title: Iron-deficiency anemia and infant development: effects of extended oral iron therapy. The effects of short-term oral iron therapy on developmental deficits in iron-deficient anemic infants. Evidence of altered central nervous system development in infants with iron deficiency anemia at 6 mo: delayed maturation of auditory brainstem responses. Iron deficiency anemia and iron therapy effects on infant developmental test performance. 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. Reversal of developmental delays in iron-deficient anaemic infants treated with iron Cognitive deficits in iron-deficient and iron-deficient anemic children. Treatment with iron increases weight gain and psychomotor development. Prevention of iron deficiency and psychomotor decline in high-risk infants through use of iron-fortified infant formula: a randomized clinical trial. Infancy: mental and motor development.
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 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 Iron deficiency anemia has long been thought to have effects on the central nervous system ( CNS ) . Finding direct evidence of this in human infants , however , has been challenging .  Auditory brainstem responses ( ABRs ) provide a noninvasive means of examining an aspect of the CNS that is rapidly maturing during the age period when iron deficiency is most common . ABRs represent the progressive activation of the auditory pathway from the acoustic nerve ( wave I ) to the lateral lemniscus ( wave V ) . The central conduction time ( CCT , or wave I-V interpeak latency ) is considered an index of CNS development because myelination of nerve fibers and maturation of synaptic relays lead to an exponential reduction in the CCT from birth to 24 mo . In 55 otherwise healthy , 6-mo-old Chilean infants ( 29 with iron deficiency anemia and 26 nonanemic control infants ) , the CCT was longer in those who had been anemic at 6 mo , with differences becoming more pronounced at 12- and 18-mo follow-ups despite effective iron therapy . The pattern of results --differences in latencies but not amplitudes , more effects on the late ABR components ( waves III and V ) , and longer CCTs ( as an overall measure of nerve conduction velocity)--suggested altered myelination as a promising explanation , consistent with recent laboratory work documenting iron 's essential role in myelin formation and maintenance . This study shows that iron deficiency anemia in 6-mo-old infants is associated with adverse effects on at least one aspect of CNS development and suggests the fruitfulness of study ing other processes that are rapidly myelinating during the first 2 y of life 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 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 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 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 ) 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 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 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
target: There is no convincing evidence that iron treatment of young children with IDA has an effect on psychomotor development or cognitive function within 30 days after commencement of therapy .
  The effect of longer-term treatment remains unclear .
background: BACKGROUND Iron deficiency and iron deficiency anaemia ( IDA ) are common in young children .
  It has been suggested that the lack of iron may have deleterious effects on children 's psychomotor development and cognitive function .
  To evaluate the benefits of iron therapy on psychomotor development and cognitive function in children with IDA , a Cochrane review was carried out in 2001 .
  This is an up date of that review .
  OBJECTIVES To determine the effects of iron therapy on psychomotor development and cognitive function in iron deficient anaemic children less than three years of age .