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 Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing .  We examined the effect of prenatal vitamin D on childhood wheezing  in an interventional study . Methods We r and omised 180 pregnant women at 27 weeks gestation to either  no vitamin D , 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol  , in an ethnically stratified , r and omised controlled trial . Supplementation improved but did not optimise vitamin D status . Research ers blind to allocation assessed offspring at 3 years . Primary outcome was any history of wheeze assessed by vali date d question naire . Secondary outcomes included atopy , respiratory infection , impulse oscillometry and exhaled nitric oxide . Primary analyses used logistic and linear regression . Results We evaluated 158 of 180 ( 88 % ) offspring at age 3 years for the primary outcome . Atopy was assessed by skin test for 95 children ( 53 % ) , serum IgE for 86 ( 48 % ) , exhaled nitric oxide for 62 ( 34 % ) and impulse oscillometry of acceptable quality for 51 ( 28 % ) . We found no difference between supplemented and control groups in risk of wheeze  [ no vitamin D : 14/50 ( 28 % ) ; any vitamin D : 26/108 ( 24 % ) ( risk ratio 0.86 ; 95 % confidence interval 0.49 , 1.50 ; P = 0.69 ) ] . There was no significant difference in atopy , eczema risk , lung function or exhaled nitric oxide between supplemented groups and controls . Conclusion Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level , was not associated with decreased wheezing in offspring at age three years . Trial Registration Controlled-Trials.com IS RCT BACKGROUND The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known , particularly within ranges comparable to the probable physiologic supply of the vitamin . OBJECTIVES The objectives were to establish the quantitative relation between steady state cholecalciferol input and the result ing serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores . DESIGN Cholecalciferol was administered daily in controlled oral doses labeled at 0 , 25 , 125 , and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha ( 41.2 degrees N latitude ) . The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment . RESULTS From a mean baseline value of 70.3 nmol/L , equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose , with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input . The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study ( ie , in the autumn ) was 12.5 micro g ( 500 IU)/d , whereas the total amount from all sources ( supplement , food , tissue stores ) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g ( approximately 3800 IU)/d . By difference , the tissue stores provided approximately 78 - 82 micro g/d . CONCLUSIONS Healthy men seem to use 3000 - 5000 IU cholecalciferol/d , apparently meeting > 80 % of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months . Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin The need , safety , and effectiveness of vitamin D supplementation during pregnancy remain controversial . In this r and omized , controlled trial , women with a singleton pregnancy at 12 to 16 weeks ' gestation received 400 , 2000 , or 4000 IU of vitamin D(3 ) per day until delivery . The primary outcome was maternal/neonatal circulating 25-hydroxyvitamin D [ 25(OH)D ] concentration at delivery , with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D(3 ) [ 1,25(OH)(2)D(3 ) ] production . Of the 494 women enrolled , 350 women continued until delivery : Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different ( p < 0.0001 ) , and the percent who achieved sufficiency was significantly different by group , greatest in 4000-IU group ( p < 0.0001 ) . The relative risk ( RR ) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups ( RR = 1.52 , 95 % CI 1.24 - 1.86 ) , the 4000- and the 400-IU groups ( RR = 1.60 , 95 % CI 1.32 - 1.95 ) but not between the 4000- and . 2000-IU groups ( RR = 1.06 , 95 % CI 0.93 - 1.19 ) . Circulating 25(OH)D had a direct influence on circulating 1,25(OH)(2)D(3 ) concentrations throughout pregnancy ( p < 0.0001 ) , with maximal production of 1,25(OH)(2)D(3 ) in all strata in the 4000-IU group . There were no differences between groups on any safety measure . Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels . It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race , whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations , especially in African Americans Chez 100 femmes enceintes , l'administration de 2 doses de 600000 UI de vitamine D du 3eme trimestre a entraine une amelioration significative des parametres biochimiques maternels et du serum du cordon , du poids de naissance et de certaines autres mesures anthropometriques du nouveau-ne comparativement a 100 femmes enceintes ne recevant pas de Background Antenatal vitamin D status may be associated with the risk of adverse pregnancy and neonatal outcomes ; however , the benefits of vitamin D supplementation during pregnancy remain unknown . Methods We conducted a double-blind placebo-controlled r and omized trial to evaluate the effect of high-dose prenatal 3rd trimester vitamin D3 supplementation on maternal and neonatal ( cord blood ) serum 25-hydroxyvitamin D ( 25(OH)D ) concentration ( primary biochemical efficacy outcome ) and maternal serum calcium concentration ( primary safety measure ) . Eligibility criteria were pregnant women aged 18 to < 35 years , at 26 to 29 weeks gestation , and residing in Dhaka , Bangladesh . 160 women were r and omized by 1:1 allocation to one of two parallel intervention groups ; placebo ( n = 80 ) or 35,000 IU/week of vitamin D3 ( n = 80 ) until delivery . All participants , study personnel and study investigators were blind to treatment allocation . Results Mean maternal 25(OH)D concentration was similar in the vitamin D and placebo groups at baseline ( 45 vs. 44 nmol/L ; p = 0.66 ) , but was significantly higher in the vitamin D group vs. placebo group among mothers at delivery ( 134 vs. 38 nmol/L ; p < 0.001 ) and newborns ( cord blood : 103 vs. 39 ; p < 0.001 ) . In the vitamin D group , 95 % of neonates and 100 % of mothers attained 25(OH)D > 50 nmol/L , versus 21 % mothers and 19 % of neonates in the placebo group . No participants met criteria for hypercalcemia , there were no known supplement-related adverse events , and major pregnancy outcomes were similar between groups . Conclusions Antenatal 3rd-trimester vitamin D3 supplementation ( 35,000 IU/week ) significantly raised maternal and cord serum 25(OH)D concentrations above 50 nmol/L in almost all participants without inducing hypercalcemia or other observed safety concerns . Doses up to 35,000 IU/week may be cautiously used in further research aim ed at establishing the clinical effects and safety of vitamin D3 supplementation in pregnancy . Trial registration This trial was registered at Clinical Trials.gov ( NCT01126528 ) In a double-blind trial of vitamin D supplements in pregnant Asian women calciferol ( ergocalciferol , 1000 IU/day ) was administered to 59 women and placebo to 67 controls during the last trimester . The two groups had similar distributions of maternal age , height , parity , number of vegetarians , countries of origin , and sex and gestation of the infants . At entry to the trial maternal serum 25-hydroxy vitamin D ( 25-OHD ) concentrations were low in both treatment and control groups and significantly lower in vegetarians than non-vegetarians . Mothers in the treatment group gained weight faster in the last trimester than those in the control group , and at term they and their infants all had adequate plasma 25-OHD concentrations , Mothers and infants in the control group , however , had low plasma concentrations of 25-OHD and calcium and raised plasma alkaline phosphatase ( bone isoenzyme ) activity . Five of these infants developed symptomatic hypocalcaemia . Almost twice as many infants in the control group were small for gestational age ( 29 % v 15 % ) , but there were no significant differences between the two groups of infants in antropometric measurements . Infants in the control group , however , had larger fontanelles , suggesting impaired ossification of the skull . Because of the benefits to mothers and infants in the treatment group and the absence of side effects , vitamin D supplements should be given to all pregnant Asian women in the United Kingdom Background : The exact role of vitamin D in the development and severity of preeclampsia is still unclear . The aim of the present study was to investigate the association between vitamin D supplement and preeclampsia in pregnant women . Material s and Methods : In this r and omized controlled trial , in 2012 , 140 nulliparous pregnant women in two groups received supplementation with 600 IU/day of vitamin D or supplementation free of vitamin D at 16 week gestation until the delivery . The main outcomes included the frequency of preeclampsia and subtypes by clinical severity and infant birth weight . Results : Mean of maternal age and gestational age at the delivery in all studied subjects were 25 ± 4.1 years and 37.4 ± 3 weeks , respectively , which were not statistically significant between the groups . Preeclampsia was observed in two subjects in case group compared to seven subjects in control group , which was not significant ( P-value = 0.09 ) . In case group , subjects with preeclampsia diagnosed as mild preeclampsia and in control group four subjects were mild , and three were severe . No significant differences were noted between the case and control groups in the frequency of preeclampsia subtypes by clinical severity . Infant birth weight in case group who was significantly higher than control group , which was statistically significant between groups ( P-value = 0.09 ) . Conclusion : In summary , our results demonstrated that vitamin D supplementation during the third trimester of pregnancy ; despite the non-significant association between vitamin D supplementation and preeclampsia , reduce the risk of preeclampsia . However , further studies needs to be done BACKGROUND In 2006 , WHO produced international growth st and ards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee . Using the same methods and conceptual approach , the Fetal Growth Longitudinal Study ( FGLS ) , part of the INTERGROWTH-21(st ) Project , aim ed to develop international growth and size st and ards for fetuses . METHODS The multicentre , population -based FGLS assessed fetal growth in geographically defined urban population s in eight countries , in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided . We used ultrasound to take fetal anthropometric measurements prospect ively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction . All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester . The five primary ultrasound measures of fetal growth 
    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: Background Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing .  We examined the effect of prenatal vitamin D on childhood wheezing  in an interventional study . Methods We r and omised 180 pregnant women at 27 weeks gestation to either  no vitamin D , 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol  , in an ethnically stratified , r and omised controlled trial . Supplementation improved but did not optimise vitamin D status . Research ers blind to allocation assessed offspring at 3 years . Primary outcome was any history of wheeze assessed by vali date d question naire . Secondary outcomes included atopy , respiratory infection , impulse oscillometry and exhaled nitric oxide . Primary analyses used logistic and linear regression . Results We evaluated 158 of 180 ( 88 % ) offspring at age 3 years for the primary outcome . Atopy was assessed by skin test for 95 children ( 53 % ) , serum IgE for 86 ( 48 % ) , exhaled nitric oxide for 62 ( 34 % ) and impulse oscillometry of acceptable quality for 51 ( 28 % ) . We found no difference between supplemented and control groups in risk of wheeze  [ no vitamin D : 14/50 ( 28 % ) ; any vitamin D : 26/108 ( 24 % ) ( risk ratio 0.86 ; 95 % confidence interval 0.49 , 1.50 ; P = 0.69 ) ] . There was no significant difference in atopy , eczema risk , lung function or exhaled nitric oxide between supplemented groups and controls . Conclusion Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level , was not associated with decreased wheezing in offspring at age three years . Trial Registration Controlled-Trials.com IS RCT BACKGROUND The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known , particularly within ranges comparable to the probable physiologic supply of the vitamin . OBJECTIVES The objectives were to establish the quantitative relation between steady state cholecalciferol input and the result ing serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores . DESIGN Cholecalciferol was administered daily in controlled oral doses labeled at 0 , 25 , 125 , and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha ( 41.2 degrees N latitude ) . The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment . RESULTS From a mean baseline value of 70.3 nmol/L , equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose , with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input . The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study ( ie , in the autumn ) was 12.5 micro g ( 500 IU)/d , whereas the total amount from all sources ( supplement , food , tissue stores ) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g ( approximately 3800 IU)/d . By difference , the tissue stores provided approximately 78 - 82 micro g/d . CONCLUSIONS Healthy men seem to use 3000 - 5000 IU cholecalciferol/d , apparently meeting > 80 % of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months . Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin The need , safety , and effectiveness of vitamin D supplementation during pregnancy remain controversial . In this r and omized , controlled trial , women with a singleton pregnancy at 12 to 16 weeks ' gestation received 400 , 2000 , or 4000 IU of vitamin D(3 ) per day until delivery . The primary outcome was maternal/neonatal circulating 25-hydroxyvitamin D [ 25(OH)D ] concentration at delivery , with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D(3 ) [ 1,25(OH)(2)D(3 ) ] production . Of the 494 women enrolled , 350 women continued until delivery : Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different ( p < 0.0001 ) , and the percent who achieved sufficiency was significantly different by group , greatest in 4000-IU group ( p < 0.0001 ) . The relative risk ( RR ) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups ( RR = 1.52 , 95 % CI 1.24 - 1.86 ) , the 4000- and the 400-IU groups ( RR = 1.60 , 95 % CI 1.32 - 1.95 ) but not between the 4000- and . 2000-IU groups ( RR = 1.06 , 95 % CI 0.93 - 1.19 ) . Circulating 25(OH)D had a direct influence on circulating 1,25(OH)(2)D(3 ) concentrations throughout pregnancy ( p < 0.0001 ) , with maximal production of 1,25(OH)(2)D(3 ) in all strata in the 4000-IU group . There were no differences between groups on any safety measure . Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels . It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race , whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations , especially in African Americans Chez 100 femmes enceintes , l'administration de 2 doses de 600000 UI de vitamine D du 3eme trimestre a entraine une amelioration significative des parametres biochimiques maternels et du serum du cordon , du poids de naissance et de certaines autres mesures anthropometriques du nouveau-ne comparativement a 100 femmes enceintes ne recevant pas de Background Antenatal vitamin D status may be associated with the risk of adverse pregnancy and neonatal outcomes ; however , the benefits of vitamin D supplementation during pregnancy remain unknown . Methods We conducted a double-blind placebo-controlled r and omized trial to evaluate the effect of high-dose prenatal 3rd trimester vitamin D3 supplementation on maternal and neonatal ( cord blood ) serum 25-hydroxyvitamin D ( 25(OH)D ) concentration ( primary biochemical efficacy outcome ) and maternal serum calcium concentration ( primary safety measure ) . Eligibility criteria were pregnant women aged 18 to < 35 years , at 26 to 29 weeks gestation , and residing in Dhaka , Bangladesh . 160 women were r and omized by 1:1 allocation to one of two parallel intervention groups ; placebo ( n = 80 ) or 35,000 IU/week of vitamin D3 ( n = 80 ) until delivery . All participants , study personnel and study investigators were blind to treatment allocation . Results Mean maternal 25(OH)D concentration was similar in the vitamin D and placebo groups at baseline ( 45 vs. 44 nmol/L ; p = 0.66 ) , but was significantly higher in the vitamin D group vs. placebo group among mothers at delivery ( 134 vs. 38 nmol/L ; p < 0.001 ) and newborns ( cord blood : 103 vs. 39 ; p < 0.001 ) . In the vitamin D group , 95 % of neonates and 100 % of mothers attained 25(OH)D > 50 nmol/L , versus 21 % mothers and 19 % of neonates in the placebo group . No participants met criteria for hypercalcemia , there were no known supplement-related adverse events , and major pregnancy outcomes were similar between groups . Conclusions Antenatal 3rd-trimester vitamin D3 supplementation ( 35,000 IU/week ) significantly raised maternal and cord serum 25(OH)D concentrations above 50 nmol/L in almost all participants without inducing hypercalcemia or other observed safety concerns . Doses up to 35,000 IU/week may be cautiously used in further research aim ed at establishing the clinical effects and safety of vitamin D3 supplementation in pregnancy . Trial registration This trial was registered at Clinical Trials.gov ( NCT01126528 ) In a double-blind trial of vitamin D supplements in pregnant Asian women calciferol ( ergocalciferol , 1000 IU/day ) was administered to 59 women and placebo to 67 controls during the last trimester . The two groups had similar distributions of maternal age , height , parity , number of vegetarians , countries of origin , and sex and gestation of the infants . At entry to the trial maternal serum 25-hydroxy vitamin D ( 25-OHD ) concentrations were low in both treatment and control groups and significantly lower in vegetarians than non-vegetarians . Mothers in the treatment group gained weight faster in the last trimester than those in the control group , and at term they and their infants all had adequate plasma 25-OHD concentrations , Mothers and infants in the control group , however , had low plasma concentrations of 25-OHD and calcium and raised plasma alkaline phosphatase ( bone isoenzyme ) activity . Five of these infants developed symptomatic hypocalcaemia . Almost twice as many infants in the control group were small for gestational age ( 29 % v 15 % ) , but there were no significant differences between the two groups of infants in antropometric measurements . Infants in the control group , however , had larger fontanelles , suggesting impaired ossification of the skull . Because of the benefits to mothers and infants in the treatment group and the absence of side effects , vitamin D supplements should be given to all pregnant Asian women in the United Kingdom Background : The exact role of vitamin D in the development and severity of preeclampsia is still unclear . The aim of the present study was to investigate the association between vitamin D supplement and preeclampsia in pregnant women . Material s and Methods : In this r and omized controlled trial , in 2012 , 140 nulliparous pregnant women in two groups received supplementation with 600 IU/day of vitamin D or supplementation free of vitamin D at 16 week gestation until the delivery . The main outcomes included the frequency of preeclampsia and subtypes by clinical severity and infant birth weight . Results : Mean of maternal age and gestational age at the delivery in all studied subjects were 25 ± 4.1 years and 37.4 ± 3 weeks , respectively , which were not statistically significant between the groups . Preeclampsia was observed in two subjects in case group compared to seven subjects in control group , which was not significant ( P-value = 0.09 ) . In case group , subjects with preeclampsia diagnosed as mild preeclampsia and in control group four subjects were mild , and three were severe . No significant differences were noted between the case and control groups in the frequency of preeclampsia subtypes by clinical severity . Infant birth weight in case group who was significantly higher than control group , which was statistically significant between groups ( P-value = 0.09 ) . Conclusion : In summary , our results demonstrated that vitamin D supplementation during the third trimester of pregnancy ; despite the non-significant association between vitamin D supplementation and preeclampsia , reduce the risk of preeclampsia . However , further studies needs to be done BACKGROUND In 2006 , WHO produced international growth st and ards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee . Using the same methods and conceptual approach , the Fetal Growth Longitudinal Study ( FGLS ) , part of the INTERGROWTH-21(st ) Project , aim ed to develop international growth and size st and ards for fetuses . METHODS The multicentre , population -based FGLS assessed fetal growth in geographically defined urban population s in eight countries , in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided . We used ultrasound to take fetal anthropometric measurements prospect ively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction . All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester . The five primary ultrasound measures of fetal growth 
    Output:
    