The effect of iron deficiency and mental stimulation on Indonesian children's cognitive performance and development. Iron deficiency anemia: adverse effects on infant psychomotor development. Treatment with iron increases weight gain and psychomotor development. Iron-Deficiency Anemia in Infancy and Social Emotional Development in Preschool-Aged Chinese Children Infancy: mental and motor development. The effects of short-term oral iron therapy on developmental deficits in iron-deficient anemic infants. Effects of iron deficiency on attention and learning processes in preschool children: Bandung, Indonesia. Cognitive deficits in iron-deficient and iron-deficient anemic children. Reversal of developmental delays in iron-deficient anaemic infants treated with iron THE EFFECTS OF THERAPY ON THE DEVELOPMENTAL SCORES OF IRON DEFICIENT INFANTS Effect of Twice Weekly Versus Daily Iron Treatment in Turkish Children with Iron Deficiency Anemia Effect of Iron Deficiency Anemia in Pregnancy on Child Mental Development in Rural China Prevention of iron deficiency and psychomotor decline in high-risk infants through use of iron-fortified infant formula: a randomized clinical trial. Randomized Trial of Early Versus Late Enteral Iron Supplementation in Infants With a Birth Weight of Less Than 1301 Grams: Neurocognitive Development at 5.3 Years' Corrected Age Iron-deficiency anemia and infant development: effects of extended oral iron therapy. Short-term developmental outcome of iron prophylaxis in infants. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls
Three studies conducted in Indonesia will be described . Soewondo ( 12 ) investigated the relation of iron deficiency and cognitive function and impact of iron supplementation on verbal intelligence , attention and concept learning among iron deficient children without anemia and iron deficient anemic children . Half of 176 children , aged 3 - 6 years , received elemental Fe for 8 weeks and the other half received  placebo . There were significant changes from pre to post intervention evaluations in ferritin , transferrin saturation , free erythrocyte protoporphyrin , and hemoglobin in the iron deficient anemic children . Pre and post treatment psychological test data showed that iron deficiency anemia produced alterations in cognitive processes related to visual attention and concept acquisition . These alterations can be reversed with iron treatment . Idjradinata ( 4 ) assessed the impact of iron supplementation on iron deficient infant 's mental and psychomotor development . Hundred twenty six subjects aged 12 to 18 month were r and omly assigned to either iron treatment or placebo intervention . After 4 months of iron supplementation , the hemoglobin , ferritin and transferrin saturation changed significantly in the iron deficient infants . A developmental delay was observed in the iron deficient anemic infants before intervention and the conditions were reversed after 4 months of iron treatment . Soemiarti ( 8) examined the effectiveness of a  training course  given to mothers of children aged 12 to 24 month on the rearing environment and consequently to the child 's development .  The subjects were 69 mothers of 20 - 35 years old . The training lasted for 21 days by giving mothers training using the program " Ibu Maju Anak Bermutu " . The rearing environment improved , also the child 's mental and psychomotor development 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 Previous work at this hospital and elsewhere has shown that anaemia in toddlers is common and is associated with psychomotor delay . It seemed unclear , however , whether this association was cause and effect or merely due to the same underprivileged environment . A double blind r and omised intervention study was , therefore , performed . After an initial assessment 97 children with anaemia ( haemoglobin 8 - 11 g/dl ) aged 17 - 19 months received either iron and vitamin C or vitamin C only ( control group ) for two months and were then reassessed . The children who received the iron had an increased rate of weight gain and more of them achieved the expected rate of development . While iron deficiency anaemia is unlikely to be the only factor in the slower development of children living in underprivileged circumstances , it can at least be easily identified and treated . Routine child health surveillance in such areas should include a haemoglobin determination OBJECTIVE : We aim ed to compare affect and behavior of 3 groups of nonanemic 4-year-old children : children with iron-deficiency anemia ( IDA ) in infancy whose anemia was not corrected before 24 months ( chronic IDA ) ( n = 27 ) ; children with IDA in infancy whose anemia was corrected before 24 months ( corrected IDA ) ( n = 70 ) ; and children who were nonanemic in infancy and at 24 months ( n = 64 ) . METHOD : Mother and child dyads were invited to a local clinic room . Children 's social referencing , wariness , frustration-tolerance behavior , and affect were observed during a set of situations encountered in the laboratory , including free play , stranger approach , novel toy , and delay of gratification . The whole procedure was videotaped . The children 's affective and behavioral displays were coded by using a time-sampling ( 5-second segments ) code scheme . Iron status of children was determined on the basis of hemoglobin concentration measured with the cyanomethemoglobin method in blood sample s obtained by fingerstick in infancy and at the ages of 24 months and 4 years . RESULTS : Children who had chronic IDA in infancy displayed less positive affect , less frustration tolerance , more passive behavior , and more physical self-soothing in the stranger approach and delay of gratification . In contrast , the behavior and affect of children whose anemia was corrected before the age of 24 months were comparable to those of children who were nonanemic throughout infancy . CONCLUSION : The results point to the potential benefits of preventing iron deficiency in infancy and treating it before it becomes chronic or severe In a prospect i ve cohort study of 196 infants from birth to age 15 mo , the relationship of iron status to psychomotor development , the effect of a short-term trial of oral iron or placebo , and the effect of longer-term oral iron therapy was assessed . Development was assessed with the Bayley Scale of Infant Development in anemic , nonanemic , iron-deficient , and control children . Anemic infants had significantly lower indices than did control or nonanemic , iron-deficient infants . Control infants and nonanemic , iron-deficient infants performed comparably . No difference between the effect of oral administration of iron or placebo was noted after 10 d or 3 mo of iron therapy . A hemoglobin concentration of less than 105 g/L and anemia duration greater than 3 mo were correlated with significantly lower motor and mental scores , suggesting that when iron deficiency progresses to anemia , adverse influences in the performance of developmental tests appear and persist , despite iron therapy 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 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 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 ) Iron-deficient anaemic infants perform worse in tests of mental and motor development than do iron-sufficient infants of a comparable age . A r and omised , double-blind trial was done to monitor the effects of iron supplementation on performance in the Bayley scales of mental and motor development among 12 - 18-month-old infants in Indonesia . Iron-deficient anaemic infants ( n = 50 ) were assigned r and omly to receive dietary ferrous sulphate or placebo for 4 month . Similar treatment r and omisation was done among nonanaemic iron-deficient ( n = 29 ) and iron-sufficient ( n = 47 ) infants . Before intervention , the mean mental and motor scores of the iron-deficient anaemic infants were significantly ( p < 0.01 ) lower than those of the nonanaemic iron-deficient and iron-sufficient classes . After intervention , developmental delays were reversed among iron-deficient anaemic infants who had received iron but they remained the same among placebo-treated iron-deficient anaemic infants . Neither ferrous sulphate nor placebo had significant effects on the scores of the other two iron-status classes . The poor performance of 12 - 18-month-old iron-deficient anaemic infants in the Bayley scales of mental and motor development can be improved to the level of performance of iron-sufficient infants by treatment with ferrous sulphate 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 This study was design ed to propose a more practical , effective , safer , inexpensive , and manageable alternative treatment of iron deficiency anemia ( IDA ) for the developing countries . The study involves 94 children between the ages of 5 months and 6 years who had been seen in the authors ' hospital and diagnosed as having iron deficiency anemia . Ninety-four children with IDA were r and omly divided into two groups : 48 children comprised the first group , which was administered conventional treatment , and 46 children comprised the second group , which was administered intermittent treatment involving iron administration 2 days a week . Twenty-three children whose age and gender distribution were compatible with the other groups were included in the study as the control group . Both groups were reevaluated for their initial hematologic parameters at the end of the treatment . When the parameters of both groups were compared with the parameters of the control group after the treatment , there were no differences between hemoglobin , hematocrit , red blood cell , mean corpuscular volume , mean corpuscular hemoglobin concentration , serum iron , and ferritin levels of conventional and intermittent treatment groups . With respect to certain parameters , such as red cell distribution , serum iron binding capacity , transferrin saturation , transferrin receptor , and transferrin receptor/log ferritin , however , intermittent treatment was superior to the conventional treatment method ( p < .05 ) . In IDA , when a conventional treatment method or an intermittent treatment method is used , there are no differences between the hematological parameters . In fact , the intermittent treatment method has been found to be superior in many parameters OBJECTIVE : To determine the impact of iron deficiency anemia ( IDA ) in pregnancy on young child development . METHODS : A 2-year follow-up of 850 children born to women who participated in a double-blind cluster r and omized controlled trial of prenatal micronutrient supplementation in western rural China . These women were r and omly assigned to receive either daily folic acid , iron/folic acid ( 60 mg iron ) , or multiple micronutrients ( with 30 mg iron ) during pregnancy . Children were categorized into the prenatal-IDA and prenatal – non-IDA groups based on the mother ’s hemoglobin in the third trimester . Each group contained 3 subgroups based on mother ’s treatment : folic acid , iron/folic acid , and multiple micronutrients .  Bayley scales of infant development were administered to the children to assess their development at 3 , 6 , 12 , 18 , and 24 months of age . RESULTS : Compared with the prenatal – non-IDA group , the prenatal-IDA group showed a significantly lower mental development index at 12 , 18 , and 24 months of age . The adjusted mean difference was 5.8 ( 95 % confidence interval [ CI ] , 1.1–10.5 ) , 5.1 ( 95 % CI , 1.2–9.0 ) , and 5.3 ( 95 % CI , 0.9–9.7 ) , respectively . Further analysis showed that the mental development indexes in the prenatal-IDA group and prenatal – non-IDA group were similar with supplementation of iron/folic acid but were significantly lower in the prenatal-IDA group with supplementation of folic acid or multiple micronutrients . CONCLUSIONS : Prenatal IDA in the third trimester is associated with mental development of the child . However , prenatal supplementation with sufficient iron protects child development even when the woman ’s IDA was not properly corrected in pregnancy 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 BACKGROUND . Iron deficiency in early childhood may impair neurodevelopment . In a masked , r and omized , controlled trial of early versus late enteral iron supplementation in preterm infants with birth weights of < 1301 g , early iron supplementation reduced the incidence of iron deficiency and the number of blood transfusions . OBJECTIVE . We sought to examine whether early enteral iron supplementation improves neurocognitive and motor development in these infants . METHODS . Children who participated in the above mentioned trial were evaluated by applying the Kaufmann Assessment Battery for Children and the Gross Motor Function Classification Scale at the age of school entry . RESULTS . Of the 204 infants initially r and omized , 10 died and 30 were lost to follow-up . A total of 164 ( 85 % of the survivors ) were evaluated at a median corrected age of 5.3 years . In this population ( n = 164 ) , the mean ( ±SD ) mental processing composite in the early iron group was 92 ( ±17 ) versus 89 ( ±16 ) in the late iron group . An abnormal neurologic examination was found in 17 of 90 versus 26 of 74 , and a Gross Motor Function Classification Scale score of > 1 was found in 2 of 90 versus 5 of 74 , respectively . Fifty-nine of 90 children in the early iron group were without disability , compared with 40 of 74 in the late iron group . Severe disability was found in 5 of 90 versus 6 of 74 children and 67 of 90 versus 49 of 74 qualified for regular schooling , respectively . CONCLUSIONS . Early enteral iron supplementation showed a trend toward a beneficial effect on long-term neurocognitive and psychomotor development and showed no evidence for any adverse effect . Because the initial study was not design ed to evaluate effects on neurocognitive development , the power was insufficient to detect small but potentially clinical ly relevant improvements . Additional studies are required to confirm the trend towards a better outcome observed in the early iron group 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 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 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
REVIEW ER 'S CONCLUSIONS There is no convincing evidence that iron treatment of young children with IDA has an effect on psychomotor development discernable within 5 - 11 days .
The effect of longer term treatment remains unclear but the data would be compatible with clinical ly significant benefit .
BACKGROUND Iron deficiency and iron deficiency anaemia ( IDA ) are common in young children .
It has been suggested that the lack of iron may have important effects on children 's psychomotor development and cognitive function .
OBJECTIVES To determine the effects of iron therapy on psychomotor development and cognitive function in iron deficient children less than 3 years of age .