Psychomotor development in children with iron

deficiency and iron-deficiency anemia

Emin Pala, Muferet Erguven, Sirin Guven, Makbule Erdogan, and Tulin Balta
Abstract
Background. Iron deficiency and iron-deficiency anemia
are the most common nutritional deficiencies in children, especially in developing countries. Iron-deficiency
anemia in infancy is associated with impaired neurodevelopment. Studies have shown an association between
iron deficiency without anemia and adverse effects on
psychomotor development.
Objective. To determine the effects of iron deficiency
and iron-deficiency anemia on psychomotor development in childhood.
Methods. We evaluated psychomotor development in
healthy children with iron deficiency and iron-deficiency
anemia with the use of the Denver II Developmental
Screening Test (DDST-II). If the child score was more
than 90th percentile compared to children in the same
age group, the test was scored as delay; it was scored
as a caution if the child score was between the 75th
and 90th percentiles. The test result was interpreted as
normal, if there was no delay and only one caution
for any item. If the child had one or more delays or
more than two cautions, the result was classified as
abnormal.
Results. DDST-II scores were abnormal in 67.3% of
subjects with iron-deficiency anemia, 21.6% of those
with iron deficiency, and 15.0% of control subjects. The
difference from the control group in the percentage of
abnormal scores was significant for subjects with irondeficiency anemia (p < .01) but not for those with iron
deficiency (p = 0.203); p > .05. (p-value, post-hoc comparison of 2 groups.)
Conclusions. Iron-deficiency anemia impaired psychomotor development during childhood. However, the
evidence on the adverse effects of iron deficiency remains
controversial. The Denver II Developmental Screening
The authors are affiliated with Umraniye Education and
Research Hospital, Istanbul, Turkey.
Please direct queries to the corresponding author: Sirin
Guven, Umraniye Egitim ve Arastirma Hastanesi, Istanbul,
Turkey; e-mail: sirin2006@gmail.com.

Test is a valuable test to detect early developmental

delays, especially in infants with risk factors.

Key words: Iron deficiency, iron-deficiency anemia,

Denver Developmental Screening Test, psychomotor
development

Introduction
Iron deficiency and iron-deficiency anemia are the
most common nutritional deficiencies in children,
especially in developing countries [1]. Globally, iron
deficiency ranks ninth among 26 risk factors included
in the Global Burden of Disease 2000 and accounts for
841,000 deaths and 35,057,000 disability-adjusted life
years lost [2].
Iron deficiency is defined as decreased total iron
body stores, without a reduction in hemoglobin. This
stage of iron deficiency can be occasionally detected by
a routine check of serum iron. However, the determination of hemoglobin alone is not sufficient to identify
patients who are iron deficient. Iron-deficiency anemia
is characterized by low serum iron concentration, low
transferrin saturation, and low hemoglobin concentration. The American Academy of Pediatrics recommends screening for anemia between the ages of 9 and
12 months, with additional screening between the ages
of 1 and 5 years for patients at risk [3]. Iron-deficiency
anemia in infancy is associated with impaired psychomotor development. Many studies indicate that
iron-deficiency anemia is associated with lowered
scores on tests of mental and motor development in
infancy and early childhood [4, 5]. In addition, studies show an association between iron deficiency and
adverse effects on cognitive development [69]. Iron
therapy for correcting anemia is insufficient to reverse
behavioral and developmental disturbances in many
infants [911]. The Denver II Developmental Screening
Test (DDST-II) is a widely used assessment of developmental progress in children 0 to 6 years of age. The

Food and Nutrition Bulletin, vol. 31, no. 3 2010, The United Nations University.

431

432

test takes approximately 20 minutes to administer and

interpret [12, 13]. The test detects slow development in
four functional areas of development: social/personal,
fine motor function, language, and gross motor functions. In 1982, this test was standardized for Turkish
children [14].

Methods
We evaluated psychomotor development in healthy
children with iron deficiency and iron-deficiency
anemia seen in our pediatric polyclinic between January 2008 and January 2009. We received approval from
the hospitals Ethics Committee. The parents completed
a 14-item questionnaire in which they reported on
their childs medical history, health conditions, and
family situation. Informed consent was obtained from
the parents of the children participating in the study.
Anthropometric measurements of all children were
taken, and they were examined by a pediatrician. The
subjects were categorized in three groups according to
their age: group 1 (6 to 12 months), group 2 (13 to 36
months), and group 3 (37 to 72 months). Children with
acute infections, chronic diseases, chronic or congenital
anemia, delayed neuromotor development, history of
neonatal asphyxia, convulsion, or hyperbilirubinemia
and children receiving iron therapy during the past 12
months were not included in the study.
Complete hematologic evaluation was performed
in 182 subjects. Blood samples were collected by venipuncture. Complete blood count (CBC) and red cell
indices were determined with an automatic cell counter
(Coulter LH 750). Serum iron and iron-binding capacity were measured spectrophotometrically by the Ferrozine method (Aero set C 8000). Serum ferritin was
determined by chemiluminescent microparticle immunoassay (Architect system B7K 590). The control group
was defined as subjects with all values in the normal
range: hemoglobin 11.0 g/dl, serum iron 30 g/dl,
ferritin 12 g/L, and transferrin saturation 14%.
The iron-deficient subjects were defined as those with
hemoglobin 11.0 g/dl and at least two abnormal
measures of iron status: serum iron 30 g/dl, ferritin
12 g/L, transferrin saturation 14%. Anemic subjects were defined as those with hemoglobin 10.9 g/dl
and two or more abnormal biochemical measurements
[15, 16].
Each subject was assessed on the DDST-II by a
trained and experienced examiner. If the child score
was more than 90th percentile compared to children
in the same age group it was scored as delay; the test
was scored as a caution if the child score was between
the 75th and 90th percentiles. A childs DDST-II was
interpreted as normal if there was no delay and only
one caution for any items. If the child had one or more

E. Pala et al.

delays or more than two cautions, the result was classified as abnormal.
Data analysis

All analyses were performed with NCSS 2007&PASS

2008 Statistical Software.All parameters were tested for
normality using the Kolmogorov-Smirnov test, along
with descriptive statistical methods (average, standard
deviation, median). Intergroup comparisons of parameters with normal distribution were evaluated by oneway analysis of variance (ANOVA). Parameters with
normal distribution include hemoglobin, hematocrit,
mean corpuscular volume, red cell distribution width,
and total iron-binding capacity. Tukey HDS test was
used in post-hoc analyses. Intergroup comparisons of
parameters with abnormal distribution were evaluated
with the Kruskal-Wallace test. Parameters with abnormal distribution include iron, ferritin, and transferrin
saturation. The Mann-Whitney U test was used for
dual group comparisons. Chi-square test was used in
comparing qualitative data. A p value of less than .05
was considered to indicate statistical significance.

Results
A total of 172 subjects completed the study; 10 subjects from the iron-deficiency anemia group were not
assessed by DDST-II and withdrew from the study.
Forty-nine subjects had iron-deficiency anemia and
23 had iron deficiency. The proportion of male to
female subjects was similar in the two groups. There
were significant differences in hemoglobin, serum
iron, and ferritin levels between the iron-deficiency
anemia, iron deficiency, and control groups (p < .01).
Hemoglobin, serum iron, and ferritin levels were significantly higher in subjects from the control group
than in subjects with iron-deficiency anemia and those
with iron deficiency (p = 0.001; p < .01). Hemoglobin
levels were significantly higher in subjects with iron
deficiency than in subjects with iron-deficiency anemia
(p = 0.001; p < .01). There were no significant differences in serum iron and ferritin levels between subjects
with iron-deficiency anemia and those with iron deficiency (p > .05) (table 1 and figs. 1 and 2).
DDST-II scores were abnormal in 67.3% of subjects
with iron-deficiency anemia, 26.1% of those with iron
deficiency, and 15.0% of control subjects. The difference
from the control group in the percentage of abnormal
scores was significant for subjects with iron-deficiency
anemia (p < .001) but not for those with iron deficiency
(p = 0.203; p > .05) (table 2 and fig. 3). Subjects with
abnormal DDST-II results showed impairment in fine
motor skills, language, and personal/social functions.

433

Iron deficiency and psychomotor development

TABLE 1. Hematologic and biochemical measurements in group 3 (36 to 72 months)a

Measurement
(g/dl)b

Hemoglobin
Hematocrit (%)b
Mean corpuscular volume (fl)b
Mean corpuscular hemoglobin (pg)b
Red cell distribution width (%)b
Iron (g/dl)c
Total iron-binding capacity (g/dl)b
Transferrin saturation (%)c
Ferritin (g/L)c

Iron-deficiency
anemia

Iron
deficiency

Control

10.50 0.69
31.21 2.12
63.35 5.41
23.69 3.51
15.73 1.44
32.73 19.86 (28)
363.36 75.04
9.06 4.68 (8.05)
7.43 4.71 (5.7)

11.85 0.65
35.05 1.67
69.12 4.09
23.95 1.66
15.03 0.40
28.91 9.57 (29)
320.91 72.31
9.57 3.55 (11)
10.22 7.97 (9)

12.60 0.58
37.61 2.09
75.83 4.21
26.50 2.32
14.53 0.21
64.60 10.11 (63)
268.35 38.10
24.28 3.74 (25)
25.47 8.01 (23)

a. Values are mean SD (median).

b. One-way ANOVA.
c. Kruskal-Wallis test.
All differences among the three groups are significant at **p < .001
14
12

MeanSD

10
8
6
4
2
0

IDA

ID

Control

IDA

612 months

ID

Control

IDA

1336 months

ID

Control

3772 months

FIG. 1. Hemoglobin levels in all groups. ID, iron deficiency; IDA, iron-deficiency anemia
80
70

MeanSD

60
50
40
30
20
10
0

IDA

ID

Control

IDA

012 months

ID

Control

IDA

1336 months

FIG.2. Serum iron levels in all groups. ID, iron deficiency; IDA, iron-deficiency anemia
TABLE 2. DDST-II results in all groups

Result

Irondeficiency
anemia

Iron
deficiency

Control

pa

Abnormal
Normal

33 (67.3%)
16 (32.7%)

6 (26.1%)
17 (73.9%)

15 (15.0%)
85 (85.0%)

.001**

a. Chi-square test
**p < .001

ID
3772 months

Control

434

E. Pala et al.
Normal
Abnormal

100
80
60

%
40
20
0

IDA

ID

Control

FIG. 3. DDST-II results in all groups

Discussion
The mechanisms by which iron deficiency affects brain
development are unclear. A hypothesis by Beard [6]
suggested that the lack of iron might lead to impairment of myelination at critical stages of brain development; Lozoff [17, 18] emphasized the importance
of protecting the developing brain from the negative
effects of iron deficiency. Iron-deficiency anemia in
infancy is associated with impaired psychomotor development. Children who had severe, chronic iron deficiency in infancy score lower on measures of mental
and motor functioning and are at risk for long-lasting
developmental disadvantages, such as learning difficulties and socioemotional problems [15, 16]. Trials of
iron supplementation in developing countries showed
benefits of iron, especially on motor development and
social-emotional behavior. Walter et al. [1921] found
that infants with anemia had significantly lower Mental
and Psychomotor Developmental Index scores than
control infants or nonanemic, iron-deficient infants.
Anemic infants failed specifically in language capabilities and body balancecoordination skills when
compared with controls.
In our study, 67.3% of subjects with iron-deficiency
anemia, 21.6% of subjects with iron deficiency, and
15.0% of control subjects had abnormal DDST-II
results. We found delay in personal/social, fine motor,
and language development skills. These findings are
similar to previous demonstrations that iron-deficiency
anemia impaired the psychomotor development during
childhood. However, the evidence for the adverse consequences of iron deficiency remains limited. Oski et
al. [7] found a significant increase in Mental Development Index scores (21.6 points) in infants aged 9 to 12
months with iron deficiency. These results indicated
that iron deficiency, even in the absence of anemia,
results in biochemical alterations that impair behavior
in infants. Recent studies showed benefits of iron supplementation for iron-deficient infants, especially on
motor development and social-emotional behavior

[810]. They suggested that earlier iron supplementation before iron deficiency becomes severe or chronic
could prevent these adverse effects. Lozoff et al. [9]
concluded that children with chronic iron deficiency
in infancy did not catch up with those with good iron
status in cognitive scores over time. They reported a
widening gap for those in low-socioeconomic-status
families. The prevalence of iron-deficiency anemia
during the first year of life has been dramatically
reduced in developed countries, mainly due to the
increase in breastfeeding and the use of iron-fortified
formula, but iron deficiency and anemia in toddlers
and preschool-aged children should not be underestimated [2224]. We found a significantly higher proportion of abnormal DDST-II results (87.5%) in children
aged 3 to 36 months. Akman et al. [25] investigated
108 children aged 6 to 30 months; they found that
subjects with iron deficiency had significantly lower
developmental test scores both on the Bayley Scales of
Infant Development I and the DDST-II compared with
the iron-sufficient subjects. The deprived environment
could contribute both to iron deficiency anemia and
to delayed development. Deprivation, especially of
the necessities of life such as water, housing, food, or
healthful environmental influences, could cause lasting
damage to intelligence, emotional well-being, and even
physical stature. Aukett et al. [26] assessed 97 anemic
children aged 17 to 19 months with the DDST-II. They
reported that even the deprived environment can
impair psychomotor development, as there is a direct
relation between iron deficiency and delayed psychomotor development. This relation might be mediated
by either neurochemical (dopaminergic) or anatomic
(hypomelination) changes.
Epir et al. [27] analyzed the influence of social class
differences on performance on the DDST-II in healthy
children 5 to 6 years of age. Social class differences
affected the DDST-II results, particularly in language
and fine motor skills. The authors questioned the
predictive validity of this test for lower-class urban
Turkish children, particularly for language and fine
motor skills.
The causes of developmental delay are multifactorial, and various environmental and hereditary factors
have been implicated. To exclude the influence of these
factors, children with acute infection, chronic diseases,
chronic or congenital anemia, delayed neuromotor
development, history of neonatal asphyxia, convulsion, or hyperbilirubinemia were not included in the
study. Moreover, all subjects included in our study were
from families with lower-middle socioeconomic backgrounds. In our study, abnormal DDST-II scores were
significantly higher in subjects with iron-deficiency
anemia (p < .01). Contrary to the results of the Aukett
study, we determined that abnormal DDST-II scores
were not significantly different in subjects with iron
deficiency and control subjects (p = 0.203; p > .05),

435

Iron deficiency and psychomotor development

although there was a slightly higher prevalence of

abnormal DDST-II results in subjects with iron deficiency (26.1%) than in the control group (15.0%). A
limitation of our study was a small number of subjects
with iron deficiency; further studies are necessary to
explain the role of iron deficiency in psychomotor
impairment.
The DDST-II gives a quick overview of the childs
development, and it also contains a behavior rating
scale. It can be administered and scored by people
who have no special training in psychological testing.
Sensitivity rates of 56% to 83% have been reported for
the DDST-II, but specificity may be as low as 43%,
rising to 80% [28]. The DDST-II is not a tool of final

diagnosis, but a quick method to process large numbers

of children in order to identify those who should be
further evaluated.

Conclusions
Iron-deficiency anemia impairs psychomotor development during childhood. Despite many studies, the
effects of iron deficiency on psychomotor development
are controversial. According to our data, the DDST-II
is a valuable test to detect early developmental delays,
especially in infants who have risk factors for developing iron deficiency.

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