Effect of iron deficiency anemia on visual evoked potential of growing children

doi:10.1016/j.braindev.2009.02.009

Brain and Development

Volume 32, Issue 3, March 2010, Pages 213-216

https://doi.org/10.1016/j.braindev.2009.02.009 Get rights and content

Abstract

Iron deficiency anemia is one of the most prevalent yet neglected nutritional deficiencies in the world. Iron is an essential micronutrient and it is ubiquitous in distribution in body. Iron deficiency leads to anemia, hampered physical growth and capacity, and decreased immunoprotective mechanisms. Impairments in cognitive and motor development in children are also seen in iron deficiency. There is increasing number of evidence to support that iron plays important role in central nervous system functions that include synthesis of neurotransmitters and myelination of the nerve. The objective of our study was to observe the effect of iron deficiency anemia on visual evoked potential (VEP) in children between 6 and 24 months of age. The subjects were categorized on the basis of hematological parameters in two groups: iron replete children in the control group (n = 25) and iron deplete children in the anemic group (n = 25). Iron status of the children was also assessed. Due care was taken to exclude all conditions known to adversely affect the visual evoked potential or the iron status of the children. Flash VEP was studied in all children from each eye individually. In both eyes each of the three waves (N1, P1 and N2) of the flash VEP showed longer latencies (p < 0.05) in the anemic group compared with the control group. A negative correlation was found between the severity of iron deficiency anemia and latencies of waves of VEP. Hence, there is a need for prevention and early detection of iron deficiency anemia in growing infants.

Introduction

Iron deficiency anemia (IDA) is one of the most prevalent yet neglected nutritional deficiencies in the world [1], [2], [3]. Based on several studies performed on animal models it appears that iron has varied roles in central nervous system like normal myelination [4], [5], [6], [7], [8], neurotransmitter synthesis and neurometabolism [9], [10], [11]. Iron uptake in brain is highest in post-natal period of rapid brain development and this increase coincides with the onset of myelination. Hypomyelination in iron deficient pups has been observed in a study assessing the effect of prenatal iron deficiency [4]. Iron deficiency at a time when myelination is at its peak is expected to have a significant effect on the myelination of the nerves and hence the normal brain functions.

Neurophysiologic methodologies are non-invasive approaches that can provide information about functional integration of the central nervous system. With increasing evidences of the role of iron in the central nervous system in animals it becomes imperative to study the effect of IDA in human infants; an age that not only has high prevalence of IDA but also is the most vulnerable age as the central nervous system development and maturation is taking place at this time [12], [13], [14]. Visual processing constitutes a very important domain of cognitive and executive functions and VEP is a robust tool for investigating the visual pathway. Although, various studies have assessed the effect of iron deficiency anemia in infants on brainstem auditory evoked potentials (BAEP) [15], [16], [17], [18], [19] but the studies using VEP [18], [20] are limited.

The present study was undertaken to evaluate the effect of iron deficiency anemia in the VEP recordings of anemic children.

Section snippets

Methods

The study included children of the age group of 6 to 24 months attending the Kalawati Saran Children’s Hospital OPD and immunization clinic.

Fifty children in total were studied in 2 groups. The control group (group I) consisting of iron replete children and anemic group (group II) consisting of iron deplete anemic children. Each group had 25 children. A detailed birth history and past medical history was taken to exclude conditions that could possibly affect the normal brain development like

Results

Table 1 shows that the baseline characteristics of the anemic and non anemic subjects were comparable.

All the children in anemic group were having iron deficiency anemia as confirmed by hematological investigations. The various hematological parameters in anemic and non anemic group are given in Table 2. The children in anemic group mostly had moderate anemia but there were four children who had severe anemia with hemoglobin levels less than 6 g/dl.

On comparing the latencies of major waves

Discussion

Our study assessed the effect of iron deficiency anemia on the functional status of one sensory pathway of the central nervous system – the visual pathway.

Our data shows that infants who had iron deficiency anemia have significantly longer absolute peak latencies of VEP as compared to the controls. It has earlier been reported that IDA delayed latencies in VEP, but it was examined only 3–4 years after having corrected the anemia [18]. In another study N2 latency of VEP showed improvement after

Acknowledgement:

I sincerely thank Dr. D. Ghosh and Dr. S.K.Sood, Department of Physiology, All India Institute of Medical Sciences; for their help and advise in writing this article.

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Evaluation of macular and optic disc radial peripapillary vessel density with optical coherence tomography angiography in iron deficiency anemia
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Iron is an essential micronutrient for normal myelination, oligodendrocyte biology and neurotransmitter synthesis. In IDA visual evoked potentials are impaired in infants and children [19,20]. It has been shown that specific iron-requiring enzymes such as glucose-6-phosphate dehydrogenase, dioxygenase, succinic dehydrogenase, and nicotinamide adenine dinucleotide hydride (NADH) dehydrogenase and cytochrome oxidase are more elevated in oligodendrocytes than in other brain cells [21].
To investigate effect of iron deficiency anemia (IDA) on macular and radial peripapillary capillary (RPC) vascular changes by optical coherence tomography angiography (OCTA).
Thirty-three patients with IDA and 33 healthy controls were enrolled in the study. Foveal avascular zone (FAZ) area, macular superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density and RPC vessel density were evaluated by the AngioVue Imaging System. Hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red cell distribution width (RDW), serum iron, total iron-binding capacity (TIBC), serum ferritin and transferrin saturation values were also recorded.
There were no statistically significant differences between the two groups in terms of FAZ area and FAZ perimeter while foveal density (FD) was significantly decreased in the IDA group. Compared to control group, IDA group revealed significantly decreased macular vessel density in all macular regions except fovea in both SCP and DCP. RPC vessel density was significantly decreased in whole image, peripapillary and superior-hemifield area wihout RNFL thinning. Hemoglobin level was positively correlated with SCP whole and RPC whole vessel density and serum iron level was also positively correlated with SCP whole vessel density.
Macular and optic disc vessel density were reduced in IDA patients. OCTA may be useful in detecting retinal ischemia before clinically visible signs of retinopathy associated with IDA appear.
Iron, zinc, and copper in retinal physiology and disease
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In children, however, iron deficiency is associated with dysfunction of the visual pathways.9,233,306 Twenty-five children aged 6–24 months with iron deficiency (serum levels of iron, ferritin, and transferrin saturation: 27.09 ± 12.62 μg/dl, 5.32 ± 2.92 ng/ml, 5.41 ± 2.78%, respectively) were shown to have significantly delayed latencies on visual evoked potentials (VEP) compared with controls.233 Iron deficiency might have hindered the function of oligodendrocytes and myelination of the visual pathways.19,234
The essential trace metals iron, zinc, and copper play important roles both in retinal physiology and disease. They are involved in various retinal functions such as phototransduction, the visual cycle, and the process of neurotransmission, being tightly bound to proteins and other molecules to regulate their structure and/or function or as unbound free metal ions. Elevated levels of “free” or loosely bound metal ions can exert toxic effects, and in order to maintain homeostatic levels to protect retinal cells from their toxicity, appropriate mechanisms exist such as metal transporters, chaperones, and the presence of certain storage molecules that tightly bind metals to form nontoxic products. The pathways to maintain homeostatic levels of metals are closely interlinked, with various metabolic pathways directly and/or indirectly affecting their concentrations, compartmentalization, and oxidation/reduction states. Retinal deficiency or excess of these metals can result from systemic depletion and/or overload or from mutations in genes involved in maintaining retinal metal homeostasis, and this is associated with retinal dysfunction and pathology. Iron accumulation in the retina, a characteristic of aging, may be involved in the pathogenesis of retinal diseases such as age-related macular degeneration (AMD). Zinc deficiency is associated with poor dark adaptation. Zinc levels in the human retina and RPE decrease with age in AMD. Copper deficiency is associated with optic neuropathy, but retinal function is maintained. The changes in iron and zinc homeostasis in AMD have led to the speculation that iron chelation and/or zinc supplements may help in its treatment.
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El pilar fundamental para la prevención de la ferropenia durante la lactancia y primera infancia es una adecuada orientación dietética. Durante los primeros 4-6 meses de vida, la leche materna es capaz de cubrir adecuadamente los requerimientos, debiendo utilizarse como alternativa, en caso necesario, una fórmula fortificada. Durante la diversificación, se recomienda introducir de forma precoz los cereales fortificados y las carnes. En el niño pequeño, el consumo diario de al menos una ración de alimentos que aporten hierro de alta biodisponibilidad, combinándolos adecuadamente con otros que favorezcan su absorción, es importante para lograr la cobertura de los requerimientos. Únicamente cuando éstos no sean cubiertos por la alimentación habitual, y en determinados grupos de riesgo, se debe realizar de forma seleccionada cribado y suplementación medicamentosa.
Infants and toddlers represent a risk population for iron deficiency (ID), due to their relatively high requirements, which are frequently associated with a poor intake of iron-rich foods. A possible association between ID and impaired cognitive and psychomotor development has been described, and it has been suggested that some of these effects can be irreversible. For this reason, prevention of ID has become a subject of much concern.
To promote an adequate dietetic iron intake is the most important approach for the prevention of ID. Exclusive breast-feeding provides adequate amounts of iron during the first 4-6 months of life, and iron-fortified formula should be used when an alternative is necessary. Fortified cereals and foods containing haem iron, such as meat, should be introduced early in complementary feeding. In toddlers, iron requirements can be satisfied with a daily consumption of at least one serving of iron-containing foods, along with enhancers of iron absorption. When daily requirements are not properly met by food intake, and in some high-risk populations, screening for ID and iron supplementation should be considered.
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Original articleEffect of iron deficiency anemia on visual evoked potential of growing children

Abstract

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgement:

Brain Res Dev Brain Res

Brain Res

Neurosci Lett

Pharmacol Biochem Behav

Am J Clin Nutr

Pediatr Neurol

Am J Kidney Dis

Infant Behav Dev

The prevalence of anaemia in the world

World Health Stat Q