment. However their
result only showed a significant relationship
P<.02) between abnormal brain magnetic reso-
nance imaging and verbal IQ. The other compo-
nents of WISC including full IQ scale showed non
significant association. The significant associa-
tion was detected with hematocrete value <27. Our
results did not find such an association. This could
be due to methodological difference with the fore
mentioned study. For this reason a need of future
studies with large samples and the inclusion of
different variables including both brain and hema-
tology and control for psychosocial factors may
contribute to clarification of this controversy.
In iron deficiency anemia children our study
showed that low hemoglobin concentration pre-
dicted the mean score of attention problems and
low IQ while mean corpuscular volume predicted
the mean motor excess score. Many studies sup-
port the relationship between iron deficiency
anemia and attention deficit or motor excess or
restless leg syndrome.3 7-39 However, the expla-
nations of this relationship were different from
one study to another. One of these studies40
found an association between the intellectual and
behavioral deficits of the iron-deficient children
and the changes of some urinary catecholamine
metabolite and suggested that the dependence
of monoamine oxidase on adequate iron stores
could be a contributing factor in these deficits.
The relationship between iron deficiency and
monoamines was supported by a recent studies
on rats.41,42 Significantly lower serum ferritin lev-
els have been observed in children with attention
deficit hyperactivity disorder than in controls,37 the
authors reported 84% of attention-deficit/hyper-
activity disorder (ADHD) children had serum fer-
ritin levels of <30 ng/mL, compared with 18% of
controls (P<.001). Although we found significant
lower level of serum ferritin in iron deficient chil-
dren than in controls, regression analysis of all the
hematological parameters as independent vari-
ables and scores of behavior and intelligence as
dependent variables showed no predictive value
of ferritin.
In a recent study,43 iron supplementation (80
mg/day) appeared to improve ADHD symptoms
in children with low serum ferritin levels but the
authors of this study suggested a need for future
investigations with larger controlled trials to con-
firm their findings.
Another study44 demonstrated that iron defi-
ciency with or without anemia could affect the
social-emotional behavior of infants. The relation-
ship of the attention and IQ to the hemoglobin
concentration and the motor excess to the main
corpuscular volume could be explained by the
decrease oxygen binding capacity which resulted
from anemia. This explanation does not exclude
by any means the changes in serum ferritin in
these changes and needs confirmation by future
studies because most of the studies that studied
the role of ferritin were done on infants and pre-
school children.
CONCLUSION
From the results of our study we can conclude
that: the children with iron deficiency anemia are
Original Research
FIGURE 3.
Relationship between motor excess
score and the mean corpuscular vol-
ume
Mubarak A, Fadel W, Said S, Hammar MA. CNS Spectr. Vol 15, No 11. 2010.
10
8
6
4
2
0
RBPC (Motor Excess Score)
Iron Deficiency
Thalassemia
Control
Mean Corpascular Volume
60 70 80 90 100
*
**
*
*
*
***
**
**
*
* * *
CNS Spectr 15:12 December 2010
637
more prone to having low attention and being
hyperactive while thalassemic children tend to
be more prone conduct problems. IQ is low in
both groups, but iron deficiency anemia children
are more affected than thalassemic. The contro-
versy about the factors contributing to behavioral
problems still needs more work to be clarified.
Our findings give some evidence that changes in
some hematological parameters, particularly the
hemoglobin concentration and mean corpuscular
volume, could contribute to attention problems,
motor behavior and IQ changes in iron deficiency
anemia. The absence of any biological correlate
to the mean score of RBPCL in the thalassemic
group could give indirect support for the role of
psychosocial factors in the emergence of behav-
ioral problems in thalassemic children, although
not excluding the role of other biological factors.
There is a correlation between medical illness
and behavioral changes, this makes psychiatrists
who deal with behavioral problems screen care-
fully for medical illness especially in children. This
also opens the door for pediatricians and primary
care physicians to be insightful for the behavior
changes that their patients have due to the medi-
cal illness.
We have to acknowledge the limitations of our
study which are mainly the small sample size and
also the lack of multicultural comparisons to evalu-
ate the behavioral norms and the degree of social
support for this group of children. For this reason
we recommend a large scale study that considers,
in addition to the hematological, other biologi-
cal parameter, the impact of differences in social
support among different cultures in shaping these
behavioral changes particularly in thalassemic
children. CNS
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Original Research
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