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: Study question What is the mortality in offspring of mothers who had influenza A(H1N1)pdm09 vaccination during pregnancy ? Methods This was a prospect i ve population based cohort study in seven healthcare regions in Sweden based on vaccinations taking place between 2 October 2009 and 26 November 2010 .  H1N1 vaccination data were linked with pregnancy and birth characteristics and offspring mortality data in 275 500 births ( of which 1203 were stillbirths ) from 137 886 mothers . Of these offspring , 41 183 had been exposed to vaccination with P and emrix , a monovalent AS03 adjuvanted H1N1 influenza vaccine , during fetal life . A primary comparison group consisted of pregnancies of women who were not vaccinated during the same calendar period . In a second comparison , non-exposed siblings of infants prenatally exposed to vaccination were used as controls . Cox regression was used to estimate hazard ratios for stillbirth , early neonatal mortality ( days 0 - 6 after birth ) , and subsequent mortality ( beginning on day 7 ) in vaccinated versus non-vaccinated women , adjusting for mother ’s age at delivery , body mass index , parity , smoking , country of birth , and disposable income and for sex of offspring . Study answer and limitations The results of this study suggest that AS03 adjuvanted H1N1 vaccination during pregnancy does not affect the risk of stillbirth , early neonatal death , or later mortality in the offspring . During follow-up , 1172 stillbirths , 380 early neonatal deaths , and 706 deaths thereafter occurred . Compared with general population controls , this corresponded to adjusted hazard ratios of 0.83 ( 95 % confidence interval 0.65 to 1.04 ) for stillbirth , 0.71 ( 0.44 to 1.14 ) for early neonatal death , and 0.97 ( 0.69 to 1.36 ) for later death . When siblings were used as controls , adjusted hazard ratios were 0.88 ( 0.59 to 1.30 ) for stillbirth , 0.82 ( 0.46 to 1.49 ) for early neonatal death , and 0.78 ( 0.52 to 1.19 ) for later death . Limitations of the study include lack of data on miscarriage before gestational week 22 , inability to ascertain which mothers had p and emic flu during pregnancy , and lack of data on factors influencing the decision to vaccinate during pregnancy . What this study adds H1N1 vaccination during pregnancy is not associated with adverse fetal outcome or offspring mortality , including when familial factors are taken into account . Funding , competing interests , data sharing This project was supported by grants from the Swedish Research Council and the Swedish Council for Working Life and Social Research . NF was employed at the Swedish Medical Product Agency at the time of the study Summary Background Despite the heightened risk of serious influenza during infancy , vaccination is not recommended in infants younger than 6 months . We aim ed to assess the safety , immunogenicity , and efficacy of maternal immunisation with trivalent inactivated influenza vaccine for protection of infants against a first episode of laboratory-confirmed influenza . Methods We did this prospect i ve , active-controlled , observer-blind , r and omised phase 4 trial at six referral centres and community health centres in Bamako , Mali . Third-trimester pregnant women ( ≥28 weeks ' gestation ) were r and omly assigned ( 1:1 ) , via a computer-generated , centre-specific list with alternate block sizes of six or 12 , to receive either trivalent inactivated influenza vaccine or quadrivalent meningococcal vaccine . Study personnel administering vaccines were not masked to treatment allocation , but allocation was concealed from clinicians , laboratory personnel , and participants . Infants were visited weekly until age 6 months to detect influenza-like illness ; laboratory-confirmed influenza diagnosed with RT-PCR . We assessed two co primary objectives : vaccine efficacy against laboratory-confirmed influenza in infants born to women immunised any time prepartum ( intention-to-treat population ) , and vaccine efficacy in infants born to women immunised at least 14 days prepartum ( per- protocol population ) . The primary outcome was the occurrence of a first case of laboratory-confirmed influenza by age 6 months . This trial is registered with Clinical Trials.gov , number NCT01430689 . Findings We did this trial from Sept 12 , 2011 , to Jan 28 , 2014 . Between Sept 12 , 2011 , and April 18 , 2013 , we r and omly assigned 4193 women to receive trivalent  inactivated influenza vaccine  ( n=2108 ) or quadrivalent meningococcal vaccine ( n=2085 ) . There were 4105 livebirths ; 1797 ( 87 % ) of 2064 infants in the trivalent inactivated influenza vaccine group and 1793 ( 88 % ) of 2041 infants in the quadrivalent meningococcal vaccine group were followed up until age 6 months . We recorded 5279 influenza-like illness episodes in 2789 ( 68 % ) infants , of which 131 ( 2 % ) episodes were laboratory-confirmed influenza . 129 ( 98 % ) cases of laboratory-confirmed influenza were first episodes ( n=77 in the quadrivalent meningococcal vaccine group vs n=52 in the trivalent inactivated influenza vaccine group ) . In the intention-to-treat population , overall infant vaccine efficacy was 33·1 % ( 95 % CI 3·7–53·9 ) ; in the per- protocol population , vaccine efficacy was 37·3 % ( 7·6–57·8 ) . Vaccine efficacy remained robust during the first 4 months of follow-up ( 67·9 % [ 95 % CI 35·1–85·3 ] by intention to treat and 70·2 % [ 35·7–87·6 ] by per protocol ) , before diminishing during the fifth month ( 57·3 % [ 30·6–74·4 ] and 60·7 [ 33·8–77·5 ] , respectively ) . Adverse event rates in women and infants were similar among groups . Pain at the injection site was more common in women given quadrivalent meningococcal vaccine than in those given trivalent inactivated influenza vaccine ( n=253 vs n=132 ; p<0·0001 ) , although 354 [ 92 % ] reactions were mild . Obstetrical and non-obstetrical serious adverse events were reported in 60 ( 3 % ) women in the quadrivalent meningococcal vaccine group and 61 ( 3 % ) women in the trivalent inactivated influenza vaccine group . Presumed neonatal infection was more common in infants in the trivalent inactivated influenza vaccine group than in those in the quadrivalent meningococcal vaccine group ( n=60 vs n=37 ; p=0·02 ) . No serious adverse events were related to vaccination . Interpretation Vaccination of pregnant women with trivalent inactivated influenza vaccine  in Mali — a poorly re source d country with high infant mortality — was technically and logistically feasible and protected infants from laboratory-confirmed influenza for 4 months . With adequate financing to procure the vaccine , implementation will parallel the access to antenatal care and immunisation coverage of pregnant women with tetanus toxoid . Funding Bill & Melinda Gates Foundation BACKGROUND There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus ( HIV ) infection and protection of their infants . METHODS We conducted two double-blind , r and omized , placebo-controlled trials of trivalent inactivated influenza vaccine ( IIV3 ) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected . The immunogenicity , safety , and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth . Immune responses were measured with a hemagglutination inhibition ( HAI ) assay , and influenza was diagnosed by means of reverse-transcriptase-polymerase-chain-reaction ( RT-PCR ) assays of respiratory sample s. RESULTS The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV . At 1 month after vaccination , seroconversion rates and the proportion of participants with HAI titers of 1:40 or more were higher among IIV3 recipients than among placebo recipients in both cohorts . Newborns of IIV3 recipients also had higher HAI titers than newborns of placebo recipients . The attack rate for RT-PCR-confirmed influenza among both HIV-uninfected placebo recipients and their infants was 3.6 % . The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8 % and 1.9 % , respectively , and the respective vaccine-efficacy rates were 50.4 % ( 95 % confidence interval [ CI ] , 14.5 to 71.2 ) and 48.8 % ( 95 % CI , 11.6 to 70.4 ) . Among HIV-infected women , the attack rate for placebo recipients was 17.0 % and the rate for IIV3 recipients was 7.0 % ; the vaccine-efficacy rate for these IIV3 recipients was 57.7 % ( 95 % CI , 0.2 to 82.1 ) . CONCLUSIONS Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV . ( Funded by the Bill and Melinda Gates Foundation and others ; Clinical Trials.gov numbers , NCT01306669 and NCT01306682 . ) Background In 2009 , pregnant women were specifically targeted by a national vaccination campaign against p and emic A/H1N1 influenza virus . The objectives of the COFLUPREG study , initially set up to assess the incidence of serious forms of A/H1N1 influenza , were to assess the consequences of maternal vaccination on pregnancy outcomes and maternal seroprotection at delivery . Methods Pregnant women , between 12 and 35 weeks of gestation , non vaccinated against A/H1N1 2009 influenza were r and omly selected to be included in a prospect i ve cohort study conducted in three maternity centers in Paris ( France ) during p and emic period . Blood sample s were planned to assess hemagglutination inhibition ( HI ) antibody against A/H1N1 2009 influenza at inclusion and at delivery . Results Among the 877 pregnant women included in the study , 678 ( 77.3 % ) had serum sample s both at inclusion and delivery , and 320 ( 36.5 % ) received p and emic A/H1N1 2009 influenza vaccine with a median interval between vaccination and delivery of 92 days ( 95 % CI 48–134 ) . At delivery , the proportion of women with seroprotection ( HI antibodies titers against A/H1N1 2009 influenza of 1∶40 or greater ) was 69.9 % in vaccinated women . Of the 422 non-vaccinated women with serological data , 11 ( 2.6 % ; 95%CI : 1.3–4.6 ) had laboratory documented A/H1N1 2009 influenza ( 1 with positive PCR and 10 with serological seroconversion ) . None of the 877 study ’s women was hospitalized for flu . No difference on pregnancy outcomes was evidence d between vaccinated women , non-vaccinated women without seroconversion and non-vaccinated women with flu . Conclusion Despite low vaccine coverage , incidence of p and emic flu was low in this cohort of pregnant women . No effect on pregnancy and delivery outcomes was evidence d after vaccination BACKGROUND Influenza immunisation during pregnancy is recommended but not widely implemented in some low-income regions . We assessed the safety and efficacy in mothers and infants of year-round maternal influenza immunisation in Nepal , where influenza viruses circulate throughout the year . METHODS In this phase 4 , r and omised , placebo-controlled trial , we enrolled two consecutive sequential annual cohorts of pregnant women from the Sarlahi district in southern Nepal . We r and omised mothers 1:1 to receive seasonally recommended trivalent inactivated influenza vaccine or saline placebo in blocks of eight , stratified by gestational age at enrolment ( 17 - 25 weeks vs 26 - 34 weeks ) . Women were eligible if they were married , 15 - 40 years of age , 17 - 34 weeks ' gestation at enrolment , and had not previously received any influen 
    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: Study question What is the mortality in offspring of mothers who had influenza A(H1N1)pdm09 vaccination during pregnancy ? Methods This was a prospect i ve population based cohort study in seven healthcare regions in Sweden based on vaccinations taking place between 2 October 2009 and 26 November 2010 .  H1N1 vaccination data were linked with pregnancy and birth characteristics and offspring mortality data in 275 500 births ( of which 1203 were stillbirths ) from 137 886 mothers . Of these offspring , 41 183 had been exposed to vaccination with P and emrix , a monovalent AS03 adjuvanted H1N1 influenza vaccine , during fetal life . A primary comparison group consisted of pregnancies of women who were not vaccinated during the same calendar period . In a second comparison , non-exposed siblings of infants prenatally exposed to vaccination were used as controls . Cox regression was used to estimate hazard ratios for stillbirth , early neonatal mortality ( days 0 - 6 after birth ) , and subsequent mortality ( beginning on day 7 ) in vaccinated versus non-vaccinated women , adjusting for mother ’s age at delivery , body mass index , parity , smoking , country of birth , and disposable income and for sex of offspring . Study answer and limitations The results of this study suggest that AS03 adjuvanted H1N1 vaccination during pregnancy does not affect the risk of stillbirth , early neonatal death , or later mortality in the offspring . During follow-up , 1172 stillbirths , 380 early neonatal deaths , and 706 deaths thereafter occurred . Compared with general population controls , this corresponded to adjusted hazard ratios of 0.83 ( 95 % confidence interval 0.65 to 1.04 ) for stillbirth , 0.71 ( 0.44 to 1.14 ) for early neonatal death , and 0.97 ( 0.69 to 1.36 ) for later death . When siblings were used as controls , adjusted hazard ratios were 0.88 ( 0.59 to 1.30 ) for stillbirth , 0.82 ( 0.46 to 1.49 ) for early neonatal death , and 0.78 ( 0.52 to 1.19 ) for later death . Limitations of the study include lack of data on miscarriage before gestational week 22 , inability to ascertain which mothers had p and emic flu during pregnancy , and lack of data on factors influencing the decision to vaccinate during pregnancy . What this study adds H1N1 vaccination during pregnancy is not associated with adverse fetal outcome or offspring mortality , including when familial factors are taken into account . Funding , competing interests , data sharing This project was supported by grants from the Swedish Research Council and the Swedish Council for Working Life and Social Research . NF was employed at the Swedish Medical Product Agency at the time of the study Summary Background Despite the heightened risk of serious influenza during infancy , vaccination is not recommended in infants younger than 6 months . We aim ed to assess the safety , immunogenicity , and efficacy of maternal immunisation with trivalent inactivated influenza vaccine for protection of infants against a first episode of laboratory-confirmed influenza . Methods We did this prospect i ve , active-controlled , observer-blind , r and omised phase 4 trial at six referral centres and community health centres in Bamako , Mali . Third-trimester pregnant women ( ≥28 weeks ' gestation ) were r and omly assigned ( 1:1 ) , via a computer-generated , centre-specific list with alternate block sizes of six or 12 , to receive either trivalent inactivated influenza vaccine or quadrivalent meningococcal vaccine . Study personnel administering vaccines were not masked to treatment allocation , but allocation was concealed from clinicians , laboratory personnel , and participants . Infants were visited weekly until age 6 months to detect influenza-like illness ; laboratory-confirmed influenza diagnosed with RT-PCR . We assessed two co primary objectives : vaccine efficacy against laboratory-confirmed influenza in infants born to women immunised any time prepartum ( intention-to-treat population ) , and vaccine efficacy in infants born to women immunised at least 14 days prepartum ( per- protocol population ) . The primary outcome was the occurrence of a first case of laboratory-confirmed influenza by age 6 months . This trial is registered with Clinical Trials.gov , number NCT01430689 . Findings We did this trial from Sept 12 , 2011 , to Jan 28 , 2014 . Between Sept 12 , 2011 , and April 18 , 2013 , we r and omly assigned 4193 women to receive trivalent  inactivated influenza vaccine  ( n=2108 ) or quadrivalent meningococcal vaccine ( n=2085 ) . There were 4105 livebirths ; 1797 ( 87 % ) of 2064 infants in the trivalent inactivated influenza vaccine group and 1793 ( 88 % ) of 2041 infants in the quadrivalent meningococcal vaccine group were followed up until age 6 months . We recorded 5279 influenza-like illness episodes in 2789 ( 68 % ) infants , of which 131 ( 2 % ) episodes were laboratory-confirmed influenza . 129 ( 98 % ) cases of laboratory-confirmed influenza were first episodes ( n=77 in the quadrivalent meningococcal vaccine group vs n=52 in the trivalent inactivated influenza vaccine group ) . In the intention-to-treat population , overall infant vaccine efficacy was 33·1 % ( 95 % CI 3·7–53·9 ) ; in the per- protocol population , vaccine efficacy was 37·3 % ( 7·6–57·8 ) . Vaccine efficacy remained robust during the first 4 months of follow-up ( 67·9 % [ 95 % CI 35·1–85·3 ] by intention to treat and 70·2 % [ 35·7–87·6 ] by per protocol ) , before diminishing during the fifth month ( 57·3 % [ 30·6–74·4 ] and 60·7 [ 33·8–77·5 ] , respectively ) . Adverse event rates in women and infants were similar among groups . Pain at the injection site was more common in women given quadrivalent meningococcal vaccine than in those given trivalent inactivated influenza vaccine ( n=253 vs n=132 ; p<0·0001 ) , although 354 [ 92 % ] reactions were mild . Obstetrical and non-obstetrical serious adverse events were reported in 60 ( 3 % ) women in the quadrivalent meningococcal vaccine group and 61 ( 3 % ) women in the trivalent inactivated influenza vaccine group . Presumed neonatal infection was more common in infants in the trivalent inactivated influenza vaccine group than in those in the quadrivalent meningococcal vaccine group ( n=60 vs n=37 ; p=0·02 ) . No serious adverse events were related to vaccination . Interpretation Vaccination of pregnant women with trivalent inactivated influenza vaccine  in Mali — a poorly re source d country with high infant mortality — was technically and logistically feasible and protected infants from laboratory-confirmed influenza for 4 months . With adequate financing to procure the vaccine , implementation will parallel the access to antenatal care and immunisation coverage of pregnant women with tetanus toxoid . Funding Bill & Melinda Gates Foundation BACKGROUND There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus ( HIV ) infection and protection of their infants . METHODS We conducted two double-blind , r and omized , placebo-controlled trials of trivalent inactivated influenza vaccine ( IIV3 ) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected . The immunogenicity , safety , and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth . Immune responses were measured with a hemagglutination inhibition ( HAI ) assay , and influenza was diagnosed by means of reverse-transcriptase-polymerase-chain-reaction ( RT-PCR ) assays of respiratory sample s. RESULTS The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV . At 1 month after vaccination , seroconversion rates and the proportion of participants with HAI titers of 1:40 or more were higher among IIV3 recipients than among placebo recipients in both cohorts . Newborns of IIV3 recipients also had higher HAI titers than newborns of placebo recipients . The attack rate for RT-PCR-confirmed influenza among both HIV-uninfected placebo recipients and their infants was 3.6 % . The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8 % and 1.9 % , respectively , and the respective vaccine-efficacy rates were 50.4 % ( 95 % confidence interval [ CI ] , 14.5 to 71.2 ) and 48.8 % ( 95 % CI , 11.6 to 70.4 ) . Among HIV-infected women , the attack rate for placebo recipients was 17.0 % and the rate for IIV3 recipients was 7.0 % ; the vaccine-efficacy rate for these IIV3 recipients was 57.7 % ( 95 % CI , 0.2 to 82.1 ) . CONCLUSIONS Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV . ( Funded by the Bill and Melinda Gates Foundation and others ; Clinical Trials.gov numbers , NCT01306669 and NCT01306682 . ) Background In 2009 , pregnant women were specifically targeted by a national vaccination campaign against p and emic A/H1N1 influenza virus . The objectives of the COFLUPREG study , initially set up to assess the incidence of serious forms of A/H1N1 influenza , were to assess the consequences of maternal vaccination on pregnancy outcomes and maternal seroprotection at delivery . Methods Pregnant women , between 12 and 35 weeks of gestation , non vaccinated against A/H1N1 2009 influenza were r and omly selected to be included in a prospect i ve cohort study conducted in three maternity centers in Paris ( France ) during p and emic period . Blood sample s were planned to assess hemagglutination inhibition ( HI ) antibody against A/H1N1 2009 influenza at inclusion and at delivery . Results Among the 877 pregnant women included in the study , 678 ( 77.3 % ) had serum sample s both at inclusion and delivery , and 320 ( 36.5 % ) received p and emic A/H1N1 2009 influenza vaccine with a median interval between vaccination and delivery of 92 days ( 95 % CI 48–134 ) . At delivery , the proportion of women with seroprotection ( HI antibodies titers against A/H1N1 2009 influenza of 1∶40 or greater ) was 69.9 % in vaccinated women . Of the 422 non-vaccinated women with serological data , 11 ( 2.6 % ; 95%CI : 1.3–4.6 ) had laboratory documented A/H1N1 2009 influenza ( 1 with positive PCR and 10 with serological seroconversion ) . None of the 877 study ’s women was hospitalized for flu . No difference on pregnancy outcomes was evidence d between vaccinated women , non-vaccinated women without seroconversion and non-vaccinated women with flu . Conclusion Despite low vaccine coverage , incidence of p and emic flu was low in this cohort of pregnant women . No effect on pregnancy and delivery outcomes was evidence d after vaccination BACKGROUND Influenza immunisation during pregnancy is recommended but not widely implemented in some low-income regions . We assessed the safety and efficacy in mothers and infants of year-round maternal influenza immunisation in Nepal , where influenza viruses circulate throughout the year . METHODS In this phase 4 , r and omised , placebo-controlled trial , we enrolled two consecutive sequential annual cohorts of pregnant women from the Sarlahi district in southern Nepal . We r and omised mothers 1:1 to receive seasonally recommended trivalent inactivated influenza vaccine or saline placebo in blocks of eight , stratified by gestational age at enrolment ( 17 - 25 weeks vs 26 - 34 weeks ) . Women were eligible if they were married , 15 - 40 years of age , 17 - 34 weeks ' gestation at enrolment , and had not previously received any influen 
    Output:
    