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Szymlek-Gay EA, Heath ALM, Gibson RS, Ferguson EL. Development and evaluation of food-based dietary recommendations for New Zealand toddlers using linear and goal programming. Eur J Nutr 2024; 64:18. [PMID: 39570416 DOI: 10.1007/s00394-024-03534-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 09/26/2024] [Indexed: 11/22/2024]
Abstract
PURPOSE We designed and evaluated food-based dietary recommendations for 12-24-mo-old New Zealand children with linear and goal programming models taking into account intakes of all nutrients concurrently. METHODS Dietary data used to define model parameters (food list, food quantities consumed, and food consumption patterns from 3-d weighed food records) were collected from 12-24-mo-old New Zealand toddlers (n = 188). Linear and goal programming models were developed to design and evaluate three sets of recommendations: (1) using all foods consumed by toddlers; (2) excluding commercial infant/toddler foods; and (3) excluding both commercial infant/toddler foods and all iron-fortified foods. RESULTS Food-based dietary recommendations for toddlers were developed which aligned with observed food consumption patterns: Non-Sweet Cereals: 3 serves/d, Vegetables: 2 serves/d, Fruit: 2 serves/d, Dairy: 2 serves/d, and Meat/Fish/Poultry/Eggs/Legumes/Nuts: 2 serves/d. However, they only ensured adequate intakes of all nutrients modeled if ≈ 500 g/d of iron-fortified toddler milk was also recommended. Food-based dietary recommendations that excluded commercial infant/toddler foods or excluded both commercial infant/toddler foods and all iron-fortified foods would not ensure adequate intakes of iron and folate, for all children. The lowest intakes, in simulated intake distributions for these nutrients, were ≤ 29% and ≤ 38% of their nutrient reference values, respectively. CONCLUSIONS Food-based dietary recommendations which successfully promote the consumption of 3 serves/d of Non-Sweet Cereals, 2 serves/d of Vegetables, 2 serves/d of Fruit, 2 serves/d of Dairy (including ≈ 500 g/d of iron-fortified toddler milk), and 2 serves/d of Meat/Fish/Poultry/Eggs/Legumes/Nuts should ensure all New Zealand toddlers meet their requirements for the 15 nutrients modeled.
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Affiliation(s)
- Ewa A Szymlek-Gay
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Melbourne Burwood Campus, 221 Burwood Highway, Burwood, VIC 3125, Australia.
| | | | - Rosalind S Gibson
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | - Elaine L Ferguson
- Department of Population Health, London School of Hygiene and Tropical Medicine, London, UK
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Turck D, Bohn T, Castenmiller J, de Henauw S, Hirsch‐Ernst K, Knutsen HK, Maciuk A, Mangelsdorf I, McArdle HJ, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Aggett P, Fairweather‐Tait S, de Sesmaisons Lecarré A, Fabiani L, Karavasiloglou N, Saad RM, Sofroniou A, Titz A, Naska A. Scientific opinion on the tolerable upper intake level for iron. EFSA J 2024; 22:e8819. [PMID: 38868106 PMCID: PMC11167337 DOI: 10.2903/j.efsa.2024.8819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2024] Open
Abstract
Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for iron. Systematic reviews were conducted to identify evidence regarding high iron intakes and risk of chronic diseases, adverse gastrointestinal effects and adverse effects of iron supplementation in infancy, young childhood and pregnancy. It is established that systemic iron overload leads to organ toxicity, but no UL could be established. The only indicator for which a dose-response could be established was black stools, which reflect the presence of large amounts of unabsorbed iron in the gut. This is a conservative endpoint among the chain of events that may lead to systemic iron overload but is not adverse per se. Based on interventions in which black stools did not occur at supplemental iron intakes of 20-25 mg/day (added to a background intake of 15 mg/day), a safe level of intake for iron of 40 mg/day for adults (including pregnant and lactating women) was established. Using allometric scaling (body weight0.75), this value was scaled down to children and adolescents and safe levels of intakes between 10 mg/day (1-3 years) and 35 mg/day (15-17 years) were derived. For infants 7-11 months of age who have a higher iron requirement than young children, allometric scaling was applied to the supplemental iron intakes (i.e. 25 mg/day) and resulted in a safe level of supplemental iron intake of 5 mg/day. This value was extended to 4-6 month-old infants and refers to iron intakes from fortified foods and food supplements, not from infant and follow-on formulae. The application of the safe level of intake is more limited than a UL because the intake level at which the risk of adverse effects starts to increase is not defined.
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3
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Park J, Wickramasinghe S, Mills DA, Lönnerdal BL, Ji P. Iron Fortification and Inulin Supplementation in Early Infancy: Evaluating the Impact on Iron Metabolism and Trace Mineral Status in a Piglet Model. Curr Dev Nutr 2024; 8:102147. [PMID: 38645881 PMCID: PMC11026733 DOI: 10.1016/j.cdnut.2024.102147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 03/18/2024] [Accepted: 03/22/2024] [Indexed: 04/23/2024] Open
Abstract
Background Infant formula in the United States contains abundant iron, raising health concerns about excess iron intake in early infancy. Objectives Using a piglet model, we explored the impact of high iron fortification and prebiotic or synbiotic supplementation on iron homeostasis and trace mineral bioavailability. Methods Twenty-four piglets were stratified and randomly assigned to treatments on postnatal day 2. Piglets were individually housed and received an iron-adequate milk diet (AI), a high-iron milk diet (HI), HI supplemented with 5% inulin (HI with a prebiotic [HIP]), or HIP with an oral gavage of Ligilactobacillus agilis YZ050, an inulin-fermenting strain, every third day (HI with synbiotic [HIS]). Milk was provided in 14 meals daily, mimicking formula feeding in infants. Fecal consistency score and body weight were recorded daily or every other day. Blood and feces were sampled weekly, and tissues collected on postnatal day 29. Data were analyzed using mixed model analysis of variance with repeated measures whenever necessary. Results Diet did not affect growth. HI increased hemoglobin, hematocrit, and serum iron compared to AI. Despite marginal adequacy, AI upregulated iron transporter genes and maintained satisfactory iron status in most pigs. HI upregulated hepcidin gene expression in liver, caused pronounced tissue iron deposition, and markedly increased colonic and fecal iron. Inulin supplementation, regardless of L. agilis YZ050, not only attenuated hepatic iron overload but also decreased colonic and fecal iron without altering pH or the expression of iron regulatory genes. HI lowered zinc (Zn) and copper (Cu) in the duodenum and liver compared to AI, whereas HIP and HIS further decreased Zn and Cu in the liver and diminished colonic and fecal trace minerals. Conclusions Early-infancy excessive iron fortification causes iron overload and compromises Zn and Cu absorption. Inulin decreases trace mineral absorption likely by enhancing gut peristalsis and stool frequency.
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Affiliation(s)
- Jungjae Park
- Department of Nutrition, University of California Davis, CA, United States
| | - Saumya Wickramasinghe
- Department of Food Science and Technology, University of California Davis, CA, United States
| | - David A. Mills
- Department of Food Science and Technology, University of California Davis, CA, United States
| | - Bo L. Lönnerdal
- Department of Nutrition, University of California Davis, CA, United States
| | - Peng Ji
- Department of Nutrition, University of California Davis, CA, United States
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4
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Domellöf M, Sjöberg A. Iron - a background article for the Nordic Nutrition Recommendations 2023. Food Nutr Res 2024; 68:10451. [PMID: 38370116 PMCID: PMC10870973 DOI: 10.29219/fnr.v68.10451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 11/14/2023] [Accepted: 12/20/2023] [Indexed: 02/20/2024] Open
Abstract
Iron absorption from foods is generally lower than that of most other nutrients and is highly variable depending on individual iron status and iron bioavailability in the meal. Several large population groups in the Nordic and Baltic countries are at risk of iron deficiency, including infants, young children, menstruating females, pregnant women as well as vegetarians. Iron deficiency leads to anemia, fatigue, and limited capacity for physical activity. Of particular concern is that iron deficiency anemia in young children is associated with impaired neurodevelopment. A comprehensive literature search has been performed and summarized. New factorial calculations have been performed considering iron losses, iron absorption and iron requirements in various population groups. Recent data on iron intakes and the prevalence of iron deficiency in the Nordic countries are presented. Average requirements and tentative recommended intakes are presented for 12 different population groups. Pregnant women and those with high menstrual blood losses should consume iron-rich food and undergo screening for iron deficiency. Infants should consume iron-rich complementary foods and cow's milk should be avoided as a drink before 12 months of age and limited to < 500 mL/day in toddlers. Vegetarians should consume a diet including wholegrains, legumes, seeds, and green vegetables together with iron absorption enhancers. There is no evidence that iron intake per se increases the risk of cancer or diabetes. Iron absorption from foods is generally lower than that of most other nutrients and can vary between <2 and 50% depending on individual iron status and iron bioavailability in the meal.
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Affiliation(s)
- Magnus Domellöf
- Department of Clinical Sciences, Umeå University, Umeå, Sweden
| | - Agneta Sjöberg
- Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden
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5
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Gutema BT, Levecke B, Sorrie MB, Megersa ND, Zewdie TH, Yesera GE, De Henauw S, Abubakar A, Abbeddou S. Effectiveness of intermittent iron and high-dose vitamin A supplementation on cognitive development of school children in southern Ethiopia: a randomized placebo-controlled trial. Am J Clin Nutr 2024; 119:470-484. [PMID: 37952928 DOI: 10.1016/j.ajcnut.2023.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 11/01/2023] [Accepted: 11/06/2023] [Indexed: 11/14/2023] Open
Abstract
BACKGROUND Iron is an essential mineral whose deficiency results in cognitive alteration, impaired emotional behaviors, and altered myelination and neurotransmission. In animal models, it has been shown that vitamin A (VA) could affect cognition. OBJECTIVES The study aimed to evaluate the effectiveness of intermittent iron and VA supplementation on cognitive development of schoolchildren, and to assess the interaction between these supplementations. METHODS Considering a 2 × 2 factorial design, 504 children were randomly assigned to 1 of the 4 arms: placebo VA and placebo iron supplement; high-dose vitamin VA and placebo iron supplement; iron supplement and placebo VA; and iron and high-dose vitamin VA supplements. Cognitive development was assessed using Raven's Coloured Progressive Matrices, digit span, Tower of London, and visual search tasks. RESULTS The mean [± standard deviation (SD)] age of the enrolled children was 9.6 (±1.6) y. One-fifth of the children had iron deficiency or anemia, whereas 2.9%, 3.9%, and 12.1% of children had low iron stores, iron deficiency anemia, and VA deficiency, respectively. Intermittent iron supplementation did not result in any significant improvement of children's cognitive development and had a negative effect on the performance index of the visual search task compared with placebo (-0.17 SD, 95% confidence interval: -0.32, -0.02). Effects were evident among children with stunting, thinness, or children coming from understimulating home environments. High-dose VA supplementation resulted in a significant improvement of digit span z-score with a mean difference of 0.30 SD (95% confidence interval: 0.14, 0.46) compared with placebo VA. VA had a more beneficial impact for girls, children infected with helminths, and those from food secure households. CONCLUSION In a population where the prevalence of iron deficiency is low, intermittent iron supplementation did not have any or negative effect on the child's cognitive development outcomes. Conversely, VA supplementation improved the child's working memory. TRIAL REGISTRATION NUMBER The study is registered at clinicaltrials.gov as NCT04137354 (https://clinicaltrials.gov/study/NCT04137354).
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Affiliation(s)
- Befikadu Tariku Gutema
- School of Public Health, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia; Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
| | - Bruno Levecke
- Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Muluken Bekele Sorrie
- School of Public Health, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia; Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Nega Degefa Megersa
- School of Nursing, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia
| | - Tadiwos Hailu Zewdie
- School of Medicine, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia
| | - Gesila Endashaw Yesera
- School of Nursing, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia
| | - Stefaan De Henauw
- Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Amina Abubakar
- Kenya Medical Research Institute (KMRI)-Wellcome Trust Research Programme, Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute, Kilifi, Kenya
| | - Souheila Abbeddou
- Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
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Rezqaoui A, Ibouzine-Dine L, Elhamzaoui A, Brouzi MYE, Dimaoui A, Hessni AE, Mesfioui A. Potential Role of Oxidative Stress in the Effects of Chronic Administration of Iron on Affective and Cognitive Behavior on Male Wistar Rat. Biol Trace Elem Res 2023; 201:4812-4826. [PMID: 36683122 DOI: 10.1007/s12011-023-03560-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 01/05/2023] [Indexed: 01/24/2023]
Abstract
In this work, we studied the impact of chronic iron exposure, in the form of iron sulfate (FeSo4), on affective and cognitive disorders and oxidative stress in the male Wistar rat. The treatment was carried out for 8 weeks, the rats received an intraperitoneal injection of iron at different doses: 0.25, 0.5, and 1 mg/kg. Affective and cognitive disorders are assessed in open field test (OFT), elevated plus maze (EPM), forced swimming test (FST), Morris water maze (MWM), and Y-maze. The hippocampus and prefrontal cortex of each animal were taken for biochemical examination. Our results show that iron exerts anxiogenic and depressogenic effects, which were observed first at the dose of 0.5 mg/kg and continued in a dose-dependent manner up to the maximum tested dose of 1 mg/kg. According to results from the MWM and Y-maze tests, continuous exposure to iron induces cognitive disorders that are defined by the disturbance of working memory and influences spatial learning performance causing a deficit of spatial memory retention. We noted that chronic exposure to iron can be associated with the appearance of a state of oxidative stress in the hippocampus and the prefrontal cortex demonstrated by an increase in lipid peroxidation, an increase in nitric oxide, and also by disturbances in the antioxidant defense systems following a determination of the concentrations of catalase. In conclusion, we can deduce from this work that chronic iron exposure can be related to the induction of cognitive and affective disorders and oxidative stress.
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Affiliation(s)
- Ayoub Rezqaoui
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco.
| | - Laila Ibouzine-Dine
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco
| | - Abdelghafour Elhamzaoui
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco
| | - Mohamed Yassine El Brouzi
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco
| | - Amal Dimaoui
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco
| | - Aboubaker El Hessni
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco
| | - Abdelhalem Mesfioui
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco
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Arcot A, Xing X, Gao X, Font SA, Murray-Kolb LE. Iron status, development, and behavior in young children in the Pennsylvania foster care system. PLoS One 2023; 18:e0289951. [PMID: 37590213 PMCID: PMC10434919 DOI: 10.1371/journal.pone.0289951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 07/28/2023] [Indexed: 08/19/2023] Open
Abstract
BACKGROUND Children in foster care are classified as a highly vulnerable population and struggle with both physical and mental health problems. Medical conditions, like poor nutritional status, remain understudied in children in foster care. To our knowledge, few studies in children in U.S. foster care have quantified the prevalence of anemia, and no studies have examined the association between anemia status and relevant developmental and behavioral outcomes. OBJECTIVE/AIMS (1) To determine the prevalence of anemia among children in or adopted from Pennsylvania foster care, between the ages of six months to ten years and (2) To examine if a child's anemia status is associated with greater odds of relevant developmental and behavioral diagnoses. METHODS We conducted a secondary data analysis utilizing the Medicaid Analytic eXtract database between 2010-2015. Children six months-ten years were included in the analysis if they were in or had been adopted from Pennsylvania foster care. Logistic regression was used to calculate adjusted odds ratios (AOR) with 95% confidence intervals for the association between iron status and health outcomes. RESULTS A total of 50,311 children were included in our sample, of which 1,365 children (2.7%) were diagnosed with anemia. Children diagnosed with anemia had greater odds of delayed milestones (AOR: 2.38 [1.64-3.45]), specific delays in development (AOR: 1.59 [1.23-2.07]), adjustment disorder (AOR: 1.59 [1.06-2.39]), and irritability (AOR: 10.57 [3.36-33.25]), than children not diagnosed with anemia. CONCLUSION The prevalence of anemia among children between six months-ten years in or adopted from the Pennsylvania foster care system is within the national rate of U.S. childhood anemia. Odds of several relevant developmental and behavioral diagnoses were greater among children diagnosed with anemia than children who were not.
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Affiliation(s)
- Amrita Arcot
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, United States of America
| | - Xueyi Xing
- Evidence-to-Impact Collaborative, Social Science Research Institute, The Pennsylvania State University, University Park, PA, United States of America
| | - Xiang Gao
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, United States of America
- Department of Nutrition and Food Hygiene, School of Public Health, Fudan University, Shanghai, China
| | - Sarah A. Font
- Department of Sociology and Criminology, The Pennsylvania State University, University Park, PA, United States of America
| | - Laura E. Murray-Kolb
- Department of Nutrition Science, Purdue University, West Lafayette, IN, United States of America
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8
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Karthikappallil R, Atkinson SH. Universal iron supplementation: the best strategy to tackle childhood anaemia in malaria-endemic countries? Wellcome Open Res 2023; 8:345. [PMID: 37786779 PMCID: PMC10541535 DOI: 10.12688/wellcomeopenres.19750.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2023] [Indexed: 10/04/2023] Open
Abstract
Iron deficiency presents a major public health concern in many malaria-endemic regions, and both conditions affect young children most severely. Daily iron supplementation is the standard public health intervention recommended to alleviate rates of iron deficiency in children, but there is controversy over whether universal supplementation could increase the incidence and severity of malaria infection. Current evidence suggests that iron supplementation of deficient individuals is safe and effective in high-transmission settings when accompanied by malaria prevention strategies. However, low-resource settings often struggle to effectively control the spread of malaria, and it remains unclear whether supplementation of iron replete individuals could increase their risk of malaria and other infections. This review explores the evidence for and against universal iron supplementation programmes, and alternative strategies that could be used to alleviate iron deficiency in malaria-endemic areas, while minimising potential harm.
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Affiliation(s)
- Roshan Karthikappallil
- Department of Paediatrics, University of Oxford, Oxford, England, UK
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, England, UK
| | - Sarah H. Atkinson
- Department of Paediatrics, University of Oxford, Oxford, England, UK
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, England, UK
- Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
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9
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Lotan A, Luza S, Opazo CM, Ayton S, Lane DJR, Mancuso S, Pereira A, Sundram S, Weickert CS, Bousman C, Pantelis C, Everall IP, Bush AI. Perturbed iron biology in the prefrontal cortex of people with schizophrenia. Mol Psychiatry 2023; 28:2058-2070. [PMID: 36750734 PMCID: PMC10575779 DOI: 10.1038/s41380-023-01979-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 01/10/2023] [Accepted: 01/20/2023] [Indexed: 02/09/2023]
Abstract
Despite loss of grey matter volume and emergence of distinct cognitive deficits in young adults diagnosed with schizophrenia, current treatments for schizophrenia do not target disruptions in late maturational reshaping of the prefrontal cortex. Iron, the most abundant transition metal in the brain, is essential to brain development and function, but in excess, it can impair major neurotransmission systems and lead to lipid peroxidation, neuroinflammation and accelerated aging. However, analysis of cortical iron biology in schizophrenia has not been reported in modern literature. Using a combination of inductively coupled plasma-mass spectrometry and western blots, we quantified iron and its major-storage protein, ferritin, in post-mortem prefrontal cortex specimens obtained from three independent, well-characterised brain tissue resources. Compared to matched controls (n = 85), among schizophrenia cases (n = 86) we found elevated tissue iron, unlikely to be confounded by demographic and lifestyle variables, by duration, dose and type of antipsychotic medications used or by copper and zinc levels. We further observed a loss of physiologic age-dependent iron accumulation among people with schizophrenia, in that the iron level among cases was already high in young adulthood. Ferritin, which stores iron in a redox-inactive form, was paradoxically decreased in individuals with the disorder. Such iron-ferritin uncoupling could alter free, chemically reactive, tissue iron in key reasoning and planning areas of the young-adult schizophrenia cortex. Using a prediction model based on iron and ferritin, our data provide a pathophysiologic link between perturbed cortical iron biology and schizophrenia and indicate that achievement of optimal cortical iron homeostasis could offer a new therapeutic target.
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Affiliation(s)
- Amit Lotan
- Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, 3010, Australia
- Department of Psychiatry and the Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Sandra Luza
- Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, 3010, Australia
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton, VIC, Australia
| | - Carlos M Opazo
- Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, 3010, Australia.
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton, VIC, Australia.
| | - Scott Ayton
- Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, 3010, Australia
| | - Darius J R Lane
- Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, 3010, Australia
| | - Serafino Mancuso
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton, VIC, Australia
| | - Avril Pereira
- Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, 3010, Australia
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton, VIC, Australia
| | - Suresh Sundram
- Department of Psychiatry, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia
- Mental Health Program, Monash Health, Melbourne, VIC, Australia
| | - Cynthia Shannon Weickert
- Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW, Australia
- School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Chad Bousman
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton, VIC, Australia
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada
- The Cooperative Research Centre (CRC) for Mental Health, Melbourne, VIC, Australia
| | - Christos Pantelis
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton, VIC, Australia
- North Western Mental Health, Melbourne, VIC, Australia
| | - Ian P Everall
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton, VIC, Australia
- North Western Mental Health, Melbourne, VIC, Australia
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Ashley I Bush
- Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, 3010, Australia.
- The Cooperative Research Centre (CRC) for Mental Health, Melbourne, VIC, Australia.
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10
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East PL, Reid B, Blanco E, Burrows R, Lozoff B, Gahagan S. Iron supplementation given to nonanemic infants: neurocognitive functioning at 16 years. Nutr Neurosci 2023; 26:40-49. [PMID: 34927561 PMCID: PMC9206691 DOI: 10.1080/1028415x.2021.2013399] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
OBJECTIVE There is concern that high iron uptake during the critical period of early brain development carries potential risks, especially for nonanemic infants. This study examined the neurocognitive functioning of 16-year-olds who were nonanemic as infants and received iron supplementation. METHODS We studied 562 Chilean adolescents (M 16.2 years; 52.7% female) who participated in a randomized controlled iron supplementation trial in infancy. Between 6 and 12 months, 346 consumed an iron-fortified formula (12.7 Fe mg/L) or, if primarily breastfed, liquid vitamins with 15 mg elemental iron as ferrous sulfate, and 216 consumed unmodified cow milk without iron or liquid vitamins without iron if primarily breastfed. RESULTS Compared to adolescents in the no-added iron condition in infancy, those in the iron-supplemented condition had poorer visual-motor integration, quantitative reasoning skills, and incurred more errors on neurocognitive tasks. Consuming larger amounts of iron-fortified formula in infancy was associated with lower arithmetic achievement. Of adolescents who had high hemoglobin at 6 months (Hb ≥ 125 g/L), those in the iron supplemented condition had poorer performance on arithmetic, quantitative reasoning, and response inhibition tests than those in the no-added iron condition. Of adolescents who had marginally low 6-month hemoglobin (Hb > 100 and < 110 g/L), those who received no-added iron incurred more errors on a visual searching task than those in the iron-supplemented condition. CONCLUSION The physiologic need for iron during the period of rapid and critical brain development in young infants should be considered vis-à-vis the risks associated with supplementing nonanemic infants with high levels of iron.Clinical Trials number: NCT01166451.
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Affiliation(s)
- Patricia L. East
- Department of Pediatrics, University of California, San
Diego, La Jolla, CA, USA
| | - Brie Reid
- Department of Psychiatry and Human Behavior, Brown
University Medical School, Providence, RI, USA
| | - Estela Blanco
- Department of Pediatrics, University of California, San
Diego, La Jolla, CA, USA
- Department of Public Health, Pontifical Catholic University
of Chile, Santiago, Chile
| | - Raquel Burrows
- Institute of Nutrition and Food Technology, University of
Chile, Santiago, Chile
| | - Betsy Lozoff
- Department of Pediatrics, University of Michigan, Ann
Arbor, MI, USA
| | - Sheila Gahagan
- Department of Pediatrics, University of California, San
Diego, La Jolla, CA, USA
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11
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McMillen SA, Dean R, Dihardja E, Ji P, Lönnerdal B. Benefits and Risks of Early Life Iron Supplementation. Nutrients 2022; 14:4380. [PMID: 36297062 PMCID: PMC9608469 DOI: 10.3390/nu14204380] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/16/2022] [Accepted: 10/17/2022] [Indexed: 01/19/2024] Open
Abstract
Infants are frequently supplemented with iron to prevent iron deficiency, but iron supplements may have adverse effects on infant health. Although iron supplements can be highly effective at improving iron status and preventing iron deficiency anemia, iron may adversely affect growth and development, and may increase risk for certain infections. Several reviews exist in this area; however, none has fully summarized all reported outcomes of iron supplementation during infancy. In this review, we summarize the risks and benefits of iron supplementation as they have been reported in controlled studies and in relevant animal models. Additionally, we discuss the mechanisms that may underly beneficial and adverse effects.
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Affiliation(s)
| | | | | | | | - Bo Lönnerdal
- Department of Nutrition, University of California, Davis, CA 95616, USA
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12
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Von Holle A, North KE, Gahagan S, Blanco E, Burrows R, Lozoff B, Howard AG, Justice AE, Graff M, Voruganti S. Infant Growth Trajectories and Lipid Levels in Adolescence: Evidence From a Chilean Infancy Cohort. Am J Epidemiol 2022; 191:1700-1709. [PMID: 35467716 PMCID: PMC9989340 DOI: 10.1093/aje/kwac057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 02/14/2022] [Accepted: 03/22/2022] [Indexed: 01/29/2023] Open
Abstract
Growth in early infancy is hypothesized to affect chronic disease risk factors later in life. To date, most reports draw on European-ancestry cohorts with few repeated observations in early infancy. We investigated the association between infant growth before 6 months and lipid levels in adolescents in a Hispanic/Latino cohort. We characterized infant growth from birth to 5 months in male (n = 311) and female (n = 285) infants from the Santiago Longitudinal Study (1991-1996) using 3 metrics: weight (kg), length (cm), and weight-for-length (g/cm). Superimposition by translation and rotation (SITAR) and latent growth mixture models (LGMMs) were used to estimate the association between infant growth characteristics and lipid levels at age 17 years. We found a positive relationship between the SITAR length velocity parameter before 6 months of age and high-density lipoprotein cholesterol levels in adolescence (11.5, 95% confidence interval; 3.4, 19.5), indicating higher high-density lipoprotein cholesterol levels occurring with faster length growth. The strongest associations from the LGMMs were between higher low-density lipoprotein cholesterol and slower weight-for-length growth, following a pattern of associations between slower growth and adverse lipid profiles. Further research in this window of time can confirm the association between early infant growth as an exposure and adolescent cardiovascular disease risk factors.
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Affiliation(s)
- Ann Von Holle
- Correspondence to Dr. Ann Von Holle, P.O. Box 12233, Durham, NC 27709 (e-mail: )
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13
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Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats. Nutrients 2022; 14:nu14193913. [PMID: 36235565 PMCID: PMC9571796 DOI: 10.3390/nu14193913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/16/2022] [Accepted: 09/20/2022] [Indexed: 11/17/2022] Open
Abstract
Iron supplements are frequently provided to infants in high-income countries despite low incidence of iron deficiency. There is growing concern regarding adverse health and development outcomes of excess iron provision in early life. Excess iron may directly damage developing organs through the formation of reactive oxygen species, alter systemic inflammatory signaling, and/or dysregulate trace mineral metabolism. To better characterize the in vivo effects of excess iron on development, we utilized a pre-weanling rat pup model. Lewis rat litters were culled to eight pups (four males and four females) and randomly assigned to daily supplementation groups receiving either vehicle control (CON; 10% w/v sucrose solution) or ferrous sulfate (FS) iron at one of the following doses: 10, 30, or 90 mg iron/kg body weight—FS-10, FS-30, and FS-90, respectively—from postnatal day (PD) 2 through 9. FS-90 litters, but not FS-30 or FS-10, failed to thrive compared to CON litters and had smaller brains on PD 10. Among the groups, FS-90 liver iron levels were highest, as were white blood cell counts. Compared to CON, circulating MCP-1 and liver zinc were increased in FS-90 pups, whereas liver copper was decreased. Growth defects due to excess FS provision in pre-weanling rats may be related to liver injury, inflammation, and altered trace mineral metabolism.
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14
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Yasuda H, Tsutsui T. Metallomics analysis for early assessment and individualized intervention of neurodevelopmental disorders. METALLOMICS : INTEGRATED BIOMETAL SCIENCE 2022; 14:6695310. [PMID: 36087072 DOI: 10.1093/mtomcs/mfac067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 07/28/2022] [Indexed: 11/12/2022]
Abstract
The children today are in the midst of the epidemic of neurodevelopmental disorders. In this metallomics study for the scalp hair samples of total 2550 children with autistic disorders (2108 males and 442 females aged 0-15 year), it was demonstrated that near one half of the infantile individuals aged 0-3 year are suffering from zinc deficiency and toxic metal burdens. Zinc level correlated closely to the index of zinc/iron ratio more than zinc/copper ratio. Furthermore, there were significant relationships between zinc deficiency and toxic metal burdens such as lead and aluminum which were inversely associated with not only zinc level but also zinc/iron ratio with higher regression coefficients of r = -0.486 and -0.551 (p < 0.00001), respectively. High-significant inverse association was detected between zinc and molybdenum concentration (r = -0.509) and also between zinc/iron ratio and molybdenum (r = -0.548). These findings suggest that infantile zinc deficiency relates to the high burdens of not only toxic but also some essential metals such as molybdenum, iron and manganese and that these various mineral imbalances play principal roles to the etiology of neurodevelopmental disorders. We expect that the early assessment and intervention of the mineral imbalances (or dis-homeostasis) in individual child open an avenue for evidence-based individualized treatment of neurodevelopmental disorders and also of the comorbid immune disorders, in near future.
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Affiliation(s)
- Hiroshi Yasuda
- La Belle Vie Research Laboratory, Tokyo; Japan.,Institute of Nature and Environmental Technology, Kanazawa University, Kanazawa, Japan
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15
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IUNS sustainable diets task force. Trends Food Sci Technol 2022. [DOI: 10.1016/j.tifs.2022.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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16
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Tang CY, Wen F. Serum ferritin levels in children with attention deficit hyperactivity disorder and tic disorder. World J Clin Cases 2022; 10:7749-7759. [PMID: 36158507 PMCID: PMC9372851 DOI: 10.12998/wjcc.v10.i22.7749] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 05/01/2022] [Accepted: 06/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Iron plays an important role in neurodevelopmental functions in the brain. Serum ferritin levels are different in children with attention deficit hyperactivity disorder and tic disorder than in healthy children.
AIM To explore the current status of iron deficiency in children with neurodevelopmental disorders and its sex and age effects.
METHODS A total of 1565 children with attention deficit hyperactivity disorder (ADHD), 1694 children with tic disorder (TD), 93 children with ASD and 1997 healthy control children were included between January 1, 2020, and December 31, 2021 at Beijing Children's Hospital. We describe the differences in age levels and ferritin levels between different disease groups and their sex differences. The differences between the sexes in each disease were analyzed using the t test. The incidence rate of low serum ferritin was used to describe the differences between different diseases and different age groups. A chi-square test was used to analyze the difference in the incidence of low serum ferritin between the disease group and the control group. Analysis of variance was used for comparisons between subgroups, and regression analysis was used for confounding factor control.
RESULTS A total of 1565 ADHD patients aged 5-12 years were included in this study, and the average serum ferritin levels of male and female children were 36.82 ± 20.64 μg/L and 35.64 ± 18.56 μg/L, respectively. A total of 1694 TD patients aged 5-12 years were included in this study, and the average serum ferritin levels of male and female children were 35.72 ± 20.15 μg/L and 34.54 ± 22.12 μg/L, respectively. As age increased, the incidence of low serum ferritin in ADHD and TD first decreased and then increased, and 10 years old was the turning point of rising levels. The incidence of ADHD with low serum ferritin was 8.37%, the incidence of TD with low serum ferritin was 11.04%, and the incidence of the healthy control group with low serum ferritin was 8.61%, among which male children with TD accounted for 9.25% and female children with TD accounted for 11.62%. There was a significant difference among the three groups (P < 0.05). In addition, there were 93 children with ASD with an average serum ferritin level of 30.99 ± 18.11 μg/L and a serum ferritin incidence of 15.05%.
CONCLUSION In conclusion, low serum ferritin is not a risk factor for ADHD or TD. The incidence of low serum ferritin levels in children with ADHD and TD between 5 and 12 years old decreases first and then increases with age.
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Affiliation(s)
- Cai-Yun Tang
- Department of Psychiatry, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Fang Wen
- Department of Psychiatry, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
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17
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Chouraqui JP. Dietary Approaches to Iron Deficiency Prevention in Childhood-A Critical Public Health Issue. Nutrients 2022; 14:1604. [PMID: 35458166 PMCID: PMC9026685 DOI: 10.3390/nu14081604] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/03/2022] [Accepted: 04/08/2022] [Indexed: 12/15/2022] Open
Abstract
Iron is an essential nutrient, and individual iron status is determined by the regulation of iron absorption, which is driven by iron requirements. Iron deficiency (ID) disproportionately affects infants, children, and adolescents, particularly those who live in areas with unfavorable socioeconomic conditions. The main reason for this is that diet provides insufficient bioavailable iron to meet their needs. The consequences of ID include poor immune function and response to vaccination, and moderate ID anemia is associated with depressed neurodevelopment and impaired cognitive and academic performances. The persistently high prevalence of ID worldwide leads to the need for effective measures of ID prevention. The main strategies include the dietary diversification of foods with more bioavailable iron and/or the use of iron-fortified staple foods such as formula or cereals. However, this strategy may be limited due to its cost, especially in low-income countries where biofortification is a promising approach. Another option is iron supplementation. In terms of health policy, the choice between mass and targeted ID prevention depends on local conditions. In any case, this remains a critical public health issue in many countries that must be taken into consideration, especially in children under 5 years of age.
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Affiliation(s)
- Jean-Pierre Chouraqui
- Pediatric Nutrition and Gastroenterology Unit, Woman, Mother and Child Department, University Hospital of Lausanne, 1011 Lausanne, Switzerland
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18
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Gut Microbiome Alterations following Postnatal Iron Supplementation Depend on Iron Form and Persist into Adulthood. Nutrients 2022; 14:nu14030412. [PMID: 35276770 PMCID: PMC8838803 DOI: 10.3390/nu14030412] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/12/2022] [Accepted: 01/14/2022] [Indexed: 12/13/2022] Open
Abstract
The gut microbiota is implicated in the adverse developmental outcomes of postnatal iron supplementation. To generate hypotheses on how changes to the gut microbiota by iron adversely affect development, and to determine whether the form of iron influences microbiota outcomes, we characterized gut microbiome and metabolome changes in Sprague-Dawley rat pups given oral supplements of ferrous sulfate (FS), ferrous bis-glycinate chelate (FC), or vehicle control (CON) on postnatal day (PD) 2−14. Iron supplementation reduced microbiome alpha-diversity (p < 0.0001) and altered short-chain fatty acids (SCFAs) and trimethylamine (TMA) in a form-dependent manner. To investigate the long-term effects of iron provision in early life, an additional cohort was supplemented with FS, FC, or CON until PD 21 and then weaned onto standard chow. At ~8 weeks of age, young adult (YA) rats that received FS exhibited more diverse microbiomes compared to CON (p < 0.05), whereas FC microbiomes were less diverse (p < 0.05). Iron provision resulted in 10,000-fold reduced abundance of Lactobacilli in pre-weanling and YA animals provided iron in early life (p < 0.0001). Our results suggest that in pre-weanling rats, supplemental iron form can generate differential effects on the gut microbiota and microbial metabolism that persist into adulthood.
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19
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Abstract
All nutrients are essential for brain development, but pre-clinical and clinical studies have revealed sensitive periods of brain development during which key nutrients are critical. An understanding of these nutrient-specific sensitive periods and the accompanying brain regions or processes that are developing can guide effective nutrition interventions as well as the choice of meaningful circuit-specific neurobehavioral tests to best determine outcome. For several nutrients including protein, iron, iodine, and choline, pre-clinical and clinical studies align to identify the same sensitive periods, while for other nutrients, such as long-chain polyunsaturated fatty acids, zinc, and vitamin D, pre-clinical models demonstrate benefit which is not consistently shown in clinical studies. This discordance of pre-clinical and clinical results is potentially due to key differences in the timing, dose, and/or duration of the nutritional intervention as well as the pre-existing nutritional status of the target population. In general, however, the optimal window of success for nutritional intervention to best support brain development is in late fetal and early postnatal life. Lack of essential nutrients during these times can lead to long-lasting dysfunction and significant loss of developmental potential.
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Affiliation(s)
- Sarah E Cusick
- Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN, USA.
| | - Amanda Barks
- University of Minnesota Medical School, Minneapolis, MN, USA
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20
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German KR, Vu PT, Comstock BA, Ohls RK, Heagerty PJ, Mayock DE, Georgieff M, Rao R, Juul SE. Enteral Iron Supplementation in Infants Born Extremely Preterm and its Positive Correlation with Neurodevelopment; Post Hoc Analysis of the Preterm Erythropoietin Neuroprotection Trial Randomized Controlled Trial. J Pediatr 2021; 238:102-109.e8. [PMID: 34324880 PMCID: PMC8629150 DOI: 10.1016/j.jpeds.2021.07.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/18/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development, third edition (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT). STUDY DESIGN This is a post hoc analysis of a randomized trial that enrolled infants born at 24-28 completed weeks of gestation. All infants in PENUT who were assessed with BSID-III at 2 years were included in this study. The associations between enteral iron dose at 60 and 90 days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders. RESULTS In total, 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged from 0 to 14.7 mg/kg/d (IQR 2.1-5.8 mg/kg/d) at day 60, with a mean of 3.6 mg/kg/d in infants treated with placebo and 4.8 mg/kg/d in infants treated with Epo. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose (P = .03). Greater iron doses were associated with greater motor and language scores but did not reach statistical significance. Results at 90 days were not significant. The effect size in the infants treated with Epo compared with placebo was consistently greater. CONCLUSIONS A positive association was seen between iron dose at 60 days and cognitive outcomes. Our results suggest that increased iron supplementation in infants born preterm, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo. TRIAL REGISTRATION Clinicaltrials.gov: NCT01378273.
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Affiliation(s)
- Kendell R. German
- Department of Pediatrics, University of Washington, Seattle, WA, United States
| | - Phuong T Vu
- Current Affiliation: Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA, United States,Department of Biostatistics, University of Washington, Seattle, WA, United States
| | - Bryan A. Comstock
- Department of Biostatistics, University of Washington, Seattle, WA, United States
| | - Robin K. Ohls
- Department of Pediatrics, University of Utah, Salt Lake City, UT, United States
| | - Patrick J. Heagerty
- Department of Biostatistics, University of Washington, Seattle, WA, United States
| | - Dennis E. Mayock
- Department of Pediatrics, University of Washington, Seattle, WA, United States
| | - Michael Georgieff
- Department of Pediatrics, University of Minnesota, MN, United States
| | - Raghavendra Rao
- Department of Pediatrics, University of Minnesota, MN, United States
| | - Sandra E. Juul
- Department of Pediatrics, University of Washington, Seattle, WA, United States
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21
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German KR, Juul SE. Iron and Neurodevelopment in Preterm Infants: A Narrative Review. Nutrients 2021; 13:nu13113737. [PMID: 34835993 PMCID: PMC8624708 DOI: 10.3390/nu13113737] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 10/19/2021] [Accepted: 10/21/2021] [Indexed: 12/24/2022] Open
Abstract
Iron is critical for brain development, playing key roles in synaptogenesis, myelination, energy metabolism and neurotransmitter production. NICU infants are at particular risk for iron deficiency due to high iron needs, preterm birth, disruptions in maternal or placental health and phlebotomy. If deficiency occurs during critical periods of brain development, this may lead to permanent alterations in brain structure and function which is not reversible despite later supplementation. Children with perinatal iron deficiency have been shown to have delayed nerve conduction speeds, disrupted sleep patterns, impaired recognition memory, motor deficits and lower global developmental scores which may be present as early as in the neonatal period and persist into adulthood. Based on this, ensuring brain iron sufficiency during the neonatal period is critical to optimizing neurodevelopmental outcomes and iron supplementation should be targeted to iron measures that correlate with improved outcomes.
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22
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Fischer JAJ, Sasai CS, Karakochuk CD. Iron-Containing Oral Contraceptives and Their Effect on Hemoglobin and Biomarkers of Iron Status: A Narrative Review. Nutrients 2021; 13:nu13072340. [PMID: 34371850 PMCID: PMC8308850 DOI: 10.3390/nu13072340] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 07/05/2021] [Accepted: 07/06/2021] [Indexed: 12/02/2022] Open
Abstract
Oral contraceptive use has been associated with decreased menstrual blood losses; thus, can independently reduce the risk of anemia and iron deficiency in women. Manufacturers have recently started to include supplemental iron in the non-hormonal placebo tablets of some contraceptives. The aims of this narrative review are: (i) to describe the relationship between oral contraceptive use and both anemia and iron status in women; (ii) to describe the current formulations of iron-containing oral contraceptives (ICOC) available on the market; and (iii) to systematically review the existing literature on the effect of ICOC on biomarkers of anemia and iron status in women. We discovered 21 brands of ICOC, most commonly including 25 mg elemental iron as ferrous fumarate, for seven days, per monthly tablet package. Our search identified one randomized trial evaluating the effectiveness of ICOC use compared to two non-ICOC on increasing hemoglobin (Hb) and iron status biomarker concentrations in women; whereafter 12 months of contraception use, there were no significant differences in Hb concentration nor markers of iron status between the groups. ICOC has the potential to be a cost-effective solution to address both family planning needs and iron deficiency anemia. Yet, more rigorous trials evaluating the effectiveness of ICOC on improving markers of anemia and iron deficiency, as well as investigating the safety of its consumption among iron-replete populations, are warranted.
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Affiliation(s)
- Jordie A. J. Fischer
- Food, Nutrition and Health, University of British Columbia, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada; (J.A.J.F.); (C.S.S.)
- Healthy Starts, BC Children’s Hospital Research Institute, 938 West 28th Ave, Vancouver, BC V5Z 4H4, Canada
| | - Carolina S. Sasai
- Food, Nutrition and Health, University of British Columbia, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada; (J.A.J.F.); (C.S.S.)
| | - Crystal D. Karakochuk
- Food, Nutrition and Health, University of British Columbia, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada; (J.A.J.F.); (C.S.S.)
- Healthy Starts, BC Children’s Hospital Research Institute, 938 West 28th Ave, Vancouver, BC V5Z 4H4, Canada
- Correspondence:
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23
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The critical roles of iron during the journey from fetus to adolescent: Developmental aspects of iron homeostasis. Blood Rev 2021; 50:100866. [PMID: 34284901 DOI: 10.1016/j.blre.2021.100866] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 06/28/2021] [Accepted: 07/01/2021] [Indexed: 12/12/2022]
Abstract
Iron is indispensable for human life. However, it is also potentially toxic, since it catalyzes the formation of harmful oxidative radicals in unbound form and may facilitate pathogen growth. Therefore, iron homeostasis needs to be tightly regulated. Rapid growth and development require large amounts of iron, while (especially young) children are vulnerable to infections with iron-dependent pathogens due to an immature immune system. Moreover, unbalanced iron status early in life may have effects on the nervous system, immune system and gut microbiota that persist into adulthood. In this narrative review, we assess the critical roles of iron for growth and development and elaborate how the body adapts to physiologically high iron demands during the journey from fetus to adolescent. As a first step towards the development of clinical guidelines for the management of iron disorders in children, we summarize the unmet needs regarding the developmental aspects of iron homeostasis.
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24
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East P, Doom JR, Blanco E, Burrows R, Lozoff B, Gahagan S. Iron deficiency in infancy and neurocognitive and educational outcomes in young adulthood. Dev Psychol 2021; 57:962-975. [PMID: 34424013 PMCID: PMC8386013 DOI: 10.1037/dev0001030] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
This study examines the extent to which iron deficiency in infancy contributes to adverse neurocognitive and educational outcomes in young adulthood directly and indirectly, through its influence on verbal cognition and attention problems in childhood. Young adults (N = 1,000, M age = 21.3 years, 52% female; of Spanish or indigenous descent) from working-class families in Santiago, Chile, completed instruments assessing memory, processing speed, mental flexibility, and educational attainment. Iron status was assessed at ages 6, 12, and 18 months, and verbal intelligence, inattention, and sluggish cognitive tempo (SCT) symptoms were assessed at age 10. Results indicated that young adults who had iron-deficiency in infancy had poor executive control at age 21. Severity of iron deficiency during infancy was associated with lower verbal IQ and more frequent inattention and SCT symptoms in childhood, and with lower educational attainment in young adulthood through its effect on inattention. No additional indirect effects were found. Interventions directed toward improving cognitive and attention deficits linked to early-life iron deficiency appear warranted and could alter the course to adult functioning. Further research on the impact of such interventions would be helpful. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Affiliation(s)
- Patricia East
- Department of Pediatrics, University of California, San Diego
| | | | - Estela Blanco
- Department of Pediatrics, University of California, San Diego
| | - Raquel Burrows
- Institute of Nutrition and Food Technology, University of Chile
| | - Betsy Lozoff
- Department of Pediatrics, University of Michigan
| | - Sheila Gahagan
- Department of Pediatrics, University of California, San Diego
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25
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McMillen S, Lönnerdal B. Postnatal Iron Supplementation with Ferrous Sulfate vs. Ferrous Bis-Glycinate Chelate: Effects on Iron Metabolism, Growth, and Central Nervous System Development in Sprague Dawley Rat Pups. Nutrients 2021; 13:1406. [PMID: 33921980 PMCID: PMC8143548 DOI: 10.3390/nu13051406] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/18/2021] [Accepted: 04/20/2021] [Indexed: 02/05/2023] Open
Abstract
Iron-fortified formulas and iron drops (both usually ferrous sulfate, FS) prevent early life iron deficiency, but may delay growth and adversely affect neurodevelopment by providing excess iron. We used a rat pup model to investigate iron status, growth, and development outcomes following daily iron supplementation (10 mg iron/kg body weight, representative of iron-fortified formula levels) with FS or an alternative, bioavailable form of iron, ferrous bis-glycinate chelate (FC). On postnatal day (PD) 2, sex-matched rat litters (n = 3 litters, 10 pups each) were randomly assigned to receive FS, FC, or vehicle control until PD 14. On PD 15, we evaluated systemic iron regulation and CNS mineral interactions and we interrogated iron loading outcomes in the hippocampus, in search of mechanisms by which iron may influence neurodevelopment. Body iron stores were elevated substantially in iron-supplemented pups. All pups gained weight normally, but brain size on PD 15 was dependent on iron source. This may have been associated with reduced hippocampal oxidative stress but was not associated with CNS mineral interactions, iron regulation, or myelination, as these were unchanged with iron supplementation. Additional studies are warranted to investigate iron form effects on neurodevelopment so that iron recommendations can be optimized for all infants.
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Affiliation(s)
| | - Bo Lönnerdal
- Department of Nutrition, University of California, Davis, CA 95616, USA;
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26
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Sensitive periods for psychosocial risk in childhood and adolescence and cardiometabolic outcomes in young adulthood. Dev Psychopathol 2021; 32:1864-1875. [PMID: 33427189 DOI: 10.1017/s0954579420001248] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Greater psychosocial risk in childhood and adolescence predicts poorer cardiometabolic outcomes in adulthood. We assessed whether the timing of psychosocial risk from infancy through adolescence predicts cardiometabolic outcomes in young adulthood. Young adults and their mothers participated in a longitudinal study beginning in infancy in Santiago, Chile (N = 1040). At infancy, 5 years, 10 years, and adolescence, mothers reported on depressive symptoms, stressful experiences, support for child development in the home, father absence, parental education, and socioeconomic status (SES) to create a psychosocial risk composite at each time point. Young adults (52.1% female; 21-27 years) provided fasting serum samples and participated in anthropometric and blood pressure (BP) assessments, including a dual-energy X-ray absorptiometry (DXA) scan for measuring body fat. Greater infant psychosocial risk was associated with a greater young adult metabolic syndrome score (β = 0.07, 95% confidence intervals (CI): 0.01 to 0.13, p = 0.02), a higher body mass index and waist circumference composite (β = 0.08, 95% CI: 0.03 to 0.13, p = 0.002), and a higher body fat (DXA) composite (β = 0.07, 95% CI: 0.01 to 0.12, p = 0.02). No psychosocial risk measure from any time point was associated with BP. Infant psychosocial risk predicted cardiometabolic outcomes in young adulthood better than psychosocial risk at 5 years, 10 years, or adolescence, mean of psychosocial risk from infancy through adolescence, and maximum of psychosocial risk at any one time. Consistent with the Developmental Origins of Health and Disease model, findings suggest that infancy is a sensitive period for psychosocial risk leading to poorer cardiometabolic outcomes in young adulthood.
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Cohen Kadosh K, Muhardi L, Parikh P, Basso M, Jan Mohamed HJ, Prawitasari T, Samuel F, Ma G, Geurts JMW. Nutritional Support of Neurodevelopment and Cognitive Function in Infants and Young Children-An Update and Novel Insights. Nutrients 2021; 13:nu13010199. [PMID: 33435231 PMCID: PMC7828103 DOI: 10.3390/nu13010199] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 12/12/2022] Open
Abstract
Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here, we show that the individual contribution of nutrients, their interaction with other micro- and macronutrients and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.
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Affiliation(s)
- Kathrin Cohen Kadosh
- School of Psychology, University of Surrey, Guildford GU2 7XH, UK; (K.C.K.); (M.B.)
| | - Leilani Muhardi
- FrieslandCampina AMEA, Singapore 039190, Singapore; (L.M.); (P.P.)
| | - Panam Parikh
- FrieslandCampina AMEA, Singapore 039190, Singapore; (L.M.); (P.P.)
| | - Melissa Basso
- School of Psychology, University of Surrey, Guildford GU2 7XH, UK; (K.C.K.); (M.B.)
- Department of General Psychology, University of Padova, 35131 Padova, Italy
| | - Hamid Jan Jan Mohamed
- Nutrition and Dietetics Programme, School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia;
| | - Titis Prawitasari
- Nutrition and Metabolic Diseases Working Group, Indonesian Pediatric Society, Jakarta 10310, Indonesia;
- Department of Pediatrics, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusomo National Referral Hospital Jakarta, Jakarta 10430, Indonesia
| | - Folake Samuel
- Department of Human Nutrition, University of Ibadan, Ibadan 200284, Nigeria;
| | - Guansheng Ma
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, 38 Xue Yuan Road, Haidian District, Beijing 100191, China;
- Laboratory of Toxicological Research and Risk assessment for Food Safety, Peking University, 38 Xue Yuan Road, Haidian District, Beijing 100191, China
| | - Jan M. W. Geurts
- FrieslandCampina, 3818 LE Amersfoort, The Netherlands
- Correspondence: ; Tel.: +31-6-53310499
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Willcox JC, Februhartanty J, Satheannoppakao W, Hutchinson C, Itsiopoulos C, Worsley A. Commercial growing up milks: usage frequency and associated child and demographic factors across four Asia Pacific countries. J Hum Nutr Diet 2021; 34:524-533. [PMID: 33406319 DOI: 10.1111/jhn.12851] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 10/31/2020] [Accepted: 11/18/2020] [Indexed: 01/21/2023]
Abstract
BACKGROUND Commercial growing up milks (GUMs) targeted at children from 12 to 36 months of age are a rapidly growing industry, particularly across the Asia Pacific. METHODS The present study assessed the frequency of use and socio-demographic and child associations of commercial GUM feeding in children, aged between 12 and 36 months, in capital cities in four Asia Pacific countries. Mothers of children aged between 12 and 36 months were surveyed, assessing GUM feeding frequency in the past month. A market research company database was used to survey across Asia Pacific urban cities, including Bangkok Thailand, Jakarta Indonesia, Singapore and Australian Capital Cities (ACC). RESULTS More than 1000 women (n = 1051) were surveyed (Bangkok, n = 263; Jakarta, n = 275; ACC, n = 252; Singapore, n = 261). The mean (SD) age of mothers was 32.4 (5.3) years and that of children was 23.6 (6.7) months. In total, 62.7% of the children were fed GUMs more than once per week with significant country variance. In comparison with ACC, Asian countries were significantly more likely to feed GUMs ≥once per week: Bangkok [odds ratio (OR) = 5.7, 95% confidence interval (CI) = 3.8-8.6]; Jakarta (OR = 3.5, 95% CI = 2.3-5.5); and Singapore (OR = 7.4, 95% CI = 4.9-11.1). Associations of GUM feeding included: maternal tertiary education; mothers younger than 30 years; working full time; and feeding of commercial infant formula under 12 months. CONCLUSIONS This is the first published study to explore commercial GUM feeding in and between countries. The incidence of GUM feeding, in contrast to international recommendations, signals the need for further research into the drivers for GUM feeding and its contribution to the diet.
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Affiliation(s)
- J C Willcox
- School of Allied Health, Human Services and Sport, La Trobe University, Melbourne, VIC, Australia
| | - J Februhartanty
- Southeast Asian Ministers of Education Organization Regional Centre for Food and Nutrition (SEAMEO RECFON)/Pusat Kajian Gizi Regional (PKGR), Universitas Indonesia, Jakarta, Indonesia
| | - W Satheannoppakao
- Department of Nutrition, Faculty of Public Health, Mahidol University, Bangkok, Thailand
| | - C Hutchinson
- Department of Nutrition, Faculty of Public Health, Mahidol University, Bangkok, Thailand
| | - C Itsiopoulos
- School of Allied Health, Human Services and Sport, La Trobe University, Melbourne, VIC, Australia.,College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, Australia
| | - A Worsley
- Institute for Physical Activity and Nutrition, Deakin University, Waurn Ponds, VIC, Australia
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29
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Perng V, Li C, Klocke CR, Navazesh SE, Pinneles DK, Lein PJ, Ji P. Iron Deficiency and Iron Excess Differently Affect Dendritic Architecture of Pyramidal Neurons in the Hippocampus of Piglets. J Nutr 2021; 151:235-244. [PMID: 33245133 DOI: 10.1093/jn/nxaa326] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 07/13/2020] [Accepted: 10/01/2020] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Both iron deficiency and overload may adversely affect neurodevelopment. OBJECTIVES The study assessed how changes in early-life iron status affect iron homeostasis and cytoarchitecture of hippocampal neurons in a piglet model. METHODS On postnatal day (PD) 1, 30 Hampshire × Yorkshire crossbreed piglets (n = 15/sex) were stratified by sex and litter and randomly assigned to experimental groups receiving low (L-Fe), adequate (A-Fe), or high (H-Fe) levels of iron supplement during the pre- (PD1-21) and postweaning periods (PD22-35). Pigs in the L-Fe, A-Fe, and H-Fe groups orally received 0, 1, and 30 mg Fe · kg weight-1 · d-1 preweaning and were fed a diet containing 30, 125, and 1000 mg Fe/kg postweaning, respectively. Heme indexes were analyzed weekly, and gene and protein expressions of iron regulatory proteins in duodenal mucosa, liver, and hippocampus were analyzed through qRT-PCR and western blot, respectively, on PD35. Hippocampal neurons stained using the Golgi-Cox method were traced and their dendritic arbors reconstructed in 3-D using Neurolucida. Dendritic complexity was quantified using Sholl and branch order analyses. RESULTS Pigs in the L-Fe group developed iron deficiency anemia (hemoglobin = 8.2 g/dL, hematocrit = 20.1%) on PD35 and became stunted during week 5 with lower final body weight than H-Fe group pigs (6.6 compared with 9.6 kg, P < 0.05). In comparison with A-Fe, H-Fe increased hippocampal ferritin expression by 38% and L-Fe decreased its expression by 52% (P < 0.05), suggesting altered hippocampal iron stores. Pigs in the H-Fe group had greater dendritic complexity in CA1/3 pyramidal neurons than L-Fe group pigs as shown by more dendritic intersections with Sholl rings (P ≤ 0.04) and a greater number of dendrites (P ≤ 0.016). CONCLUSIONS In piglets, the developing hippocampus is susceptible to perturbations by dietary iron, with deficiency and overload differentially affecting dendritic arborization.
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Affiliation(s)
- Vivian Perng
- Department of Nutrition, University of California, Davis, Davis, CA, USA
| | - Chong Li
- Department of Nutrition, University of California, Davis, Davis, CA, USA
| | - Carolyn R Klocke
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA
| | - Shya E Navazesh
- Department of Nutrition, University of California, Davis, Davis, CA, USA
| | - Danna K Pinneles
- Department of Nutrition, University of California, Davis, Davis, CA, USA
| | - Pamela J Lein
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA
| | - Peng Ji
- Department of Nutrition, University of California, Davis, Davis, CA, USA
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30
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Affiliation(s)
- Schuyler Tong
- Department of Pediatrics and Pediatric Hematology Oncology, University of California at San Francisco Benioff Children's Hospital Oakland, Oakland, CA
| | - Elliott Vichinsky
- Department of Pediatrics and Pediatric Hematology Oncology, University of California at San Francisco Benioff Children's Hospital Oakland, Oakland, CA.,Pediatric Hematology Oncology, University of California, San Francisco, CA
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31
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Björmsjö M, Hernell O, Lönnerdal B, Berglund SK. Reducing Iron Content in Infant Formula from 8 to 2 mg/L Does Not Increase the Risk of Iron Deficiency at 4 or 6 Months of Age: A Randomized Controlled Trial. Nutrients 2020; 13:E3. [PMID: 33374970 PMCID: PMC7821997 DOI: 10.3390/nu13010003] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/10/2020] [Accepted: 12/17/2020] [Indexed: 02/05/2023] Open
Abstract
Many infant formulas are fortified with iron at 8-14 mg/L whereas breast milk contains about 0.3 mg/L. Another major difference between breast milk and infant formula is its high concentration of lactoferrin, a bioactive iron-binding protein. The aim of the present study was to investigate how reducing the iron content and adding bovine lactoferrin to infant formula affects iron status, health and development. Swedish healthy full-term formula-fed infants (n = 180) were randomized in a double-blind controlled trial. From 6 weeks to 6 months of age, 72 infants received low-iron formula (2 mg/L) fortified with bovine lactoferrin (1.0 g/L) (Lf+), 72 received low-iron formula un-fortified with lactoferrin (Lf-) and 36 received standard formula with 8 mg of iron/L and no lactoferrin fortification as controls (CF). Iron status and prevalence of iron deficiency (ID) were assessed at 4 and 6 months. All iron status indicators were unaffected by lactoferrin. At 4 and 6 months, the geometric means of ferritin for the combined low-iron groups compared to the CF-group were 67.7 vs. 88.7 and 39.5 vs. 50.9 µg/L, respectively (p = 0.054 and p = 0.056). No significant differences were found for other iron status indicators. In the low-iron group only one infant (0.7%) at 4 months and none at 6 months developed ID. Conclusion: Iron fortification of 2 mg/L is an adequate level during the first half of infancy for healthy term infants in a well-nourished population. Adding lactoferrin does not affect iron status.
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Affiliation(s)
- Maria Björmsjö
- Department of Clinical Sciences, Pediatrics, Umeå University, 901 87 Umeå, Sweden; (M.B.); (O.H.)
| | - Olle Hernell
- Department of Clinical Sciences, Pediatrics, Umeå University, 901 87 Umeå, Sweden; (M.B.); (O.H.)
| | - Bo Lönnerdal
- Department of Nutrition, University of California, Davis, CA 95616, USA;
| | - Staffan K. Berglund
- Department of Clinical Sciences, Pediatrics, Umeå University, 901 87 Umeå, Sweden; (M.B.); (O.H.)
- Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, 901 87 Umeå, Sweden
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32
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Kangas ST, Salpéteur C, Nikièma V, Talley L, Briend A, Ritz C, Friis H, Kaestel P. Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition. Clin Nutr 2020; 39:3512-3519. [DOI: 10.1016/j.clnu.2020.03.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 02/28/2020] [Accepted: 03/10/2020] [Indexed: 02/04/2023]
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33
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Fischer JA, Pei LX, Goldfarb DM, Albert A, Elango R, Kroeun H, Karakochuk CD. Is untargeted iron supplementation harmful when iron deficiency is not the major cause of anaemia? Study protocol for a double-blind, randomised controlled trial among non-pregnant Cambodian women. BMJ Open 2020; 10:e037232. [PMID: 32801202 PMCID: PMC7430471 DOI: 10.1136/bmjopen-2020-037232] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
INTRODUCTION The WHO recommends daily oral iron supplementation for 12 weeks in women and adolescents where anaemia prevalence is greater than 40%. However, if iron deficiency is not a major cause of anaemia, then, at best, untargeted iron supplementation is a waste of resources; at worst, it could cause harm. Further, different forms of iron with varying bioavailability may present greater risks of harm. METHODS AND ANALYSIS A 12-week three-arm, double-blind, randomised controlled supplementation trial was conducted in Cambodia to determine if there is potential harm associated with untargeted iron supplementation. We will recruit and randomise 480 non-pregnant women (ages 18-45 years) to receive one of three interventions: 60 mg elemental iron as ferrous sulfate (the standard, commonly used form), 18 mg ferrous bisglycinate (a highly bioavailable iron amino acid chelate) or placebo. We will measure ferritin concentrations (to evaluate non-inferiority between the two forms of iron), as well as markers of potential harm in blood and stool (faecal calprotectin, gut pathogen abundance and DNA damage) at baseline and 12 weeks. Mixed-effects generalised linear models will be used to assess the effect of iron on ferritin concentration and markers of potential harm at 12 weeks. ETHICS AND DISSEMINATION Ethical approval was obtained from the University of British Columbia Clinical Research Ethics Board (H18-02610), the Children's and Women's Health Centre of British Columbia Research Ethics Board (H18-02610) and the National Ethics Committee for Health Research in Cambodia (273-NECHR). Findings will be published in peer-reviewed journals, presented to stakeholders and policymakers globally and shared within participants' communities. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Registry (NCT04017598).
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Affiliation(s)
- Jordie Aj Fischer
- Department of Food, Nutrition and Health, The University of British Columbia, Vancouver, British Columbia, Canada
- Healthy Starts, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada
| | - Lulu X Pei
- Department of Food, Nutrition and Health, The University of British Columbia, Vancouver, British Columbia, Canada
- Healthy Starts, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada
| | - David M Goldfarb
- Healthy Starts, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Arianne Albert
- Department of Biostatistics, Women's Health Research Institute, Vancouver, British Columbia, Canada
| | - Rajavel Elango
- Healthy Starts, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada
- School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Hou Kroeun
- Helen Keller International Cambodia, Phnom Penh, British Columbia, Cambodia
| | - Crystal D Karakochuk
- Department of Food, Nutrition and Health, The University of British Columbia, Vancouver, British Columbia, Canada
- Healthy Starts, British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada
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East P, Doom J, Blanco E, Burrows R, Lozoff B, Gahagan S. Young adult outcomes associated with lower cognitive functioning in childhood related to iron-fortified formula in infancy. Nutr Neurosci 2020; 25:709-718. [PMID: 32778008 DOI: 10.1080/1028415x.2020.1804099] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Objective: This study examined how the lower cognitive skills in children who consumed iron-fortified formula in infancy relate to outcomes in young adulthood.Methods: Participants were 443 Chilean young adults (M age = 21.2y, 55% female) who took part in a randomized controlled iron-deficiency anemia preventive trial during infancy (6-12 m). Slightly over half of participants (n = 237) received iron-fortified formula (12.7 mg/L) and 206 received a low-iron formula (2.3 mg/L). Spatial memory, IQ, and visual-motor integration were measured at age 10, and neurocognition, emotion regulation, educational level, and attainment of adult developmental milestones were assessed at age 21.Results: Consumption of iron-fortified formula in infancy was associated with poorer performance on neurocognitive tests in childhood, and these effects related to poorer neurocognitive, emotional, and educational outcomes in young adulthood. Dosage effects associated with consumption of iron-fortified formula were found for lower educational attainment and, marginally, slower mental processing. Those who received iron-fortified formula and had low age 10 cognitive abilities performed most poorly on neurocognitive tests at age 21.Conclusion: Findings suggest that the long-term development of infants who consume iron-fortified formula may be adversely affected.Clinical Trials number: NCT01166451.
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Affiliation(s)
- Patricia East
- Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA
| | - Jenalee Doom
- Department of Psychology, University of Denver, Denver, CO, USA
| | - Estela Blanco
- Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.,Public Health Doctoral Program, University of Chile, Santiago, Chile
| | - Raquel Burrows
- Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile
| | - Betsy Lozoff
- Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
| | - Sheila Gahagan
- Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA
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35
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Hart SJ, Zimmerman K, Linardic CM, Cannon S, Pastore A, Patsiogiannis V, Rossi P, Santoro SL, Skotko BG, Torres A, Valentini D, Vellody K, Worley G, Kishnani PS. Detection of iron deficiency in children with Down syndrome. Genet Med 2020; 22:317-325. [PMID: 31417190 PMCID: PMC8039980 DOI: 10.1038/s41436-019-0637-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 08/05/2019] [Indexed: 11/08/2022] Open
Abstract
PURPOSE Current American Academy of Pediatrics guidelines for children with Down syndrome (DS) recommend a complete blood count (CBC) at birth and hemoglobin annually to screen for iron deficiency (ID) and ID anemia (IDA) in low-risk children. We aimed to determine if macrocytosis masks the diagnosis of ID/IDA and to evaluate the utility of biochemical and red blood cell indices for detecting ID/IDA in DS. METHODS We reviewed data from 856 individuals from five DS specialty clinics. Data included hemoglobin, mean corpuscular volume, red cell distribution width (RDW), percent transferrin saturation (TS), ferritin, and c-reactive protein. Receiver operating characteristic curves were calculated. RESULTS Macrocytosis was found in 32% of the sample. If hemoglobin alone was used for screening, all individuals with IDA would have been identified, but ID would have been missed in all subjects. RDW had the highest discriminability of any single test for ID/IDA. The combination of RDW with ferritin or TS led to 100% sensitivity, and RDW combined with ferritin showed the highest discriminability for ID/IDA. CONCLUSION We provide evidence to support that a CBC and ferritin be obtained routinely for children over 1 year old with DS rather than hemoglobin alone for detection of ID.
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Affiliation(s)
- Sarah J Hart
- Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
| | - Kanecia Zimmerman
- Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
| | - Corinne M Linardic
- Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
- Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA
| | - Sheila Cannon
- Down Syndrome Center of Western Pennsylvania, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Anna Pastore
- Laboratory of Molecular Genetics and Functional Genomics, Division of Genetic and Rare Disease, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
| | - Vasiliki Patsiogiannis
- Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA
| | - Paolo Rossi
- Laboratory of Molecular Genetics and Functional Genomics, Division of Genetic and Rare Disease, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
- Department of Pediatrics, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
| | - Stephanie L Santoro
- Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA
- Division of Genetics, Nationwide Children's Hospital, Columbus, OH, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Brian G Skotko
- Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Amy Torres
- Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA
| | - Diletta Valentini
- Department of Pediatrics, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
| | - Kishore Vellody
- Down Syndrome Center of Western Pennsylvania, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Gordon Worley
- Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
| | - Priya S Kishnani
- Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
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Arija V, Hernández-Martínez C, Tous M, Canals J, Guxens M, Fernández-Barrés S, Ibarluzea J, Babarro I, Soler-Blasco R, Llop S, Vioque J, Sunyer J, Julvez J. Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study. Nutrients 2019; 11:nu11122999. [PMID: 31817835 PMCID: PMC6949977 DOI: 10.3390/nu11122999] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 11/26/2019] [Accepted: 11/28/2019] [Indexed: 01/14/2023] Open
Abstract
Early iron status plays an important role in prenatal neurodevelopment. Iron deficiency and high iron status have been related to alterations in child cognitive development; however, there are no data about iron intake during pregnancy with other environmental factors in relation to long term cognitive functioning of children. The aim of this study is to assess the relationship between maternal iron status and iron intake during pregnancy and child neuropsychological outcomes at 7 years of age. We used data from the INMA Cohort population-based study. Iron status during pregnancy was assessed according to serum ferritin levels, and iron intake was assessed with food frequency questionnaires. Working memory, attention, and executive function were assessed in children at 7 years old with the N-Back task, Attention Network Task, and the Trail Making Test, respectively. The results show that, after controlling for potential confounders, normal maternal serum ferritin levels (from 12 mg/L to 60 mg/L) and iron intake (from 14.5 mg/day to 30.0 mg/day), respectively, were related to better scores in working memory and executive functioning in offspring. Since these functions have been associated with better academic performance and adaptation to the environment, maintaining a good state of maternal iron from the beginning of pregnancy could be a valuable strategy for the community.
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Affiliation(s)
- Victoria Arija
- Nutrition and Public Health Unit, Research Group on Nutrition and Mental Health (NUTRISAM), Faculty of Medicine and Health Science, Universitat Rovira i Virgili, 43201 Reus, Spain; (V.A.); (C.H.-M.); (M.T.); (J.C.)
- Pere Virgili Institute for Health Research (IISPV), Universitat Rovira i Virgili, 43003 Tarragona, Spain
| | - Carmen Hernández-Martínez
- Nutrition and Public Health Unit, Research Group on Nutrition and Mental Health (NUTRISAM), Faculty of Medicine and Health Science, Universitat Rovira i Virgili, 43201 Reus, Spain; (V.A.); (C.H.-M.); (M.T.); (J.C.)
- Pere Virgili Institute for Health Research (IISPV), Universitat Rovira i Virgili, 43003 Tarragona, Spain
- Department of Psychology, Research Center for Behavioral Assessment (CRAMC), Universitat Rovira i Virgili, 43003 Tarragona, Spain
| | - Mónica Tous
- Nutrition and Public Health Unit, Research Group on Nutrition and Mental Health (NUTRISAM), Faculty of Medicine and Health Science, Universitat Rovira i Virgili, 43201 Reus, Spain; (V.A.); (C.H.-M.); (M.T.); (J.C.)
- Pere Virgili Institute for Health Research (IISPV), Universitat Rovira i Virgili, 43003 Tarragona, Spain
| | - Josefa Canals
- Nutrition and Public Health Unit, Research Group on Nutrition and Mental Health (NUTRISAM), Faculty of Medicine and Health Science, Universitat Rovira i Virgili, 43201 Reus, Spain; (V.A.); (C.H.-M.); (M.T.); (J.C.)
- Pere Virgili Institute for Health Research (IISPV), Universitat Rovira i Virgili, 43003 Tarragona, Spain
- Department of Psychology, Research Center for Behavioral Assessment (CRAMC), Universitat Rovira i Virgili, 43003 Tarragona, Spain
| | - Mónica Guxens
- ISGlobal- Instituto de Salud Global de Barcelona, 08036 Barcelona, Spain; (M.G.); (S.F.-B.); (J.S.)
- Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; (J.I.); (J.V.)
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), 15706 Santiago de Compostela, Spain
- Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre-Sophia Children’s Hospital, 3000CD Rotterdam, The Netherlands
| | - Silvia Fernández-Barrés
- ISGlobal- Instituto de Salud Global de Barcelona, 08036 Barcelona, Spain; (M.G.); (S.F.-B.); (J.S.)
- Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; (J.I.); (J.V.)
| | - Jesús Ibarluzea
- Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; (J.I.); (J.V.)
- Department of Health, Public Health Division of Gipuzkoa, 20014 San Sebastian, Spain;
- BIODONOSTIA Health Research Institute, 20014 San Sebastian, Spain
- Faculty of Psychology, University of the Basque Country (UPV/EHU), 20018 San Sebastian, Spain
| | - Izaro Babarro
- Department of Health, Public Health Division of Gipuzkoa, 20014 San Sebastian, Spain;
| | - Raquel Soler-Blasco
- Epidemiology and Environmental Health Joint Research Unit, FISABIO−Universitat Jaume I−Universitat de València, 46010 Valencia, Spain; (R.S.-B.); (S.L.)
| | - Sabrina Llop
- Epidemiology and Environmental Health Joint Research Unit, FISABIO−Universitat Jaume I−Universitat de València, 46010 Valencia, Spain; (R.S.-B.); (S.L.)
| | - Jesús Vioque
- Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; (J.I.); (J.V.)
- Unit of Nutritional Epidemiology, Universidad Miguel Hernandez, 03550 Alicante, Spain
| | - Jordi Sunyer
- ISGlobal- Instituto de Salud Global de Barcelona, 08036 Barcelona, Spain; (M.G.); (S.F.-B.); (J.S.)
- Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; (J.I.); (J.V.)
| | - Jordi Julvez
- Pere Virgili Institute for Health Research (IISPV), Universitat Rovira i Virgili, 43003 Tarragona, Spain
- ISGlobal- Instituto de Salud Global de Barcelona, 08036 Barcelona, Spain; (M.G.); (S.F.-B.); (J.S.)
- Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; (J.I.); (J.V.)
- Correspondence: ; Tel.: +31-932-147-349
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Hare DJ, Braat S, Cardoso BR, Morgan C, Szymlek-Gay EA, Biggs BA. Health outcomes of iron supplementation and/or food fortification in iron-replete children aged 4-24 months: protocol for a systematic review and meta-analysis. Syst Rev 2019; 8:253. [PMID: 31676010 PMCID: PMC6824107 DOI: 10.1186/s13643-019-1185-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 10/05/2019] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Direct supplementation or food fortification with iron are two public health initiatives intended to reduce the prevalence of iron deficiency (ID) and iron deficiency anaemia (IDA) in 4-24-month-old infants. In most high-income countries where IDA prevalence is < 15%, the recommended daily intake levels of iron from supplements and/or consumption of fortified food products are at odds with World Health Organisation (WHO) guidelines that recommend shorter-term (3 months/year) supplementation only in populations with IDA prevalence > 40%. Emerging concerns about delayed neurological effects of early-life iron overexposure have raised questions as to whether recommended guidelines in high-income countries are unnecessarily excessive. This systematic review will gather evidence from supplementation/fortification trials, comparing health outcomes in studies where iron-replete children did or did not receive additional dietary iron; and determine if replete children at study outset were not receiving additional iron show changes in haematological indices of ID/IDA over the trial duration. METHODS We will perform a systematic review of the literature, including all studies of iron supplementation and/or fortification, including study arms with confirmed iron-replete infants at the commencement of the trial. This includes both dietary iron intervention or placebo/average dietary intakes. One reviewer will conduct searches in electronic databases of published and ongoing trials (Medline, Web of Science, Scopus, CENTRAL, EBSCO [e.g. CINAHL Complete, Food Science and Technology Abstracts], Embase, ClinicalTrials.gov, ClinicalTrialsRegister.eu and who.it/trialsearch), digital theses and dissertations (WorldCat, Networked Digital Library of Theses and Dissertations, DART-Europe E-theses Portal, Australasian Digital Theses Program, Theses Canada Portal and ProQuest). For eligible studies, one reviewer will use a data extraction form, and a second reviewing entered data for accuracy. Both reviewers will independently perform quality assessments before qualitative and, if appropriate, quantitative synthesis as a meta-analysis. We will resolve any discrepancies through discussion or consult a third author to resolve discrepancies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement will be used as the basis for reporting. DISCUSSION Recommended iron supplementation and food fortification practices in high-income countries have been criticised for being both excessive and based on outdated or underpowered studies. This systematic review will build a case for revisiting iron intake guidelines for infants through the design of new trials where health effects of additional iron intake in iron-replete infants are the primary outcome. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42018093744.
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Affiliation(s)
- Dominic J. Hare
- The Peter Doherty Institute for Infection and Immunity at The University of Melbourne, 792 Elizabeth Street, Melbourne, VIC 3000 Australia
- Department of Medicine at the Royal Melbourne Hospital and The University of Melbourne, 300 Grattan Street, Parkville, VIC 3052 Australia
- Melbourne Dementia Research Centre at The Florey Institute of Neuroscience and Mental Health and The University of Melbourne, 30 Royal Parade, Parkville, VIC 3052 Australia
| | - Sabine Braat
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC 3010 Australia
| | - Bárbara R. Cardoso
- Melbourne Dementia Research Centre at The Florey Institute of Neuroscience and Mental Health and The University of Melbourne, 30 Royal Parade, Parkville, VIC 3052 Australia
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Locked Bag 20000, Geelong, VIC 3220 Australia
| | - Christopher Morgan
- Burnet Institute, 85 Commercial Road, Melbourne, VIC 3004 Australia
- Melbourne School of Population and Global Health, The University of Melbourne, 235 Bouverie Street, Carlton, VIC 3053 Australia
- School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004 Australia
| | - Ewa A. Szymlek-Gay
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Locked Bag 20000, Geelong, VIC 3220 Australia
| | - Beverley-Ann Biggs
- The Peter Doherty Institute for Infection and Immunity at The University of Melbourne, 792 Elizabeth Street, Melbourne, VIC 3000 Australia
- Department of Medicine at the Royal Melbourne Hospital and The University of Melbourne, 300 Grattan Street, Parkville, VIC 3052 Australia
- Victorian Infectious Diseases Service, Royal Melbourne Hospital, 300 Grattan Street, Parkville, VIC 3052 Australia
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Ji P, B Nonnecke E, Doan N, Lönnerdal B, Tan B. Excess Iron Enhances Purine Catabolism Through Activation of Xanthine Oxidase and Impairs Myelination in the Hippocampus of Nursing Piglets. J Nutr 2019; 149:1911-1919. [PMID: 31373370 DOI: 10.1093/jn/nxz166] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 06/17/2019] [Accepted: 06/20/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Few studies have addressed the risk of nutritional iron overexposure in infancy. We previously found that excess dietary iron in nursing piglets resulted in iron overload in the liver and hippocampus and diminished socialization with novel conspecifics in a test for social novelty preference. OBJECTIVES This experiment aimed to identify metabolites and metabolic pathways affected by iron overload in the liver and hippocampus of nursing piglets. METHODS Liver and hippocampal tissues collected from 22-d-old piglets (Hampshire × Yorkshire crossbreed; 5.28 ± 0.53 kg body weight; 50% male) that received orally 0 (NI group) or 50 mg iron/(d · kg body weight) (HI group) from postnatal day (PD) 2 to PD21 were analyzed for mRNA and protein expression and enzyme activity of xanthine oxidase (XO). Untargeted metabolomics was performed using GC-MS. Expression of myelin basic protein (MBP) in the hippocampus was determined using western blot. RESULTS There were 108 and 126 metabolites identified in the hippocampus and liver, respectively. Compared with NI, HI altered 15 metabolites (P < 0.05, q < 0.2) in the hippocampus, including a reduction in myo-inositol (0.86-fold) and N-acetylaspartic acid (0.84-fold), 2 metabolites important for neuronal function and myelination. Seven metabolites involved in purine and pyrimidine metabolism (e.g., hypoxanthine, xanthine, and β-alanine) were coordinately changed in the hippocampus (P < 0.05, q < 0.2), suggesting that iron excess enhanced purine catabolism. The mRNA expression (2.3-fold) (P < 0.05) and activity of XO, a rate-limiting enzyme in purine degradation, was increased. Excess iron increased hippocampal lipid peroxidation by 74% (P < 0.05) and decreased MBP by 44% (P = 0.053). The hepatic metabolome was unaffected. CONCLUSIONS In nursing piglets, excess iron enhances hippocampal purine degradation through activation of XO, which may induce oxidative stress and alter energy metabolism in the developing brain.
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Affiliation(s)
- Peng Ji
- Department of Nutrition, University of California, Davis, Davis, CA, USA
| | - Eric B Nonnecke
- Department of Nutrition, University of California, Davis, Davis, CA, USA
| | - Nicole Doan
- Department of Nutrition, University of California, Davis, Davis, CA, USA
| | - Bo Lönnerdal
- Department of Nutrition, University of California, Davis, Davis, CA, USA
| | - Bie Tan
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China
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Iglesias Vázquez L, Canals J, Voltas N, Jardí C, Hernández C, Bedmar C, Escribano J, Aranda N, Jiménez R, Barroso JM, Ribot B, Arija V. Does the fortified milk with high iron dose improve the neurodevelopment of healthy infants? Randomized controlled trial. BMC Pediatr 2019; 19:315. [PMID: 31488098 PMCID: PMC6727503 DOI: 10.1186/s12887-019-1679-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 08/20/2019] [Indexed: 01/01/2023] Open
Abstract
Background Since iron plays an important role in several physiological processes, its deficiency but also overload may harm the development of children. The aim was to assess the effect of iron–fortified milk on the iron biochemical status and the neurodevelopment of children at 12 months of age. Methods Randomized controlled trial conducted in 133 Spanish children, allocated in two groups to receive formula milk fortified with 1.2 or 0.4 mg/100 mL of iron between 6 and 12 months of age. Psychomotor (PDI) and Mental (MDI) Development Index were assessed by the Bayley Scales before and after the intervention. Maternal obstetrical and psychosocial variables were recorded. The biochemical iron status of children was measured and data about breastfeeding, anthropometry and infections during the first year of life were registered. Results Children fortified with 1.2 mg/100 mL of iron, compared with 0.4 mg/100 mL, showed higher serum ferritin (21.5 vs 19.1 μg/L) and lower percentage of both iron deficiency (1.1 to 5.9% vs 3.8 to 16.7%, respectively, from 6 to 12 months) and iron deficiency anemia (4.3 to 1.1% vs 0 to 4.2%, respectively, from 6 to 12 months) at the end of the intervention. No significant differences were found on neurodevelopment from 6 to 12 months between children who received high dose of Fe compared with those who received low dose. Conclusion Despite differences on the iron status were observed, there were no effects on neurodevelopment of well–nourished children in a developed country after iron supplementation with doses within dietary recommendations. Follow–up studies are needed to test for long–term neurodevelopmental improvement. Trial registration Retrospectively registered in ClinicalTrials.gov with the ID: NCT02690675.
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Affiliation(s)
- Lucía Iglesias Vázquez
- Unit of Preventive Medicine and Public Health, Faculty of Medicine and Health Science, Universitat Rovira i Virgili, Reus, Spain
| | - Josefa Canals
- CRAMC (Centre de Recerca en Avaluació I Mesura de la Conducta), Unit of Psychology, Universitat Rovira i Virgili, Tarragona, Spain
| | - Núria Voltas
- CRAMC (Centre de Recerca en Avaluació I Mesura de la Conducta), Unit of Psychology, Universitat Rovira i Virgili, Tarragona, Spain
| | - Cristina Jardí
- Unit of Preventive Medicine and Public Health, Faculty of Medicine and Health Science, Universitat Rovira i Virgili, Reus, Spain
| | - Carmen Hernández
- CRAMC (Centre de Recerca en Avaluació I Mesura de la Conducta), Unit of Psychology, Universitat Rovira i Virgili, Tarragona, Spain
| | - Cristina Bedmar
- Unit of Preventive Medicine and Public Health, Faculty of Medicine and Health Science, Universitat Rovira i Virgili, Reus, Spain
| | - Joaquín Escribano
- Unit of Pediatrics, Faculty of Medicine and Health Science, Hospital Universitari Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain.,IISPV (Institut d'Investigació Sanitària Pere Virgili), Reus, Spain
| | - Núria Aranda
- Unit of Preventive Medicine and Public Health, Faculty of Medicine and Health Science, Universitat Rovira i Virgili, Reus, Spain.,IISPV (Institut d'Investigació Sanitària Pere Virgili), Reus, Spain
| | - Rosa Jiménez
- Unit of Pediatrics, Faculty of Medicine and Health Science, Hospital Universitari Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain
| | - Josep Maria Barroso
- Unit of Pediatrics, Faculty of Medicine and Health Science, Hospital Universitari Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain
| | - Blanca Ribot
- Unit of Preventive Medicine and Public Health, Faculty of Medicine and Health Science, Universitat Rovira i Virgili, Reus, Spain
| | - Victoria Arija
- Unit of Preventive Medicine and Public Health, Faculty of Medicine and Health Science, Universitat Rovira i Virgili, Reus, Spain. .,IISPV (Institut d'Investigació Sanitària Pere Virgili), Reus, Spain. .,IDIAP (Institut Universitari d'Investigació en Atenció Primària) Jordi Gol, Barcelona, Spain.
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Gahagan S, Delker E, Blanco E, Burrows R, Lozoff B. Randomized Controlled Trial of Iron-Fortified versus Low-Iron Infant Formula: Developmental Outcomes at 16 Years. J Pediatr 2019; 212:124-130.e1. [PMID: 31253407 PMCID: PMC7152502 DOI: 10.1016/j.jpeds.2019.05.030] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 03/28/2019] [Accepted: 05/13/2019] [Indexed: 01/25/2023]
Abstract
OBJECTIVES To test differences in cognitive outcomes among adolescents randomly assigned previously as infants to iron-fortified formula or low-iron formula as part of an iron deficiency anemia prevention trial. STUDY DESIGN Infants were recruited from community clinics in low- to middle-income neighborhoods in Santiago, Chile. Entrance criteria included term, singleton infants; birth weight of ≥3.0 kg; and no major congenital anomalies, perinatal complications, phototherapy, hospitalization >5 days, chronic illness, or iron deficiency anemia at 6 months. Six-month-old infants were randomized to iron-fortified (12 mg/L) or low-iron (2.3 mg/L) formula for 6 months. At 16 years of age, cognitive ability, visual perceptual ability, visual memory, and achievement in math, vocabulary, and comprehension were assessed, using standardized measures. We compared differences in developmental test scores according to randomization group. RESULTS At the follow-up assessment, the 405 participants averaged 16.2 years of age and 46% were male. Those randomized to iron-fortified formula had lower scores than those randomized to low-iron formula for visual memory, arithmetic achievement, and reading comprehension achievement. For visual motor integration, there was an interaction with baseline infancy hemoglobin, such that the iron-fortified group outperformed the low-iron group when 6-month hemoglobin was low and underperformed when 6-month hemoglobin was high. CONCLUSIONS Adolescents who received iron-fortified formula as infants from 6 to 12 months of age at levels recommended in the US had poorer cognitive outcomes compared with those who received a low-iron formula. The prevention of iron deficiency anemia in infancy is important for brain development. However, the optimal level of iron supplementation in infancy is unclear. TRIAL REGISTRATION Clinicaltrials.gov: NCT01166451.
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Affiliation(s)
- Sheila Gahagan
- Department of Pediatrics, Division of Child Development and Community Health, University of California, San Diego, La Jolla, CA; Center for Human Growth and Development and Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI.
| | - Erin Delker
- Department of Pediatrics, Division of Child Development and Community Health, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA 92093-0927,Epidemiology, San Diego State University / University of California at San Diego Joint Doctoral Program, 4305 University Avenue, San Diego, CA, USA, 92105
| | - Estela Blanco
- Department of Pediatrics, Division of Child Development and Community Health, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA 92093-0927,Public Health, University of Chile, Doctoral Program, Avenida Independencia 939, Santiago, Chile
| | - Raquel Burrows
- Institute of Nutrition and Food Technology, University of Chile, Av. El Líbano 5524, Santiago, Chile
| | - Betsy Lozoff
- Center for Human Growth and Development and Department of Pediatrics and Communicable Diseases, University of Michigan, 300 N. Ingalls Bldg. 1063NE, Ann Arbor, MI 48109
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Doom JR, Gahagan S, Caballero G, Encina P, Lozoff B. Infant iron deficiency, iron supplementation, and psychosocial stress as predictors of neurocognitive development in Chilean adolescents. Nutr Neurosci 2019; 24:520-529. [PMID: 31397220 DOI: 10.1080/1028415x.2019.1651105] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Objective: The aim of the current study was to examine the unique and joint contributions of iron deficiency, iron supplementation, and psychosocial stress in infancy and stress in adolescence to neurocognitive functioning in adolescence.Methods: The current study (N = 796; Mage = 14.4y) involved a prospective cohort of low- and middle-socioeconomic status adolescents in Santiago, Chile. As infants, they had participated in an iron supplementation trial. Infant iron status was assessed at 12-18 months, and mothers answered questions about family psychosocial stress at 6-12 months and in adolescence (maternal depressive symptoms, home support for child development, stressful life events, father absence, socioeconomic status, and parental education). Neurocognitive functioning was assessed in adolescence using the Balloon Analogue Risk Task, Stockings of Cambridge, Trail Making Test, Purdue Pegboard Test, and Wisconsin Card Sorting Test.Results: Greater psychosocial stress in infancy predicted less risk-taking, poorer planning abilities and fluid cognition, and slower processing speed in adolescence. Iron deficiency anemia in infancy predicted less risk-taking. Greater adolescent psychosocial stress predicted difficulties in set-shifting. There were no interactions between infant psychosocial stress and iron deficiency predicting adolescent neurocognitive functioning.Conclusion: These results suggest that interventions to reduce infant psychosocial stress may be more likely to prevent multiple neurocognitive deficits in adolescence than interventions to reduce infant iron deficiency.
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Affiliation(s)
- Jenalee R Doom
- Department of Psychology, University of Denver, Denver, CO, USA.,Department of Pediatrics, Medical School, University of Michigan, Ann Arbor, MI, USA.,Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA
| | - Sheila Gahagan
- Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA.,Division of Child Development and Community Health, University of California, San Diego, CA, USA
| | - Gabriela Caballero
- Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile [alt. Institute of Nutrition and Food Technology, University of Chile], Santiago, Chile
| | - Pamela Encina
- Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile [alt. Institute of Nutrition and Food Technology, University of Chile], Santiago, Chile
| | - Betsy Lozoff
- Department of Pediatrics, Medical School, University of Michigan, Ann Arbor, MI, USA.,Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA
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Geletu A, Lelisa A, Baye K. Provision of low-iron micronutrient powders on alternate days is associated with lower prevalence of anaemia, stunting, and improved motor milestone acquisition in the first year of life: A retrospective cohort study in rural Ethiopia. MATERNAL & CHILD NUTRITION 2019; 15:e12785. [PMID: 30676693 PMCID: PMC7198932 DOI: 10.1111/mcn.12785] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 12/22/2018] [Accepted: 01/08/2019] [Indexed: 12/31/2022]
Abstract
Inappropriate complementary feeding contributes to growth faltering, anaemia, and cognitive impairments. Limited programmatic evidence exists on the effectiveness of low-iron micronutrient powders (MNPs) on anaemia and motor development when provided every other day in the first year of life. This study used an existing demonstration project to evaluate associations between exposure of low-iron MNPs, anaemia, and motor development of infants in Southern Ethiopia. Using a retrospective cohort design, 200 infants aged 9 to 12 months (98 MNP exposed; 102 unexposed) were recruited, and data on socio-economic characteristics, anthropometric measures, dietary diversity scores (DDS), haemoglobin concentrations, and motor development acquisition were collected, and MNP exposed and unexposed groups were compared. Logistic regressions were run to identify predictors of acquisition of motor development milestones. Sociodemographic characteristics and dietary diversity scores were similar between MNP exposed and unexposed groups. Provision of low-iron (6 mg) MNP every other day, for 3 months, was associated with reduced risk of anaemia and stunting and increased achievement of motor development. After adjusting for age, infants exposed to MNPs had a higher likelihood of standing alone (AOR = 3.1; 95% CI [1.53, 6.46]) and walking alone (4.9; 95% CI [2.12, 11.37]) than unexposed ones. Exposure to MNPs, DDS, stunting, and mothers education were associated with acquisition of motor development milestones. Provision of low-iron dose MNPs on alternate days is associated with lower prevalence of anaemia, stunting, and increased motor development achievements. Integrating routine monitoring of motor development milestones with growth monitoring and anaemia screening can inform nutrition interventions to support optimal brain development.
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Affiliation(s)
- Ashenafi Geletu
- Center for Food Science and Nutrition, College of Natural and Computational SciencesAddis Ababa UniversityAddis AbabaEthiopia
- Department of Chemistry, College of Natural and computational SciencesKotebe Metropolitan UniversityAddis AbabaEthiopia
| | - Azeb Lelisa
- Infant and Young Child Nutrition ProgramNutrition InternationalAddis AbabaEthiopia
| | - Kaleab Baye
- Center for Food Science and Nutrition, College of Natural and Computational SciencesAddis Ababa UniversityAddis AbabaEthiopia
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Georgieff MK, Krebs NF, Cusick SE. The Benefits and Risks of Iron Supplementation in Pregnancy and Childhood. Annu Rev Nutr 2019; 39:121-146. [PMID: 31091416 DOI: 10.1146/annurev-nutr-082018-124213] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Iron deficiency is the most common micronutrient deficiency in the world and disproportionately affects pregnant women and young children. Iron deficiency has negative effects on pregnancy outcomes in women and on immune function and neurodevelopment in children. Iron supplementation programs have been successful in reducing this health burden. However, iron supplementation of iron-sufficient individuals is likely not necessary and may carry health risks for iron-sufficient and potentially some iron-deficient populations. This review considers the physiology of iron as a nutrient and how this physiology informs decision-making about weighing the benefits and risks of iron supplementation in iron-deficient, iron-sufficient, and iron-overloaded pregnant women and children.
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Affiliation(s)
- Michael K Georgieff
- Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, Minnesota 55454, USA; ,
| | - Nancy F Krebs
- Department of Pediatrics, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado 80045, USA;
| | - Sarah E Cusick
- Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, Minnesota 55454, USA; ,
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Wang Y, Wu Y, Li T, Wang X, Zhu C. Iron Metabolism and Brain Development in Premature Infants. Front Physiol 2019; 10:463. [PMID: 31105583 PMCID: PMC6494966 DOI: 10.3389/fphys.2019.00463] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 04/04/2019] [Indexed: 12/12/2022] Open
Abstract
Iron is important for a remarkable array of essential functions during brain development, and it needs to be provided in adequate amounts, especially to preterm infants. In this review article, we provide an overview of iron metabolism and homeostasis at the cellular level, as well as its regulation at the mRNA translation level, and we emphasize the importance of iron for brain development in fetal and early life in preterm infants. We also review the risk factors for disrupted iron metabolism that lead to high risk of developing iron deficiency and subsequent adverse effects on neurodevelopment in preterm infants. At the other extreme, iron overload, which is usually caused by excess iron supplementation in iron-replete preterm infants, might negatively impact brain development or even induce brain injury. Maintaining the balance of iron during the fetal and neonatal periods is important, and thus iron status should be monitored routinely and evaluated thoroughly during the neonatal period or before discharge of preterm infants so that iron supplementation can be individualized.
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Affiliation(s)
- Yafeng Wang
- Department of Neonatology (NICU), Children’s Hospital Affiliated Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Clinical Neuroscience, Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
| | - Yanan Wu
- Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tao Li
- Department of Neonatology (NICU), Children’s Hospital Affiliated Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Clinical Neuroscience, Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
| | - Xiaoyang Wang
- Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Physiology, Sahlgrenska Academy, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
| | - Changlian Zhu
- Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Clinical Neuroscience, Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
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45
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Armitage AE, Moretti D. The Importance of Iron Status for Young Children in Low- and Middle-Income Countries: A Narrative Review. Pharmaceuticals (Basel) 2019; 12:E59. [PMID: 30995720 PMCID: PMC6631790 DOI: 10.3390/ph12020059] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 04/09/2019] [Accepted: 04/12/2019] [Indexed: 12/21/2022] Open
Abstract
Early childhood is characterised by high physiological iron demand to support processes including blood volume expansion, brain development and tissue growth. Iron is also required for other essential functions including the generation of effective immune responses. Adequate iron status is therefore a prerequisite for optimal child development, yet nutritional iron deficiency and inflammation-related iron restriction are widespread amongst young children in low- and middle-income countries (LMICs), meaning iron demands are frequently not met. Consequently, therapeutic iron interventions are commonly recommended. However, iron also influences infection pathogenesis: iron deficiency reduces the risk of malaria, while therapeutic iron may increase susceptibility to malaria, respiratory and gastrointestinal infections, besides reshaping the intestinal microbiome. This means caution should be employed in administering iron interventions to young children in LMIC settings with high infection burdens. In this narrative review, we first examine demand and supply of iron during early childhood, in relation to the molecular understanding of systemic iron control. We then evaluate the importance of iron for distinct aspects of physiology and development, particularly focusing on young LMIC children. We finally discuss the implications and potential for interventions aimed at improving iron status whilst minimising infection-related risks in such settings. Optimal iron intervention strategies will likely need to be individually or setting-specifically adapted according to iron deficiency, inflammation status and infection risk, while maximising iron bioavailability and considering the trade-offs between benefits and risks for different aspects of physiology. The effectiveness of alternative approaches not centred around nutritional iron interventions for children should also be thoroughly evaluated: these include direct targeting of common causes of infection/inflammation, and maternal iron administration during pregnancy.
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Affiliation(s)
- Andrew E Armitage
- MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
| | - Diego Moretti
- Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Sciences and Technology, ETH Zürich, CH-8092 Zürich, Switzerland.
- Nutrition Group, Health Department, Swiss Distance University of Applied Sciences, CH-8105 Regensdorf, Switzerland.
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Masuda K, Chitundu M. Multiple Micronutrient Supplementation Using Spirulina platensis during the First 1000 Days is Positively Associated with Development in Children under Five Years: A Follow up of A Randomized Trial in Zambia. Nutrients 2019; 11:E730. [PMID: 30934863 PMCID: PMC6520735 DOI: 10.3390/nu11040730] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Revised: 03/22/2019] [Accepted: 03/28/2019] [Indexed: 12/18/2022] Open
Abstract
Early childhood development relies on various micronutrients. We recently reported that home fortification of complementary foods using spirulina reduced the time to attain motor milestones in Zambian infants. The objective of this study is to estimate the long-term associations between spirulina supplementation during the first 1000 days and child gross motor development, fine motor development, language, and personal⁻social skills at preschool age. We used longitudinal data from a randomized trial conducted in Zambia. In 2015, 501 infants (age, 6⁻18 months) were provided daily supplements of maize-soy-based porridge with spirulina (SP) and without spirulina (CON). Supplementation period lasted for 16 months. In January 2018, children who participated in the initial trial were resurveyed (CON: 182 children; SP: 188 children; now aged 36⁻48 months). We assessed the infants' gross motor development, fine motor development, language, and personal⁻social skills using a modified version of Malawi Development Assessment Tool. The initial clinical trial registration number was NCT03523182. Children in the SP group had higher scores in gross and fine motor development, language, and social skills than those in the CON group. Home fortification of complementary foods using spirulina during the first 1000 days improved development among Zambian children at preschool age.
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Affiliation(s)
- Kazuya Masuda
- Institute of Economic Research, Hitotsubashi University, Tokyo 186-8603, Japan.
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Ji P, Lönnerdal B, Kim K, Jinno CN. Iron Oversupplementation Causes Hippocampal Iron Overloading and Impairs Social Novelty Recognition in Nursing Piglets. J Nutr 2019; 149:398-405. [PMID: 30624730 DOI: 10.1093/jn/nxy227] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 07/23/2018] [Accepted: 08/14/2018] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND Iron oversupplementation in healthy term infants may adversely affect growth and cognitive development. OBJECTIVE We hypothesized that early-life iron excess causes systemic and central nervous system iron overload, and compromises social behavior. METHODS The nursing pig was used as a translational model in a completely randomized study. On postnatal day (PD) 1, 24 pigs (1.57 ± 0.28 kg mean ± standard deviation body wt) were assigned to the following treatment groups: 1) nonsupplemented iron-deficient group (NON); 2) control group (CON), intramuscularly injected with iron dextran (100 mg Fe) on PD2; 3) moderate iron group (MOD), orally administered ferrous sulfate at 10 mg Fe · kg body wt-1 · d-1; and 4) high iron group (HIG), orally administered ferrous sulfate at 50 mg Fe · kg-1 · d-1. Piglets were nursed by sows during the study from PD1 to PD21. Tissue iron was analyzed by atomic absorption spectrophotometry. Messenger RNA and protein expression of iron regulator and transporters were analyzed by quantitative reverse transcriptase-polymerase chain reaction and Western blot. A sociability test was performed on PD19-20. RESULTS Both MOD and HIG treatments (5.51 and 9.85 µmol/g tissue), but not CON (0.54 µmol/g), increased hepatic iron as compared with NON (0.25 µmol/g, P < 0.05). Similarly, the hippocampal iron concentrations in the MOD and HIG groups were 14.9% and 31.8% higher than that of NON, respectively (P < 0.05). In comparison with NON, MOD and HIG treatment repressed DMT1 in duodenal mucosa by 4- and 46-fold, respectively (P < 0.05); HIG drastically induced HAMP in liver by 540-fold (P < 0.05); iron-supplemented groups reduced TFRC in the hippocampus by <1-fold (P < 0.05). However, duodenal expression of ferroportin, the predominant transporter in basal membrane, was not affected by treatment. Despite normal sociability, the MOD and HIG pigs displayed deficits in social novelty recognition (P = 0.004). CONCLUSIONS Duodenal ferroportin was hyporesponsive to iron excess (MOD and HIG), which caused hippocampal iron overload and impaired social novelty recognition in nursing pigs.
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Affiliation(s)
- Peng Ji
- Departments of Nutrition University of California Davis, Davis, CA
| | - Bo Lönnerdal
- Departments of Nutrition University of California Davis, Davis, CA
| | - Kwangwook Kim
- Departments of Animal Science, University of California Davis, Davis, CA
| | - Cynthia N Jinno
- Departments of Animal Science, University of California Davis, Davis, CA
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Dietary iron absorption during early postnatal life. Biometals 2019; 32:385-393. [DOI: 10.1007/s10534-019-00181-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 02/08/2019] [Indexed: 12/12/2022]
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Abstract
Chronic kidney disease is an ongoing deterioration of renal function that often progresses to end-stage renal disease. Management goals in children include slowing disease progression, prevention and treatment of complications, and optimizing growth, development, and quality of life. Nutritional management is critically important to achieve these goals. Control of blood pressure, proteinuria, and metabolic acidosis with dietary and pharmacologic measures may slow progression of chronic kidney disease. Although significant progress in management has been made, further research is required to resolve many outstanding controversies. We review recent developments in pediatric chronic kidney disease, focusing on dietary measures to improve outcomes.
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