An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function

Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, CA, USA.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 04/2007; 85(4):931-45.
Source: PubMed


This review, intended for a broad scientific readership, summarizes evidence relevant to whether a causal relation exists between dietary iron deficiency with (ID+A) or without (ID-A) anemia during development and deficits in subsequent cognitive or behavioral performance. An overview of expert opinion and major evidence in humans and animals is provided. Cognitive and behavioral effects observed in humans with ID-A and in animals with ID+/-A are provided in tables. The degree to which 5 conditions of causality are satisfied and whether deleterious effects of ID-A might be expected to occur are discussed. On the basis of the existing literature, our major conclusions are as follows. Although most of the 5 conditions of causality (association, plausible biological mechanisms, dose response, ability to manipulate the effect, and specificity of cause and effect) are partially satisfied in humans, animals, or both, a causal connection has not been clearly established. In animals, deficits in motor activity are consistently associated with severe ID+A, but adverse effects on performance in tests that target cognitive function have not been clearly shown. Resistance to iron treatment was observed in most trials of children <2 y of age with ID+A, but not in older children. Similar observations were made in rodents when ID+A occurred before rather than after weaning. In children >2 y of age and in adolescents with ID-A, evidence suggests cognitive or behavioral deficits; however, the surprisingly small number of studies conducted in either humans or animals prevents a thorough assessment.

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    • "The World Health Organization (WHO) defines anemia as hemoglobin concentrations that are below recommended thresholds [3] [5]. The main causes of anemia are dietary iron deficiency; infectious diseases such as malaria, hookworm infections, and schistosomiasis; deficiencies of other key micronutrients including folate, vitamin B12, and vitamin A; or inherited conditions that affect red blood cells (RBCs), such as thalassaemia [6]. The prevalence of anemia during pregnancy is quite high (42%) globally and above 57.1% in Africa, signifying it as a severe public health problem in the region [3]. "
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    ABSTRACT: Anemia is a major public health problem worldwide. In Ethiopia, a nationally representative and consistent evidence is lacking on the prevalence and determinants during pregnancy. We conducted an in-depth analysis of demographic and health survey for the year 2011 which is a representative data collected from all regions in Ethiopia. Considering maternal anemia as an outcome variable, predicting variables from sociodemographic, household, and reproductive/obstetric characteristics were identified for analyses. Logistic regression model was applied to identify predictors at P < 0.05 . The prevalence of anemia among pregnant women was 23%. Maternal age, region, pregnancy trimester, number of under five children, previous history of abortion (termination of pregnancy), breastfeeding practices, and number of antenatal care visits were key independent predictors of anemia during pregnancy. In conclusion, the level of anemia during pregnancy is a moderate public health problem in Ethiopia. Yet, special preventive measures should be undertaken for pregnant women who are older in age and having too many under five children and previous history of abortion. Further evidence is expected to be generated concerning why pregnant mothers from the eastern part of the country and those with better access to radio disproportionately develop anemia more than their counterparts.
    Anemia 09/2015; 2015(4):649815. DOI:10.1155/2015/649815
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    • "There is considerable evidence about the important role of iron in cognitive, behavioral, and motor development (Beard 2001). It is a component of many enzymes involved in neurotransmitter synthesis, and in iron deficiency (ID), due to decreased activity of associated enzymes, monoamine neurotransmitter systems may be affected (McCann and Ames 2007). A decrease in brain iron concentration is accompanied by changes in serotonergic and dopaminergic systems, in cortical fiber conduction, and myelogenesis (Erikson et al. 2001). "
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    ABSTRACT: Iron has an important role in cognitive, behavioral, and motor development. A high prevalence of iron deficiency (ID) has been reported in people with autism. Children with autism are at risk for ID and this condition may increase the severity of psychomotor and behavioral problems, some of which already inherently exist in these children. Aim of the study: The aim of this study is to investigate the association between autism and iron deficiency in autistic children in the Northern West Bank and to identify food selectivity and compare indices of food selectivity among children with autism, children with mental disorders and typically developing children (normal children).Background: Autism is a developmental disorder characterized by qualitative abnormalities of social interaction, impairments in communication, and unusual forms of repetitive behavior . Research shows that a high prevalence of iron deficiency has been reported in children with autism spectrum disorders. Inadequate dietary iron intake was considered as a cause of iron deficiency, and low iron intake was thought to be associated with food selectivity which is commonly seen in children with autistic disorders. Method: 90 children with an age range of 3 to 13 years participated in a case control study distributed into study group and two control groups. Thirty children diagnosed with autism according to DSMIV and ICD-10 criteria served as a study group, 30 children with mental disorders other than autism served as a control group, and 30 typically developing children taken from the public functioned as a second control group. The three groups were matched for age, gender and geographical area. Serum ferritin, hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width values were measured and analyzed with food habit survey and demographic data. Results: ID was detected in 20% (N = 6/30) of autistic children based on Serum ferritin level (SF< 10µ/l), compared with 0% for the two control groups (p= 0.0001). Anemia was defined as hemoglobin <110g/l for children under the age of 6 years and hemoglobin <120g/l for children between 6 and 13 years of age .When analysis done for HGB to these six children (children who have low serum ferritin); it was found that 66.6% (4/6) of the children two were pre-school male children (HGB is less than 110g/1), and the other two were one male and one female of school children (HGB is less than 120g/l) have iron deficiency anemia, and the iron deficiency anemia was 13.3% (4\30) for all autistic group. The results indicated that these differences were for males. It was found also that the frequency of low iron intake in these children was associated with feeding difficulties and food selectivity; there was a significant difference between children in the autistic group who chose foods with a red color as a favorite 23% (7/30) compared to the other two control groups: 0%, respectively (p= 0.0001). The results demonstrated also a significant difference in the frequency of snacks per day (≥ 4) in autistic children 40% (12/30) compared to both mental disorder 16.7 % (n = 5/30) (p = 0.006) and typically developing children 6.7% (n = 2/30) groups (p = 0.001).Conclusions: Results of this study indicated that there is an association between autism, iron deficiency and anemia. Low levels of serum ferritin in autistic children might be a sign of iron deficiency and an early precursor of iron deficiency anemia. These findings suggest that food selectivity is more common in children with autism than in typically developing children. These findings suggest that ferritin levels should be measured in children with autism as a part of routine investigation
    Critical Public Health 01/2015; 16(2422-8419). · 0.88 Impact Factor
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    • "The MD values in gray matter are known to be lowered by metals including iron and copper with paramagnetic properties because of the effects of paramagnetic properties on MRI (Sener 2002). Furthermore, some metals, such as iron and copper, have long been suggested to play essential roles in the dopaminergic system , and, these metals are required for dopamine production (McCann and Ames 2007 "
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    ABSTRACT: Dopaminergic transmission plays a critical role in working memory (WM). Mean diffusivity (MD) is a sensitive and unique neuroimaging tool for detecting microstructural differences particularly in the areas of the dopaminergic system. Despite previous investigation of the effects of WM training (WMT) on dopamine receptor binding potentials, the effects of WMT on MD remain unknown. In this study, we investigated these effects in young adult subjects who either underwent WMT or received no intervention for 4 weeks. Before and after the intervention or no-intervention periods, subjects underwent scanning sessions in diffusion-weighted imaging to measure MD. Compared with no intervention, WMT resulted in an increase in MD in the bilateral caudate, right putamen, left dorsolateral prefrontal cortex (DLPFC), right anterior cingulate cortex (ACC), right substantia nigra, and ventral tegmental area. Furthermore, the increase in performance on WMT tasks was significantly positively correlated with the mean increase in MD in the clusters of the left DLPFC and of the right ACC. These results suggest that WMT caused microstructural changes in the regions of the dopaminergic system in a way that is usually interpreted as a reduction in neural components.
    Brain Structure and Function 07/2014; 220(6). DOI:10.1007/s00429-014-0845-2 · 5.62 Impact Factor
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