human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 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 : Low birth weight infants are at risk for iron deficiency ( ID ) . Most LBW infants have marginally low birth weight ( MLBW , 2000–2500 g ) and it is not known whether they benefit from iron supplements . The objective of this trial was to study the effects of iron supplementation in MLBW infants . METHOD : In a r and omized controlled trial , we assigned 285 healthy , MLBW infants to receive iron supplements at a dose of 0 ( placebo ) , 1 , or 2 mg/kg per day between 6 weeks and 6 months of age .  Hemoglobin levels , ferritin levels , transferrin saturation , mean cell volume , and transferrin receptor levels were analyzed at 6 months . Growth and morbidity were monitored . RESULTS : Iron supplementation result ed in significant dose-dependent effects on hemoglobin and all iron status indicators at 6 months . The prevalence of ID at 6 months was 36 % in the placebo group , 8.2 % in the 1 mg/kg per day group , and 3.8 % in the 2 mg/kg per day group ( P < .001 ) . The prevalence rates of ID anemia ( IDA ) were 9.9 % , 2.7 % , and 0 % , respectively ( P = .004 ) . Among infants who were exclusively breastfed at 6 weeks , the prevalence of IDA was 18 % in the placebo group . There were no significant differences between groups in growth or morbidity . CONCLUSIONS : MLBW infants have relatively high risks of ID and IDA , especially if they are breastfed . Iron supplementation at 2 mg/kg per day from 6 weeks to 6 months reduces this risk effectively , with no short-term adverse effects on morbidity or growth AIMS To prospect ively evaluate the iron nutritional status of preterm infants fed either a term ( 0.5 mg/dl iron ) or preterm ( 0.9 mg/dl ) formulas fortified with iron after hospital discharge . METHODS Healthy low birthweight preterm infants were r and omly assigned into three groups at the time of hospital discharge . Group A were fed an iron fortified preterm formula ( 0.9 mg/dl iron ) until 6 months corrected age ; group B , a fortified term formula ( 0.5 mg/l iron ) until 6 months corrected age group C , the preterm formula between hospital discharge and term , then the term formula until 6 months corrected age . RESULTS Seventy eight infants were followed up to 6 months corrected age . Iron intake from formula differed significantly between the groups ( A , 1.17 mg/kg/day ( SD 0.32 ) > C , 0.86 mg/kg/day ( SD 0.40 ) = B , 0.81 mg/kg/day ( SD 0.23 ) ; p < 0.0001 ) . Haemoglobin concentrations were similar to those of iron sufficient preterm infants of the same postnatal age , and term infants of the same postmenstrual age ( after 3 months of age ) . There were no significant differences in haemoglobin concentration ( p = 0.391 ) , plasma ferritin ( A vs B , p = 0.322 ) , or in the incidence of iron deficiency ( A vsB , p = 0.534 ) . CONCLUSIONS Iron fortified formulas containing between 0.5 and 0.9 mg/dl iron seem to meet the iron nutritional needs of preterm infants after hospital discharge OBJECTIVES To test the utility of zinc protoporphyrin to heme ratio ( ZnPP/H ) as an indicator of iron status in premature infants and to evaluate the effect of oral iron supplements on oxidative injury . We hypothesized that iron sulfate supplementation would decrease the ZnPP/H in preterm infants . STUDY DESIGN Infants eligible for this prospect i ve study were : hospitalized , 24 to 32 weeks of gestation , 7 to 60 days old , feeding > or = 70 mL/kg/d , with a ZnPP/H > or = the mean for age .  Iron dose was determined by the ZnPP/H.  Iron status and oxidative injury were evaluated at study entry and completion . Concurrent control subjects met entry criteria but were not enrolled and were not treated with iron during the study interval . Statistical evaluation included repeated measures analysis of variance and Z-score conversions . RESULTS Entry ZnPP/H of iron-treated subjects ( n = 16 ) and control subjects ( n = 16 ) were not different . The ZnPP/H of iron-treated infants was lower at study end ( P < .05 ) but did not change in control infants . Iron treatment ( 3 to 12 mg/kg/day ) was not associated with changes in conventional measures of iron status nor in measures of oxidative injury . CONCLUSIONS Iron sulfate supplementation ( 3 - 12 mg/kg/d ) decreases ZnPP/H , is tolerated , and is not associated with increased oxidative injury Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists OBJECTIVE To evaluate whether our current practice of giving iron 18 mg daily to 6-week-old infants with very low birth weight ( VLBW ) was associated with increased oxidative stress markers or decreased antioxidant status . STUDY DESIGN The study was a prospect i ve observational study of 21 healthy VLBW infants ( born at gestational age < 32 weeks , birth weight < 1500 g ) . Blood and urine were sample d twice before starting iron supplementation at 6 weeks postnatal age and after 1 week of iron supplementation at age 7 weeks . Urine 8-isoprostane was analyzed by gas chromatography-mass spectrometry and plasma total hydroperoxides were measured . Antioxidant status was assessed by ascorbic acid ( vitamin C ) , alpha-tocopherol ( vitamin E ) , ferric-reducing ability of plasma , and plasma glutathione . RESULTS After 1 week of iron supplementation , no significant changes in urine 8-isoprostane or plasma total hydroperoxides were seen , and plasma antioxidants were largely unchanged . CONCLUSIONS Markers of oxidative stress in urine and plasma antioxidant status in healthy VLBW infants fed human milk remained unchanged after high-dose oral iron supplementation Objectives . To examine whether early enteral iron supplementation ( EI ) would improve serum ferritin as a measure of nutritional iron status at 2 months of age and would prevent definite iron deficiency ( ID ) in infants with a birth weight of < 1301 g. Methods . Infants were r and omly assigned to receive enteral iron supplementation of 2 to 6 mg/kg/day as soon as enteral feedings of > 100 mL/kg/day were tolerated ( EI ) or at 61 days of life ( late enteral iron supplementation [ LI ] ) . Nutritional iron status was assessed : 1 ) at birth , 2 ) at 61 days of life , 3 ) when the infants reached a weight of 1.6 times birth weight , and 4 ) before blood was transfused at a hematocrit of < .25 . ID was defined by any one of the following criteria : ferritin , < 12 μg/L ; transferrin saturation , < 17 % ; or increase of absolute reticulocyte counts by > 50 % one week after the onset of enteral iron supplementation . Restrictive red cell transfusion guidelines were followed and all transfusions were documented . Erythropoietin was not administered . The primary outcome variables were : 1 ) ferritin at 61 days and 2 ) the number of infants with ID . Results . Ferritin at 61 days was not different between the groups . Infants in the LI group were more often iron-deficient ( 26/65 vs 10/68 ) and received more blood transfusions after day 14 of life . No adverse effects of EI were noted . Conclusions . EI is feasible and probably safe in infants with birth weight < 1301 g. EI may reduce the incidence of ID and the number of late blood transfusions . ID may occur in very low birth weight infants despite early supplementation with iron and should be considered in the case of progressive anemia . preterm infant , iron supplementation , iron deficiency , blood transfusion Aims : To determine the haematological effects of iron supplementation in predominantly breast fed term low birth weight ( LBW ) infants . Methods : Seventy three healthy term LBW ( < 2500 g ) , predominantly breast fed infants aged 50–80 days were r and omised into two groups to receive either iron ( 3 mg/kg/day ) ( iron supplemented ( IS ) group ; n = 37 ) or placebo drops ( placebo ( P ) group ; n = 36 ) . Haematological parameters and anthropometry were measured at baseline and repeated after four and eight weeks . Results : A total of 62 subjects ( 32 in the IS group and 30 in the P group ) came for the first follow up and 26 ( 13 in the IS group and  
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 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 : Low birth weight infants are at risk for iron deficiency ( ID ) . Most LBW infants have marginally low birth weight ( MLBW , 2000–2500 g ) and it is not known whether they benefit from iron supplements . The objective of this trial was to study the effects of iron supplementation in MLBW infants . METHOD : In a r and omized controlled trial , we assigned 285 healthy , MLBW infants to receive iron supplements at a dose of 0 ( placebo ) , 1 , or 2 mg/kg per day between 6 weeks and 6 months of age .  Hemoglobin levels , ferritin levels , transferrin saturation , mean cell volume , and transferrin receptor levels were analyzed at 6 months . Growth and morbidity were monitored . RESULTS : Iron supplementation result ed in significant dose-dependent effects on hemoglobin and all iron status indicators at 6 months . The prevalence of ID at 6 months was 36 % in the placebo group , 8.2 % in the 1 mg/kg per day group , and 3.8 % in the 2 mg/kg per day group ( P < .001 ) . The prevalence rates of ID anemia ( IDA ) were 9.9 % , 2.7 % , and 0 % , respectively ( P = .004 ) . Among infants who were exclusively breastfed at 6 weeks , the prevalence of IDA was 18 % in the placebo group . There were no significant differences between groups in growth or morbidity . CONCLUSIONS : MLBW infants have relatively high risks of ID and IDA , especially if they are breastfed . Iron supplementation at 2 mg/kg per day from 6 weeks to 6 months reduces this risk effectively , with no short-term adverse effects on morbidity or growth AIMS To prospect ively evaluate the iron nutritional status of preterm infants fed either a term ( 0.5 mg/dl iron ) or preterm ( 0.9 mg/dl ) formulas fortified with iron after hospital discharge . METHODS Healthy low birthweight preterm infants were r and omly assigned into three groups at the time of hospital discharge . Group A were fed an iron fortified preterm formula ( 0.9 mg/dl iron ) until 6 months corrected age ; group B , a fortified term formula ( 0.5 mg/l iron ) until 6 months corrected age group C , the preterm formula between hospital discharge and term , then the term formula until 6 months corrected age . RESULTS Seventy eight infants were followed up to 6 months corrected age . Iron intake from formula differed significantly between the groups ( A , 1.17 mg/kg/day ( SD 0.32 ) > C , 0.86 mg/kg/day ( SD 0.40 ) = B , 0.81 mg/kg/day ( SD 0.23 ) ; p < 0.0001 ) . Haemoglobin concentrations were similar to those of iron sufficient preterm infants of the same postnatal age , and term infants of the same postmenstrual age ( after 3 months of age ) . There were no significant differences in haemoglobin concentration ( p = 0.391 ) , plasma ferritin ( A vs B , p = 0.322 ) , or in the incidence of iron deficiency ( A vsB , p = 0.534 ) . CONCLUSIONS Iron fortified formulas containing between 0.5 and 0.9 mg/dl iron seem to meet the iron nutritional needs of preterm infants after hospital discharge OBJECTIVES To test the utility of zinc protoporphyrin to heme ratio ( ZnPP/H ) as an indicator of iron status in premature infants and to evaluate the effect of oral iron supplements on oxidative injury . We hypothesized that iron sulfate supplementation would decrease the ZnPP/H in preterm infants . STUDY DESIGN Infants eligible for this prospect i ve study were : hospitalized , 24 to 32 weeks of gestation , 7 to 60 days old , feeding > or = 70 mL/kg/d , with a ZnPP/H > or = the mean for age .  Iron dose was determined by the ZnPP/H.  Iron status and oxidative injury were evaluated at study entry and completion . Concurrent control subjects met entry criteria but were not enrolled and were not treated with iron during the study interval . Statistical evaluation included repeated measures analysis of variance and Z-score conversions . RESULTS Entry ZnPP/H of iron-treated subjects ( n = 16 ) and control subjects ( n = 16 ) were not different . The ZnPP/H of iron-treated infants was lower at study end ( P < .05 ) but did not change in control infants . Iron treatment ( 3 to 12 mg/kg/day ) was not associated with changes in conventional measures of iron status nor in measures of oxidative injury . CONCLUSIONS Iron sulfate supplementation ( 3 - 12 mg/kg/d ) decreases ZnPP/H , is tolerated , and is not associated with increased oxidative injury Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists OBJECTIVE To evaluate whether our current practice of giving iron 18 mg daily to 6-week-old infants with very low birth weight ( VLBW ) was associated with increased oxidative stress markers or decreased antioxidant status . STUDY DESIGN The study was a prospect i ve observational study of 21 healthy VLBW infants ( born at gestational age < 32 weeks , birth weight < 1500 g ) . Blood and urine were sample d twice before starting iron supplementation at 6 weeks postnatal age and after 1 week of iron supplementation at age 7 weeks . Urine 8-isoprostane was analyzed by gas chromatography-mass spectrometry and plasma total hydroperoxides were measured . Antioxidant status was assessed by ascorbic acid ( vitamin C ) , alpha-tocopherol ( vitamin E ) , ferric-reducing ability of plasma , and plasma glutathione . RESULTS After 1 week of iron supplementation , no significant changes in urine 8-isoprostane or plasma total hydroperoxides were seen , and plasma antioxidants were largely unchanged . CONCLUSIONS Markers of oxidative stress in urine and plasma antioxidant status in healthy VLBW infants fed human milk remained unchanged after high-dose oral iron supplementation Objectives . To examine whether early enteral iron supplementation ( EI ) would improve serum ferritin as a measure of nutritional iron status at 2 months of age and would prevent definite iron deficiency ( ID ) in infants with a birth weight of < 1301 g. Methods . Infants were r and omly assigned to receive enteral iron supplementation of 2 to 6 mg/kg/day as soon as enteral feedings of > 100 mL/kg/day were tolerated ( EI ) or at 61 days of life ( late enteral iron supplementation [ LI ] ) . Nutritional iron status was assessed : 1 ) at birth , 2 ) at 61 days of life , 3 ) when the infants reached a weight of 1.6 times birth weight , and 4 ) before blood was transfused at a hematocrit of < .25 . ID was defined by any one of the following criteria : ferritin , < 12 μg/L ; transferrin saturation , < 17 % ; or increase of absolute reticulocyte counts by > 50 % one week after the onset of enteral iron supplementation . Restrictive red cell transfusion guidelines were followed and all transfusions were documented . Erythropoietin was not administered . The primary outcome variables were : 1 ) ferritin at 61 days and 2 ) the number of infants with ID . Results . Ferritin at 61 days was not different between the groups . Infants in the LI group were more often iron-deficient ( 26/65 vs 10/68 ) and received more blood transfusions after day 14 of life . No adverse effects of EI were noted . Conclusions . EI is feasible and probably safe in infants with birth weight < 1301 g. EI may reduce the incidence of ID and the number of late blood transfusions . ID may occur in very low birth weight infants despite early supplementation with iron and should be considered in the case of progressive anemia . preterm infant , iron supplementation , iron deficiency , blood transfusion Aims : To determine the haematological effects of iron supplementation in predominantly breast fed term low birth weight ( LBW ) infants . Methods : Seventy three healthy term LBW ( < 2500 g ) , predominantly breast fed infants aged 50–80 days were r and omised into two groups to receive either iron ( 3 mg/kg/day ) ( iron supplemented ( IS ) group ; n = 37 ) or placebo drops ( placebo ( P ) group ; n = 36 ) . Haematological parameters and anthropometry were measured at baseline and repeated after four and eight weeks . Results : A total of 62 subjects ( 32 in the IS group and 30 in the P group ) came for the first follow up and 26 ( 13 in the IS group and  
    Output:
    