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 : The long-term impact of early malnutrition on human capital outcomes remains unclear , and existing evidence has come largely from observational studies . Objective : We compared the impact of a nutritional supplement given during pregnancy or lactation in rural Gambia on educational performance and cognitive ability in offspring at their maturity . Design : This study was a follow-up of a r and omized trial of prenatal high protein and energy supplementation conducted between 1989 and 1994 . Subjects were 16–22 y of age at follow-up , and information was collected on schooling achievement and cognitive ability by using the Raven 's progressive matrices test , Mill Hill vocabulary test , and forward and backward digit-span tests . Results : A total of 1459 individuals were traced and interviewed and represented 71 % of the original cohort and 81 % of the surviving cohort . There was no difference in cognitive ability or educational attainment between treatment groups by using any of the methods of assessment . Conclusion : We have shown little evidence to support a long-term effect of prenatal protein-energy supplementation compared with supplementation during lactation on cognitive development  in rural Gambians . This trial was registered at http://www.controlled-trials.com as IS RCT N72582014 CONTEXT The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother 's behavior or her interaction with the infant . OBJECTIVE To assess whether prolonged and exclusive breastfeeding improves children 's cognitive ability at age 6.5 years . DESIGN Cluster-r and omized trial , with enrollment from June 17 , 1996 , to December 31 , 1997 , and follow-up from December 21 , 2002 , to April 27 , 2005 . SETTING Thirty-one Belarussian maternity hospitals and their affiliated polyclinics . PARTICIPANTS A total of 17,046 healthy breastfeeding infants were enrolled , of whom 13,889 ( 81.5 % ) were followed up at age 6.5 years . INTERVENTION Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF . MAIN OUTCOME MEASURES Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence , and teacher evaluations of academic performance in reading , writing , mathematics , and other subjects . RESULTS The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months ( 43.3 % for the experimental group vs 6.4 % for the control group ; P < .001 ) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months . The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures , with cluster-adjusted mean differences ( 95 % confidence intervals ) of + 7.5 ( + 0.8 to + 14.3 ) for verbal IQ , + 2.9 ( -3.3 to + 9.1 ) for performance IQ , and + 5.9 ( -1.0 to + 12.8 ) for full-scale IQ . Teachers ' academic ratings were significantly higher in the experimental group for both reading and writing . CONCLUSION These results , based on the largest r and omized trial ever conducted in the area of human lactation , provide strong evidence that prolonged and exclusive breastfeeding improves children 's cognitive development . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N37687716 Background Research directed to optimizing maternal nutrition commencing prior to conception remains very limited , despite suggestive evidence of its importance in addition to ensuring an optimal nutrition environment in the periconceptional period and throughout the first trimester of pregnancy . Methods / Study design This is an individually r and omized controlled trial of the impact on birth length ( primary outcome ) of the time at which a maternal nutrition intervention is commenced : Arm 1 : ≥ 3 mo preconception vs. Arm 2 : 12 - 14 wk gestation vs. Arm 3 : none.192 ( derived from 480 ) r and omized mothers and living offspring in each arm in each of four research sites ( Guatemala , India , Pakistan , Democratic Republic of the Congo ) . The intervention is a daily 20 g lipid-based ( 118 kcal ) multi-micronutient ( MMN ) supplement .  Women r and omized to receive this intervention with body mass index ( BMI ) < 20 or whose gestational weight gain is low will receive an additional 300 kcal/d as a balanced energy-protein supplement . Research ers will visit homes biweekly to deliver intervention and monitor compliance , pregnancy status and morbidity ; ensure prenatal and delivery care ; and promote breast feeding . The primary outcome is birth length . Secondary outcomes include : fetal length at 12 and 34 wk ; incidence of low birth weight ( LBW ) ; neonatal/infant anthropometry 0 - 6 mo of age ; infectious disease morbidity ; maternal , fetal , newborn , and infant epigenetics ; maternal and infant nutritional status ; maternal and infant microbiome ; gut inflammatory biomarkers and bioactive and nutritive compounds in breast milk . The primary analysis will compare birth Length-for-Age Z-score ( LAZ ) among trial arms ( independently for each site , estimated effect size : 0.35 ) . Additional statistical analyses will examine the secondary outcomes and a pooled analysis of data from all sites . Discussion Positive results of this trial will support a paradigm shift in attention to nutrition of all females of child-bearing age . Trial registration Clinical Trials.gov NCT01883193 Background Previous studies suggest that over-nutrition in early infancy may programme long-term susceptibility to insulin resistance . Objective To assess the association of breast milk and quantity of infant formula and cows ' milk intake during infancy with insulin resistance measures in early adulthood . Design Long-term follow-up of the Barry Caerphilly Growth cohort , into which mothers and their offspring had originally been r and omly assigned , between 1972–1974 , to receive milk supplementation or not .  Participants were the offspring , aged 23–27 years at follow-up ( n = 679 ) .  Breastfeeding and formula/cows ' milk intake was recorded prospect ively by nurses . The main outcomes were insulin sensitivity ( ISI0 ) and insulin secretion ( CIR30 ) . Results 573 ( 84 % ) individuals had valid glucose and insulin results and complete covariate information . There was little evidence of associations of breastfeeding versus any formula/cows ' milk feeding or of increasing quartiles of formula/cows ' milk consumption during infancy ( <3 months ) with any outcome measure in young adulthood . In fully adjusted models , the differences in outcomes between breastfeeding versus formula/cows ' milk feeding at 3 months were : fasting glucose ( −0.07 mmol/l ; 95 % CI : −0.19 , 0.05 ) ; fasting insulin ( 8.0 % ; −8.7 , 27.6 ) ; ISI0 ( −6.1 % ; −11.3 , 12.1 ) and CIR30 ( 3.8 % ; −19.0 , 32.8 ) . There was also little evidence that increasing intakes of formula/cows ' milk at 3 months were associated with fasting glucose ( increase per quartile of formula/cows ' milk intake = 0.00 mmol/l ; −0.03 , 0.03 ) ; fasting insulin ( 0.8 % ; −3.2 , 5.1 ) ; ISI 0 ( −0.9 % ; −5.1 , 3.5 ) and CIR30 ( −2.6 % ; −8.4 , 3.6 ) . Conclusions We found no evidence that increasing consumption of formula/cows ' milk in early infancy was associated with insulin resistance in young adulthood Background Nutritionists advise pregnant women to eat fish to obtain adequate docosahexaenoic acid ( DHA ) , an essential nutrient important for optimal brain development . However , concern exists that this advice will lead to excess intake of methylmercury , a developmental neurotoxicant . Objective Conduct a pilot intervention to increase consumption of high-DHA , low-mercury fish in pregnancy . Methods In April-October 2010 we recruited 61 women in the greater Boston , MA area at 12–22 weeks gestation who consumed < = 2 fish servings/month , and obtained outcome data from 55 . We r and omized participants to 3 arms : Advice to consume low-mercury/high-DHA fish ( n=18 ) ; Advice + grocery store gift cards ( GC ) to purchase fish ( n=17 ) ; or Control messages ( n=20 ) . At baseline and 12-week follow-up we estimated intake of fish , DHA and mercury using a 1-month fish intake food frequency question naire , and measured plasma DHA and blood and hair total mercury . Results Baseline characteristics and mean ( range ) intakes of fish [ 21 ( 0–125 ) g/day ] and DHA from fish [ 91 ( 0–554 ) mg/d ] were similar in all 3 arms . From baseline to follow-up , intake of fish [ Advice : 12 g/day ( 95 % CI : -5 , 29 ) , Advice+GC : 22 g/day ( 5 , 39 ) ] and DHA [ Advice : 70 mg/d ( 3 , 137 ) , Advice+GC : 161 mg/d ( 93 , 229 ) ] increased in both intervention groups , compared with controls . At follow-up , no control women consumed > = 200mg/d of DHA from fish , compared with 33 % in the Advice arm ( p=0.005 ) and 53 % in the Advice+GC arm ( p=0.0002 ) . We did not detect any differences in mercury intake or in biomarker levels of mercury and DHA between groups . Conclusions An educational intervention  increased consumption of fish and DHA but not mercury . Future studies are needed to determine intervention effects on pregnancy and childhood health outcomes .Trial registration Registered on clinical trials.gov as Background The in utero environment is known to affect fetal development however many of the mechanisms by which this occurs remain unknown . The aim of this study was to examine the association between maternal dietary macronutrient intake and lifestyle throughout pregnancy and neonatal weight and adiposity . Methods This was an analysis of 542 mother and infant pairs from the ROLO study ( R and omised cOntrol trial of LOw glycaemic index diet versus no dietary intervention to prevent recurrence of fetal macrosomia ) . Food diaries as well as food frequency and lifestyle and physical activity question naires were completed during pregnancy . Maternal anthropometry was measured throughout pregnancy and neonatal anthropometry was measured at birth . Results Multiple linear regression analysis revealed the main maternal factor associated with increased birth weight was greater gestational weight gain R2adj23.3 % ( F = 11.547 , p < 0.001 ) . The main maternal factor associated with increased birth length was non-smoking status R2adj27.8 % ( F = 6.193 , p < 0.001 ) . Neonatal central adiposity ( determined using waist : length ratio ) was negatively associated with maternal age , and positively associated with the following parameters : smoking status , maternal pre-pregnancy arm circumference , percentage energy from saturated fat in late pregnancy , postpr and ial glucose at 28 weeks gestation and membership of the control group with a positive trend towards association with trimester 2 glycaemic load R2adj 38.1 % ( F = 8.000 , p < 0.001 ) . Conclusions Several maternal diet and lifestyle factors were associated with neonatal anthropometry .  Low glycaemic index dietary intervention in pregnancy was found to have a beneficial effect on neonatal central adiposity . Additionally , central adiposity was positively associated with maternal dietary fat intake and postpr and ial glucose highlighting the important role of healthy diet in pregnancy in promoting normal neonatal adiposity . Trial registration Current Controlled Trials IS RCT N54392969 Balanced glucose metabolism ensures optimal fetal growth with long-term health implication s conferred on both mother and child . We examined whether supplementation of probiotics with dietary counselling affects glucose metabolism in normoglycaemic pregnant women . At the first trimester of pregnancy 256 women were r and omised to receive nutrition counselling to modify dietary intake according to current recommendations or as controls ; the dietary intervention group was further r and omised to receive probiotics ( Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 ; diet/probiotics ) or placebo ( diet/placebo ) in a double-blind manner , whilst the control group received placebo ( control/placebo ) . Blood glucose concentrations were lowest in the diet/probiotics group during pregnancy ( baseline-adjusted means 4.45 , 4.60 and 4.56 mmol/l in diet/probiotics , diet/placebo and control/placebo , respectively ; P = 0.025 ) and over the 12 months ' postpartum period ( baseline-adjusted means 4.87 
    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 : The long-term impact of early malnutrition on human capital outcomes remains unclear , and existing evidence has come largely from observational studies . Objective : We compared the impact of a nutritional supplement given during pregnancy or lactation in rural Gambia on educational performance and cognitive ability in offspring at their maturity . Design : This study was a follow-up of a r and omized trial of prenatal high protein and energy supplementation conducted between 1989 and 1994 . Subjects were 16–22 y of age at follow-up , and information was collected on schooling achievement and cognitive ability by using the Raven 's progressive matrices test , Mill Hill vocabulary test , and forward and backward digit-span tests . Results : A total of 1459 individuals were traced and interviewed and represented 71 % of the original cohort and 81 % of the surviving cohort . There was no difference in cognitive ability or educational attainment between treatment groups by using any of the methods of assessment . Conclusion : We have shown little evidence to support a long-term effect of prenatal protein-energy supplementation compared with supplementation during lactation on cognitive development  in rural Gambians . This trial was registered at http://www.controlled-trials.com as IS RCT N72582014 CONTEXT The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother 's behavior or her interaction with the infant . OBJECTIVE To assess whether prolonged and exclusive breastfeeding improves children 's cognitive ability at age 6.5 years . DESIGN Cluster-r and omized trial , with enrollment from June 17 , 1996 , to December 31 , 1997 , and follow-up from December 21 , 2002 , to April 27 , 2005 . SETTING Thirty-one Belarussian maternity hospitals and their affiliated polyclinics . PARTICIPANTS A total of 17,046 healthy breastfeeding infants were enrolled , of whom 13,889 ( 81.5 % ) were followed up at age 6.5 years . INTERVENTION Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF . MAIN OUTCOME MEASURES Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence , and teacher evaluations of academic performance in reading , writing , mathematics , and other subjects . RESULTS The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months ( 43.3 % for the experimental group vs 6.4 % for the control group ; P < .001 ) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months . The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures , with cluster-adjusted mean differences ( 95 % confidence intervals ) of + 7.5 ( + 0.8 to + 14.3 ) for verbal IQ , + 2.9 ( -3.3 to + 9.1 ) for performance IQ , and + 5.9 ( -1.0 to + 12.8 ) for full-scale IQ . Teachers ' academic ratings were significantly higher in the experimental group for both reading and writing . CONCLUSION These results , based on the largest r and omized trial ever conducted in the area of human lactation , provide strong evidence that prolonged and exclusive breastfeeding improves children 's cognitive development . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N37687716 Background Research directed to optimizing maternal nutrition commencing prior to conception remains very limited , despite suggestive evidence of its importance in addition to ensuring an optimal nutrition environment in the periconceptional period and throughout the first trimester of pregnancy . Methods / Study design This is an individually r and omized controlled trial of the impact on birth length ( primary outcome ) of the time at which a maternal nutrition intervention is commenced : Arm 1 : ≥ 3 mo preconception vs. Arm 2 : 12 - 14 wk gestation vs. Arm 3 : none.192 ( derived from 480 ) r and omized mothers and living offspring in each arm in each of four research sites ( Guatemala , India , Pakistan , Democratic Republic of the Congo ) . The intervention is a daily 20 g lipid-based ( 118 kcal ) multi-micronutient ( MMN ) supplement .  Women r and omized to receive this intervention with body mass index ( BMI ) < 20 or whose gestational weight gain is low will receive an additional 300 kcal/d as a balanced energy-protein supplement . Research ers will visit homes biweekly to deliver intervention and monitor compliance , pregnancy status and morbidity ; ensure prenatal and delivery care ; and promote breast feeding . The primary outcome is birth length . Secondary outcomes include : fetal length at 12 and 34 wk ; incidence of low birth weight ( LBW ) ; neonatal/infant anthropometry 0 - 6 mo of age ; infectious disease morbidity ; maternal , fetal , newborn , and infant epigenetics ; maternal and infant nutritional status ; maternal and infant microbiome ; gut inflammatory biomarkers and bioactive and nutritive compounds in breast milk . The primary analysis will compare birth Length-for-Age Z-score ( LAZ ) among trial arms ( independently for each site , estimated effect size : 0.35 ) . Additional statistical analyses will examine the secondary outcomes and a pooled analysis of data from all sites . Discussion Positive results of this trial will support a paradigm shift in attention to nutrition of all females of child-bearing age . Trial registration Clinical Trials.gov NCT01883193 Background Previous studies suggest that over-nutrition in early infancy may programme long-term susceptibility to insulin resistance . Objective To assess the association of breast milk and quantity of infant formula and cows ' milk intake during infancy with insulin resistance measures in early adulthood . Design Long-term follow-up of the Barry Caerphilly Growth cohort , into which mothers and their offspring had originally been r and omly assigned , between 1972–1974 , to receive milk supplementation or not .  Participants were the offspring , aged 23–27 years at follow-up ( n = 679 ) .  Breastfeeding and formula/cows ' milk intake was recorded prospect ively by nurses . The main outcomes were insulin sensitivity ( ISI0 ) and insulin secretion ( CIR30 ) . Results 573 ( 84 % ) individuals had valid glucose and insulin results and complete covariate information . There was little evidence of associations of breastfeeding versus any formula/cows ' milk feeding or of increasing quartiles of formula/cows ' milk consumption during infancy ( <3 months ) with any outcome measure in young adulthood . In fully adjusted models , the differences in outcomes between breastfeeding versus formula/cows ' milk feeding at 3 months were : fasting glucose ( −0.07 mmol/l ; 95 % CI : −0.19 , 0.05 ) ; fasting insulin ( 8.0 % ; −8.7 , 27.6 ) ; ISI0 ( −6.1 % ; −11.3 , 12.1 ) and CIR30 ( 3.8 % ; −19.0 , 32.8 ) . There was also little evidence that increasing intakes of formula/cows ' milk at 3 months were associated with fasting glucose ( increase per quartile of formula/cows ' milk intake = 0.00 mmol/l ; −0.03 , 0.03 ) ; fasting insulin ( 0.8 % ; −3.2 , 5.1 ) ; ISI 0 ( −0.9 % ; −5.1 , 3.5 ) and CIR30 ( −2.6 % ; −8.4 , 3.6 ) . Conclusions We found no evidence that increasing consumption of formula/cows ' milk in early infancy was associated with insulin resistance in young adulthood Background Nutritionists advise pregnant women to eat fish to obtain adequate docosahexaenoic acid ( DHA ) , an essential nutrient important for optimal brain development . However , concern exists that this advice will lead to excess intake of methylmercury , a developmental neurotoxicant . Objective Conduct a pilot intervention to increase consumption of high-DHA , low-mercury fish in pregnancy . Methods In April-October 2010 we recruited 61 women in the greater Boston , MA area at 12–22 weeks gestation who consumed < = 2 fish servings/month , and obtained outcome data from 55 . We r and omized participants to 3 arms : Advice to consume low-mercury/high-DHA fish ( n=18 ) ; Advice + grocery store gift cards ( GC ) to purchase fish ( n=17 ) ; or Control messages ( n=20 ) . At baseline and 12-week follow-up we estimated intake of fish , DHA and mercury using a 1-month fish intake food frequency question naire , and measured plasma DHA and blood and hair total mercury . Results Baseline characteristics and mean ( range ) intakes of fish [ 21 ( 0–125 ) g/day ] and DHA from fish [ 91 ( 0–554 ) mg/d ] were similar in all 3 arms . From baseline to follow-up , intake of fish [ Advice : 12 g/day ( 95 % CI : -5 , 29 ) , Advice+GC : 22 g/day ( 5 , 39 ) ] and DHA [ Advice : 70 mg/d ( 3 , 137 ) , Advice+GC : 161 mg/d ( 93 , 229 ) ] increased in both intervention groups , compared with controls . At follow-up , no control women consumed > = 200mg/d of DHA from fish , compared with 33 % in the Advice arm ( p=0.005 ) and 53 % in the Advice+GC arm ( p=0.0002 ) . We did not detect any differences in mercury intake or in biomarker levels of mercury and DHA between groups . Conclusions An educational intervention  increased consumption of fish and DHA but not mercury . Future studies are needed to determine intervention effects on pregnancy and childhood health outcomes .Trial registration Registered on clinical trials.gov as Background The in utero environment is known to affect fetal development however many of the mechanisms by which this occurs remain unknown . The aim of this study was to examine the association between maternal dietary macronutrient intake and lifestyle throughout pregnancy and neonatal weight and adiposity . Methods This was an analysis of 542 mother and infant pairs from the ROLO study ( R and omised cOntrol trial of LOw glycaemic index diet versus no dietary intervention to prevent recurrence of fetal macrosomia ) . Food diaries as well as food frequency and lifestyle and physical activity question naires were completed during pregnancy . Maternal anthropometry was measured throughout pregnancy and neonatal anthropometry was measured at birth . Results Multiple linear regression analysis revealed the main maternal factor associated with increased birth weight was greater gestational weight gain R2adj23.3 % ( F = 11.547 , p < 0.001 ) . The main maternal factor associated with increased birth length was non-smoking status R2adj27.8 % ( F = 6.193 , p < 0.001 ) . Neonatal central adiposity ( determined using waist : length ratio ) was negatively associated with maternal age , and positively associated with the following parameters : smoking status , maternal pre-pregnancy arm circumference , percentage energy from saturated fat in late pregnancy , postpr and ial glucose at 28 weeks gestation and membership of the control group with a positive trend towards association with trimester 2 glycaemic load R2adj 38.1 % ( F = 8.000 , p < 0.001 ) . Conclusions Several maternal diet and lifestyle factors were associated with neonatal anthropometry .  Low glycaemic index dietary intervention in pregnancy was found to have a beneficial effect on neonatal central adiposity . Additionally , central adiposity was positively associated with maternal dietary fat intake and postpr and ial glucose highlighting the important role of healthy diet in pregnancy in promoting normal neonatal adiposity . Trial registration Current Controlled Trials IS RCT N54392969 Balanced glucose metabolism ensures optimal fetal growth with long-term health implication s conferred on both mother and child . We examined whether supplementation of probiotics with dietary counselling affects glucose metabolism in normoglycaemic pregnant women . At the first trimester of pregnancy 256 women were r and omised to receive nutrition counselling to modify dietary intake according to current recommendations or as controls ; the dietary intervention group was further r and omised to receive probiotics ( Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 ; diet/probiotics ) or placebo ( diet/placebo ) in a double-blind manner , whilst the control group received placebo ( control/placebo ) . Blood glucose concentrations were lowest in the diet/probiotics group during pregnancy ( baseline-adjusted means 4.45 , 4.60 and 4.56 mmol/l in diet/probiotics , diet/placebo and control/placebo , respectively ; P = 0.025 ) and over the 12 months ' postpartum period ( baseline-adjusted means 4.87 
    Output:
    