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: In order to determine whether giving iron to iron-deficient children increases their susceptibility to malaria , 213 Gambian children aged between 6 months and 5 years with iron-deficiency anaemia were r and omized to receive either oral iron or placebo during the rainy season when malaria transmission is maximal . Haematological and iron measurements improved significantly in the group given iron . Regular morbidity surveys showed that fever associated with parasitaemia occurred more frequently in the iron-treated group than in the placebo group . This difference was not significant for all parasitaemias grouped together , but became significant and progressively larger for parasitaemias of ten or more positive fields per 100 high power fields ( P less than 0.025 ) , and for parasitaemias of 50 or more positive fields per 100 high power fields ( P less than 0.01 ) . Three children in the iron-treated group but none in the placebo group had more than one episode of fever and parasitaemia . Splenomegaly rates rose appreciably during the study in both groups , but in children at age 2 years the splenomegaly rate at the end of the study was significantly greater in the iron-treated group . We concluded that there is a significantly increased risk of fever associated with severe malarial parasitaemia for children with iron-deficiency anaemia given iron during the season of maximal malaria transmission in this part of The Gambia CONTEXT The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother 's behavior or her interaction with the infant . OBJECTIVE To assess whether prolonged and exclusive breastfeeding improves children 's cognitive ability at age 6.5 years . DESIGN Cluster-r and omized trial , with enrollment from June 17 , 1996 , to December 31 , 1997 , and follow-up from December 21 , 2002 , to April 27 , 2005 . SETTING Thirty-one Belarussian maternity hospitals and their affiliated polyclinics . PARTICIPANTS A total of 17,046 healthy breastfeeding infants were enrolled , of whom 13,889 ( 81.5 % ) were followed up at age 6.5 years . INTERVENTION Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF . MAIN OUTCOME MEASURES Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence , and teacher evaluations of academic performance in reading , writing , mathematics , and other subjects . RESULTS The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months ( 43.3 % for the experimental group vs 6.4 % for the control group ; P < .001 ) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months . The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures , with cluster-adjusted mean differences ( 95 % confidence intervals ) of + 7.5 ( + 0.8 to + 14.3 ) for verbal IQ , + 2.9 ( -3.3 to + 9.1 ) for performance IQ , and + 5.9 ( -1.0 to + 12.8 ) for full-scale IQ . Teachers ' academic ratings were significantly higher in the experimental group for both reading and writing . CONCLUSION These results , based on the largest r and omized trial ever conducted in the area of human lactation , provide strong evidence that prolonged and exclusive breastfeeding improves children 's cognitive development . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N37687716 BACKGROUND In developing countries , incomplete resolution of anemia with iron supplementation is often attributed to poor compliance or inadequate duration of supplementation , but it could result from deficiencies of other micronutrients . OBJECTIVE Our objective was to assess children 's hematologic  response to supervised , long-term iron supplementation and the relation of this response to other micronutrient deficiencies , anthropometry , morbidity , and usual dietary intake . DESIGN Rural Mexican children aged 18 - 36 mo ( n = 219 ) were supplemented for 12 mo with either 20 mg Fe , 20 mg Zn , both iron and zinc , or placebo . Children were categorized as iron-unsupplemented ( IUS ; n = 109 ) or iron supplemented ( IS ; n = 108 ) . Hemoglobin , hematocrit , mean corpuscular volume , mean cell hemoglobin , plasma concentrations of micronutrients that can affect hematopoiesis , anthropometry , and diet were assessed at 0 , 6 , and 12 mo ; morbidity was assessed biweekly . RESULTS At baseline , 70 % of children had low hemoglobin ( < /=115 g/L ) , 60 % had low hematocrit , 48 % were ferritin deficient , 10 % had deficient and 33 % had low plasma vitamin B-12 concentrations , 29 % had deficient vitamin A concentrations , and 70 % had deficient vitamin E concentrations . Iron supplementation increased ferritin from 11 + /- 14 microg/L at baseline to 31 + /- 18 microg/L after 6 mo ( P < 0.001 ) and 41 + /- 17 microg/L after 12 mo . However , anemia persisted in 30 % and 31 % of supplemented children at 6 and 12 mo , respectively , and was not significantly different between the IUS and IS groups at 12 mo . Initial plasma vitamin B-12 , height-for-age , and dietary quality predicted the hematopoietic response to iron . CONCLUSION Lack of hemoglobin response to iron was associated with indicators of chronic undernutrition and multiple micronutrient deficiencies A r and omized , double-blind , placebo-controlled iron supplementation trial was conducted in Kenya to examine the effect of iron supplements on appetite and growth in 87 primary school children .  Sustained-release ferrous sulfate ( 150 mg ) or placebo tablets were provided daily at school for 14 wk . Prior to tablet administration , baseline anthropometry , iron nutritional status ( hemoglobin and serum ferritin ) , parasitic infections and clinical indicators of morbidity were measured . A baseline appetite test was conducted twice on each child by quantitatively measuring the ad libitum consumption of a midmorning snack . In addition , each child was asked for a subjective assessment of his or her appetite . Follow-up exams and appetite tests were identical to those at baseline . Findings indicated that provision of iron supplements result ed in improved growth and improved appetite ( in terms of both energy intake of the snack and child report of appetite ) as compared with children receiving the placebo . The increased energy intake from the snack was 10 % of the daily estimated energy intake for children of this same age group living elsewhere in Kenya . Further research into the underlying physiological mechanisms may shed light on the relationship between iron nutritional status and appetite Conflicting evidence exists on the possible role of iron supplementation in the predisposition to malaria infection or the enhancement of its clinical severity . Where anemia prevalence is > 40 % , current guidelines are to provide low-dose daily iron to young children for up to 18 mo . Earlier studies used doses higher than the current guidelines , intermittent doses , or have supplemented for duration s < or = 4 mo . We aim ed to assess the effect of low-dose , long-term iron supplementation on malaria infection using a double-blind , placebo-controlled , r and omized design , and to examine possible subgroup effects by season and child age . The study was conducted in Pemba Isl and , Zanzibar , where Plasmodium falciparum malaria has year-round high transmission . A community-based sample of 614 children 4 - 71 mo old was r and omly allocated to 10 mg/d iron or placebo for 12 mo . Outcome measures were the prevalence and density of malaria infection , which was assessed by blood films at monthly intervals . At baseline , 94.4 % were anemic ( hemoglobin < 110 g/L ) , 48.1 % were stunted ( height-for-age Z-score less than -2 ) and > 80 % had malaria-positive blood films . No significant differences in malariometric indices were observed between children in the iron-supplemented and placebo groups . Parasite density was higher in certain months and in younger children , but iron supplementation was not associated with any malarial infection outcome in any season or age subgroup . We conclude that in this environment of high malaria transmission , daily oral low-dose supplementation of iron for 12 mo did not affect the prevalence of malaria infection or parasite density Iron deficiency and helminth infections are two common conditions of children in developing countries . The consequences of helminth infection in young children are not well described , and the efficacy of low dose iron supplementation is not well documented in malaria-endemic setting s. A 12-mo r and omized , placebo controlled , double-blind trial of 10 mg daily iron and /or mebendazole ( 500 mg ) every 3 mo was conducted in a community-based sample of 459 Zanzibari children age 6 - 71 mo with hemoglobin > 70 g/L at baseline . The trial was design ed to examine treatment effects on growth , anemia and appetite in two age subgroups . Iron did not affect growth retardation , hemoglobin concentration or mild or moderate anemia ( hemoglobin < 110 g/L or < 90 g/L , respectively ) , but iron significantly improved serum ferritin and erythrocyte protoporphyrin .  Mebendazole significantly reduced wasting malnutrition . but only in children < 30 mo old . The adjusted odds ratios ( AORs ) for mebendazole in this age group were 0.38 ( 95 % CI : 0.16 , 0.90 ) for weight-for-height less than -1 Z-score and 0.29 ( 0.09 , 0.91 ) for small arm circumference . In children < 24 mo old , mebendazole also reduced moderate anemia ( AOR : 0.41 , 0.18 , 0.94 ) . Both iron and mebendazole improved children 's appetite , according to mothers ' report . In this study , iron 's effect on anemia was limited , likely constrained by infection , inflammation and perhaps other nutrient deficiencies . Mebendazole treatment caused unexpected and significant reductions in wasting malnutrition and anemia in very young children with light infections . We hypothesize that incident helminth infections may stimulate inflammatory immune responses in young children , with deleterious effects on protein metabolism and erythropoiesis Ninety-nine anemic children aged 1 - 8 y were divided into four groups . Each group was supplemented for 2 mo with vitamin A , iron , vitamin A plus Fe , or a placebo .  Clinical , hematological , and Fe biochemical evaluations were performed at the beginning and end of the study . Vitamin A supplementation produced significant elevations in the serum levels of retinol , blood hemoglobin , hematocrit , erythrocytes , serum Fe , and percent transferrin saturation ( % TS ) and had no effect on total Fe binding capacity ( TIBC ) or serum ferritin . Fe supplementation did not affect serum retinol . However , it improved hematological and Fe nutrition indicators , including TIBC and serum ferritin . The simultaneous administration of vitamin A and Fe result ed in a better response of serum Fe and % TS than when the supplement consisted only of vitamin A or Fe alone . Vitamin A benefits hematological condition and Fe metabolism BACKGROUND The coexistence of multiple micronutrient deficiencies is a widespread public health problem in many regions of the world . Interactions between zinc deficiency and vitamin A metabolism have been reported but no longitudinal studies have evaluated the effect of iron deficiency on vitamin A. OBJECTIVE The objective of this study was to investigate the effect of supplementation with iron , zinc , or both on vitamin A and its metabolically related proteins retinol binding protein ( RBP ) and transthyretin . DESIGN The study was a longitudinal , double-blind , placebo-controlled trial in which 219 rural Mexican children aged 18 - 36 mo were r and omly assigned to receive 20 mg Zn/d , 20 mg Fe/d , 20 mg Zn/d plus 20 mg Fe/d , or placebo . RESULTS Six months after supplementation , plasma retinol increased in all supplemented groups . Compared with placebo , zinc supplementation was associated with significantly higher plasma retinol and transthyretin but the increase in RBP was not significant . Iron supplementation significantly increased plasma retinol , RBP , and transthyretin . Supplementation with zinc plus iron significantly increased plasma retinol but not RBP or transthyretin .  Children deficient in zinc , iron , or vitamin A ( as indicated by nutrient plasma concentration ) at the beginning of the study had a significantly greater increase in retinol than did children with adequate nutrient status . CONCLUSIONS Supplementation with zinc , iron , or both improved indicators of vitamin A status . The results of this study agree with previous observations of a metabolic interaction between zinc and vitamin A and suggest an interaction between iron and vit 
    Output:
    
agent
Limited evidence suggested that iron supplementation produced a small improvement in cognitive development but had no effect on physical growth .
CONCLUSIONS : In 2 to 5 year olds , daily iron supplementation increases hemoglobin and ferritin .
There is a concerning lack of data on the effect of iron supplementation on clinical ly important outcomes including anemia , ID anemia , ID , and cognitive development .
***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: In order to determine whether giving iron to iron-deficient children increases their susceptibility to malaria , 213 Gambian children aged between 6 months and 5 years with iron-deficiency anaemia were r and omized to receive either oral iron or placebo during the rainy season when malaria transmission is maximal . Haematological and iron measurements improved significantly in the group given iron . Regular morbidity surveys showed that fever associated with parasitaemia occurred more frequently in the iron-treated group than in the placebo group . This difference was not significant for all parasitaemias grouped together , but became significant and progressively larger for parasitaemias of ten or more positive fields per 100 high power fields ( P less than 0.025 ) , and for parasitaemias of 50 or more positive fields per 100 high power fields ( P less than 0.01 ) . Three children in the iron-treated group but none in the placebo group had more than one episode of fever and parasitaemia . Splenomegaly rates rose appreciably during the study in both groups , but in children at age 2 years the splenomegaly rate at the end of the study was significantly greater in the iron-treated group . We concluded that there is a significantly increased risk of fever associated with severe malarial parasitaemia for children with iron-deficiency anaemia given iron during the season of maximal malaria transmission in this part of The Gambia CONTEXT The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother 's behavior or her interaction with the infant . OBJECTIVE To assess whether prolonged and exclusive breastfeeding improves children 's cognitive ability at age 6.5 years . DESIGN Cluster-r and omized trial , with enrollment from June 17 , 1996 , to December 31 , 1997 , and follow-up from December 21 , 2002 , to April 27 , 2005 . SETTING Thirty-one Belarussian maternity hospitals and their affiliated polyclinics . PARTICIPANTS A total of 17,046 healthy breastfeeding infants were enrolled , of whom 13,889 ( 81.5 % ) were followed up at age 6.5 years . INTERVENTION Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF . MAIN OUTCOME MEASURES Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence , and teacher evaluations of academic performance in reading , writing , mathematics , and other subjects . RESULTS The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months ( 43.3 % for the experimental group vs 6.4 % for the control group ; P < .001 ) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months . The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures , with cluster-adjusted mean differences ( 95 % confidence intervals ) of + 7.5 ( + 0.8 to + 14.3 ) for verbal IQ , + 2.9 ( -3.3 to + 9.1 ) for performance IQ , and + 5.9 ( -1.0 to + 12.8 ) for full-scale IQ . Teachers ' academic ratings were significantly higher in the experimental group for both reading and writing . CONCLUSION These results , based on the largest r and omized trial ever conducted in the area of human lactation , provide strong evidence that prolonged and exclusive breastfeeding improves children 's cognitive development . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N37687716 BACKGROUND In developing countries , incomplete resolution of anemia with iron supplementation is often attributed to poor compliance or inadequate duration of supplementation , but it could result from deficiencies of other micronutrients . OBJECTIVE Our objective was to assess children 's hematologic  response to supervised , long-term iron supplementation and the relation of this response to other micronutrient deficiencies , anthropometry , morbidity , and usual dietary intake . DESIGN Rural Mexican children aged 18 - 36 mo ( n = 219 ) were supplemented for 12 mo with either 20 mg Fe , 20 mg Zn , both iron and zinc , or placebo . Children were categorized as iron-unsupplemented ( IUS ; n = 109 ) or iron supplemented ( IS ; n = 108 ) . Hemoglobin , hematocrit , mean corpuscular volume , mean cell hemoglobin , plasma concentrations of micronutrients that can affect hematopoiesis , anthropometry , and diet were assessed at 0 , 6 , and 12 mo ; morbidity was assessed biweekly . RESULTS At baseline , 70 % of children had low hemoglobin ( < /=115 g/L ) , 60 % had low hematocrit , 48 % were ferritin deficient , 10 % had deficient and 33 % had low plasma vitamin B-12 concentrations , 29 % had deficient vitamin A concentrations , and 70 % had deficient vitamin E concentrations . Iron supplementation increased ferritin from 11 + /- 14 microg/L at baseline to 31 + /- 18 microg/L after 6 mo ( P < 0.001 ) and 41 + /- 17 microg/L after 12 mo . However , anemia persisted in 30 % and 31 % of supplemented children at 6 and 12 mo , respectively , and was not significantly different between the IUS and IS groups at 12 mo . Initial plasma vitamin B-12 , height-for-age , and dietary quality predicted the hematopoietic response to iron . CONCLUSION Lack of hemoglobin response to iron was associated with indicators of chronic undernutrition and multiple micronutrient deficiencies A r and omized , double-blind , placebo-controlled iron supplementation trial was conducted in Kenya to examine the effect of iron supplements on appetite and growth in 87 primary school children .  Sustained-release ferrous sulfate ( 150 mg ) or placebo tablets were provided daily at school for 14 wk . Prior to tablet administration , baseline anthropometry , iron nutritional status ( hemoglobin and serum ferritin ) , parasitic infections and clinical indicators of morbidity were measured . A baseline appetite test was conducted twice on each child by quantitatively measuring the ad libitum consumption of a midmorning snack . In addition , each child was asked for a subjective assessment of his or her appetite . Follow-up exams and appetite tests were identical to those at baseline . Findings indicated that provision of iron supplements result ed in improved growth and improved appetite ( in terms of both energy intake of the snack and child report of appetite ) as compared with children receiving the placebo . The increased energy intake from the snack was 10 % of the daily estimated energy intake for children of this same age group living elsewhere in Kenya . Further research into the underlying physiological mechanisms may shed light on the relationship between iron nutritional status and appetite Conflicting evidence exists on the possible role of iron supplementation in the predisposition to malaria infection or the enhancement of its clinical severity . Where anemia prevalence is > 40 % , current guidelines are to provide low-dose daily iron to young children for up to 18 mo . Earlier studies used doses higher than the current guidelines , intermittent doses , or have supplemented for duration s < or = 4 mo . We aim ed to assess the effect of low-dose , long-term iron supplementation on malaria infection using a double-blind , placebo-controlled , r and omized design , and to examine possible subgroup effects by season and child age . The study was conducted in Pemba Isl and , Zanzibar , where Plasmodium falciparum malaria has year-round high transmission . A community-based sample of 614 children 4 - 71 mo old was r and omly allocated to 10 mg/d iron or placebo for 12 mo . Outcome measures were the prevalence and density of malaria infection , which was assessed by blood films at monthly intervals . At baseline , 94.4 % were anemic ( hemoglobin < 110 g/L ) , 48.1 % were stunted ( height-for-age Z-score less than -2 ) and > 80 % had malaria-positive blood films . No significant differences in malariometric indices were observed between children in the iron-supplemented and placebo groups . Parasite density was higher in certain months and in younger children , but iron supplementation was not associated with any malarial infection outcome in any season or age subgroup . We conclude that in this environment of high malaria transmission , daily oral low-dose supplementation of iron for 12 mo did not affect the prevalence of malaria infection or parasite density Iron deficiency and helminth infections are two common conditions of children in developing countries . The consequences of helminth infection in young children are not well described , and the efficacy of low dose iron supplementation is not well documented in malaria-endemic setting s. A 12-mo r and omized , placebo controlled , double-blind trial of 10 mg daily iron and /or mebendazole ( 500 mg ) every 3 mo was conducted in a community-based sample of 459 Zanzibari children age 6 - 71 mo with hemoglobin > 70 g/L at baseline . The trial was design ed to examine treatment effects on growth , anemia and appetite in two age subgroups . Iron did not affect growth retardation , hemoglobin concentration or mild or moderate anemia ( hemoglobin < 110 g/L or < 90 g/L , respectively ) , but iron significantly improved serum ferritin and erythrocyte protoporphyrin .  Mebendazole significantly reduced wasting malnutrition . but only in children < 30 mo old . The adjusted odds ratios ( AORs ) for mebendazole in this age group were 0.38 ( 95 % CI : 0.16 , 0.90 ) for weight-for-height less than -1 Z-score and 0.29 ( 0.09 , 0.91 ) for small arm circumference . In children < 24 mo old , mebendazole also reduced moderate anemia ( AOR : 0.41 , 0.18 , 0.94 ) . Both iron and mebendazole improved children 's appetite , according to mothers ' report . In this study , iron 's effect on anemia was limited , likely constrained by infection , inflammation and perhaps other nutrient deficiencies . Mebendazole treatment caused unexpected and significant reductions in wasting malnutrition and anemia in very young children with light infections . We hypothesize that incident helminth infections may stimulate inflammatory immune responses in young children , with deleterious effects on protein metabolism and erythropoiesis Ninety-nine anemic children aged 1 - 8 y were divided into four groups . Each group was supplemented for 2 mo with vitamin A , iron , vitamin A plus Fe , or a placebo .  Clinical , hematological , and Fe biochemical evaluations were performed at the beginning and end of the study . Vitamin A supplementation produced significant elevations in the serum levels of retinol , blood hemoglobin , hematocrit , erythrocytes , serum Fe , and percent transferrin saturation ( % TS ) and had no effect on total Fe binding capacity ( TIBC ) or serum ferritin . Fe supplementation did not affect serum retinol . However , it improved hematological and Fe nutrition indicators , including TIBC and serum ferritin . The simultaneous administration of vitamin A and Fe result ed in a better response of serum Fe and % TS than when the supplement consisted only of vitamin A or Fe alone . Vitamin A benefits hematological condition and Fe metabolism BACKGROUND The coexistence of multiple micronutrient deficiencies is a widespread public health problem in many regions of the world . Interactions between zinc deficiency and vitamin A metabolism have been reported but no longitudinal studies have evaluated the effect of iron deficiency on vitamin A. OBJECTIVE The objective of this study was to investigate the effect of supplementation with iron , zinc , or both on vitamin A and its metabolically related proteins retinol binding protein ( RBP ) and transthyretin . DESIGN The study was a longitudinal , double-blind , placebo-controlled trial in which 219 rural Mexican children aged 18 - 36 mo were r and omly assigned to receive 20 mg Zn/d , 20 mg Fe/d , 20 mg Zn/d plus 20 mg Fe/d , or placebo . RESULTS Six months after supplementation , plasma retinol increased in all supplemented groups . Compared with placebo , zinc supplementation was associated with significantly higher plasma retinol and transthyretin but the increase in RBP was not significant . Iron supplementation significantly increased plasma retinol , RBP , and transthyretin . Supplementation with zinc plus iron significantly increased plasma retinol but not RBP or transthyretin .  Children deficient in zinc , iron , or vitamin A ( as indicated by nutrient plasma concentration ) at the beginning of the study had a significantly greater increase in retinol than did children with adequate nutrient status . CONCLUSIONS Supplementation with zinc , iron , or both improved indicators of vitamin A status . The results of this study agree with previous observations of a metabolic interaction between zinc and vitamin A and suggest an interaction between iron and vit 
    Output:
    