title: The effects of short-term oral iron therapy on developmental deficits in iron-deficient anemic infants. Once-weekly and 5-days a week iron supplementation differentially affect cognitive function but not school performance in Thai children. Iron deficiency anemia and educational achievement. A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development. Preliminary findings on iron supplementation and learning achievement of rural Indonesian children. Effects of iron deficiency on attention and learning processes in preschool children: Bandung, Indonesia. Effect of iron supplementation on cognition in Greek preschoolers Short-term developmental outcome of iron prophylaxis in infants. Impact of iron supplementation on cognitive functions in preschool and school-aged children: the Indian experience. Iron deficiency and educational achievement in Thailand. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials
abstract: To assess the effects of iron therapy on developmental test scores in infants with iron deficiency anemia , 68 Guatemalan babies 6 to 24 months of age , with and without mild iron deficiency anemia , were tested with the Bayley Scales of Infant Development before and after one week of oral iron treatment . The two major findings of the study were developmental deficits in the anemic group prior to treatment , and lack of rapid improvement with short-term oral iron therapy . The mean pretreatment Mental Development Index of the anemic group was significantly lower than that of nonanemic infants . The anemic group 's pretreatment Psychomotor Development Index was also lower than that of the nonanemic control group . In a double-blind r and omized study , six to eight days of oral iron therapy did not reverse these deficits . Consequently , the deficits of the anemic group can not be unequivocably attributed to iron lack . However , no significant differences were found between anemic and nonanemic groups in birth histories , socioeconomic level , or general nutritional status which might otherwise explain the lower developmental test scores of the anemic babies Many studies have reported comparable hemoglobin response in subjects given intermittent and daily iron supplements .  However , the effect of intermittent iron supplementation on impaired cognitive function , one of the serious consequences of iron deficiency among children , has not been studied . We investigated the effects of 1 d/wk ( weekly ) and 5 d/wk ( daily ) iron supplementation on changes in results of intelligence quotient ( IQ ) , Thai language , and mathematics tests among Thai primary schoolchildren . A double-blind , r and omized , placebo-controlled trial was conducted . Primary schoolchildren ( n = 397 ) were r and omly assigned to receive iron supplements daily or weekly or placebo . Ferrous sulfate ( 300 mg ) or placebo tablets were given under direct observation by the research er for 16 wk . Changes in IQ , and Thai language and mathematics scores were then compared . The increases in hemoglobin concentration were comparable in the weekly and daily iron supplementation groups but serum ferritin increased more in the children supplemented daily . Children receiving daily iron supplements , however , had a significantly lower increase in IQ ( 3 + /- 12 points ) than those receiving the supplement weekly ( 6 + /- 12 points ) or placebo ( 6 + /- 12 points ) , whereas the last-mentioned two groups did not differ . Z-scores of Thai language and mathematics test results did not differ among the groups . We conclude that weekly iron supplementation is the regimen of choice in this study community The present study investigates the effect of iron supplementation on measures of school performance among 78 iron-deficient anemic and 41 nonanemic children in an economically deprived rural area in Central Java , Indonesia . All the subjects were treated for ancylostomiasis before iron supplementation . They were r and omly assigned to either an iron or placebo group . Hematological and behavioral measurements were obtained immediately before ( T1 ) and after ( T2 ) the iron and placebo treatments . Iron treatment for a 3-mo period result ed in substantive increases in mean Hgb , Hct , and transferrin saturation among the iron-deficient anemic children . Furthermore , changes in the iron status of iron-deficient anemic children were associated with significant changes in the school achievement test scores of iron-deficient anemic children . T2 evaluation of achievement test scores indicated that the difference between iron-treated anemic and nonanemic children was still statistically significant . However , when T1 scores were entered as a covariate , iron-deficient anemic subjects treated with iron obtained significantly higher delta achievement scores . Findings from the present study indicate that iron supplementation among iron-deficient anemic children benefits learning processes as measured by the school achievement test scores BACKGROUND Deficiencies of iron and zinc are associated with delayed development , growth faltering , and increased infectious-disease morbidity during infancy and childhood . Combined iron and zinc supplementation may therefore be a logical preventive strategy . OBJECTIVE The objective of the study was to compare the effects of combined iron and zinc supplementation in infancy with the effects of iron and zinc as single micronutrients on growth , psychomotor development , and incidence of infectious disease . DESIGN Indonesian infants ( n = 680 ) were r and omly assigned to daily supplementation with 10 mg Fe ( Fe group ) , 10 mg Zn ( Zn group ) , 10 mg Fe and 10 mg Zn ( Fe+Zn group ) , or placebo from 6 to 12 mo of age . Anthropometric indexes , developmental indexes ( Bayley Scales of Infant Development ; BSID ) , and morbidity were recorded . RESULTS At 12 mo , two-factor analysis of variance showed a significant interaction between iron and zinc for weight-for-age z score , knee-heel length , and BSID psychomotor development . Weight-for-age z score was higher in the Zn group than in the placebo and Fe+Zn groups , knee-heel length was higher in the Zn and Fe groups than in the placebo group , and the BSID psychomotor development index was higher in the Fe group than in the placebo group . No significant effect on morbidity was found . CONCLUSIONS Single supplementation with zinc significantly improved growth , and single supplementation with iron significantly improved growth and psychomotor development , but combined supplementation with iron and zinc had no significant effect on growth or development . Combined , simultaneous supplementation with iron and zinc to infants can not be routinely recommended at the iron-to-zinc ratio used in this study The effects of oral iron supplementation on blood iron levels and learning achievement in 130 rural Indonesian school children were assessed in this double-blind study . The children were classified into anemic and nonanemic groups according to their initial hemoglobin and transferrin saturation levels and were r and omly assigned to either iron or placebo treatment for 3 mo . Hematological , anthropometric , and learning-achievement data were collected before ( T1 ) and after ( T2 ) the treatment period and 3 mo later . The means and st and ard deviations suggest that supplementation with 10 mg ferrous sulfate per kilogram body weight per day for 3 mo result ed in an apparent improvement in anemic subjects ' hematological status and learning-achievement scores . No tests of statistical comparisons are reported A double-blind clinical trial was conducted in Indonesia to assess effects of iron supplementation on performance of iron-depleted and iron-deficient anemic children in discrimination and oddity learning tasks . Half these children received elemental Fe for 8 wk ; the others received a placebo . There were significant changes from pre- to postintervention evaluations in ferritin , transferrin saturation , free erythrocyte protoporphyrin , and hemoglobin among the anemic and iron-depleted children ; no changes were observed among the placebos or any of the iron-replete children . The magnitude of hematological changes in anemic children treated with iron was small ; yet , after treatment the children 's mean ferritin , transferrin saturation , and hemoglobin values were above the cutoff points used for the definition of iron-deficiency anemia ( IDA ) . Pre- and posttreatment psychological test data show that IDA produces alterations in cognitive processes related to visual attention and concept acquisition , alterations reversed with iron treatment Objective : To examine effects of iron supplementation on vigilance , attention and conceptual learning in preschool children in Greece . Design : R and omized Double-Blind Placebo Controlled trial of iron . R and omization stratified by iron status and day care center ( DCC ) . Setting : Nine public DCCs in Athens , Greece . Subjects : In all , 49 3–4-y olds ( 21 anemic , 28 good iron status ) with birth weight not less than 2500 g , currently healthy ; benign past medical history , IQ ≥1 s.d . below the age-adjusted mean , serum Pb ≤200 ppb ( none exceeded 50 ppb ) , and height , weight and head circumference for age ≥10th percentile  . Anemia defined as : ( 1 ) pretreatment Hgb < 112 g/l and TS < 16 % and ferritin < 12 μg/L OR ( 2 ) Hgb rise of > 10 g/l ( T2–T0 ) with iron supplementation . Good iron status was defined as baseline levels of Hgb > 120 g/l and either TS > 20 % or serum ferritin > 12 μg/l . Intervention : The intervention consisted of a 2–month supplementation of 15 mg iron ( and MV ) vs placebo ( MV alone ) . Results : After iron treatment , the anemic subjects made significantly fewer errors of commission ( 14 % higher specificity , P<0.05 ) , exhibited 8 % higher accuracy ( P<0.05 ) and were significantly more efficient ( mean difference=1.09 , P<0.05 ) than those given placebo . These effects of iron were not found among preschoolers with good iron status . No effects of iron treatment were found on the Oddity Learning task . Conclusions : This study demonstrated that iron supplementation of iron-deficient anemic preschoolers results in an improvement in discrimination , specifically selective attention . Sponsorship : University of California , Davis and Nutricia Corporation BACKGROUND Previous studies on the cognitive effects of iron treatment have focused on anemic or non-anemic iron-deficient infants . The effect of iron supplementation on cognitive development among iron-sufficient infants has not been studied . The aim of the present study was to examine the effect of iron supplementation on performance in the Bayley Scales of Infant Development ( BSID ) and anthropometric measurement in 6-month-old iron-sufficient healthy infants . METHODS Healthy , iron-sufficient infants who were 6 months of age and were attending the Well Baby Clinic were considered for enrollment . Infants were r and omly assigned to take ferrous sulfate supplementation ( 1 mg/kg per day ) or no supplementation and were followed for 3 months . Anthropometric measurement , hematologic status and BSID were evaluated on admission and after 3 months . RESULTS Seven infants in the intervention group and nine in the control group completed the study . No significant differences were observed in anthropometric measurements and complete blood counts between the two groups after the 3 month study period . The mean transferrin saturation ( TS ) level decreased significantly in the control group during the study period ( from 15.3+/-2.6 to 7.8+/-5.1 % ; P = 0.0117 ) , but no such reduction was seen in the intervention group . At the end of the study , the TS of the control group was found to be significantly lower than that of the intervention group ( 7.8+/-5.1 vs. 19.9+/-7.9 % , respectively ; P = 0.0033 ) . The BSID scores of infants in both groups were within the normal range on admission and at the end of the study period . CONCLUSIONS Short-term iron supplementation did not change developmental test scores despite the hematologic response in iron-sufficient healthy infants . The high prevelance of iron-deficiency anemia and its relationship with adverse developmental outcome suggests that prevention of iron-deficiency anemia with prophylaxis needs to be emphasized , rather than treatment Four studies examined impacts of iron supplementation on school children of various ages and both sexes . The first study investigated impact of iron-folic acid supplements for 60 d on cognition in 94 boys and girls aged 5 - 8 y. Improvement in total scores of the anemics was significantly higher than the nonanemics in 7 - 8-y-old children only . The second study assessed impacts of supplementation on cognition in 14 pairs of 5 - 6-y-old anemic boys , with clear beneficial effects on cognitive function . The third study investigated effects of varying dosages of elemental iron on cognitive function in 48 boys aged 8 - 15 y , with different levels of improvement . The fourth study investigated impacts of iron supplementation on 163 anemic girls aged 8 - 15 y with treatment and evaluations at 4 and 8 mo , with significantly improved scores in cognitive function after the eighth month This double-blind clinical trial was conducted in Thail and to assess the impact of iron treatment on the IQ and educational attainment of 1358 9 - 11-y-old children . The children were classified into one of three groups : iron replete , iron depleted , and iron-deficient anemic . The Raven Progressive Matrices was used to measure IQ . A Thai language and a math test were administered to assess school attainment . A 50-mg/d tablet of ferrous sulphate was given for 2 wk and a 100 mg/d tablet , for 14 wk . An anthelminthic drug was given on the day of the blood test before treatment and 3 mo after the intervention started . There is evidence of a positive association between iron status and IQ and a language school achievement test but there is no support for the internal validity of the hypothesis that this association is causal BACKGROUND Up to 25 % of adolescent girls in the USA are iron deficient . This double-blind , placebo-controlled clinical trial assessed the effects of iron supplementation on cognitive function in adolescent girls with non-anaemic iron deficiency . METHODS 716 girls who enrolled at four Baltimore high schools were screened for non-anaemic iron deficiency ( serum ferritin < or = 12 micrograms/L with normal haemoglobin ) . 98 ( 13.7 % ) girls had non-anaemic iron deficiency of whom 81 were enrolled in the trial . Participants were r and omly assigned oral ferrous sulphate ( 650 mg twice daily ) or placebo for 8 weeks . The effect of iron treatment was assessed by question naires and haematological and cognitive tests , which were done before treatment started and repeated after the intervention . We used four tests of attention and memory to measure cognitive functioning . Intention-to-treat and per- protocol analyses were done . FINDINGS Of the 81 enrolled girls with non-anaemic iron deficiency , 78 ( 96 % ) completed the study ( 39 in each group ) . Five girls ( three control , two treatment ) developed anaemia during the intervention and were excluded from the analyses . Thus , 73 girls were included in the per- protocol analysis . Ethnic distribution , mean age , serum ferritin concentrations , haemoglobin concentrations , and cognitive test scores of the groups did not differ significantly at baseline . Postintervention haematological measures of iron status were significantly improved in the treatment group ( serum ferritin 27.3 vs 12.1 micrograms/L , p < 0.001 ) . Regression analysis showed that girls who received iron performed better on a test of verbal learning and memory than girls in the control group ( p < 0.02 ) . INTERPRETATION In this urban population of non-anaemic iron-deficient adolescent girls , iron supplementation improved verbal learning and memory The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials
target: Overall , the studies suggest a modest positive effect of iron supplementation on cognition and psychomotor outcomes in anemic infants and children after supplementation periods of at least 2 months of duration
background: A systematic review was conducted to summarize the evidence currently available from r and omized controlled trials ( RCTs ) concerning the effect of iron intake of infants , children and adolescents on measures of cognitive development and function .