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 : Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommo date increased blood flow to the placenta . Failure of this process impedes uterine artery blood flow , and this may be detected by uterine artery Doppler flow studies . However , the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown . OBJECTIVE : We sought to determine the utility of early second‐trimester uterine artery Doppler studies as a predictor of small‐for‐gestational‐age neonates . STUDY DESIGN : Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospect i ve cohort study at 8 institutions across the United States . Participants were seen at 3 study visits during pregnancy and again at delivery . Three indices of uterine artery Doppler flow ( resistance index , pulsatility index , and diastolic notching ) were measured in the right and left uterine arteries between 16 weeks 0 days ' and 22 weeks 6 days ' gestation . Test characteristics for varying thresholds in the prediction of small for gestational age ( defined as birthweight < 5th percentile for gestational age [ Alex and er growth curve ] ) were evaluated . RESULTS : Uterine artery Doppler indices , birthweight , and gestational age at birth were available for 8024 women .  Birthweight < 5th percentile for gestational age occurred in 358 ( 4.5 % ) births . Typical thresholds for the uterine artery Doppler indices were all associated with birthweight < 5th percentile for gestational age ( P < .0001 for each ) , but the positive predictive values for these cutoffs were all < 15 % and areas under receiver operating characteristic curves ranged from 0.50‐0.60 . Across the continuous scales for these measures , the areas under receiver operating characteristic curves ranged from 0.56‐0.62 . Incorporating maternal age , early pregnancy body mass index , race/ethnicity , smoking status prior to pregnancy , chronic hypertension , and pregestational diabetes in the prediction model result ed in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63‐0.66 . CONCLUSION : In this large prospect i ve cohort , early second‐trimester uterine artery Doppler studies were not a clinical ly useful test for predicting small‐for‐gestational‐age babies Although prenatal exposure to water disinfection by-products does not appear to affect the duration of gestation , its impact on fetal growth remains an open question . The authors studied the associations between prenatal exposure to disinfection by-products and fetal growth restriction ( FGR ) and preterm birth in the PELAGIE cohort , a French birth cohort comprising 3,421 pregnant women recruited between 2002 and 2006 . Exposure was assessed by estimating levels of  trihalomethanes ( THMs ) in tap water during pregnancy and maternal water use and by measuring maternal urinary levels of trichloroacetic acid ( TCAA ) during early pregnancy in a nested case-control design that compared 174 FGR cases , 114 preterm births , and 399 controls . Higher uptake of THMs ( especially brominated THMs ) was associated with a higher risk of FGR . Women with TCAA detected in their urine ( > 0.01 mg/L ) had a higher risk of FGR than those with TCAA levels below the detection limit ( adjusted odds ratio = 1.8 , 95 % confidence interval : 0.9 , 3.7 ) and had an odds ratio for preterm birth below 1 ( adjusted odds ratio = 0.8 , 95 % confidence interval : 0.3 , 2.6 ) . Results from this prospect i ve study , the first to use a biomarker of disinfection by-product exposure , suggest that prenatal exposure affects fetal growth , but the causal agent or agents remain to be identified OBJECTIVES Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction . Yet , the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching . The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery . METHODS We report cohort outcomes for a prospect i ve multicenter r and omized management study of fetal growth restriction ( Trial of R and omized Umbilical and Fetal Flow in Europe ( TRUFFLE ) ) performed in 20 European perinatal centers between 2005 and 2010 . Women with a singleton fetus at 26 - 32 weeks of gestation , with abdominal circumference < 10(th ) percentile and umbilical artery Doppler pulsatility index > 95(th ) percentile , were recruited . The main outcome measure was a composite of fetal or neonatal death or severe morbidity : survival to discharge with severe brain injury , bronchopulmonary dysplasia , proven neonatal sepsis or necrotizing enterocolitis . RESULTS Five-hundred and three of 542 eligible women formed the study group . Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g ; 12 ( 2.4 % ) babies died in utero . Gestational age at delivery was 30.7 ± 2.3 weeks , and birth weight was 1013 ± 321 g. Overall , 81 % of deliveries were indicated by fetal condition and 97 % were by Cesarean section . Of 491 liveborn babies , outcomes were available for 490 amongst whom there were 27 ( 5.5 % ) deaths and 118 ( 24 % ) babies suffered severe morbidity . These babies were smaller at birth ( 867 ± 251 g ) and born earlier ( 29.6 ± 2.0 weeks ) . Death and severe morbidity were significantly related to gestational age , both at study entry and delivery and also with the presence of maternal hypertensive morbidity . The median time to delivery was 13 days for women without hypertension , 8 days for those with gestational hypertension , 4 days for pre-eclampsia and 3 days for HELLP syndrome . CONCLUSIONS Fetal outcome in this study was better than expected from contemporary reports : perinatal death was uncommon ( 8 % ) and 70 % survived without severe neonatal morbidity . The intervals to delivery , death and severe morbidity were related to the presence and severity of maternal hypertensive conditions BACKGROUND Disturbed one-carbon ( 1-C ) metabolism in the mother is associated with poor fetal growth but causality of this relationship has not been established . METHODS We studied the association between maternal total homocysteine and offspring birthweight in the Pune Maternal Nutrition Study ( PMNS , Pune , India ) and Parthenon Cohort Study ( Mysore , India ) . We tested for evidence of causality within a Mendelian r and omization framework , using a methylenetetrahydrofolatereductase ( MTHFR ) gene variant rs1801133 ( earlier known as 677C→T ) by instrumental variable and triangulation analysis , separately and using meta- analysis . RESULTS Median ( IQR ) homocysteine concentration and mean ( SD ) birthweight were 8.6 µmol/l ( 6.7,10.8 ) and 2642 g ( 379 ) in the PMNS and 6.0 µmol/l ( 5.1,7.1 ) and 2871 g ( 443 ) in the Parthenon study . Offspring birthweight  was inversely related to maternal homocysteine concentration-PMNS : -22 g/SD [ 95 % confidence interval ( CI ) : ( -50 , 5 ) , adjusted for gestational age and offspring gender ] ; Parthenon : -57 g ( -92 , -21 ) ; meta- analysis : -40 g ( -62 , -17 ) ] . Maternal risk genotype at rs1801133 predicted higher homocysteine concentration [ PMNS : 0.30 SD/allele ( 0.14 , 0.46 ) ; Parthenon : 0.21 SD ( 0.02 , 0.40 ) ; meta- analysis : 0.26 SD ( 0.14 , 0.39 ) ] ; and lower birthweight [ PMNS : -46 g ( -102 , 11 , adjusted for gestational age , offspring gender and rs1801133 genotype ) ; Parthenon : -78 g ( -170 , 15 ) ; meta- analysis : -61 g ( -111 , -10 ) ] . Instrumental variable and triangulation analysis supported a causal association between maternal homocysteine concentration and offspring birthweight . CONCLUSIONS Our findings suggest a causal role for maternal homocysteine ( 1-C metabolism ) in fetal growth . Reducing maternal homocysteine concentrations may improve fetal growth BACKGROUND There is evidence that intrauterine growth restriction , result ing in newborn girls that are small for gestational age ( SGA ) , may be related to the onset of polycystic ovary syndrome ( PCOS ) . Thus , we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age ( AGA ) . METHODS This was a prospect i ve birth cohort study of 384 women born at term between June 1 , 1978 , and May 31 , 1979 , in Ribeirão Preto , Brazil . After exclusion , 165 women effectively participated in this study , of whom 43 were SGA and 122 were AGA . The prevalence of PCOS was analysed . At a mean age of 29 years , the women agreed to follow the study protocol , which included :  anamnesis , physical examination , serum tests [ follicle stimulating hormone , luteinizing hormone , total and free testosterone , dehydroepi and rostenedione sulphate , 17-OH-progesterone , fasting insulin , sex steroid-binding globulin ( SHBG ) and fasting glucose ] and pelvic ultrasound . Data regarding gestational age , birthweight , age at menarche and maternal data were obtained from the files of the cohort . The adjusted relative risk ( RR ) values of the SGA , insulin resistance , body mass index , maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS . RESULTS The prevalence of PCOS was higher in the SGA group than in the AGA group [ adjusted RR = 2.44 , 95 % CI ( 1.39 - 4.28 ) ] . Hyper and rogenism was more prevalent in the SGA women than in the AGA women ( P = 0.011 ) . Circulating SHBG was lower in the SGA women than in the AGA women ( P = 0.041 ) , but fasting insulinemia was similar in both groups . CONCLUSIONS The prevalence of PCOS in SGA women was twice as high as in AGA women in our study population OBJECTIVE To compare the utility of routine third-trimester ultrasound examination at 36 weeks ' gestation with that at 32 weeks in detecting  fetal growth restriction ( FGR ) . METHODS This was an open-label parallel r and omized trial ( ROUTE study ) conducted at a single general hospital serving a geographically well-defined catchment area in Barcelona , Spain , between May 2011 and April 2014 . Women with no adverse medical or obstetric history and a singleton pregnancy without fetal abnormalities at routine second-trimester scan were assigned r and omly to undergo a scan at 32 weeks ' gestation ( n = 1272 ) or at 36 weeks ' gestation ( n = 1314 ) . Primary outcome measures were detection rates of FGR ( customized birth weight < 10(th ) centile ) and severe FGR ( customized birth weight < 3(rd ) centile ) . RESULTS There were no significant differences in perinatal outcome between those who underwent a scan at 32 weeks ' gestation and those who underwent a scan at 36 weeks ' gestation . Severe FGR at birth was associated significantly with emergency Cesarean delivery for fetal distress ( odds ratio ( OR ) , 3.4 ( 95 % CI , 1.8 - 6.7 ) ) , neonatal admission ( OR , 2.23 ( 95 % CI , 1.23 - 4.05 ) ) , hypoglycemia ( OR , 9.5 ( 95 % CI , 1.8 - 49.8 ) ) and hyperbilirubinemia ( OR , 9.0 ( 95 % CI , 4.6 - 17.6 ) ) . Despite similar false-positive rates ( FPRs ) ( 6.4 % vs 8.2 % ) , FGR detection rates were superior at 36 vs 32 weeks ' gestation ( sensitivity , 38.8 % vs 22.5 % ; P = 0.006 ) , with positive and negative likelihood ratios of 6.1 vs 2.7 and 0.65 vs 0.84 , respectively . In cases of severe FGR , FPRs for both scans were also similar ( 8.5 % vs 8.7 % ) , but detection rates were superior at 36 vs 32 weeks ' gestation ( 61.4 % vs 32 
    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 : Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommo date increased blood flow to the placenta . Failure of this process impedes uterine artery blood flow , and this may be detected by uterine artery Doppler flow studies . However , the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown . OBJECTIVE : We sought to determine the utility of early second‐trimester uterine artery Doppler studies as a predictor of small‐for‐gestational‐age neonates . STUDY DESIGN : Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospect i ve cohort study at 8 institutions across the United States . Participants were seen at 3 study visits during pregnancy and again at delivery . Three indices of uterine artery Doppler flow ( resistance index , pulsatility index , and diastolic notching ) were measured in the right and left uterine arteries between 16 weeks 0 days ' and 22 weeks 6 days ' gestation . Test characteristics for varying thresholds in the prediction of small for gestational age ( defined as birthweight < 5th percentile for gestational age [ Alex and er growth curve ] ) were evaluated . RESULTS : Uterine artery Doppler indices , birthweight , and gestational age at birth were available for 8024 women .  Birthweight < 5th percentile for gestational age occurred in 358 ( 4.5 % ) births . Typical thresholds for the uterine artery Doppler indices were all associated with birthweight < 5th percentile for gestational age ( P < .0001 for each ) , but the positive predictive values for these cutoffs were all < 15 % and areas under receiver operating characteristic curves ranged from 0.50‐0.60 . Across the continuous scales for these measures , the areas under receiver operating characteristic curves ranged from 0.56‐0.62 . Incorporating maternal age , early pregnancy body mass index , race/ethnicity , smoking status prior to pregnancy , chronic hypertension , and pregestational diabetes in the prediction model result ed in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63‐0.66 . CONCLUSION : In this large prospect i ve cohort , early second‐trimester uterine artery Doppler studies were not a clinical ly useful test for predicting small‐for‐gestational‐age babies Although prenatal exposure to water disinfection by-products does not appear to affect the duration of gestation , its impact on fetal growth remains an open question . The authors studied the associations between prenatal exposure to disinfection by-products and fetal growth restriction ( FGR ) and preterm birth in the PELAGIE cohort , a French birth cohort comprising 3,421 pregnant women recruited between 2002 and 2006 . Exposure was assessed by estimating levels of  trihalomethanes ( THMs ) in tap water during pregnancy and maternal water use and by measuring maternal urinary levels of trichloroacetic acid ( TCAA ) during early pregnancy in a nested case-control design that compared 174 FGR cases , 114 preterm births , and 399 controls . Higher uptake of THMs ( especially brominated THMs ) was associated with a higher risk of FGR . Women with TCAA detected in their urine ( > 0.01 mg/L ) had a higher risk of FGR than those with TCAA levels below the detection limit ( adjusted odds ratio = 1.8 , 95 % confidence interval : 0.9 , 3.7 ) and had an odds ratio for preterm birth below 1 ( adjusted odds ratio = 0.8 , 95 % confidence interval : 0.3 , 2.6 ) . Results from this prospect i ve study , the first to use a biomarker of disinfection by-product exposure , suggest that prenatal exposure affects fetal growth , but the causal agent or agents remain to be identified OBJECTIVES Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction . Yet , the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching . The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery . METHODS We report cohort outcomes for a prospect i ve multicenter r and omized management study of fetal growth restriction ( Trial of R and omized Umbilical and Fetal Flow in Europe ( TRUFFLE ) ) performed in 20 European perinatal centers between 2005 and 2010 . Women with a singleton fetus at 26 - 32 weeks of gestation , with abdominal circumference < 10(th ) percentile and umbilical artery Doppler pulsatility index > 95(th ) percentile , were recruited . The main outcome measure was a composite of fetal or neonatal death or severe morbidity : survival to discharge with severe brain injury , bronchopulmonary dysplasia , proven neonatal sepsis or necrotizing enterocolitis . RESULTS Five-hundred and three of 542 eligible women formed the study group . Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g ; 12 ( 2.4 % ) babies died in utero . Gestational age at delivery was 30.7 ± 2.3 weeks , and birth weight was 1013 ± 321 g. Overall , 81 % of deliveries were indicated by fetal condition and 97 % were by Cesarean section . Of 491 liveborn babies , outcomes were available for 490 amongst whom there were 27 ( 5.5 % ) deaths and 118 ( 24 % ) babies suffered severe morbidity . These babies were smaller at birth ( 867 ± 251 g ) and born earlier ( 29.6 ± 2.0 weeks ) . Death and severe morbidity were significantly related to gestational age , both at study entry and delivery and also with the presence of maternal hypertensive morbidity . The median time to delivery was 13 days for women without hypertension , 8 days for those with gestational hypertension , 4 days for pre-eclampsia and 3 days for HELLP syndrome . CONCLUSIONS Fetal outcome in this study was better than expected from contemporary reports : perinatal death was uncommon ( 8 % ) and 70 % survived without severe neonatal morbidity . The intervals to delivery , death and severe morbidity were related to the presence and severity of maternal hypertensive conditions BACKGROUND Disturbed one-carbon ( 1-C ) metabolism in the mother is associated with poor fetal growth but causality of this relationship has not been established . METHODS We studied the association between maternal total homocysteine and offspring birthweight in the Pune Maternal Nutrition Study ( PMNS , Pune , India ) and Parthenon Cohort Study ( Mysore , India ) . We tested for evidence of causality within a Mendelian r and omization framework , using a methylenetetrahydrofolatereductase ( MTHFR ) gene variant rs1801133 ( earlier known as 677C→T ) by instrumental variable and triangulation analysis , separately and using meta- analysis . RESULTS Median ( IQR ) homocysteine concentration and mean ( SD ) birthweight were 8.6 µmol/l ( 6.7,10.8 ) and 2642 g ( 379 ) in the PMNS and 6.0 µmol/l ( 5.1,7.1 ) and 2871 g ( 443 ) in the Parthenon study . Offspring birthweight  was inversely related to maternal homocysteine concentration-PMNS : -22 g/SD [ 95 % confidence interval ( CI ) : ( -50 , 5 ) , adjusted for gestational age and offspring gender ] ; Parthenon : -57 g ( -92 , -21 ) ; meta- analysis : -40 g ( -62 , -17 ) ] . Maternal risk genotype at rs1801133 predicted higher homocysteine concentration [ PMNS : 0.30 SD/allele ( 0.14 , 0.46 ) ; Parthenon : 0.21 SD ( 0.02 , 0.40 ) ; meta- analysis : 0.26 SD ( 0.14 , 0.39 ) ] ; and lower birthweight [ PMNS : -46 g ( -102 , 11 , adjusted for gestational age , offspring gender and rs1801133 genotype ) ; Parthenon : -78 g ( -170 , 15 ) ; meta- analysis : -61 g ( -111 , -10 ) ] . Instrumental variable and triangulation analysis supported a causal association between maternal homocysteine concentration and offspring birthweight . CONCLUSIONS Our findings suggest a causal role for maternal homocysteine ( 1-C metabolism ) in fetal growth . Reducing maternal homocysteine concentrations may improve fetal growth BACKGROUND There is evidence that intrauterine growth restriction , result ing in newborn girls that are small for gestational age ( SGA ) , may be related to the onset of polycystic ovary syndrome ( PCOS ) . Thus , we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age ( AGA ) . METHODS This was a prospect i ve birth cohort study of 384 women born at term between June 1 , 1978 , and May 31 , 1979 , in Ribeirão Preto , Brazil . After exclusion , 165 women effectively participated in this study , of whom 43 were SGA and 122 were AGA . The prevalence of PCOS was analysed . At a mean age of 29 years , the women agreed to follow the study protocol , which included :  anamnesis , physical examination , serum tests [ follicle stimulating hormone , luteinizing hormone , total and free testosterone , dehydroepi and rostenedione sulphate , 17-OH-progesterone , fasting insulin , sex steroid-binding globulin ( SHBG ) and fasting glucose ] and pelvic ultrasound . Data regarding gestational age , birthweight , age at menarche and maternal data were obtained from the files of the cohort . The adjusted relative risk ( RR ) values of the SGA , insulin resistance , body mass index , maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS . RESULTS The prevalence of PCOS was higher in the SGA group than in the AGA group [ adjusted RR = 2.44 , 95 % CI ( 1.39 - 4.28 ) ] . Hyper and rogenism was more prevalent in the SGA women than in the AGA women ( P = 0.011 ) . Circulating SHBG was lower in the SGA women than in the AGA women ( P = 0.041 ) , but fasting insulinemia was similar in both groups . CONCLUSIONS The prevalence of PCOS in SGA women was twice as high as in AGA women in our study population OBJECTIVE To compare the utility of routine third-trimester ultrasound examination at 36 weeks ' gestation with that at 32 weeks in detecting  fetal growth restriction ( FGR ) . METHODS This was an open-label parallel r and omized trial ( ROUTE study ) conducted at a single general hospital serving a geographically well-defined catchment area in Barcelona , Spain , between May 2011 and April 2014 . Women with no adverse medical or obstetric history and a singleton pregnancy without fetal abnormalities at routine second-trimester scan were assigned r and omly to undergo a scan at 32 weeks ' gestation ( n = 1272 ) or at 36 weeks ' gestation ( n = 1314 ) . Primary outcome measures were detection rates of FGR ( customized birth weight < 10(th ) centile ) and severe FGR ( customized birth weight < 3(rd ) centile ) . RESULTS There were no significant differences in perinatal outcome between those who underwent a scan at 32 weeks ' gestation and those who underwent a scan at 36 weeks ' gestation . Severe FGR at birth was associated significantly with emergency Cesarean delivery for fetal distress ( odds ratio ( OR ) , 3.4 ( 95 % CI , 1.8 - 6.7 ) ) , neonatal admission ( OR , 2.23 ( 95 % CI , 1.23 - 4.05 ) ) , hypoglycemia ( OR , 9.5 ( 95 % CI , 1.8 - 49.8 ) ) and hyperbilirubinemia ( OR , 9.0 ( 95 % CI , 4.6 - 17.6 ) ) . Despite similar false-positive rates ( FPRs ) ( 6.4 % vs 8.2 % ) , FGR detection rates were superior at 36 vs 32 weeks ' gestation ( sensitivity , 38.8 % vs 22.5 % ; P = 0.006 ) , with positive and negative likelihood ratios of 6.1 vs 2.7 and 0.65 vs 0.84 , respectively . In cases of severe FGR , FPRs for both scans were also similar ( 8.5 % vs 8.7 % ) , but detection rates were superior at 36 vs 32 weeks ' gestation ( 61.4 % vs 32 
    Output:
    