Journal http://jcn.sagepub.com/ of Child Neurology
Effect of Chronic Iron Deficiency on Neuropsychological Domains in Infants Beatriz Beltrán-Navarro, Esmeralda Matute, Edgar Vásquez-Garibay and Daniel Zarabozo J Child Neurol published online 29 August 2011 DOI: 10.1177/0883073811416867 The online version of this article can be found at: http://jcn.sagepub.com/content/early/2011/08/26/0883073811416867
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Original Article
Effect of Chronic Iron Deficiency on Neuropsychological Domains in Infants
Journal of Child Neurology 000(00) 1-7 ª The Author(s) 2011 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073811416867 http://jcn.sagepub.com
Beatriz Beltra´n-Navarro, MSc1, Esmeralda Matute, PhD1, Edgar Va´squez-Garibay, PhD2, and Daniel Zarabozo, PhD1
Abstract The aim of this study was to assess the effects of chronic iron deficiency on neuropsychological traits in infants. We established the nutritional iron status and assessed the neuropsychological characteristics of 58 Mexican 14- to 18-month-old infants. The Bayley Scales of Infant Development, preschool language scales and an environmental sound perception task designed expressly for the study, were used. The infants’ mothers were asked to fill out 2 questionnaires concerning their child’s sociodemographic background. Six different neuropsychological domains were analyzed. Results showed that the chronic iron deficiency group did show significantly lower scores on language, environmental sound perception, and motor measures, when compared with infants with normal nutritional iron status at 6 and 14 to 18 months. Our conclusion is that the development of language and motor skills and environmental sound perception appeared to be sensitive to the effects of chronic iron deficiency in infants. Keywords iron deficiency, neuropsychological development, infants, anemia Received June 2, 2011. Accepted for publication June 19, 2011.
Iron deficiency is the most prevalent childhood nutritional disorder worldwide.1,2 It can be related to such factors as a diet low in iron, impaired intestinal iron absorption, and parasitic infections. Since iron intervenes in numerous metabolic processes, including oxygen transportation, adenosine triphosphate production, metabolism of neurotransmitters, DNA synthesis, and myelin production, several health processes could be affected in children who have a low concentration of this element. Iron deficiency is classified in 3 stages: (1) iron depletion, a decrease in the normal reserve that has no functional consequences; (2) iron deficiency without anemia, biochemical changes reflected in the normal seric ferritin reserve; and, (3) iron deficiency anemia, subnormal concentrations of seric ferritin and hemoglobin. Previous findings related to the effects of iron deficiency without anemia on cognitive development in infants are inconsistent. Some studies indicate no association, but low performance scores on the Bayley scales of infant development3; whereas others have found lower performance among infants on the mental,4 motor,5 and behavioral6 tests included in those scales. In more recent studies, an adverse effect of iron deficiency without anemia on motor development has been reported more consistently, based on observations of motor activity at home7 and using motor development assessment tools such as the Peabody Developmental Motor Scale, the infant neurological international battery, and the Bayley behavioral rating scale; or through more informal assessments of the gross motor development milestones and a sequential/bi-manual coordination toy retrieval task.8
With respect to iron deficiency anemia, study results are more consistent and show a broader cognitive, motor and behavioral impairment in infants. However, they cannot be considered conclusive. Several studies of infants indicate that iron deficiency anemia is associated with significantly lower performances on the mental,3,4,9-12 motor,4,9,10,12 and behavioral tasks3,11,12 included in the Bayley Scales of Infant Development, the Denver Developmental Screening Test,4 in observations of motor activity recorded in the home,7 in a motor development assessment battery,8 and in behavioral observations measuring the duration and frequency of free play in both the laboratory13,14 and at home.14 In addition, the functional isolation hypothesis has been explored in infants with iron deficiency anemia. This hypothesis, derived from research on generalized undernutrition, holds that a decrease in the activity of malnourished infants leads them to seek less stimulation from their physical and social environments. In response to the
1
Instituto de Neurociencias, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico 2 Instituto de Nutricio´n Humana, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico Corresponding Author: Esmeralda Matute, PhD, Universidad de Guadalajara, Instituto de Neurociencias, Francisco de Quevedo 180, C.P. 44130, Guadalajara, Jalisco, Mexico Email:
[email protected]
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Journal of Child Neurology 000(00)
infants’ behavior, caregivers thus tend to offer less stimulation. Over time, these altered behavior patterns can impede the child’s normal acquisition of environmental information and adversely affect her/his development.14 Although existing studies of the effects of chronic iron deficiency on infant abilities are few, some have found significantly lower scores on the Bayley mental3,10,12 and motor12 scales in infants who have been affected by iron deficiency anemia for more than 3 months. As we have seen, most of those studies used standardized developmental tests, such as the Bayley scales, and took global scores as the principal measure of outcomes.3,4,9-12 Few, however, have done analyses of specific items related to language,12,15 attention,16 recognition memory,16,17 object permanence,17 and gross motor development.7,8,10,12,18 In this study, the effects of chronic iron deficiency on neuropsychological traits were assessed in 14- to 18-month-old infants who had been diagnosed with iron deficiency 1 year earlier. To evaluate them, we used Aylward’s general neuropsychological design19 for early neuropsychological assessment. Our hypothesis was that, even at such an early age, the effects of chronic iron deficiency on neuropsychological development would be detectable, but that no underperformance would be found when infants at this age (14 to 18 months) presented iron deficiency for the first time.
Methods Selection and Description of Participants Subjects were recruited from a previous study20 (n ¼ 154) conducted at ‘‘Doctor Juan I. Menchaca’’ Civil Hospital in Guadalajara, Jalisco, Mexico. In Monterrosa et al20 research, infants were followed from birth to 6 months in a nutritional evaluation. We invited all parents of Monterrosa et al20 sample that could be reached by telephone or at home when their infants were 14 to 18 months old. A total of 74 families were contacted (48%), as the rest were no longer living at the addresses recorded for the earlier study, but of those 74 only 58 mothers (38% of the total of Monterrosa et al20 sample) gave their written consent for the blood venipuncture test required to determine their infants’ current nutritional iron status (serum ferritin and hemoglobin), and for the neuropsychological assessment. The Ethics Committee/Institutional Review Boards of the Instituto de Neurociencias (Neuroscience Institute) at Universidad de Guadalajara (University of Guadalajara) and the ‘‘Doctor Juan I. Menchaca’’ Civil Hospital approved the study design. The inclusion criteria for Monterrosa et al20 study were: first or second child, physiological gestation 37 weeks, birth weight 2500 grams, no perinatal pathology, no congenital malformations or genetic alterations, no prenatal infections, Apgar 7 at 5 minutes, and no chronic illness or neonatal hypoxia sequelae. Mothers’ ages ranged from 18 to 33 years (mean, 25.5 years) and no iron deficiency, with or without anemia, had occurred during their pregnancies. The infants had been given a blood venipuncture test at 6 months to verify their nutritional iron status (seric ferritin and hemoglobin concentration) but no neuropsychological assessments were conducted at that time, nor were their developmental milestones registered. All the infants that presented iron deficiency with or without anemia at that time received oral iron therapy (daily doses of 15 mg/kg of ferrous sulfate for 2 months). The diagnostic biochemical criteria used by the previous study20 and in this study, were those proposed by the World Health Organization2: for the normal iron nutritional status group, hemoglobin (grams
per deciliter) 11 and seric ferritin (micrograms per liter) 12; for the iron deficiency without anemia group, hemoglobin (grams per deciliter) 11 and seric ferritin (micrograms per liter)
