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: Abstract Objective : To study the association between coffee consumption during pregnancy and the risk of stillbirth and infant death in the first year of life . Design : Prospect i ve follow up study . Setting : Aarhus University Hospital , Denmark , 1989 - 96 . Participants : 18 478 singleton pregnancies in women with valid information about coffee consumption during pregnancy . Main outcome measures : Stillbirth ( delivery of a dead fetus at ≥28 weeks ' gestation ) and infant death ( death of a liveborn infant during the first year of life ) . Results : Pregnant women who drank eight or more cups of coffee per day during pregnancy had an increased risk of stillbirth compared with women who did not drink coffee ( odds ratio=3.0 , 95 % confidence interval 1.5 to 5.9 ) . After adjustment for smoking habits and alcohol intake during pregnancy , the relative risk of stillbirth decreased slightly . Adjustment for parity , maternal age , marital status , years of education , occupational status , and body mass index did not substantially change the estimates of association . There was no significant association between coffee consumption and death in the first year of life after adjustment for smoking habits during pregnancy . Conclusion : Drinking coffee during pregnancy is associated with an increased risk of stillbirth but not with infant death . What is already known on this topic Results from studies in monkeys suggest that high daily doses of caffeine in pregnancy increase the risk of stillbirth , but evidence from studies in humans has been lacking What this study adds Pregnant women who drank eight or more cups of coffee a day had more than twice the risk of stillbirth compared with women who did not drink coffee during BACKGROUND In a prospect i ve study the effect of the behavioral risk factors of both partners on fecundability  was studied . METHODS Information was collected on smoking habits , alcohol consumption , and caffeine intake ( e.g. coffee , tea , and cola consumption ) by interviewing 259 female nonmedical hospital workers , i.e. , clerical staff , cleaners , kitchen and restaurant workers , and their partners , who were planning a pregnancy . The occurrence of pregnancy was tested prospect ively during the 12 months after enrollment . RESULTS Among the participants as well as among their partners , smoking a moderate number of cigarettes ( 1 - 10/day ) was associated with higher fecundability ( i.e. , the probability of becoming pregnant each month ) than among those not smoking ( participant : OR = 1.4 ( 95 % CI , 0.9 - 2.2 ) ; partner : OR = 2.1 ( 95 % CI , 1.2 - 3.5 ) ) . The level of alcohol consumption in the female partner was not related to fecundability . However , in the male partner , there was a positive influence for drinking more than 10 alcoholic drinks per week compared with that observed for those drinking less than 5 ( OR = 1.6 ; 95 % CI , 1.0 - 2.4 ) . Participants with a moderate caffeine intake ( 400 - 700 mg/day ) showed a higher fecundability than those with a lower intake level ( ORadjusted = 2.1 ( 95 % CI , 1.2 - 3.7 ) ) . Heavy caffeine intake ( > 700 mg/day ) among partners was negatively related to fecundability when compared with the lowest intake level ( ORadjusted = 0.6 ( 95 % CI , 0.3 - 0.97 ) ) . CONCLUSIONS This study does not support the hypothesis that moderate cigarette smoking , caffeine intake , and alcohol consumption have an adverse influence on fecundability STUDY QUESTION Is caffeine and caffeinated beverage consumption associated with the risk of spontaneous abortion ( SAB )  ? SUMMARY ANSWER While preconceptional caffeine consumption was not material ly associated with an increased risk of SAB , consumption during early pregnancy was associated with a small increased risk of SAB , although the relation was not linear . WHAT IS KNOWN ALREADY Caffeine has been hypothesized as a risk factor for SAB since the 1980s ; however , results from previous studies have been conflicting . STUDY DESIGN , SIZE , DURATION This prospect i ve cohort study included 5132 Danish women planning pregnancy and enrolled from 2007 to 2010 . PARTICIPANTS / MATERIAL S , SETTING , METHODS Participants were women who conceived after entry into the Snart-Gravid cohort and who were aged 18 - 40 , in a stable relationship with a male partner , and did not use fertility treatments to conceive . Women reported their daily caffeine and caffeinated beverage consumption on question naires before conception and during early pregnancy . All exposure measurements were prospect i ve with respect to outcome ascertainment . We estimated hazard ratios ( HRs ) of SAB for categories of caffeine consumption in milligrams ( mg ) per day and the corresponding 95 % confidence intervals ( CIs ) using Cox proportional hazards regression models with gestational weeks as the time scale . MAIN RESULTS AND THE ROLE OF CHANCE There were 732 women ( 14.3 % ) who were identified as having a SAB . In the preconceptional period , caffeine consumption was not material ly associated with SAB risk ( HR comparing ≥300 with < 100 mg/day : 1.09 ; 95 % CI : 0.89 , 1.33 ) . In early pregnancy , the HRs for 100 - 199 , 200 - 299 and ≥300 mg/day of caffeine consumption were 1.62 ( 95 % CI : 1.19 , 2.22 ) , 1.48 ( 95 % CI : 1.03 , 2.13 ) and 1.23 ( 95 % CI : 0.61 , 2.46 ) , respectively , compared with that for < 100 mg/day . LIMITATIONS , REASONS FOR CAUTION The observed results may be affected by non-differential exposure misclassification , reverse causation and residual confounding . WIDER IMPLICATION S OF THE FINDINGS This is the largest study to date of prospect ively measured , preconception caffeine consumption and risk of SAB . We were able to reduce the likelihood of differential left truncation bias and recall bias present in other analyses . STUDY FUNDING /COMPETING INTERESTS Snart-Gravid was funded by the NICHD ( R21 - 050264 ) . Dr. Hahn 's work was funded in part by the BU Reproductive , Perinatal , and Pediatric Epidemiology Training Grant NIH # T32HD052458 . There are no competing interests BACKGROUND We examined  fertility-specific distress ( FSD ) and general distress by type of fertility barrier ( FB ) . METHODS In a r and om sample telephone survey , 580 US women reported their fertility intentions and histories . Six groups of women were identified : ( i ) no FBs , ( ii ) infertile with intent , ( iii ) infertile without intent , ( iv ) other fertility problems , ( v ) miscarriages and ( vi ) situational barriers . Multiple regression analyses were used to compare groups with FBs . RESULTS Sixty-one percent reported FBs and 28 % reported an inability to conceive for at least 12 months . The infertile with intent group had the highest FSD , which was largely explained by ( a ) self- identification as infertile and ( b ) seeking medical help for fertility . The no FB group had a mean Center for Epidemiological Studies Depression scale score above the commonly used cut-off of 16 , although 23 % of the women with FBs did score above 16 . CONCLUSIONS FBs are common . Self- identification as infertile is the largest source of FSD . More women with FBs had elevated general distress than women without FBs ; mean general distress was below 16 for all FB groups . It may be that , for some women ( even those with children ) , FBs can have lasting emotional consequences , but many women do heal from the emotional distress that may accompany fertility difficulties Caffeine consumption has been equivocally associated with  miscarriage  , despite an absence of prospect i ve longitudinal measurement of caffeine intake during sensitive windows of human development . In response to this critical data gap , we analyzed daily caffeine consumption while attempting pregnancy through 12 menstrual cycles at risk for pregnancy and found that caffeine consumption did not increase the risk or hazard of miscarriage  , even after adjusting for relevant covariates OBJECTIVE Coffee consumption has been inversely associated with  type 2 diabetes risk , but its mechanisms are largely unknown . We aim ed to examine whether plasma levels of sex hormones and sex hormone – binding globulin ( SHBG ) may account for the inverse association between coffee consumption and type 2 diabetes risk . RESEARCH DESIGN AND METHODS We conducted a case-control study nested in the prospect i ve Women 's Health Study ( WHS ) . During a median follow-up of 10 years , 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age , race , duration of follow-up , and time of blood draw . RESULTS Caffeinated coffee was positively associated with SHBG but not with sex hormones . Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming ≥4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers ( P for trend = 0.01 ) . In contrast , neither decaffeinated coffee nor tea was associated with SHBG or sex hormones . The multivariable-adjusted odds ratio ( OR ) of type 2 diabetes for women consuming ≥4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 ( 95 % CI 0.23–0.94 ; P for trend = 0.047 ) . The association was largely attenuated after further adjusting for SHBG ( OR 0.71 [ 95 % CI 0.31–1.61 ] ; P for trend = 0.47 ) . In addition , carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming ≥2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG . CONCLUSIONS Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women PURPOSE Common polymorphisms in the N-acetyltransferase-2 ( NAT2 ) metabolic enzyme determine slow or rapid acetylator phenotypes . We investigated the effects of alcohol , smoking , and caffeine on fecundability , and determined whether the effects were modified by NAT2 . METHODS Three NAT2 polymorphisms were genotyped in 319 women office workers participating in a prospect i ve pregnancy study ( 1990 - 1994 ) . Women were ages 20 - 41 and at risk for pregnancy . Discrete-time survival analysis was used to determine the effects of alcohol , smoking , and caffeine on fecundability and evaluate effect modification by NAT2 . RESULTS We followed 319 women ( 161 slow acetylators , 158 rapid ) for an average of 8 menstrual cycles , result ing in 124 pregnancies . There was no effect of caffeine on fecundability . Drinking ≥1 alcoholic drink per day and current smoking were significantly associated with reduced fecundability , but only among slow acetylators ( adjusted fecundability odds ratio [ FOR ] for smoking = 0.34 ; 95 % confidence interval , 0.22 - 0.90 ; adjusted FOR for ≥1 drink per day = 0.20 ; 0.05 - 0.92 ) . There was no effect among rapid acetylators . CONCLUSIONS NAT2 status significantly modified the effects of alcohol and smoking on fecundability , emphasizing the importance of incorporating genetic and metabolic information in studies of reproductive health . Replication of this study is warranted BACKGROUND Consumption of caffeine and alcohol is suspected to affect pregnancy outcome . Use of both stimulants is widespread and even minor effects on fetal viability are of public health interest . METHODS We performed a nested case-control study using prospect i ve data from a population -based cohort comprising 11088 women aged 20 - 29 years . From this cohort , women who experienced either a spontaneous abortion ( n = 303 ) or who gave birth ( n = 1381 ) during follow-up [ mean time : 2.1 years ( range : 1.6 - 3.4 ) ] were selected . Associations between self-reported exposures to caffeine and /or alcohol at enrolment and spontaneous abortion were analysed by means of logistic regression . RESULTS Compared with women with a pre-pregnancy intake of < 75 mg caffeine per day , the adjusted odds ratio ( 95 % confidence interval ) for spontaneous abortion was 1.26 ( 0.77 - 2.06 ) , 1.45 ( 0.87 - 2.41 ) , 1.44 ( 0.87 - 2.37 ) and 1.72 ( 1.00 - 2.96 ) for a pre-pregnancy intake on 75 - 300 , 301 - 500 ,  
    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: Abstract Objective : To study the association between coffee consumption during pregnancy and the risk of stillbirth and infant death in the first year of life . Design : Prospect i ve follow up study . Setting : Aarhus University Hospital , Denmark , 1989 - 96 . Participants : 18 478 singleton pregnancies in women with valid information about coffee consumption during pregnancy . Main outcome measures : Stillbirth ( delivery of a dead fetus at ≥28 weeks ' gestation ) and infant death ( death of a liveborn infant during the first year of life ) . Results : Pregnant women who drank eight or more cups of coffee per day during pregnancy had an increased risk of stillbirth compared with women who did not drink coffee ( odds ratio=3.0 , 95 % confidence interval 1.5 to 5.9 ) . After adjustment for smoking habits and alcohol intake during pregnancy , the relative risk of stillbirth decreased slightly . Adjustment for parity , maternal age , marital status , years of education , occupational status , and body mass index did not substantially change the estimates of association . There was no significant association between coffee consumption and death in the first year of life after adjustment for smoking habits during pregnancy . Conclusion : Drinking coffee during pregnancy is associated with an increased risk of stillbirth but not with infant death . What is already known on this topic Results from studies in monkeys suggest that high daily doses of caffeine in pregnancy increase the risk of stillbirth , but evidence from studies in humans has been lacking What this study adds Pregnant women who drank eight or more cups of coffee a day had more than twice the risk of stillbirth compared with women who did not drink coffee during BACKGROUND In a prospect i ve study the effect of the behavioral risk factors of both partners on fecundability  was studied . METHODS Information was collected on smoking habits , alcohol consumption , and caffeine intake ( e.g. coffee , tea , and cola consumption ) by interviewing 259 female nonmedical hospital workers , i.e. , clerical staff , cleaners , kitchen and restaurant workers , and their partners , who were planning a pregnancy . The occurrence of pregnancy was tested prospect ively during the 12 months after enrollment . RESULTS Among the participants as well as among their partners , smoking a moderate number of cigarettes ( 1 - 10/day ) was associated with higher fecundability ( i.e. , the probability of becoming pregnant each month ) than among those not smoking ( participant : OR = 1.4 ( 95 % CI , 0.9 - 2.2 ) ; partner : OR = 2.1 ( 95 % CI , 1.2 - 3.5 ) ) . The level of alcohol consumption in the female partner was not related to fecundability . However , in the male partner , there was a positive influence for drinking more than 10 alcoholic drinks per week compared with that observed for those drinking less than 5 ( OR = 1.6 ; 95 % CI , 1.0 - 2.4 ) . Participants with a moderate caffeine intake ( 400 - 700 mg/day ) showed a higher fecundability than those with a lower intake level ( ORadjusted = 2.1 ( 95 % CI , 1.2 - 3.7 ) ) . Heavy caffeine intake ( > 700 mg/day ) among partners was negatively related to fecundability when compared with the lowest intake level ( ORadjusted = 0.6 ( 95 % CI , 0.3 - 0.97 ) ) . CONCLUSIONS This study does not support the hypothesis that moderate cigarette smoking , caffeine intake , and alcohol consumption have an adverse influence on fecundability STUDY QUESTION Is caffeine and caffeinated beverage consumption associated with the risk of spontaneous abortion ( SAB )  ? SUMMARY ANSWER While preconceptional caffeine consumption was not material ly associated with an increased risk of SAB , consumption during early pregnancy was associated with a small increased risk of SAB , although the relation was not linear . WHAT IS KNOWN ALREADY Caffeine has been hypothesized as a risk factor for SAB since the 1980s ; however , results from previous studies have been conflicting . STUDY DESIGN , SIZE , DURATION This prospect i ve cohort study included 5132 Danish women planning pregnancy and enrolled from 2007 to 2010 . PARTICIPANTS / MATERIAL S , SETTING , METHODS Participants were women who conceived after entry into the Snart-Gravid cohort and who were aged 18 - 40 , in a stable relationship with a male partner , and did not use fertility treatments to conceive . Women reported their daily caffeine and caffeinated beverage consumption on question naires before conception and during early pregnancy . All exposure measurements were prospect i ve with respect to outcome ascertainment . We estimated hazard ratios ( HRs ) of SAB for categories of caffeine consumption in milligrams ( mg ) per day and the corresponding 95 % confidence intervals ( CIs ) using Cox proportional hazards regression models with gestational weeks as the time scale . MAIN RESULTS AND THE ROLE OF CHANCE There were 732 women ( 14.3 % ) who were identified as having a SAB . In the preconceptional period , caffeine consumption was not material ly associated with SAB risk ( HR comparing ≥300 with < 100 mg/day : 1.09 ; 95 % CI : 0.89 , 1.33 ) . In early pregnancy , the HRs for 100 - 199 , 200 - 299 and ≥300 mg/day of caffeine consumption were 1.62 ( 95 % CI : 1.19 , 2.22 ) , 1.48 ( 95 % CI : 1.03 , 2.13 ) and 1.23 ( 95 % CI : 0.61 , 2.46 ) , respectively , compared with that for < 100 mg/day . LIMITATIONS , REASONS FOR CAUTION The observed results may be affected by non-differential exposure misclassification , reverse causation and residual confounding . WIDER IMPLICATION S OF THE FINDINGS This is the largest study to date of prospect ively measured , preconception caffeine consumption and risk of SAB . We were able to reduce the likelihood of differential left truncation bias and recall bias present in other analyses . STUDY FUNDING /COMPETING INTERESTS Snart-Gravid was funded by the NICHD ( R21 - 050264 ) . Dr. Hahn 's work was funded in part by the BU Reproductive , Perinatal , and Pediatric Epidemiology Training Grant NIH # T32HD052458 . There are no competing interests BACKGROUND We examined  fertility-specific distress ( FSD ) and general distress by type of fertility barrier ( FB ) . METHODS In a r and om sample telephone survey , 580 US women reported their fertility intentions and histories . Six groups of women were identified : ( i ) no FBs , ( ii ) infertile with intent , ( iii ) infertile without intent , ( iv ) other fertility problems , ( v ) miscarriages and ( vi ) situational barriers . Multiple regression analyses were used to compare groups with FBs . RESULTS Sixty-one percent reported FBs and 28 % reported an inability to conceive for at least 12 months . The infertile with intent group had the highest FSD , which was largely explained by ( a ) self- identification as infertile and ( b ) seeking medical help for fertility . The no FB group had a mean Center for Epidemiological Studies Depression scale score above the commonly used cut-off of 16 , although 23 % of the women with FBs did score above 16 . CONCLUSIONS FBs are common . Self- identification as infertile is the largest source of FSD . More women with FBs had elevated general distress than women without FBs ; mean general distress was below 16 for all FB groups . It may be that , for some women ( even those with children ) , FBs can have lasting emotional consequences , but many women do heal from the emotional distress that may accompany fertility difficulties Caffeine consumption has been equivocally associated with  miscarriage  , despite an absence of prospect i ve longitudinal measurement of caffeine intake during sensitive windows of human development . In response to this critical data gap , we analyzed daily caffeine consumption while attempting pregnancy through 12 menstrual cycles at risk for pregnancy and found that caffeine consumption did not increase the risk or hazard of miscarriage  , even after adjusting for relevant covariates OBJECTIVE Coffee consumption has been inversely associated with  type 2 diabetes risk , but its mechanisms are largely unknown . We aim ed to examine whether plasma levels of sex hormones and sex hormone – binding globulin ( SHBG ) may account for the inverse association between coffee consumption and type 2 diabetes risk . RESEARCH DESIGN AND METHODS We conducted a case-control study nested in the prospect i ve Women 's Health Study ( WHS ) . During a median follow-up of 10 years , 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age , race , duration of follow-up , and time of blood draw . RESULTS Caffeinated coffee was positively associated with SHBG but not with sex hormones . Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming ≥4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers ( P for trend = 0.01 ) . In contrast , neither decaffeinated coffee nor tea was associated with SHBG or sex hormones . The multivariable-adjusted odds ratio ( OR ) of type 2 diabetes for women consuming ≥4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 ( 95 % CI 0.23–0.94 ; P for trend = 0.047 ) . The association was largely attenuated after further adjusting for SHBG ( OR 0.71 [ 95 % CI 0.31–1.61 ] ; P for trend = 0.47 ) . In addition , carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming ≥2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG . CONCLUSIONS Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women PURPOSE Common polymorphisms in the N-acetyltransferase-2 ( NAT2 ) metabolic enzyme determine slow or rapid acetylator phenotypes . We investigated the effects of alcohol , smoking , and caffeine on fecundability , and determined whether the effects were modified by NAT2 . METHODS Three NAT2 polymorphisms were genotyped in 319 women office workers participating in a prospect i ve pregnancy study ( 1990 - 1994 ) . Women were ages 20 - 41 and at risk for pregnancy . Discrete-time survival analysis was used to determine the effects of alcohol , smoking , and caffeine on fecundability and evaluate effect modification by NAT2 . RESULTS We followed 319 women ( 161 slow acetylators , 158 rapid ) for an average of 8 menstrual cycles , result ing in 124 pregnancies . There was no effect of caffeine on fecundability . Drinking ≥1 alcoholic drink per day and current smoking were significantly associated with reduced fecundability , but only among slow acetylators ( adjusted fecundability odds ratio [ FOR ] for smoking = 0.34 ; 95 % confidence interval , 0.22 - 0.90 ; adjusted FOR for ≥1 drink per day = 0.20 ; 0.05 - 0.92 ) . There was no effect among rapid acetylators . CONCLUSIONS NAT2 status significantly modified the effects of alcohol and smoking on fecundability , emphasizing the importance of incorporating genetic and metabolic information in studies of reproductive health . Replication of this study is warranted BACKGROUND Consumption of caffeine and alcohol is suspected to affect pregnancy outcome . Use of both stimulants is widespread and even minor effects on fetal viability are of public health interest . METHODS We performed a nested case-control study using prospect i ve data from a population -based cohort comprising 11088 women aged 20 - 29 years . From this cohort , women who experienced either a spontaneous abortion ( n = 303 ) or who gave birth ( n = 1381 ) during follow-up [ mean time : 2.1 years ( range : 1.6 - 3.4 ) ] were selected . Associations between self-reported exposures to caffeine and /or alcohol at enrolment and spontaneous abortion were analysed by means of logistic regression . RESULTS Compared with women with a pre-pregnancy intake of < 75 mg caffeine per day , the adjusted odds ratio ( 95 % confidence interval ) for spontaneous abortion was 1.26 ( 0.77 - 2.06 ) , 1.45 ( 0.87 - 2.41 ) , 1.44 ( 0.87 - 2.37 ) and 1.72 ( 1.00 - 2.96 ) for a pre-pregnancy intake on 75 - 300 , 301 - 500 ,  
    Output:
    