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: OBJECTIVE To determine the effect of dietary supplementation of calcium plus conjugated linoleic acid ( calcium-CLA ) in reducing the incidence of vascular endothelial dysfunction in pregnant women at high risk of developing pregnancy-induced hypertension ( PIH ) . PATIENTS AND METHODS This r and omized , double-blind , placebo-controlled trial conducted at 4 outpatient clinics in 2 developing countries recruited 48 healthy primigravidas younger than 19 years or older than 35 years who had a family history of pre-eclampsia and diastolic notch . Twenty-four participants received daily elemental calcium ( 600 mg ) plus CLA ( 450 mg ) and 24 received placebo from week 18 to 22 of pregnancy until delivery . RESULTS Calcium-CLA supplementation reduced significantly the incidence of PIH ( 2 cases [ 8 % ] in the study group vs. 10 cases [ 42 % ] in the placebo group ; relative risk , 0.20 ; 95 % confidence interval , 0.05 - 0.82 ; P=.01 ) . Endothelial dysfunction was also significantly reduced after calcium-CLA supplementation ( in 18 women [ 75 % ] vs. 4 women [ 17 % ] ; P<.001 ) , compared with the placebo group ( in 15 [ 63 % ] vs. 9 women [ 38 % ] ; P=.08 ) . CONCLUSION In pregnant women at high risk for PIH , calcium-CLA supplementation decreases the incidence of PIH and improves endothelial function Background It has been suggested that a higher calcium intake might favourably modify cardiovascular risk factors . However , findings of an ultimately decreased risk of cardiovascular disease ( CVD ) are limited . Instead , recent evidence warns that taking calcium supplements might increase myocardial infa rct ion ( MI ) risk . Objective To prospect ively evaluate the associations of dietary calcium intake and calcium supplementation with MI and stroke risk and overall CVD mortality . Methods Data from 23 980 Heidelberg cohort participants of the European Prospect i ve Investigation into Cancer and Nutrition study , aged 35–64 years and free of major CVD events at recruitment , were analysed . Multivariate Cox regression models were used to estimate HRs and 95 % CIs . Results After an average follow-up time of 11 years , 354 MI and 260 stroke cases and 267 CVD deaths were documented . Compared with the lowest quartile , the third quartile of total dietary and dairy calcium intake had a significantly reduced MI risk , with a HR of 0.69 ( 95 % CI 0.50 to 0.94 ) and 0.68 ( 95 % CI 0.50 to 0.93 ) , respectively . Associations for stroke risk and CVD mortality were overall null . In comparison with non-users of any supplements , users of calcium supplements had a statistically significantly increased MI risk ( HR=1.86 ; 95 % CI 1.17 to 2.96 ) , which was more pronounced for calcium supplement only users ( HR=2.39 ; 95 % CI 1.12 to 5.12 ) . Conclusions Increasing calcium intake from diet might not confer significant cardiovascular benefits , while calcium supplements , which might raise MI risk , should be taken with caution Objective . To test the hypothesis that calcium supplementation inhibits the underlying pathological processes in women with preeclampsia . Methods . Seven hundred and eight nulliparous women were enrolled in a WHO r and omized double-blind trial , who received 1.5 g of calcium or placebo from 20 weeks of pregnancy or earlier . Platelet count , serum urate , and urinary protein/creatinine ratio were measured at or near 35 gestational weeks . Results . No difference was detected in rates of abnormal platelet count ( relative risk [ RR ] 1.18 ; 95 % confidence interval [ CI ] , 0.63 to 2.18 ) , serum urate level ( 1.0 ; 0.64 to 1.57 ) or urine protein/creatinine ratio ( 1.01 ; 0.76 to 1.34 ) . This was consistent with the main trial finding of no difference in the incidence of ‘ dipstick ’ proteinuria between women receiving calcium and those receiving placebo ( 8312 women ; RR , 1.01 ; 95 % CI , 0.88 to 1.15 ) . Conclusions . An effect of calcium supplementation in the second half of pregnancy on the rate of abnormal laboratory measures associated with preeclampsia was not demonstrated Background : To prevent pre-eclampsia in population s with insufficient dietary calcium ( Ca ) intake , the World Health Organisation ( WHO ) recommends routine Ca supplementation during antenatal care ( ANC ) . WHO guidelines suggest a complex dosing regimen , requiring as many as 5 pill-taking events per day when combined with iron and folic acid ( IFA ) supplements . Poor adherence may undermine public health effectiveness , so simpler regimens may be preferable . This trial will compare the effect of the WHO-recommended ( higher-dose ) regimen vs. a simpler , lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients . Design and methods : This is a parallel , non-inferiority , cluster-r and omized trial ; we examined 16 primary care health facilities in Kenya , 1047 pregnant women between 16 - 30 weeks gestational age . Higher-dose regimen : 1.5 g elemental calcium in 3 separate doses ( 500 mg Ca/pill ) and IFA ( 60 mg Fe + 400 µg folic acid ) taken with evening dose . Lower-dose regimen : 1.0 g calcium in 2 separate doses ( 500 mg Ca/pill ) with IFA taken as above . Measurements : Primary outcome is Ca pills consumed per day , measured by pill counts . Secondary outcomes include IFA pills consumed per day , client knowledge , motivation , social support , and satisfaction , measured at 4 to 10 weeks post-enrolment . Statistical analyses : Unit of r and omization is the healthcare facility ; unit of analysis is individual client . Intent-to-treat analysis will be implemented with multi-level models to account for clustering . Expected public health impact : If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen , developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save re sources . Significance for public health Pre-eclampsia is a leading cause of maternal mortality . Based on clinical evidence of significant reduction in risk of pre-eclampsia , the WHO recommends including calcium ( Ca ) supplementation in antenatal care services in setting s with inadequate dietary Ca intakes . A high daily amount of Ca administered in a complex dosing regimen is recommended to maximize efficacy and bioavailability . Factors such as client adherence , motivation , cost and logistical complexities may undermine effectiveness when implemented in public health programs . This cluster-r and omized trial will compare Ca supplement consumption between higher and lower-dose regimens delivered through antenatal care in Kenya , integrated with iron-folic acid supplementation . If a lower-dose regimen improves adherence , women ’s Ca supplement consumption may be comparable to that achieved under a complex , higher-dose regimen . Evidence gained from this trial will guide public health planning for antenatal calcium supplementation programs to maximize benefits through reducing logistical , cost and adherence barriers Calcium supplementation in mothers with low calcium intake has been of interest recently because of its association with optimal fetal growth and improved pre-eclampsia-related outcomes . While the effects of calcium supplementation have demonstrated benefits in prolonging gestation and subsequently improving birthweight , no specific studies have identified the longitudinal effects of supplementation on fetal growth in utero . Data were analysed in the context of the World Health Organization trial of calcium supplementation in calcium-deficient women . Five hundred and ten healthy , primiparous pregnant Argentinean women were r and omised ( at < 20 weeks gestation ) to either placebo  ( n = 230 ) or  calcium supplements ( 1500 mg calcium/day in 3 divided doses ; n = 231 ) . Growth parameters in utero were assessed with serial ultrasound scans . Birthweight , length , head , abdominal and thigh circumferences were recorded at delivery . No differences were found in fetal biometric measurements recorded at 20 , 24 , 28 , 32 and 36 weeks gestation between fetuses of women who were supplemented with calcium and those who were not . Similarly , neonatal characteristics and anthropometric measurements recorded at delivery were comparable in both groups . We conclude that calcium supplementation of 1500 mg calcium/day in pregnant women with low calcium intake does not appear to impact on fetal somatic or skeletal growth To study the effect of calcium and vitamin D supplementation on the incidence of toxaemia of pregnancy , 200 r and omly selected pregnant women ( supplemented group ) , were put on calcium ( 375 mg/day ) and vitamin D ( 1,200 IU/day ) supplements at 20 - 24 weeks of pregnancy onwards . Another 200 pregnant women constituted the non-supplemented group . At 32 and 36 weeks of pregnancy the systolic and diastolic blood pressure of non-toxemic women was significantly lower in the supplemented group than in the non-supplemented group . However , the incidence of toxaemia in the supplemented group ( 6 % ) was not significantly different from that in the non-supplemented group ( 9 % ) BACKGROUND Pregnancy and lactation in adolescents with habitually low calcium intake may adversely affect maternal bone mass . OBJECTIVE We investigated the effect of calcium plus vitamin D supplementation during pregnancy on bone mass during lactation in Brazilian adolescent mothers with low-calcium diets ( ∼600 mg/d ) . DESIGN Pregnant adolescents ( 14 - 19 y ) r and omly received daily calcium ( 600 mg ) plus vitamin D3 ( 200 IU ) ( n = 30 ) or a placebo ( n = 26 ) from 26 wk of pregnancy ( baseline ) until parturition . The bone mineral content ( BMC ) , bone area ( BA ) , and bone mineral density ( BMD ) at the total body , lumbar spine , and hip ( total and femoral neck ) were evaluated by using dual-energy X-ray absorptiometry at 5 and 20 wk postpartum . Serum hormones and 25-hydroxyvitamin D [ 25(OH)D ] were measured . Group comparisons were adjusted for significant covariates . RESULTS The mean serum 25(OH)D concentration was 59 nmol/L at baseline . In comparison with the placebo , 25(OH)D tended to be 14 - 15 nmol/L higher postpartum in the supplemented group ( P = 0.08 ) . Total body and hip BMC and BMD decreased over time ( P ≤ 0.005 ) in both groups with a group × time interaction at the femoral neck ( P < 0.04 ) . Supplemented mothers had higher lumbar spine BA ( 6.7 % ; P = 0.002 ) and lumbar spine BMC ( 7.9 % , P = 0.08 ) than did mothers who consumed the placebo at 5 wk postpartum . At 20 wk postpartum , differences between groups were more evident , with higher lumbar spine BMC ( 13.9 % ) , lumbar spine BA ( 6.2 % ) , and lumbar spine BMD ( 10.6 % ) in the supplemented group ( P ≤ 0.008 ) . CONCLUSIONS Calcium plus vitamin D supplementation during pregnancy of adolescents with low calcium intake  results in higher lumbar spine bone mass and a reduced rate of femoral neck bone loss during lactation . Additional studies are required to determine whether bone effects are temporary or long-lasting . This trial was registered at clinical trials.gov as NCT01732328 BACKGROUND Growth and bone mineral accretion in Gambian infants are poorer than those in Western population s. The calcium intake of Gambian women is low , typically 300 - 400 mg Ca/d , and they have low breast-milk calcium concentrations , which result in low calcium intakes for their breastfed infants . A low maternal calcium supply in pregnancy may limit fetal mineral accretion and breast-milk calcium concentrations and thereby affect infant growth and bone mineral accretion . OBJECTIVE We investigated the effects of calcium supplementation in Gambian women during pregnancy on breast-milk calcium concentrations and infant birth weight , growth , and bone mineral accretion . DESIGN A r and omized , double-blind , placebo-controlled supplementation study was conducted in 125 Gambian women who received 1500 mg Ca/d ( as calcium carbonate ) or placebo from 20 wk of gestation until delivery . Infant birth weight and gestational age were recorded . Breast milk was collected , and infant anthropometric and bone measurements were performed at 2 , 13 , and  
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To determine the effect of dietary supplementation of calcium plus conjugated linoleic acid ( calcium-CLA ) in reducing the incidence of vascular endothelial dysfunction in pregnant women at high risk of developing pregnancy-induced hypertension ( PIH ) . PATIENTS AND METHODS This r and omized , double-blind , placebo-controlled trial conducted at 4 outpatient clinics in 2 developing countries recruited 48 healthy primigravidas younger than 19 years or older than 35 years who had a family history of pre-eclampsia and diastolic notch . Twenty-four participants received daily elemental calcium ( 600 mg ) plus CLA ( 450 mg ) and 24 received placebo from week 18 to 22 of pregnancy until delivery . RESULTS Calcium-CLA supplementation reduced significantly the incidence of PIH ( 2 cases [ 8 % ] in the study group vs. 10 cases [ 42 % ] in the placebo group ; relative risk , 0.20 ; 95 % confidence interval , 0.05 - 0.82 ; P=.01 ) . Endothelial dysfunction was also significantly reduced after calcium-CLA supplementation ( in 18 women [ 75 % ] vs. 4 women [ 17 % ] ; P<.001 ) , compared with the placebo group ( in 15 [ 63 % ] vs. 9 women [ 38 % ] ; P=.08 ) . CONCLUSION In pregnant women at high risk for PIH , calcium-CLA supplementation decreases the incidence of PIH and improves endothelial function Background It has been suggested that a higher calcium intake might favourably modify cardiovascular risk factors . However , findings of an ultimately decreased risk of cardiovascular disease ( CVD ) are limited . Instead , recent evidence warns that taking calcium supplements might increase myocardial infa rct ion ( MI ) risk . Objective To prospect ively evaluate the associations of dietary calcium intake and calcium supplementation with MI and stroke risk and overall CVD mortality . Methods Data from 23 980 Heidelberg cohort participants of the European Prospect i ve Investigation into Cancer and Nutrition study , aged 35–64 years and free of major CVD events at recruitment , were analysed . Multivariate Cox regression models were used to estimate HRs and 95 % CIs . Results After an average follow-up time of 11 years , 354 MI and 260 stroke cases and 267 CVD deaths were documented . Compared with the lowest quartile , the third quartile of total dietary and dairy calcium intake had a significantly reduced MI risk , with a HR of 0.69 ( 95 % CI 0.50 to 0.94 ) and 0.68 ( 95 % CI 0.50 to 0.93 ) , respectively . Associations for stroke risk and CVD mortality were overall null . In comparison with non-users of any supplements , users of calcium supplements had a statistically significantly increased MI risk ( HR=1.86 ; 95 % CI 1.17 to 2.96 ) , which was more pronounced for calcium supplement only users ( HR=2.39 ; 95 % CI 1.12 to 5.12 ) . Conclusions Increasing calcium intake from diet might not confer significant cardiovascular benefits , while calcium supplements , which might raise MI risk , should be taken with caution Objective . To test the hypothesis that calcium supplementation inhibits the underlying pathological processes in women with preeclampsia . Methods . Seven hundred and eight nulliparous women were enrolled in a WHO r and omized double-blind trial , who received 1.5 g of calcium or placebo from 20 weeks of pregnancy or earlier . Platelet count , serum urate , and urinary protein/creatinine ratio were measured at or near 35 gestational weeks . Results . No difference was detected in rates of abnormal platelet count ( relative risk [ RR ] 1.18 ; 95 % confidence interval [ CI ] , 0.63 to 2.18 ) , serum urate level ( 1.0 ; 0.64 to 1.57 ) or urine protein/creatinine ratio ( 1.01 ; 0.76 to 1.34 ) . This was consistent with the main trial finding of no difference in the incidence of ‘ dipstick ’ proteinuria between women receiving calcium and those receiving placebo ( 8312 women ; RR , 1.01 ; 95 % CI , 0.88 to 1.15 ) . Conclusions . An effect of calcium supplementation in the second half of pregnancy on the rate of abnormal laboratory measures associated with preeclampsia was not demonstrated Background : To prevent pre-eclampsia in population s with insufficient dietary calcium ( Ca ) intake , the World Health Organisation ( WHO ) recommends routine Ca supplementation during antenatal care ( ANC ) . WHO guidelines suggest a complex dosing regimen , requiring as many as 5 pill-taking events per day when combined with iron and folic acid ( IFA ) supplements . Poor adherence may undermine public health effectiveness , so simpler regimens may be preferable . This trial will compare the effect of the WHO-recommended ( higher-dose ) regimen vs. a simpler , lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients . Design and methods : This is a parallel , non-inferiority , cluster-r and omized trial ; we examined 16 primary care health facilities in Kenya , 1047 pregnant women between 16 - 30 weeks gestational age . Higher-dose regimen : 1.5 g elemental calcium in 3 separate doses ( 500 mg Ca/pill ) and IFA ( 60 mg Fe + 400 µg folic acid ) taken with evening dose . Lower-dose regimen : 1.0 g calcium in 2 separate doses ( 500 mg Ca/pill ) with IFA taken as above . Measurements : Primary outcome is Ca pills consumed per day , measured by pill counts . Secondary outcomes include IFA pills consumed per day , client knowledge , motivation , social support , and satisfaction , measured at 4 to 10 weeks post-enrolment . Statistical analyses : Unit of r and omization is the healthcare facility ; unit of analysis is individual client . Intent-to-treat analysis will be implemented with multi-level models to account for clustering . Expected public health impact : If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen , developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save re sources . Significance for public health Pre-eclampsia is a leading cause of maternal mortality . Based on clinical evidence of significant reduction in risk of pre-eclampsia , the WHO recommends including calcium ( Ca ) supplementation in antenatal care services in setting s with inadequate dietary Ca intakes . A high daily amount of Ca administered in a complex dosing regimen is recommended to maximize efficacy and bioavailability . Factors such as client adherence , motivation , cost and logistical complexities may undermine effectiveness when implemented in public health programs . This cluster-r and omized trial will compare Ca supplement consumption between higher and lower-dose regimens delivered through antenatal care in Kenya , integrated with iron-folic acid supplementation . If a lower-dose regimen improves adherence , women ’s Ca supplement consumption may be comparable to that achieved under a complex , higher-dose regimen . Evidence gained from this trial will guide public health planning for antenatal calcium supplementation programs to maximize benefits through reducing logistical , cost and adherence barriers Calcium supplementation in mothers with low calcium intake has been of interest recently because of its association with optimal fetal growth and improved pre-eclampsia-related outcomes . While the effects of calcium supplementation have demonstrated benefits in prolonging gestation and subsequently improving birthweight , no specific studies have identified the longitudinal effects of supplementation on fetal growth in utero . Data were analysed in the context of the World Health Organization trial of calcium supplementation in calcium-deficient women . Five hundred and ten healthy , primiparous pregnant Argentinean women were r and omised ( at < 20 weeks gestation ) to either placebo  ( n = 230 ) or  calcium supplements ( 1500 mg calcium/day in 3 divided doses ; n = 231 ) . Growth parameters in utero were assessed with serial ultrasound scans . Birthweight , length , head , abdominal and thigh circumferences were recorded at delivery . No differences were found in fetal biometric measurements recorded at 20 , 24 , 28 , 32 and 36 weeks gestation between fetuses of women who were supplemented with calcium and those who were not . Similarly , neonatal characteristics and anthropometric measurements recorded at delivery were comparable in both groups . We conclude that calcium supplementation of 1500 mg calcium/day in pregnant women with low calcium intake does not appear to impact on fetal somatic or skeletal growth To study the effect of calcium and vitamin D supplementation on the incidence of toxaemia of pregnancy , 200 r and omly selected pregnant women ( supplemented group ) , were put on calcium ( 375 mg/day ) and vitamin D ( 1,200 IU/day ) supplements at 20 - 24 weeks of pregnancy onwards . Another 200 pregnant women constituted the non-supplemented group . At 32 and 36 weeks of pregnancy the systolic and diastolic blood pressure of non-toxemic women was significantly lower in the supplemented group than in the non-supplemented group . However , the incidence of toxaemia in the supplemented group ( 6 % ) was not significantly different from that in the non-supplemented group ( 9 % ) BACKGROUND Pregnancy and lactation in adolescents with habitually low calcium intake may adversely affect maternal bone mass . OBJECTIVE We investigated the effect of calcium plus vitamin D supplementation during pregnancy on bone mass during lactation in Brazilian adolescent mothers with low-calcium diets ( ∼600 mg/d ) . DESIGN Pregnant adolescents ( 14 - 19 y ) r and omly received daily calcium ( 600 mg ) plus vitamin D3 ( 200 IU ) ( n = 30 ) or a placebo ( n = 26 ) from 26 wk of pregnancy ( baseline ) until parturition . The bone mineral content ( BMC ) , bone area ( BA ) , and bone mineral density ( BMD ) at the total body , lumbar spine , and hip ( total and femoral neck ) were evaluated by using dual-energy X-ray absorptiometry at 5 and 20 wk postpartum . Serum hormones and 25-hydroxyvitamin D [ 25(OH)D ] were measured . Group comparisons were adjusted for significant covariates . RESULTS The mean serum 25(OH)D concentration was 59 nmol/L at baseline . In comparison with the placebo , 25(OH)D tended to be 14 - 15 nmol/L higher postpartum in the supplemented group ( P = 0.08 ) . Total body and hip BMC and BMD decreased over time ( P ≤ 0.005 ) in both groups with a group × time interaction at the femoral neck ( P < 0.04 ) . Supplemented mothers had higher lumbar spine BA ( 6.7 % ; P = 0.002 ) and lumbar spine BMC ( 7.9 % , P = 0.08 ) than did mothers who consumed the placebo at 5 wk postpartum . At 20 wk postpartum , differences between groups were more evident , with higher lumbar spine BMC ( 13.9 % ) , lumbar spine BA ( 6.2 % ) , and lumbar spine BMD ( 10.6 % ) in the supplemented group ( P ≤ 0.008 ) . CONCLUSIONS Calcium plus vitamin D supplementation during pregnancy of adolescents with low calcium intake  results in higher lumbar spine bone mass and a reduced rate of femoral neck bone loss during lactation . Additional studies are required to determine whether bone effects are temporary or long-lasting . This trial was registered at clinical trials.gov as NCT01732328 BACKGROUND Growth and bone mineral accretion in Gambian infants are poorer than those in Western population s. The calcium intake of Gambian women is low , typically 300 - 400 mg Ca/d , and they have low breast-milk calcium concentrations , which result in low calcium intakes for their breastfed infants . A low maternal calcium supply in pregnancy may limit fetal mineral accretion and breast-milk calcium concentrations and thereby affect infant growth and bone mineral accretion . OBJECTIVE We investigated the effects of calcium supplementation in Gambian women during pregnancy on breast-milk calcium concentrations and infant birth weight , growth , and bone mineral accretion . DESIGN A r and omized , double-blind , placebo-controlled supplementation study was conducted in 125 Gambian women who received 1500 mg Ca/d ( as calcium carbonate ) or placebo from 20 wk of gestation until delivery . Infant birth weight and gestational age were recorded . Breast milk was collected , and infant anthropometric and bone measurements were performed at 2 , 13 , and  
    Output:
    