OBJECTIVES This study examined effects of iron deficiency anemia (IDA) on specific domains of infant cognitive function and the role of IDA-related socioemotional deficits in mediating and/or moderating these effects. METHODS Infants were recruited during routine 9-month visits to an inner-city clinic. IDA was defined as hemoglobin level <110 g/L with ≥2 abnormal iron deficiency indicators (mean corpuscular volume, red cell distribution width, zinc protoporphyrin, transferrin saturation, and ferritin). At 9 and 12 months, the Fagan Test of Infant Intelligence (FTII); A-not-B task; Emotionality, Activity, and Sociability Temperament Survey; and Behavior Rating Scale were administered. Analyses were adjusted for potential confounders, including age and sociodemographic variables. RESULTS Twenty-eight infants met criteria for IDA, 28 had nonanemic iron deficiency (NA ID) and 21 had iron sufficiency (IS). There was a linear effect for object permanence at 9 months: infants with IDA were least likely to exhibit object permanence, IS most likely, and NA ID intermediate. Infants with IDA and those with hemoglobin level ≤105 g/L showed poorer recognition memory on the FTII than infants without IDA. The Behavior Rating Scale orientation/engagement measure partially mediated these effects. Stronger effects of IDA on these outcomes were seen in infants who scored more poorly on the socioemotional measures. CONCLUSIONS These data indicate poorer object permanence and short-term memory encoding and/or retrieval in infants with IDA at 9 months. These cognitive effects were attributable, in part, to IDA-related deficits in socioemotional function. Children with poor socioemotional performance seem to be more vulnerable to the effects of IDA on cognitive function.

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...

OBJECTIVES-The purpose of this work was to determine whether iron-deficiency anemia in infancy represents a risk factor for deficits in attention and memory development using event-related potentials.METHODS-Artifact-free event-related potential data were obtained at 9 and/or 12 months from 15 infants with iron-deficiency anemia and 19 who were iron sufficient during a test of the infant's ability to discriminate a highly familiar stimulus, the mother's face, from a stranger's face.RESULTS-A midlatency negative component associated with attention and a late-occurring positive slow wave associated with memory updating were identified at both ages in the irondeficiency anemia and iron-sufficient groups. Consistent with the age-appropriate pattern of development at 9 months, the iron-sufficient group showed a greater attentional response (negative component) to the mother and a greater updating of memory for the stranger (positive slow wave). This pattern of responses was not evident in the iron-deficiency anemia group until 12 months, suggesting a delay in cognitive development.CONCLUSIONS-These data suggest that iron-deficiency anemia adversely affects the allocation of neurophysiologic resources to attention and recognition memory during the processing of information about familiar and unfamiliar stimuli. This delay in cognitive development may reflect alterations in efficiency of central nervous system functions that seem related to early iron deficiency. Assessing specific neurocognitive functions with brain-based measures in human infants is challenging. Event-related potentials (ERPs) provide a noninvasive means for measuring transient changes in the brain's electrical activity in response to stimuli, allowing the evaluation of attention and memory in very young infants. ERP studies informed by animal models of diet-induced ID have shown impaired recognition memory in human infants with prenatal ID because of maternal diabetes during pregnancy. [7][8][9] The study reported here examined infant recognition memory in relation to IDA during its period of peak postnatal prevalence (6-24 months). This study was part of an integrated cross-species program project on the brain and behavior effects of early ID in human infants, nonhuman primate infants, and developing rodents. As part of a hypothesis-driven neurodevelopmental approach, the hippocampus and/ or related behaviors were assessed in all 3 species. Recognition memory was assessed using ERP in the human infant project.We hypothesized that postnatal IDA would alter attention and recognition memory because of the effect of iron on hippocampal development and function. To examine this hypothesis, we recorded ERPs in a procedure specifically focused on the infant's ability to recognize a highly familiar stimulus, the mother's face, and to discriminate the mother's face from a stranger's face. Two ERP components of particular interest have been identified in studies of infant memory: a midlatency negative component (NC) associated with attention and a l...

Maternal iron status is thought to be related to postpartum depressive symptoms. The purpose of the present study was to evaluate the relationship between pre- and postnatal maternal iron status and depressive symptoms in pilot (n = 137) and confirmatory (n = 567) samples of Chinese women. Iron status was evaluated at mid- and late pregnancy and 3 days postpartum. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess maternal postpartum depression 24–48 hours after delivery and 6 weeks later. In the pilot sample, correlations between early- and late-pregnancy maternal Hb and EPDS scores at 6 weeks were r = 0.07 and −0.01, respectively (nonsignificant). In the confirmatory sample, the correlations between maternal iron measures (Hb, MCV, ZPP, ferritin, sTfR, and sTfR Index) in mid- or late pregnancy or 3 days postpartum and EPDS scores shortly after delivery or at 6 weeks were also low (r values < 0.10). EPDS scores in anemic and nonanemic mothers did not differ, regardless of sample or timing of maternal iron status assessment. In addition, women with or without possible PPD were similar in iron status in both samples. Thus, there was no relationship between maternal iron status and postpartum depression in these samples.

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Iron deficiency has been shown to impair dopamine functioning in rodent models, but it is challenging to obtain evidence of such effects in human infants. Because spontaneous eye-blink rate may provide a noninvasive assessment of dopamine functioning, we hypothesized that eye-blink rate would be lower in infants with iron-deficiency anemia and would increase with iron therapy. A 4-min eye-blink assessment was conducted for quiet, alert infants sitting on their mother's lap. Data were available for 61 9- to 10-mo-old infants from inner-city Detroit (19 iron-deficient anemic, 23 nonanemic iron-deficient, and 19 nonanemic iron-sufficient). Iron-deficient and iron-sufficient nonanemic groups had similar eye-blink rates (P = 0.90) and were therefore combined. We used Poisson regression based on generalized estimation equation methodology to test for differences between iron-deficient anemic and nonanemic infants in blinks/min and change after 3 mo of iron therapy. Iron-deficient anemic infants had a lower initial eye-blink rate than nonanemic infants (mean +/- SD) (4.0 +/- 1.9 vs. 5.3 +/- 2.8 blinks/min; P = 0.02; effect size = 0.6 SD). At 12 mo, eye-blink rate increased by 2.1 blinks/min in the iron-deficient anemic group (P = 0.008); there was no change in the nonanemic group (P = 0.96). These results are consistent with reduced dopamine function in iron-deficient anemic infants. The clinical importance of a lower eye-blink rate is unclear, but impaired dopamine functioning is likely to have broader impact, given the role dopamine plays in regulating movement, motivation, cognition, and hormone release.

Objective This study was conducted to compare quality of mother-infant interactions during feeding in infants with or without iron deficiency anemia (IDA). Method Infants and caregivers were screened at their 9- to 10-month-old health maintenance visits at an inner-city clinic in Detroit. Those who were full-term and healthy received a venipuncture blood sample to assess iron status. Of the 77 infants who met final iron status criteria, 68 infants and mothers were videotaped during feeding interaction at the Child Development Research Laboratory. The quality of mother-infant interaction during feeding was scored on the Nursing Child Assessment Feeding Scale (NCAFS). Twenty-five infants with IDA (HB < 110 g/L and at least 2 abnormal iron measures) were compared to 43 non-anemic infants (HB ≥ 110 g/L) using ANOVA and GLM models with covariate control. Results Mothers of IDA infants responded with significantly less sensitivity to infant cues and less cognitive and social-emotional growth fostering behavior than mothers of non-anemic infants. The pattern of results was similar for scales of contingent behaviors. The magnitude of the differences in maternal ratings was large (0.8-1.0 SD after covariate adjustment). IDA infants were rated significantly lower on clarity of cues and overall (effect sizes 0.5 SD). Conclusion IDA in infancy was associated with less optimal mother-infant interactions during feeding. Future interventions might target feeding interaction and consider effects on infant iron status and developmental/behavioral outcomes among IDA infants, as well as infant feeding practices per se.