Behavioral consequences of developmental iron deficiency in infant rhesus monkeys

Golub, Mari S.; Hogrefe, Casey E.; Germann, Stacey L.; Capitanio, John P.; Lozoff, Betsy

doi:10.1016/j.ntt.2005.10.005

Cited by 82 publications

(68 citation statements)

References 65 publications

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“…An additional serum sample was obtained at 6 and 12 months for measurement of serum transferrin, total iron binding capacity (TIBC), transferrin saturation (TfS), and serum iron. Methods for these assays have been described previously [19, 24]. When the persistent differences in RBC numbers seen in the first cohort were confirmed in the second cohort, a more detailed hematological assessment was conducted in the infants of the second cohort prior to release from the project at 2 years of age.…”

Section: Methodsmentioning

confidence: 99%

Developmental plasticity of red blood cell homeostasis

et al. 2014

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Most human physiologic set points like body temperature are tightly regulated and show little variation between healthy individuals. Red blood cell (RBC) characteristics such as hematocrit (HCT) and mean cell volume (MCV) are stable within individuals but can vary by 20% from one healthy person to the next. The mechanisms for the majority of this inter-individual variation are unknown and do not appear to involve common genetic variation. Here we show that environmental conditions present during development, namely in utero iron availability, can exert long-term influence on a set point related to the RBC life cycle. In a controlled study of rhesus monkeys and a retrospective study of humans, we use a mathematical model of in vivo RBC population dynamics to show that in utero iron deficiency is associated with a lowered threshold for RBC clearance and turnover. This in utero effect is plastic, persisting at least two years after birth and after the cessation of iron deficiency. Our study reports a rare instance of developmental plasticity in the human hematologic systems and also shows how mathematical modeling can be used to identify cellular mechanisms involved in the adaptive control of homeostatic set points.

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Section: Methodsmentioning

confidence: 99%

Developmental plasticity of red blood cell homeostasis

et al. 2014

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“…Golub et al (2006) established the finding that an inadequate intake of iron from the diet during pregnancy in rhesus monkeys lead to impaired neurologic function at birth. Leela and Thanga (2002) reported that about 80% of children aged between 5 and 10 years had iron deficiency anaemia.…”

Section: Introductionmentioning

confidence: 99%

Effect of anaemia on cognitive function in children

Handa

Ahamad

Kesari

et al. 2009

IJFSNPH

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Study was carried out on 150 school going children to study the relationship between iron deficiency anaemia and cognitive function. Children's were grouped into moderate anaemic, mild anaemic and nonanaemic. Haemoglobin levels were estimated by cyanmethaemoglobin method. Results indicate that 53.33% were mild anaemic, 12% moderate anaemic and 34.67% non-anaemic. Results significantly (p < 0.05) indicates that moderate anaemic children performed poor on attention, design fluency, verbal working memory N-back 2, visual working memory N-back 2, planning, dictation, mathematical calculations, intelligence, immediate verbal learning and visual and verbal memory. Moreover, mild anaemic children performed significantly poor (p < 0.05) in attention, visual working memory N-back 2, dictation, mathematical calculations, intelligence, immediate verbal learning and visual and verbal memory. We concluded that non-anaemic children performed significantly better on cognitive function tests than mild and moderate anaemic. All data are expressed as mean ± SD and were analysed by analysis of variance by using SPSS software. Effect of anaemia on cognitive function in children17

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“…A non-human primate model with measures and ages closely comparable to the human infant study used diet to induce periods of iron deprivation. 7 To identify underlying neural mechanisms, a rodent model investigated the behavioral domain and related brain systems, again with experimental manipulation of dietary iron to produce ID and to support causal inferences. 8,9…”

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confidence: 99%

Dose-Response Relationships between Iron Deficiency with or without Anemia and Infant Social-Emotional Behavior

Lozoff¹,

Clark²,

Jing³

et al. 2008

The Journal of Pediatrics

160

132

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Objective-To assess dose-response relations between severity of iron deficiency (ID) and infant social-emotional behavior.Study design-Cohort of 9-to 10-month-old African-American infants (n = 77 with final iron status classification). Infants were provided oral iron for 3 months. Social-emotional outcomes included mother and examiner ratings at 9 and 12 months and quantitative behavioral coding from videotape at 12 months. General linear model analyses tested for linear effects of iron status group (ordered from worst to best -iron-deficient anemic (IDA), non-anemic iron-deficient (NA ID), ironsufficient (IS)) and determined thresholds for effects.Results-There were significant (p < .05) linear effects of poorer iron status for shyness (increasing, maternal rating), orientation-engagement and soothability (decreasing, examiner ratings), and the following quantitatively-coded behaviors: positive affect (decreasing) and latencies to engage with the examiner (increasing) and move away from the examiner (decreasing). The threshold for all but one effect was ID with or without anemia vs. IS.Conclusions-Infant social-emotional behavior appears to be adversely affected by ID with or without anemia. ID without anemia is not detected by common screening procedures and is more widespread than IDA. Infant social-emotional behavior can profoundly influence the caregiving environment, with repercussions for overall development.The prevalence of iron deficiency anemia (IDA) has markedly declined in US infants in the last 30 years. However, poor, minority, and immigrant infants and toddlers remain at increased Corresponding author: Betsy Lozoff, M.D., Center for Human Growth and Development, 300 N Ingalls, University of Michigan, Ann Arbor, MI 48109-5406. Tel: 734-764-2443; Fax: 734-936-9288; E-mail: blozoff@umich.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Though findings of rapid improvement in mental test scores have not been replicated, 4 socialemotional alterations are among the most consistent findings. Virtually every study that compared social-emotional behavior of IDA to non-anemic (NA) infants found them to be more wary, hesitant, solemn, unhappy, or closer to their mothers. 5 Four of 6 randomized trials of supplemental iron that assessed this domain showed affective benefits of iron (e.g., more positive affect, social interaction, etc.). 5 Notwithstanding the consistency of results, socialemotional effects have captured less attention than cognitive ones, but they could equally result from direct effects of ID on associated brain systems. Furthermore, there h...

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Behavioral consequences of developmental iron deficiency in infant rhesus monkeys

Cited by 82 publications

References 65 publications

Developmental plasticity of red blood cell homeostasis

Developmental plasticity of red blood cell homeostasis

Effect of anaemia on cognitive function in children

Dose-Response Relationships between Iron Deficiency with or without Anemia and Infant Social-Emotional Behavior

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