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: Background Anemia continues to be a major public health problem among children in many regions of the world , and it is still not clear which strategy to treat it is most effective . Objective To evaluate the efficacy and children 's acceptance of several recognized strategies to treat anemia . Methods Non-breastfed children ( n = 577 ) , 6 to 43 mo of age , were screened for the trial ; 267 were anemic ( hemoglobin < 11.7 g/dL ) , and 266 of those were r and omized into 1 of 5 treatments to received daily either : an iron supplement ( IS ) , an iron+folic acid supplement ( IFS ) , a multiple micronutrient supplement ( MMS ) , a micronutrient-fortified complementary food as porridge powder ( FCF ) , or zinc+iron+ascorbic acid fortified water ( FW ) . The iron content of each daily dose was 20 , 12.5 , 10 , 10 and 6.7 mg respectively . Hemoglobin ( Hb ) , ferritin , total iron , weight and height were measured at baseline and after 4 months of treatment . Morbidity , treatment acceptability and adherence were recorded during the intervention . Results All treatments significantly increased Hb and total iron concentration ; ferritin did not change significantly . Groups MMS , IS and IFS  increased Hb ( g/dL ) [ 1.50 ( 95%CI : 1.17 , 1.83 ) , 1.48 [ ( 1.18 , 1.78 ) and 1.57 ( 1.26 , 1.88 ) , respectively ] and total iron ( ( μg/dL ) [ 0.15 ( 0.01 , 0.29 ) , 0.19 ( 0.06 , 0.31 ) and 0.12(-0.01 , 0.25 ) , respectively ] significantly more than FCF [ 0.92 ( 0.64 , 1.20 ) ] but not to FW group [ 0.14 ( 0.04 , 0.24 ) ] . The prevalence of anemia was reduced to a greater extent in the MMS and IFS groups ( 72 % and 69 % , respectively ) than in the FCF group ( 45 % ) ( p < 0.05 ) . There were no significant differences in anthropometry or in the number of episodes of diarrhea and respiratory infections among treatment groups . The supplements MMS and IS were less acceptable to children , than IFS , FCF and FW . Conclusion The three supplements IS , ISF and MMS  increased Hb more than the FCF ; the supplements that contained micronutrients ( IFS and MMS ) were more effective for reducing the prevalence of anemia . In general , fortified foods were better accepted by the study participants than supplements . Clinical Trial.gov Objective : Gingival overgrowth is an important adverse effect of phenytoin ( PHT ) therapy , occurring in about half of the patients . This study aim ed to evaluate the effect of oral folic acid supplementation ( 0.5 mg/day ) for the prevention of PHT-induced gingival overgrowth ( PIGO )  in children with epilepsy aged 6–15 years on PHT monotherapy for 6 months . Methods : This was a r and omized , double-blind , placebo-controlled trial conducted at a tertiary level hospital from May 2008 to June 2009 . Children aged 6–15 years started on PHT monotherapy within last 1 month were eligible for inclusion . Preexisting gingival overgrowth , use of other folic acid antagonists , and macrocytic anemia were exclusion criteria . Trial subjects were r and omized to receive either folic acid or placebo . The primary outcome measure was incidence of any degree of gingival overgrowth after 6 months of PHT monotherapy . The trial was registered with clinical trials.gov ( NCT00781196 ) . Results : A total of 120 children were recruited , 62 and 58 , respectively , in folic acid and placebo arms . The 2 arms were comparable at baseline . Twenty-one percent of patients in the folic acid arm developed PIGO , as compared with 88 % receiving placebo ( p < 0.001 ) . Absolute risk reduction of PIGO by folic acid was 67 % ( 95 % confidence interval 54%–80 % ) , and relative risk reduction was 0.76 . Conclusions : Oral folic acid was found to decrease the incidence of PIGO  in children on PHT monotherapy , in a statistically significant and clinical ly relevant manner . Classification of evidence : This study provides Class I evidence that folic acid supplementation , 0.5 mg/day , is associated with prevention of gingival overgrowth in children taking PHT monotherapy Background Seven genes involved in folate metabolism are located on chromosome 21 . Previous studies have shown that folate deficiency may contribute to mental retardation in Down 's syndrome ( DS ) . Methodology We investigated the effect of oral folate supplementation ( daily dose of 1.0±0.3 mg/kg ) on cognitive functions in DS children , aged from 3 to 30 months . They received 1 mg/kg leucovorin or placebo daily , for 12 months , in a single-centre , r and omised , double-blind study . Folinic acid ( leucovorin , LV ) was preferred to folic acid as its bioavailability is higher . The developmental age ( DA ) of the patients was assessed on the Brunet-Lezine scale , from baseline to the end of treatment . Results The intent-to-treat analysis ( 113 patients ) did not show a positive effect of leucovorin treatment . However , it identified important factors influencing treatment effect , such as age , sex , and concomitant treatments , including thyroid treatment in particular . A per protocol analysis was carried out on patients evaluated by the same examiner at the beginning and end of the treatment period . This analysis of 87 patients ( 43 LV-treated vs. 44 patients on placebo )  revealed a positive effect of leucovorin on developmental age ( DA ) . DA was 53.1 % the normal value with leucovorin and only 44.1 % with placebo ( p<0.05 ) . This positive effect of leucovorin was particularly strong in patients receiving concomitant thyroxin treatment ( 59.5 % vs. 41.8 % , p<0.05 ) . No adverse event related to leucovorin was observed . Conclusion These results suggest that leucovorin improves the psychomotor development of children with Down 's syndrome , at least in some subgroups of the DS population , particularly those on thyroxin treatment . Trial Registration Clinical Trials.gov , One hundred eighty-four premature infants , < 1800 g at birth and < 36 wk gestation , were entered into a study investigating the role of additional folate and vitamin B-12 supplementation of the anemia of prematurity .  All patients initially received vitamin E and iron in accordance with accepted st and ards . Patients were r and omly assigned to four groups to receive orally 0.1 mg folate/d for 4 mo , 100 micrograms vitamin B-12 intramuscularly monthly for 4 mo , both supplements , or neither . All other activities including parenteral nutrition were carried out according to established practice s , irrespective of study group . By 10 - 12 wk , infants treated with vitamin B-12 alone or combined with folate had higher hemoglobin values than the untreated ( P < 0.0005 ) or solely folate-treated ( P < 0.01 ) groups . These findings held true irrespective of wide variations in treatment and feeding practice s. The only uncontrolled hematologic nutritional factor , selenium , showed a similar pattern of decline for 10 - 12 wk in all study patients , whether or not they received additional vitamin supplements Background —Accelerated vascular disease is common in chronic renal failure ( CRF ) and accounts for significant mortality and morbidity . Elevated homocysteine levels may contribute by an effect on endothelial function . Methods and Results —We performed a double-blind placebo-controlled r and omized crossover trial of folic acid at 5 mg/m2 in 25 normotensive children 12±3 ( 7 to 17 ) years of age with CRF ( glomerular filtration rate 26.8±13.2 mL/min per 1.73 m2 ) of noninflammatory etiology . Each subject underwent two 8-week periods of folic acid and placebo separated by an 8-week washout period . The effect of folic acid  on homocysteine levels , LDL oxidation , and both endothelial-dependent and -independent vascular function were measured . After oral folic acid , serum folate levels rose from 11.7±4.25 to 635±519 & mgr;g/L ( P = 0.001 ) , red cell folate levels rose from 364±195 to 2891±2623 & mgr;g/L ( P < 0.001 ) , and total homocysteine levels fell from 10.28±4.16 to 8.62±2.32 & mgr;mol/L ( P = 0.03 ) . In addition , there was a significant improvement in flow-mediated dilatation ( FMD ) ( endothelial-dependent dilatation ) from 7.21±2.8 % to 8.47±3.01 % ( P = 0.036 ) with no change in response to glyceryl trinitrate ( endothelial-independent dilatation ) . There was no significant change in FMD or glyceryl trinitrate during the placebo phase . There was , however , no significant difference in final FMD after placebo or folic acid . Lag times for LDL oxidation were prolonged during the treatment phase ( 58.4±18.7 to 68.1±25.9 minutes , P = 0.01 ) . Conclusion —Folic acid supplementation in children with CRF  may improve endothelial function with an increased resistance of LDL to oxidation Abstract Hyperhomocysteinemia is emerging as an independent predictor of cardiovascular disease and hypertension among children . The aim of the study was to examine the effects of oral folic acid on homocysteine and blood pressure .  Folic acid supplementation has been found to reduce homocysteine levels and in some cases blood pressure .  Five hundred and twenty children participated in the study , and 26 of them were found to be hyperhomocysteinemic ; 20 of these children r and omly received 5 mg oral folic acid supplement while the other six children were the controls . Serum homocysteine ( P < 0.001 ) levels as well as systolic ( P < 0.001 ) and diastolic ( P = 0.045 ) blood pressure were statistically significantly decreased in the intervention group compared with the controls , while folic acid levels were statistically significantly increased ( P < 0.001 ) . Total serum homocysteine levels were correlated with age , serum folate , body mass index , and blood pressure . It appears that folic acid may be a safe and effective supplement to reduce homocysteine and possibly blood pressure , which consequently may prevent cardiovascular disease in children in early life Objectives To assess whether supplementation with antioxidants , folinic acid , or both improves the psychomotor and language development of children with Down ’s syndrome . Design R and omised controlled trial with two by two factorial design . Setting Children living in the Midl and s , Greater London , and the south west of Engl and . Participants 156 infants aged under 7 months with trisomy 21 . Intervention Daily oral supplementation with antioxidants ( selenium 10 μg , zinc 5 mg , vitamin A 0.9 mg , vitamin E 100 mg , and vitamin C 50 mg ) , folinic acid ( 0.1 mg ) , antioxidants and folinic acid combined , or placebo . Main outcome measures Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation ; biochemical markers in blood and urine at age 12 months . Results Children r and omised to antioxidant supplements attained similar developmental outcomes to those without antioxidants ( mean Griffiths developmental quotient 57.3 v 56.1 ; adjusted mean difference 1.2 points , 95 % confidence interval −2.2 to 4.6 ) . Comparison of children r and omised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient ( mean 57.6 v 55.9 ; adjusted mean difference 1.7 , −1.7 to 5.1 ) . No between group differences were seen in the mean numbers of words said or signed :  for antioxidants versus none the ratio of means was 0.85 ( 95 % confidence interval 0.6 to 1.2 ) , and for folinic acid versus none it was 1.24 ( 0.87 to 1.77 ) . No significant differences were found between any of the groups in the biochemical outcomes measured . Adjustment for potential confounders did not appreciably change the results . Conclusions This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down ’s syndrome . Trial registration Clinical trials NCT00378456 The effect of 250 μg folic acid (FA)/day or placebo given 
    Output:
    
agent
We conclude that both serum and erythrocyte folate values reflect folate intake ; however , serum folate reacts more rapidly to folate intake than erythrocyte folate .
As to health outcomes , we found no evidence indicating that additional intake of folate can influence haematological parameters in non-anaemic paediatric patients .
We were unable to find evidence of a favourable effect of folate supplementation on the growth of infants .
However , the limited data available suggest that supplementing the diet of low-birth-weight infants with folic acid may moderate the rapid fall of serum and red cell folate in the first months of life
***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: Background Anemia continues to be a major public health problem among children in many regions of the world , and it is still not clear which strategy to treat it is most effective . Objective To evaluate the efficacy and children 's acceptance of several recognized strategies to treat anemia . Methods Non-breastfed children ( n = 577 ) , 6 to 43 mo of age , were screened for the trial ; 267 were anemic ( hemoglobin < 11.7 g/dL ) , and 266 of those were r and omized into 1 of 5 treatments to received daily either : an iron supplement ( IS ) , an iron+folic acid supplement ( IFS ) , a multiple micronutrient supplement ( MMS ) , a micronutrient-fortified complementary food as porridge powder ( FCF ) , or zinc+iron+ascorbic acid fortified water ( FW ) . The iron content of each daily dose was 20 , 12.5 , 10 , 10 and 6.7 mg respectively . Hemoglobin ( Hb ) , ferritin , total iron , weight and height were measured at baseline and after 4 months of treatment . Morbidity , treatment acceptability and adherence were recorded during the intervention . Results All treatments significantly increased Hb and total iron concentration ; ferritin did not change significantly . Groups MMS , IS and IFS  increased Hb ( g/dL ) [ 1.50 ( 95%CI : 1.17 , 1.83 ) , 1.48 [ ( 1.18 , 1.78 ) and 1.57 ( 1.26 , 1.88 ) , respectively ] and total iron ( ( μg/dL ) [ 0.15 ( 0.01 , 0.29 ) , 0.19 ( 0.06 , 0.31 ) and 0.12(-0.01 , 0.25 ) , respectively ] significantly more than FCF [ 0.92 ( 0.64 , 1.20 ) ] but not to FW group [ 0.14 ( 0.04 , 0.24 ) ] . The prevalence of anemia was reduced to a greater extent in the MMS and IFS groups ( 72 % and 69 % , respectively ) than in the FCF group ( 45 % ) ( p < 0.05 ) . There were no significant differences in anthropometry or in the number of episodes of diarrhea and respiratory infections among treatment groups . The supplements MMS and IS were less acceptable to children , than IFS , FCF and FW . Conclusion The three supplements IS , ISF and MMS  increased Hb more than the FCF ; the supplements that contained micronutrients ( IFS and MMS ) were more effective for reducing the prevalence of anemia . In general , fortified foods were better accepted by the study participants than supplements . Clinical Trial.gov Objective : Gingival overgrowth is an important adverse effect of phenytoin ( PHT ) therapy , occurring in about half of the patients . This study aim ed to evaluate the effect of oral folic acid supplementation ( 0.5 mg/day ) for the prevention of PHT-induced gingival overgrowth ( PIGO )  in children with epilepsy aged 6–15 years on PHT monotherapy for 6 months . Methods : This was a r and omized , double-blind , placebo-controlled trial conducted at a tertiary level hospital from May 2008 to June 2009 . Children aged 6–15 years started on PHT monotherapy within last 1 month were eligible for inclusion . Preexisting gingival overgrowth , use of other folic acid antagonists , and macrocytic anemia were exclusion criteria . Trial subjects were r and omized to receive either folic acid or placebo . The primary outcome measure was incidence of any degree of gingival overgrowth after 6 months of PHT monotherapy . The trial was registered with clinical trials.gov ( NCT00781196 ) . Results : A total of 120 children were recruited , 62 and 58 , respectively , in folic acid and placebo arms . The 2 arms were comparable at baseline . Twenty-one percent of patients in the folic acid arm developed PIGO , as compared with 88 % receiving placebo ( p < 0.001 ) . Absolute risk reduction of PIGO by folic acid was 67 % ( 95 % confidence interval 54%–80 % ) , and relative risk reduction was 0.76 . Conclusions : Oral folic acid was found to decrease the incidence of PIGO  in children on PHT monotherapy , in a statistically significant and clinical ly relevant manner . Classification of evidence : This study provides Class I evidence that folic acid supplementation , 0.5 mg/day , is associated with prevention of gingival overgrowth in children taking PHT monotherapy Background Seven genes involved in folate metabolism are located on chromosome 21 . Previous studies have shown that folate deficiency may contribute to mental retardation in Down 's syndrome ( DS ) . Methodology We investigated the effect of oral folate supplementation ( daily dose of 1.0±0.3 mg/kg ) on cognitive functions in DS children , aged from 3 to 30 months . They received 1 mg/kg leucovorin or placebo daily , for 12 months , in a single-centre , r and omised , double-blind study . Folinic acid ( leucovorin , LV ) was preferred to folic acid as its bioavailability is higher . The developmental age ( DA ) of the patients was assessed on the Brunet-Lezine scale , from baseline to the end of treatment . Results The intent-to-treat analysis ( 113 patients ) did not show a positive effect of leucovorin treatment . However , it identified important factors influencing treatment effect , such as age , sex , and concomitant treatments , including thyroid treatment in particular . A per protocol analysis was carried out on patients evaluated by the same examiner at the beginning and end of the treatment period . This analysis of 87 patients ( 43 LV-treated vs. 44 patients on placebo )  revealed a positive effect of leucovorin on developmental age ( DA ) . DA was 53.1 % the normal value with leucovorin and only 44.1 % with placebo ( p<0.05 ) . This positive effect of leucovorin was particularly strong in patients receiving concomitant thyroxin treatment ( 59.5 % vs. 41.8 % , p<0.05 ) . No adverse event related to leucovorin was observed . Conclusion These results suggest that leucovorin improves the psychomotor development of children with Down 's syndrome , at least in some subgroups of the DS population , particularly those on thyroxin treatment . Trial Registration Clinical Trials.gov , One hundred eighty-four premature infants , < 1800 g at birth and < 36 wk gestation , were entered into a study investigating the role of additional folate and vitamin B-12 supplementation of the anemia of prematurity .  All patients initially received vitamin E and iron in accordance with accepted st and ards . Patients were r and omly assigned to four groups to receive orally 0.1 mg folate/d for 4 mo , 100 micrograms vitamin B-12 intramuscularly monthly for 4 mo , both supplements , or neither . All other activities including parenteral nutrition were carried out according to established practice s , irrespective of study group . By 10 - 12 wk , infants treated with vitamin B-12 alone or combined with folate had higher hemoglobin values than the untreated ( P < 0.0005 ) or solely folate-treated ( P < 0.01 ) groups . These findings held true irrespective of wide variations in treatment and feeding practice s. The only uncontrolled hematologic nutritional factor , selenium , showed a similar pattern of decline for 10 - 12 wk in all study patients , whether or not they received additional vitamin supplements Background —Accelerated vascular disease is common in chronic renal failure ( CRF ) and accounts for significant mortality and morbidity . Elevated homocysteine levels may contribute by an effect on endothelial function . Methods and Results —We performed a double-blind placebo-controlled r and omized crossover trial of folic acid at 5 mg/m2 in 25 normotensive children 12±3 ( 7 to 17 ) years of age with CRF ( glomerular filtration rate 26.8±13.2 mL/min per 1.73 m2 ) of noninflammatory etiology . Each subject underwent two 8-week periods of folic acid and placebo separated by an 8-week washout period . The effect of folic acid  on homocysteine levels , LDL oxidation , and both endothelial-dependent and -independent vascular function were measured . After oral folic acid , serum folate levels rose from 11.7±4.25 to 635±519 & mgr;g/L ( P = 0.001 ) , red cell folate levels rose from 364±195 to 2891±2623 & mgr;g/L ( P < 0.001 ) , and total homocysteine levels fell from 10.28±4.16 to 8.62±2.32 & mgr;mol/L ( P = 0.03 ) . In addition , there was a significant improvement in flow-mediated dilatation ( FMD ) ( endothelial-dependent dilatation ) from 7.21±2.8 % to 8.47±3.01 % ( P = 0.036 ) with no change in response to glyceryl trinitrate ( endothelial-independent dilatation ) . There was no significant change in FMD or glyceryl trinitrate during the placebo phase . There was , however , no significant difference in final FMD after placebo or folic acid . Lag times for LDL oxidation were prolonged during the treatment phase ( 58.4±18.7 to 68.1±25.9 minutes , P = 0.01 ) . Conclusion —Folic acid supplementation in children with CRF  may improve endothelial function with an increased resistance of LDL to oxidation Abstract Hyperhomocysteinemia is emerging as an independent predictor of cardiovascular disease and hypertension among children . The aim of the study was to examine the effects of oral folic acid on homocysteine and blood pressure .  Folic acid supplementation has been found to reduce homocysteine levels and in some cases blood pressure .  Five hundred and twenty children participated in the study , and 26 of them were found to be hyperhomocysteinemic ; 20 of these children r and omly received 5 mg oral folic acid supplement while the other six children were the controls . Serum homocysteine ( P < 0.001 ) levels as well as systolic ( P < 0.001 ) and diastolic ( P = 0.045 ) blood pressure were statistically significantly decreased in the intervention group compared with the controls , while folic acid levels were statistically significantly increased ( P < 0.001 ) . Total serum homocysteine levels were correlated with age , serum folate , body mass index , and blood pressure . It appears that folic acid may be a safe and effective supplement to reduce homocysteine and possibly blood pressure , which consequently may prevent cardiovascular disease in children in early life Objectives To assess whether supplementation with antioxidants , folinic acid , or both improves the psychomotor and language development of children with Down ’s syndrome . Design R and omised controlled trial with two by two factorial design . Setting Children living in the Midl and s , Greater London , and the south west of Engl and . Participants 156 infants aged under 7 months with trisomy 21 . Intervention Daily oral supplementation with antioxidants ( selenium 10 μg , zinc 5 mg , vitamin A 0.9 mg , vitamin E 100 mg , and vitamin C 50 mg ) , folinic acid ( 0.1 mg ) , antioxidants and folinic acid combined , or placebo . Main outcome measures Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation ; biochemical markers in blood and urine at age 12 months . Results Children r and omised to antioxidant supplements attained similar developmental outcomes to those without antioxidants ( mean Griffiths developmental quotient 57.3 v 56.1 ; adjusted mean difference 1.2 points , 95 % confidence interval −2.2 to 4.6 ) . Comparison of children r and omised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient ( mean 57.6 v 55.9 ; adjusted mean difference 1.7 , −1.7 to 5.1 ) . No between group differences were seen in the mean numbers of words said or signed :  for antioxidants versus none the ratio of means was 0.85 ( 95 % confidence interval 0.6 to 1.2 ) , and for folinic acid versus none it was 1.24 ( 0.87 to 1.77 ) . No significant differences were found between any of the groups in the biochemical outcomes measured . Adjustment for potential confounders did not appreciably change the results . Conclusions This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down ’s syndrome . Trial registration Clinical trials NCT00378456 The effect of 250 μg folic acid (FA)/day or placebo given 
    Output:
    