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 [6–9]. Iron
therapy for correcting anemia is insufficient to reverse
behavioral and developmental disturbances in many
infants [9–11]. 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

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Complete blood count (CBC) and red cell indices were determined with an automatic cell counter (Coulter LH 750). The proportion of male to female subjects was similar in the two groups. iron deficiency. We received approval from the hospital’s Ethics Committee. Blood samples were collected by venipuncture. delayed neuromotor development. and ferritin levels between the iron-deficiency anemia. Serum ferritin was determined by chemiluminescent microparticle immunoassay (Architect system B7K 590).001. and transferrin saturation ≥ 14%. and group 3 (37 to 72 months).0 g/dl. There were no significant differences in serum iron and ferritin levels between subjects with iron-deficiency anemia and those with iron deficiency (p > . along with descriptive statistical methods (average. Hemoglobin. Results A total of 172 subjects completed the study. Intergroup comparisons of parameters with abnormal distribution were evaluated with the Kruskal-Wallace test. In 1982. “delays” or more than two “cautions”. ferritin. serum iron ≥ 30 µg/dl.05) (table 1 and figs. 26. or hyperbilirubinemia and children receiving iron therapy during the past 12 months were not included in the study. Children with acute infections. mean corpuscular volume. and personal/social functions. red cell distribution width. p < . 10 subjects from the iron-deficiency anemia group were not assessed by DDST-II and withdrew from the study. and total iron-binding capacity. chronic or congenital anemia. ferritin ≥ 12 µg/L. Chi-square test was used in comparing qualitative data. The difference from the control group in the percentage of abnormal scores was significant for subjects with iron-deficiency anemia (p < . Subjects with abnormal DDST-II results showed impairment in fine motor skills. Anthropometric measurements of all children were taken.All parameters were tested for normality using the Kolmogorov-Smirnov test. fine motor function. and they were examined by a pediatrician. Anemic subjects were defined as those with hemoglobin ≤ 10. Serum iron and iron-binding capacity were measured spectrophotometrically by the Ferrozine method (Aero set C 8000). median).05) (table 2 and fig. and transferrin saturation. health conditions. Data analysis All analyses were performed with NCSS 2007&PASS 2008 Statistical Software. Parameters with abnormal distribution include iron. Pala et al. serum iron. The subjects were categorized in three groups according to their age: group 1 (6 to 12 months).3% of subjects with iron-deficiency anemia. If the child had one or more E. . 1 and 2). Hemoglobin levels were significantly higher in subjects with iron deficiency than in subjects with iron-deficiency anemia (p = 0.0% of control subjects. the test was scored as a “caution” if the child score was between the 75th and 90th percentiles. 3). Tukey HDS test was used in post-hoc analyses. Complete hematologic evaluation was performed in 182 subjects. A child’s DDST-II was interpreted as “normal” if there was no delay and only one “caution” for any items.01).203. Each subject was assessed on the DDST-II by a trained and experienced examiner. There were significant differences in hemoglobin. and gross motor functions. DDST-II scores were abnormal in 67. chronic diseases. and control groups (p < . The Mann-Whitney U test was used for dual group comparisons.05 was considered to indicate statistical significance.0 g/dl and at least two abnormal measures of iron status: serum iron ≤ 30 µg/dl.001) but not for those with iron deficiency (p = 0. Intergroup comparisons of parameters with normal distribution were evaluated by oneway analysis of variance (ANOVA). language. The iron-deficient subjects were defined as those with hemoglobin ≥11.9 g/dl and two or more abnormal biochemical measurements [15. 16].01). p < . and family situation. p > . 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. this test was standardized for Turkish children [14]. The test detects slow development in four functional areas of development: social/personal. the result was classified as “abnormal”.001. Forty-nine subjects had iron-deficiency anemia and 23 had iron deficiency. ferritin ≤ 12 µg/L. 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. group 2 (13 to 36 months). and 15. history of neonatal asphyxia. A p value of less than . standard deviation. Informed consent was obtained from the parents of the children participating in the study. serum iron. hematocrit. Parameters with normal distribution include hemoglobin. The parents completed a 14-item questionnaire in which they reported on their child’s medical history. convulsion.1% of those with iron deficiency. 13]. The control group was defined as subjects with all values in the normal range: hemoglobin ≥ 11.01). If the child score was more than 90th percentile compared to children in the same age group it was scored as “delay”.432 test takes approximately 20 minutes to administer and interpret [12. transferrin saturation ≤ 14%. language.

001** a. DDST-II results in all groups Result Irondeficiency anemia Iron deficiency Control pa Abnormal Normal 33 (67.51 15. One-way ANOVA. IDA. iron-deficiency anemia TABLE 2.43 ± 4. ID.91 ± 72.44 32.1%) 17 (73.86 (28) 363.58 37.01 (23) a.65 35.83 ± 4.35 ± 38.31 9.68 (8. Values are mean ± SD (median).36 ± 75. Serum iron levels in all groups.74 (25) 25.57 (29) 320.05) 7. iron-deficiency anemia 80 70 Mean±SD 60 50 40 30 20 10 0 IDA ID Control IDA 0–12 months ID Control IDA 13–36 months FIG.7%) 6 (26. b.67 69.41 23.001 14 12 Mean±SD 10 8 6 4 2 0 IDA ID Control IDA 6–12 months ID Control IDA 13–36 months ID Control 37–72 months FIG.06 ± 4.12 63.22 ± 7.433 Iron deficiency and psychomotor development TABLE 1. 1.21 64.10 24.50 ± 0.05 ± 1.21 26.60 ± 10.3%) 16 (32.04 9.7) 11.97 (9) 12.73 ± 19.95 ± 1.50 ± 2.53 ± 0.12 ± 4.001 ID 37–72 months Control .28 ± 3.57 ± 3.66 15.73 ± 1. Kruskal-Wallis test.09 75. iron deficiency.32 14.0%) 85 (85. iron deficiency.35 ± 5. c.85 ± 0.0%) .40 28.60 ± 0.91 ± 9.61 ± 2. Chi-square test **p < . IDA. ID. All differences among the three groups are significant at **p < .47 ± 8. 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 (µg/dl)c Total iron-binding capacity (µg/dl)b Transferrin saturation (%)c Ferritin (µg/L)c Iron-deficiency anemia Iron deficiency Control 10.21 ± 2.09 23. Hemoglobin levels in all groups.71 (5.69 ± 3.03 ± 0.69 31.9%) 15 (15.11 (63) 268.2.55 (11) 10.

Normal Abnormal 100 80 60 % 40 20 0 IDA ID Control FIG. We found delay in personal/social. housing.6 points) in infants aged 9 to 12 months with iron deficiency.6% of subjects with iron deficiency. . mainly due to the increase in breastfeeding and the use of iron-fortified formula. food. p > . Lozoff et al.5%) in children aged 3 to 36 months. [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. Oski et al. fine motor. Akman et al.0% of control subjects had abnormal DDST-II results. especially on motor development and social-emotional behavior.01). [26] assessed 97 anemic children aged 17 to 19 months with the DDST-II. [19–21] found that infants with anemia had significantly lower Mental and Psychomotor Developmental Index scores than control infants or nonanemic. The causes of developmental delay are multifactorial. In our study. [7] found a significant increase in Mental Development Index scores (21. 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. delayed neuromotor development. 18] emphasized the importance of protecting the developing brain from the negative effects of iron deficiency. 3. abnormal DDST-II scores were significantly higher in subjects with iron-deficiency anemia (p < . Contrary to the results of the Aukett study. iron-deficient infants.203.3% of subjects with iron-deficiency anemia. all subjects included in our study were from families with lower-middle socioeconomic backgrounds. but iron deficiency and anemia in toddlers and preschool-aged children should not be underestimated [22–24]. A hypothesis by Beard [6] suggested that the lack of iron might lead to impairment of myelination at critical stages of brain development. They reported a widening gap for those in low-socioeconomic-status families. especially on motor development and social-emotional behavior [8–10]. as there is a direct relation between iron deficiency and delayed psychomotor development. especially of the necessities of life such as water. The prevalence of iron-deficiency anemia during the first year of life has been dramatically reduced in developed countries. and language development skills. and even physical stature. 16]. history of neonatal asphyxia. Deprivation. results in biochemical alterations that impair behavior in infants. The authors questioned the predictive validity of this test for lower-class urban Turkish children.05). or healthful environmental influences. and various environmental and hereditary factors have been implicated. These results indicated that iron deficiency. In our study. They suggested that earlier iron supplementation before iron deficiency becomes severe or chronic could prevent these adverse effects. Trials of iron supplementation in developing countries showed benefits of iron. such as learning difficulties and socioemotional problems [15. [25] investigated 108 children aged 6 to 30 months. Pala et al. Iron-deficiency anemia in infancy is associated with impaired psychomotor development. Aukett et al. They reported that even the deprived environment can impair psychomotor development. Children who had severe. chronic diseases. or hyperbilirubinemia were not included in the study. However. particularly for language and fine motor skills. This relation might be mediated by either neurochemical (dopaminergic) or anatomic (hypomelination) changes. Epir et al. DDST-II results in all groups Discussion The mechanisms by which iron deficiency affects brain development are unclear. Moreover. The deprived environment could contribute both to iron deficiency anemia and to delayed development. children with acute infection. Anemic infants failed specifically in language capabilities and body balance–coordination skills when compared with controls. chronic iron deficiency in infancy score lower on measures of mental and motor functioning and are at risk for long-lasting developmental disadvantages. and 15. Lozoff [17. we determined that abnormal DDST-II scores were not significantly different in subjects with iron deficiency and control subjects (p = 0.434 E. [27] analyzed the influence of social class differences on performance on the DDST-II in healthy children 5 to 6 years of age. 67. To exclude the influence of these factors. could cause lasting damage to intelligence. chronic or congenital anemia. convulsion. the evidence for the adverse consequences of iron deficiency remains limited. particularly in language and fine motor skills. These findings are similar to previous demonstrations that iron-deficiency anemia impaired the psychomotor development during childhood. We found a significantly higher proportion of abnormal DDST-II results (87. Recent studies showed benefits of iron supplementation for iron-deficient infants. Walter et al. emotional well-being. even in the absence of anemia. Social class differences affected the DDST-II results. 21.

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