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: Summary Whether infant vitamin D supplementation may have long-term bone benefits is unclear . In this study , breastfed infants who received vitamin dosages greater than 400 IU/day did not have higher bone mineralization at 3 years . This study provides important data to inform pediatric public health recommendations for vitamin D. Introduction North American health agencies recommend breastfed infants should be supplemented with 400 IU of vitamin D/day to support bone health . Few studies examined the long-term benefits of early life vitamin D supplementation on bone mineralization . The objective of this study was to determine if a dose-response relationship exists between infant vitamin D supplementation , vitamin D status , and bone outcomes at 3 years of age . Methods This was a double-blind r and omized trial of 132 , 1-month-old healthy , breastfed infants from Montréal , Canada , between 2007 and 2010 . In this longitudinal analysis , 87 infants ( 66 % ) returned for follow-up at 3 years of age , between 2010 and 2013 . At 1 month of age , participants were r and omly assigned to receive oral cholecalciferol ( vitamin D3 ) supplements of 400 , 800 , 1200 , or 1600 IU/day until 12 months of age . Lumbar spine vertebrae 1–4 ( LS ) bone mineral density ( BMD ) , LS and whole body bone mineral content ( BMC ) , and mineral accretion were measured by dual-energy x-ray absorptiometry at 3 years . Results At follow-up , the treatment groups were similar in terms of diet , sun exposure , and demographics . There were no significant differences among the groups in LS or whole body BMC , BMD , or accretion . Although , 25(OH)D concentrations were not different among the groups , higher doses ( 1200 and 1600 IU/day ) achieved higher 25(OH)D area under the curve from 1 to 36 months vs. 400 IU/day . Conclusions This is the first longitudinal follow-up of an infant vitamin D dose-response study which examines bone mineralization at 3 years of age . Dosages higher than 400 IU/day do not appear to provide additional benefits to the bone at follow-up . Larger studies with more ethnically diverse groups are needed to confirm these results The daily supplementation of vitamin D is m and atory for infants . However , there are still conflicting opinions about the exact daily dose . Thus , we aim ed to evaluate a daily supplementation dose of 200 IU is sufficient and compared the supplementation doses of 200 and 400 IU per day . One hundred and sixty-nine infants were r and omly assigned to two groups ( group1 , 200 IU/day ; group 2 , 400 IU/day ) and there were 75 infants in group 1 and 64 were in group 2 with a total number of 139 . The median levels of 25-hydroxyvitamin D3 were significantly increased in group 2 at the age of 4 months ( group 1 , 39.60 mcg/L ; group 2 , 56.55 mcg/L ; p < 0.0001 ) . We clearly demonstrated that at the age of 4 months , none of the infants on the group 2 had a serum level of 25-hydroxyvitamin D3 less than 30 mcg/L. However , 21.3 % of the infants in group 1 had a level below 30 mcg/L. Thus , in order to avoid vitamin D deficiency and rickets , we recommend supplementation dose of vitamin D at 400 IU/day as a safe and effective dose IMPORTANCE Vitamin D supplementation in infancy is required to support healthy bone mineral accretion . A supplement of 400 IU of vitamin D per day is thought to support plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations between 40 and 50 nmol/L ; some advocate 75 to 150 nmol/L for bone health . OBJECTIVE To investigate the efficacy of different dosages of vitamin D in supporting 25(OH)D concentrations in infants . DESIGN , SETTING , AND PARTICIPANTS Double-blind r and omized clinical trial conducted among 132 one-month-old healthy , term , breastfed infants from Montréal , Québec , Canada , between March 2007 and August 2010 . Infants were followed up for 11 months ending August 2011 ( 74 % completed study ) . INTERVENTION Participants were r and omly assigned to receive oral cholecalciferol ( vitamin D3 ) supplements of 400 IU/d ( n=39 ) , 800 IU/d ( n=39 ) , 1200 IU/d ( n=38 ) , or 1600 IU/d ( n=16 ) . MAIN OUTCOMES AND MEASURES The primary outcome was a plasma 25(OH)D concentration of 75 nmol/L or greater in 97.5 % of infants at 3 months . Secondary outcomes included 25(OH)D concentrations of 75 nmol/L or greater in 97.5 % of infants at 6 , 9 , and 12 months ; 25(OH)D concentrations of 50 nmol/L or greater across all times ; growth ; and whole body and regional bone mineral content . Data were analyzed by intention to treat using available data , logistic regression , and mixed-model analysis of variance . RESULTS By 3 months , 55 % ( 95 % CI , 38%-72 % ) of infants in the 400-IU/d group achieved a 25(OH)D concentration of 75 nmol/L or greater vs 81%(95 % CI , 65%-91 % ) in the 800-IU/d group , 92 % ( 95 % CI , 77%-98 % ) in the 1200-IU/d group , and 100 % in the 1600-IU/d group . This concentration was not sustained in 97.5 % of infants at 12 months in any of the groups . The 1600-IU/d dosage was discontinued prematurely because of elevated plasma 25(OH)D concentrations . All dosages established 25(OH)D concentrations of 50 nmol/L or greater in 97 % ( 95 % CI , 94%-100 % ) of infants at 3 months and sustained this in 98 % ( 95 % CI , 94%-100 % ) to 12 months . Growth and bone mineral content did not differ by dosage . CONCLUSIONS AND RELEVANCE Among healthy , term , breastfed infants , only a vitamin D supplement dosage of 1600 IU/d ( but not dosages of 400 , 800 , or 1200 IU/d ) increased plasma 25(OH)D concentration to 75 nmol/L or greater in 97.5 % of infants at 3 months . However , this dosage increased 25(OH)D concentrations to levels that have been associated with hypercalcemia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00381914 Background The rate of non-compliance with vitamin D supplementation is as high as 45 % . This is why r and omised controlled trials are needed to analyse the response to low doses of vitamin D3 . Objective ( 1 ) To compare supplementation with 250 versus 500 units of vitamin D3 and ( 2 ) to analyse sun exposure time/ultraviolet B ( UVB ) exposure during the first 6 weeks of life . Design 40 breastfed infants ( skin photo-types I , II ) were recruited in Berlin , Germany ( 52.5 ° N ) , during summer ( n=20 ) and winter ( n=20 ) and r and omised into equal groups on either 250 or 500 units of  vitamin D3 per day . Outcome measures were : parameters of vitamin D and bone metabolism at delivery and 6 weeks later , sun exposure time , UVB dosimetry and surrounding factors including maternal diet . Results At delivery 25-hydroxy vitamin D levels were insufficient : 68 ( 53–83 ) nmol/l in each group . 6 weeks later levels were sufficient : 139 ( 114–164 ) nmol/l on 250 units of vitamin D3 per day and 151 ( 126–176 ) nmol/l on 500 units/day . There was no seasonal variation . Daily sun exposure time was 0.4–3.5 h and higher in summer . UVB exposure was 0.01–0.08 minimal erythema dose/day . Calcium levels were within normal . Conclusions In Berlin , Germany , supplementation with 250 units of vitamin D3 is sufficient for breastfed infants during their first 6 weeks of life in summer and winter . UVB exposure is very low throughout the year The biological equivalency of ergocalciferol ( D2 ) and cholecalciferol ( D3 ) has been debated ; several comparisons have appeared in the adult literature but are scarce in pediatrics . The objective of this study was to compare increases in plasma 25-hydroxyvitamin D [ 25(OH)D ] concentrations and attainment of 50 and 75 mol/L status cutoffs following 3 mo of daily supplementation with D2 compared with D3 .  Healthy , breast-fed , 1-mo-old infants ( n = 52 ) received 10 μg ( 400 ic ) of either D2 or D3 daily . At 1 and 4 mo of age , plasma 25-hydroxyergocalciferol and 25-hydroxycholecalciferol concentrations were determined by liquid chromatography t and em MS ( LC-MS/MS ) and total 25(OH)D by chemiluminescent immunoassay ( DiaSorin Liaison ) . Data were analyzed using t tests and χ2 by intent to treat . A total of 23 % of infants were deficient ( ≤24.9 nmol/L ) at baseline and 2 % at follow-up on the basis of LC-MS/MS . At 4 mo , 96 % were breastfed and there were no differences in compliance , breastfeeding rates , or sun exposure among groups . The change in total 25(OH)D measured by LC-MS/MS did not differ between the D2 ( 17.6 ± 26.7 nmol/L ) and D3 ( 22.2 ± 20.2 nmol/L ) groups . In the combined groups , the baseline plasma 25(OH)D concentration was inversely related to the change in total 25(OH)D ( r = −0.52 ; P < 0.001 ) . Overall , 86 % of infants met the 50 nmol/L cutoff at follow-up ; however , fewer infants in the D2 group ( 75 % ) met this level compared with the D3 group ( 96 % ) ( P < 0.05 ) . Similar results were obtained by immunoassay . In conclusion , the increase in the 25(OH)D concentration among the D2 and D3 groups did not differ , suggesting daily intake of either isoform is acceptable for infants < 4 mo OBJECTIVE : To investigate the effect of vitamin D3 supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul , Afghanistan . METHODS : This double-blind placebo-controlled trial r and omized 3046 high-risk 1- to 11-month-old infants to receive 6 quarterly doses of oral vitamin D3 ( cholecalciferol 100 000 IU ) or placebo in inner city Kabul . Data on diarrheal episodes ( ≥3 loose/liquid stools in 24 hours ) was gathered through active and passive surveillance over 18 months of follow-up . Time to first diarrheal illness was analyzed by using Kaplan-Meier plots . Incidence rates and hazard ratios ( HRs ) were calculated by using recurrent event Poisson regression models . RESULTS : No significant difference existed in survival time to first diarrheal illness ( log rank P = .55 ) . The incidences of diarrheal episodes were 3.43 ( 95 % confidence interval [ CI ] , 3.28–3.59 ) and 3.59 per child-year ( 95 % CI , 3.44–3.76 ) in the placebo and intervention arms , respectively . Vitamin D3 supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat ( HR , 1.05 ; 95 % CI , 0.98–1.17 ; P = .15 ) or per protocol ( HR , 1.05 ; 95 % CI , 0.98–1.12 ; P = .14 ) analyses . The lack of preventive benefit remained when the r and omized population was stratified by age groups , nutritional status , and seasons . CONCLUSIONS : Quarterly supplementation with vitamin D3 conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study . Similar supplementation to comparable population s is not recommended . Additional research in alternative setting s may be helpful in elucidating the role of vitamin D 
    Output:
    
agent
They do not provide any additional evidence that larger , more generous amounts of daily vitamin D beyond the customary recommended 400 IU daily dose , affect any significant outcome .
Larger amounts may lead to serum 25 hydroxy vitamin D concentrations that have been reported to be potentially associated with adverse effects .
Summary There are still many unanswered questions left , in particular whether or not more ‘ generous ’ amounts of vitamin D in infancy may improve long-term health outcomes such as prevention of osteoporosis , allergies , or cancer
***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: Summary Whether infant vitamin D supplementation may have long-term bone benefits is unclear . In this study , breastfed infants who received vitamin dosages greater than 400 IU/day did not have higher bone mineralization at 3 years . This study provides important data to inform pediatric public health recommendations for vitamin D. Introduction North American health agencies recommend breastfed infants should be supplemented with 400 IU of vitamin D/day to support bone health . Few studies examined the long-term benefits of early life vitamin D supplementation on bone mineralization . The objective of this study was to determine if a dose-response relationship exists between infant vitamin D supplementation , vitamin D status , and bone outcomes at 3 years of age . Methods This was a double-blind r and omized trial of 132 , 1-month-old healthy , breastfed infants from Montréal , Canada , between 2007 and 2010 . In this longitudinal analysis , 87 infants ( 66 % ) returned for follow-up at 3 years of age , between 2010 and 2013 . At 1 month of age , participants were r and omly assigned to receive oral cholecalciferol ( vitamin D3 ) supplements of 400 , 800 , 1200 , or 1600 IU/day until 12 months of age . Lumbar spine vertebrae 1–4 ( LS ) bone mineral density ( BMD ) , LS and whole body bone mineral content ( BMC ) , and mineral accretion were measured by dual-energy x-ray absorptiometry at 3 years . Results At follow-up , the treatment groups were similar in terms of diet , sun exposure , and demographics . There were no significant differences among the groups in LS or whole body BMC , BMD , or accretion . Although , 25(OH)D concentrations were not different among the groups , higher doses ( 1200 and 1600 IU/day ) achieved higher 25(OH)D area under the curve from 1 to 36 months vs. 400 IU/day . Conclusions This is the first longitudinal follow-up of an infant vitamin D dose-response study which examines bone mineralization at 3 years of age . Dosages higher than 400 IU/day do not appear to provide additional benefits to the bone at follow-up . Larger studies with more ethnically diverse groups are needed to confirm these results The daily supplementation of vitamin D is m and atory for infants . However , there are still conflicting opinions about the exact daily dose . Thus , we aim ed to evaluate a daily supplementation dose of 200 IU is sufficient and compared the supplementation doses of 200 and 400 IU per day . One hundred and sixty-nine infants were r and omly assigned to two groups ( group1 , 200 IU/day ; group 2 , 400 IU/day ) and there were 75 infants in group 1 and 64 were in group 2 with a total number of 139 . The median levels of 25-hydroxyvitamin D3 were significantly increased in group 2 at the age of 4 months ( group 1 , 39.60 mcg/L ; group 2 , 56.55 mcg/L ; p < 0.0001 ) . We clearly demonstrated that at the age of 4 months , none of the infants on the group 2 had a serum level of 25-hydroxyvitamin D3 less than 30 mcg/L. However , 21.3 % of the infants in group 1 had a level below 30 mcg/L. Thus , in order to avoid vitamin D deficiency and rickets , we recommend supplementation dose of vitamin D at 400 IU/day as a safe and effective dose IMPORTANCE Vitamin D supplementation in infancy is required to support healthy bone mineral accretion . A supplement of 400 IU of vitamin D per day is thought to support plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations between 40 and 50 nmol/L ; some advocate 75 to 150 nmol/L for bone health . OBJECTIVE To investigate the efficacy of different dosages of vitamin D in supporting 25(OH)D concentrations in infants . DESIGN , SETTING , AND PARTICIPANTS Double-blind r and omized clinical trial conducted among 132 one-month-old healthy , term , breastfed infants from Montréal , Québec , Canada , between March 2007 and August 2010 . Infants were followed up for 11 months ending August 2011 ( 74 % completed study ) . INTERVENTION Participants were r and omly assigned to receive oral cholecalciferol ( vitamin D3 ) supplements of 400 IU/d ( n=39 ) , 800 IU/d ( n=39 ) , 1200 IU/d ( n=38 ) , or 1600 IU/d ( n=16 ) . MAIN OUTCOMES AND MEASURES The primary outcome was a plasma 25(OH)D concentration of 75 nmol/L or greater in 97.5 % of infants at 3 months . Secondary outcomes included 25(OH)D concentrations of 75 nmol/L or greater in 97.5 % of infants at 6 , 9 , and 12 months ; 25(OH)D concentrations of 50 nmol/L or greater across all times ; growth ; and whole body and regional bone mineral content . Data were analyzed by intention to treat using available data , logistic regression , and mixed-model analysis of variance . RESULTS By 3 months , 55 % ( 95 % CI , 38%-72 % ) of infants in the 400-IU/d group achieved a 25(OH)D concentration of 75 nmol/L or greater vs 81%(95 % CI , 65%-91 % ) in the 800-IU/d group , 92 % ( 95 % CI , 77%-98 % ) in the 1200-IU/d group , and 100 % in the 1600-IU/d group . This concentration was not sustained in 97.5 % of infants at 12 months in any of the groups . The 1600-IU/d dosage was discontinued prematurely because of elevated plasma 25(OH)D concentrations . All dosages established 25(OH)D concentrations of 50 nmol/L or greater in 97 % ( 95 % CI , 94%-100 % ) of infants at 3 months and sustained this in 98 % ( 95 % CI , 94%-100 % ) to 12 months . Growth and bone mineral content did not differ by dosage . CONCLUSIONS AND RELEVANCE Among healthy , term , breastfed infants , only a vitamin D supplement dosage of 1600 IU/d ( but not dosages of 400 , 800 , or 1200 IU/d ) increased plasma 25(OH)D concentration to 75 nmol/L or greater in 97.5 % of infants at 3 months . However , this dosage increased 25(OH)D concentrations to levels that have been associated with hypercalcemia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00381914 Background The rate of non-compliance with vitamin D supplementation is as high as 45 % . This is why r and omised controlled trials are needed to analyse the response to low doses of vitamin D3 . Objective ( 1 ) To compare supplementation with 250 versus 500 units of vitamin D3 and ( 2 ) to analyse sun exposure time/ultraviolet B ( UVB ) exposure during the first 6 weeks of life . Design 40 breastfed infants ( skin photo-types I , II ) were recruited in Berlin , Germany ( 52.5 ° N ) , during summer ( n=20 ) and winter ( n=20 ) and r and omised into equal groups on either 250 or 500 units of  vitamin D3 per day . Outcome measures were : parameters of vitamin D and bone metabolism at delivery and 6 weeks later , sun exposure time , UVB dosimetry and surrounding factors including maternal diet . Results At delivery 25-hydroxy vitamin D levels were insufficient : 68 ( 53–83 ) nmol/l in each group . 6 weeks later levels were sufficient : 139 ( 114–164 ) nmol/l on 250 units of vitamin D3 per day and 151 ( 126–176 ) nmol/l on 500 units/day . There was no seasonal variation . Daily sun exposure time was 0.4–3.5 h and higher in summer . UVB exposure was 0.01–0.08 minimal erythema dose/day . Calcium levels were within normal . Conclusions In Berlin , Germany , supplementation with 250 units of vitamin D3 is sufficient for breastfed infants during their first 6 weeks of life in summer and winter . UVB exposure is very low throughout the year The biological equivalency of ergocalciferol ( D2 ) and cholecalciferol ( D3 ) has been debated ; several comparisons have appeared in the adult literature but are scarce in pediatrics . The objective of this study was to compare increases in plasma 25-hydroxyvitamin D [ 25(OH)D ] concentrations and attainment of 50 and 75 mol/L status cutoffs following 3 mo of daily supplementation with D2 compared with D3 .  Healthy , breast-fed , 1-mo-old infants ( n = 52 ) received 10 μg ( 400 ic ) of either D2 or D3 daily . At 1 and 4 mo of age , plasma 25-hydroxyergocalciferol and 25-hydroxycholecalciferol concentrations were determined by liquid chromatography t and em MS ( LC-MS/MS ) and total 25(OH)D by chemiluminescent immunoassay ( DiaSorin Liaison ) . Data were analyzed using t tests and χ2 by intent to treat . A total of 23 % of infants were deficient ( ≤24.9 nmol/L ) at baseline and 2 % at follow-up on the basis of LC-MS/MS . At 4 mo , 96 % were breastfed and there were no differences in compliance , breastfeeding rates , or sun exposure among groups . The change in total 25(OH)D measured by LC-MS/MS did not differ between the D2 ( 17.6 ± 26.7 nmol/L ) and D3 ( 22.2 ± 20.2 nmol/L ) groups . In the combined groups , the baseline plasma 25(OH)D concentration was inversely related to the change in total 25(OH)D ( r = −0.52 ; P < 0.001 ) . Overall , 86 % of infants met the 50 nmol/L cutoff at follow-up ; however , fewer infants in the D2 group ( 75 % ) met this level compared with the D3 group ( 96 % ) ( P < 0.05 ) . Similar results were obtained by immunoassay . In conclusion , the increase in the 25(OH)D concentration among the D2 and D3 groups did not differ , suggesting daily intake of either isoform is acceptable for infants < 4 mo OBJECTIVE : To investigate the effect of vitamin D3 supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul , Afghanistan . METHODS : This double-blind placebo-controlled trial r and omized 3046 high-risk 1- to 11-month-old infants to receive 6 quarterly doses of oral vitamin D3 ( cholecalciferol 100 000 IU ) or placebo in inner city Kabul . Data on diarrheal episodes ( ≥3 loose/liquid stools in 24 hours ) was gathered through active and passive surveillance over 18 months of follow-up . Time to first diarrheal illness was analyzed by using Kaplan-Meier plots . Incidence rates and hazard ratios ( HRs ) were calculated by using recurrent event Poisson regression models . RESULTS : No significant difference existed in survival time to first diarrheal illness ( log rank P = .55 ) . The incidences of diarrheal episodes were 3.43 ( 95 % confidence interval [ CI ] , 3.28–3.59 ) and 3.59 per child-year ( 95 % CI , 3.44–3.76 ) in the placebo and intervention arms , respectively . Vitamin D3 supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat ( HR , 1.05 ; 95 % CI , 0.98–1.17 ; P = .15 ) or per protocol ( HR , 1.05 ; 95 % CI , 0.98–1.12 ; P = .14 ) analyses . The lack of preventive benefit remained when the r and omized population was stratified by age groups , nutritional status , and seasons . CONCLUSIONS : Quarterly supplementation with vitamin D3 conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study . Similar supplementation to comparable population s is not recommended . Additional research in alternative setting s may be helpful in elucidating the role of vitamin D 
    Output:
    