title: Iron-deficiency anemia and infant development: effects of extended oral iron therapy. Behavioral effects of iron supplementation in infants in Madang, Papua New Guinea. The effects of short-term oral iron therapy on developmental deficits in iron-deficient anemic infants. Iron deficiency anemia and educational achievement. Iron deficiency anemia and iron therapy effects on infant developmental test performance. Effects of an energy and micronutrient supplement on play behavior in undernourished children in Indonesia THE EFFECTS OF THERAPY ON THE DEVELOPMENTAL SCORES OF IRON DEFICIENT INFANTS Improvements in cognitive performance for schoolchildren in Zaire, Africa, following an iron supplement and treatment for intestinal parasites. 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. Effects of iron supplementation and anthelmintic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study Iron deficiency anemia: adverse effects on infant psychomotor development. Iron fortified follow on formula from 9 to 18 months improves iron status but not development or growth: a randomised trial Cognitive deficits in iron-deficient and iron-deficient anemic children. A developmental view of the effects of an energy and micronutrient supplement in undernourished children in Indonesia Impact of iron supplementation on cognitive functions in preschool and school-aged children: the Indian experience. Prevention of iron deficiency and psychomotor decline in high-risk infants through use of iron-fortified infant formula: a randomized clinical trial. Iron deficiency and educational achievement in Thailand. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls
abstract: OBJECTIVE To determine whether extended oral iron therapy corrects lower developmental test scores in infants with iron-deficiency anemia . STUDY DESIGN Double-blind , controlled trial in Costa Rica involving 32 12- to 23-month-old infants with iron-deficiency anemia and 54 nonanemic control subjects . Anemic infants were treated with orally administered iron for 6 months ; half the nonanemic children were treated with iron and half with placebo .  Developmental test scores and hematologic status were evaluated before treatment , after 3 months , and after 6 months . RESULTS Iron-deficient anemic infants received lower mental test scores than nonanemic infants at all three time points ( p < 0.05 pretreatment and at 3 months , p = 0.07 at 6 months ) . There were no significant differences in motor test scores . More of the anemic infants were rated as unusually tearful and unhappy . Anemic infants came from families with lower maternal education and less support for child development and were less likely to be breast fed , were weaned earlier , and consumed more cow milk . CONCLUSIONS Lower mental test scores persisted in infants with iron-deficiency anemia despite extended oral iron therapy and an excellent hematologic response . Iron-deficiency anemia may serve as a marker for a variety of nutritional and family disadvantages that may adversely affect infant development The effect of iron supplementation on attending behavior of 96 1-y-old infants was assessed in a double-blind , r and omized , controlled trial of iron dextran  in Papua New Guinea . The treatment group received an injection of iron dextran at 2 mo ; the controls received a placebo injection . Because many children had malarial parasitemia at testing , presence of malaria was used in the analysis . A significant interaction was found between iron and malaria infection on total fixation time : iron-supplemented groups and placebo-treated parasitemic children showed significantly higher total fixation scores than did placebo-treated aparasitemic children . Blood analysis of iron status showed similar results , with lowest iron status evident in the placebo-treated aparasitemic group . There was no effect of treatment on rate of habituation or dishabituation . Supplemental iron treatment has a significant effect on attention but the direction of the effect depends on the presence of malaria infection 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 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 The behavioral effects of iron deficiency and its treatment were evaluated in a double-blind r and omized controlled community-based study of 191 Costa Rican infants , 12 to 23 months of age , with various degrees of iron deficiency . The Bayley Scales of Infant Development were administered before and both 1 week and 3 months after IM or oral administration of iron . Appropriate placebo-treated control infants were also tested . Infants with iron deficiency anemia showed significantly lower mental and motor test scores , even after considering factors relating to birth , nutrition , family background , parental IQ , and the home environment . After 1 week , neither IM nor oral iron treatments differed from placebo treatment in effects on scores . After 3 months , lower mental and motor test scores were no longer observed among iron-deficient anemic infants whose anemia and iron deficiency were both corrected ( 36 % ) . However , significantly lower mental and motor test scores persisted among the majority of initially anemic infants ( 64 % ) who had more severe or chronic iron deficiency . Although no longer anemic , they still showed biochemical evidence of iron deficiency after 3 months of treatment . These persistent lower scores suggest either that iron therapy adequate for correcting anemia is insufficient to reverse behavioral and developmental disturbances in many infants or that certain ill effects are long-lasting , depending on the timing , severity , or chronicity of iron deficiency anemia in infancy Objectives : This paper reports the effects of an energy and micronutrient supplementation on quantitative and qualitative aspects of play among poorly nourished children . At issue is whether the supplement led to a progression in complexity of play . Design : two cohorts of children were r and omly assigned to three treatments : E=1171 kJ+12 mg iron ; M=12 mg iron+209 kJ ; S=104 kJ. Supplementation was given for 6 months . Evaluations of play behavior were repeated four times . Setting : The sites were six tea plantations in Pangalengan , West Java . Subjects : The present study utilized a sub sample of 55 children recruited for the larger Pangalengan project 6 months into the study . Thirty-eight children were recruited late enough to allow for longitudinal observations . The remaining cases were used for cross sectional observations only . Inclusion criteria were : no chronic disease ; length-for-age ≤−1 st and ard deviation ( s.d . ) and weight-for-length between −1 and −2 s.d . of the median of the reference of the World Health Organization . Methods : The children were videotaped during play . These tapes were coded for eight mutually exclusive categories of activities . Four activities coded represented manipulative , relational , functional and symbolic play . Results : Treatment did not affect qualitative play . Girls that received E increased functional play but boys showed the opposite effect . Children in the S group were breastfed more during play as compared to the E group . Children in the E group waited less to begin play . Sponsorship : Nestlé Foundation . European Journal of Clinical Nutrition ( 2000 ) 54 , Suppl 2 , It has been proposed that iron deficiency in infants and children is associated with behavioral alterations . To test this hypothesis , 24 infants with iron deficiency anemia , ages 9 to 26 mos , were r and omly assigned to a treatment and control group . Bayley Scales of Infant Development were administered before the institution of treatment with intramuscular iron or placebo and the test was readministered in 5 to 8 days . Mean hemoglobin level in the 2 groups was similar . It averaged 8.6 in the controls and 8.7 gm/dl in the treatment group . The 2 groupa did not differ with respect to age , sex , racial composition , or initial Bayley scores of Mental Development Index or Physical Development Index . Infants treated with iron showed a statistically significant ( p = .01 ) increase in their scores on the Mental Development Index averaging a mean gain of 13.6 points in a mean time of 6.8 days . No changes were observed in the control group . The treated group was also found to become more alert and responsive and demonstrated improvement in tests of gross and fine motor coordination . All improvement occurred independent of significant increases in hemoglobin level . These findings support the hypothesis that iron deficiency , and not anemia , in infants produces developmental alterations and that these changes are rapidly reversible with iron therapy Tested 47 first-year primary school children at a mission school in rural Zaire for cognitive ability with the Kaufman Assessment Battery for Children ( K-ABC ) adopted to the language of Kituba . Within a day of this test , each child was evaluated for blood hemoglobin ( Hgb ) level and the presence of intestinal parasites . Half of the children received an iron supplement ( 20 mg Fe ) for 30 days and those children positive for the intestinal parasites of ankylostome or ascaris were r and omly selected to receive either a vermifuge treatment or placebo . All of the children were again evaluated medically and cognitively 4 weeks after the initiation of treatment . Using discriminant analysis , performance on the Mental Processing Composite of the K-ABC 1 month after treatment in combination with increases in blood Hgb result ed in the successful classification of 74 % in terms whether a child had received both iron supplement and vermifuge treatment ( p = .007 ) . With respect to our home evaluation for each child , factors related to the nutritional and economic well-being of the home environment proved a reliable marker for Simultaneous Processing ability . However , the present findings also suggest that over the short-term , changes in blood Hgb that accompany both vermifuge and iron supplement treatment together can improve certain aspects of cognitive ability , perhaps by means of heightened attentional capacity 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 Abstract Objective : To measure the effects of iron supplementation and anthelmintic treatment on iron status , anaemia , growth , morbidity , and development of children aged 6–59 months . Design : Double blind , placebo controlled r and omised factorial trial of iron supplementation and anthelmintic treatment . Setting : Community in Pemba Isl and , Zanzibar . Participants : 614 preschool children aged 6–59 months . Main outcome measures : Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups . Results : Before intervention , anaemia was prevalent and severe , and geohelminth infections were prevalent and light — Plasmodium falciparum infection was nearly universal . Iron supplementation significantly improved iron status , but not haemoglobin status . Iron supplementation improved language development by 0.8 ( 95 % confidence interval 0.2 to 1.4 ) points on the 20 point scale . Iron supplementation also improved motor development , but this effect was modified by baseline haemoglobin concentrations ( P=0.015 for interaction term ) and was apparent only in children with baseline haemoglobin concentrations < 90 g/l . In children with a baseline haemoglobin concentration of 68 g/l ( one st and ard deviation below the mean value ) , iron treatment increased scores by 1.1 ( 0.1 to 2.1 ) points on the 18 point motor scale . Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura , but not by hookworms . Mebendazole  increased development scores by 0.4 ( −0.3 to 1.1 ) points on the motor scale and 0.3 ( −0.3 to 0.9 ) points on the language scale . Conclusions : Iron supplementation improved motor and language development of preschool children in rural Africa . The effects of iron on motor development were limited to children with more severe anaemia ( baseline haemoglobin concentration < 90 g/l ) . Mebendazole had a positive effect on motor and language development , but this was not statistically significant . What is already known on this topic Iron is needed for development and functioning of the human brain Anaemic children show developmental delays , but it is not yet clear whether iron deficiency causes these deficits or whether iron supplementation can reverse them Helminth infections in schoolchildren are associated with cognitive deficits , but few studies have been made of helminth infection and early child development What this study adds Low doses of oral iron supplementation given daily improved language development in children aged 1–4 years in Zanzibar Iron supplementation improved motor development , but only in children with initial haemoglobin concentrations below 90 g/l The effects of routine anthelmintic treatment on motor and language milestones were positive , but non-significant , with our sample In a double-blind , placebo-control prospect i ve cohort study of 196 infants from birth to 15 months of age , assessment was made at 12 months of age of the relationship between iron status and psychomotor development , the effect of a short-term ( 10-day ) trial of oral iron vs placebo , and the effect of long-term ( 3 months ) oral iron therapy . Development was assessed with the mental and psychomotor indices and the infant behavior record of the Bayley Scales of Infant Development in 39 anemic , 30 control , and 127 nonanemic iron-deficient children . Anemic infants had significantly lower Mental and Psychomotor Developmental Index scores than control infants or nonanemic iron-deficient infants ( one-way analysis of variance , P less than .0001 ) . Control infants and nonanemic iron-deficient infants performed comparably . No difference was noted between the effect of oral administration of iron or placebo after 10 days or after 3 months of iron therapy . Among anemic infants a hemoglobin concentration less than 10.5 g/dL and duration of anemia of greater than 3 months were correlated with significantly lower motor and mental scores ( P less than .05 ) . Anemic infants failed specifically in language capabilities and body balance-coordination skills when compared with controls . These results , in a design in which intervening variables were closely controlled , suggest that when iron deficiency progresses to anemia , but not before , adverse influences in the performance of developmental tests appear and persist for at least 3 months despite correction of anemia with iron therapy . If these impairments prove to be long st and ing , prevention of iron deficiency anemia in early infancy becomes the only way to avoid them AIMS Iron deficiency anaemia is associated , in observational studies , with developmental disadvantage . This study tested the hypothesis that feeding iron supplemented formula from 9 to 18 months of age would improve developmental performance . SUBJECTS AND METHODS 493 healthy children aged 9 months being fed pasteurised cows ’ milk were recruited from three UK centres . They were r and omised to : cows ’ milk as before , formula containing 0.9 mg/litre iron , or formula containing 1.2 mg/litre iron , until 18 months of age . Bayley mental and psychomotor developmental indices were measured at 18 months , as were growth and haematological indices . RESULTS Children fed iron fortified formula had higher plasma ferritin concentrations , but there were no significant intergroup differences in development or growth . CONCLUSIONS There are no developmental or growth advantages in children given iron supplemented formula , but a benefit for a minority who were anaemic , or the possibility that a benefit may emerge at a later age , can not be excluded Eighteen- to 60-month-old iron-deficient anemic children given iron therapy ( n = 25 ) and a control group matched for mother 's educational level showed no significant difference in mean mental development score at baseline . The control group 's mean score was increased significantly over baseline score at 3 and 6 months and was significantly higher than the experimental group 's mean score at 3 months . Although the experimental group demonstrated hematologic correction over 6 months , mean mental development score showed no significant improvement . Scores for an iron deficient not anemic group given iron ( n = 22 ) , despite complete hematologic correction over the six months of observation , and for its control group , did not change significantly . Baseline scores for an iron-deficient not anemic placebo group ( n = 23 ) and for its control group were not significantly different . At 3 months the control group score had increased significantly , whereas that for the experimental group had not . When experimental and control subjects were matched on baseline mental development score , the control subjects experienced increases in scores over time , further confirming an impaired ability to improve scores with repeated testing in the experimental groups . Behavioral rating data ( responsiveness to examiner , responsiveness to environment , and emotional tone ) revealed significant differences between the iron-deficient anemic group and its control group at 3 and 6 months , with the control group rated more responsive , suggesting that iron deficiency , alone or in association with anemia , may have some lasting effect on behavior and development . Group differences were also found between the mean number of occurrences of multiple stressful events . Failure to show improvement in scores in the iron-deficient anemic group may reflect the fact that those children were less testable than were children in the control group , despite repeated testings , a theory supported by the infant behavior rating data . This may be related to some irreversible behavioral deficit or to an adverse environmental milieu ( e.g. , stress ) Objectives : This paper presents the results of a structural equation model testing whether the longitudinal data of the Pangalengan subjects fit the theoretical model regarding the intellectual delay of undernourished children . Design : Two cohorts of children were r and omly assigned to three treatments : E=1171 kJ+12 mg iron ; M=12 mg iron+209 kJ ; S=104 kJ. Supplementation was given for 6 months . Setting : The sites were six tea plantations in Indonesia . Subjects : A 12-month-old ( n=53 ) and an 18-month-old ( n=83 ) cohort were recruited from day-care-centers . Inclusion criteria were : no chronic disease ; length-for-age=<1 st and ard deviation ( s.d . ) and weight-for-length between −1 and −2 s.d . of the median of the reference of the World Health Organization . Methods : Twenty-four-hour dietary intakes were assessed using the weighted individual inventory technique . Body weight and length were obtained using st and ard procedures ; motor development was assessed with the Bayley Scale and with a custom made scale for motor development leading to bipedal locomotion . Four-hour observations were made of the child ’s interactions with the environment . Carrying a child in the arms and exploratory behavior were used as indicators of caregiving and exploration . All measurements were obtained every 2 months . Results : The original model did not fit the data . The model was then modified with the inclusion of two new pathways : from activity and from motor development to mental development . Following these adjustments the model fit the data for each cohort and for both cohorts combined . Sponsorship : Nestlé Foundation . European Journal of Clinical Nutrition ( 2000 ) 54 , Suppl 2 , 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 OBJECTIVE To determine the efficacy of iron-fortified infant formula in preventing  developmental delays and abnormal behavior . DESIGN Double-blind , r and omized , controlled trial . SETTING Urban hospital clinic . PARTICIPANTS A total of 283 healthy , bottle-fed infants from very low income families . Children with prematurity , low birth weight , and major anomalies and those who had received more than 2 weeks of evaporated-milk feedings were excluded . The groups were similar for sociodemographic background variables . Fifty-eight infants ( 20.5 % ) dropped out before any outcome data were gathered ; 225 , 204 , 186 , and 154 remained at 6- , 9- , 12- , and 15-month assessment s , respectively . INTERVENTION Iron-fortified formula ( 12.8 mg iron per liter ) versus regular formula ( 1.1 mg iron per liter ) . MAIN OUTCOME MEASURES Iron status was measured on venous blood by determination of hemoglobin , serum iron and iron-binding capacity , serum ferritin , and free erythrocyte protoporphyrin values . The Bayley Scales of Infant Development ( mental and psychomotor indexes ) and two factors of the Infant Behavior Record ( test affect and task orientation ) were the outcomes of interest . RESULTS All measures of iron status were significantly different between groups ( p < 0.001 ) . Psychomotor development patterns differed between groups ( F3,520 , 3.4 ; p = 0.02 ) with time . Mean values were similar at 6 months but differed at 9 and 12 months of age ( p < 0.001 ) , with a decline of 6.4 points in the regular-formula group . By 15 months of age the differences were no longer significant ( p = 0.23 ) . Mental development and behavior were not affected . CONCLUSIONS Iron-fortified formula significantly reduced iron deficiency in a high-risk group of infants and prevented a decline in psychomotor development quotients . This effect may be transient , and its long-term significance needs further study 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
target: Iron supplementation improves mental development score modestly .
  This effect is particularly apparent for intelligence tests above 7 years of age and in initially anaemic or iron-deficient anaemic subjects .
  There is no convincing evidence that iron treatment has an effect on mental development in children below 27 months of age or on motor development
background: OBJECTIVE To evaluate the effect of iron supplementation on  mental and motor development in children through a systematic review of r and omised controlled trials ( RCTs ) .