The Safety of Boostrix Following Routine Immunization of Pregnant Women

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to assess the safety of Boostrix administered on or after the first day of the 27th week of pregnancy by conducting a post-marketing study that provided safety information to the public and healthcare providers. This was one of the largest cohorts of pregnant women vaccinated with Boostrix in the U.S. Through partnership between Kaiser Permanente Southern California (KPSC) and the sponsor, GlaxoSmithKline (GSK), information about the safety of maternal vaccination with Boostrix and maternal and infant adverse events (AEs) in a community setting was gained.

Official Title
-----------------
An Observational, Retrospective Cohort Database Study to Assess the Safety of Boostrix (U.S. Formulation), a Reduced Tetanus, Diphtheria, Acellular Pertussis Vaccine (Tdap), Following Routine Immunization of Pregnant Women in the United States

Conditions
-----------------
Whooping Cough

Intervention / Treatment
-----------------
* Other: Safety assessment following routine immunization with Boostrix


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women with prenatal care and continuous membership (allowing up to a 31-day gap) at KPSC between the 1st day of the 27th week of pregnancy and the index (vaccination) date. Exposed cohort (from the 27th week of gestation): Pregnant women vaccinated with Boostrix on or after the 1st day of the 27th week of pregnancy; who were not vaccinated with any other Tdap vaccine at any other time during the pregnancy in scope of this study. Unexposed cohort: Women matched to the exposed cohort and pregnant sometime during the approximate estimated period between January 1, 2012-December 31, 2014 and did not receive any Tdap vaccine during the pregnancy in scope of this study. For the analysis of congenital anomalies among live births, at birth and through six months of age, the following additional inclusion criteria for infants will be applied: Live born Born in KPSC hospitals Note: Pregnant women vaccinated with Boostrix during pregnancy before the 27th week of gestation, with membership at the date of vaccination, and who were not vaccinated with any other Tdap vaccine at any other time during the pregnancy in scope of this study will be part of a descriptive analysis (secondary objective).
Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Exposed cohort women-on or after 1st day of 27th week of pregnancy<br>This group consisted of pregnant women who received the Tdap vaccine (Boostrix) on or after the 1st day of the 27th week of pregnancy during the period January 1, 2018 to January 31, 2019 who were not vaccinated with any other Tdap vaccine at any other time during the pregnancy. | Other: Safety assessment following routine immunization with Boostrix<br>* Subject-level data was collected for pregnant women and their infants through the Electronic Health Records.<br>|
| Unexposed historical cohort women<br>This group consisted of women matched to Exposed cohort women-on or after 1st day of 27th week of pregnancy group and pregnant at least one day during the historical period between January 1, 2012-December 31, 2014 and did not receive any Tdap vaccine during the pregnancy. | Other: Safety assessment following routine immunization with Boostrix<br>* Subject-level data was collected for pregnant women and their infants through the Electronic Health Records.<br>|
| Exposed cohort women-before 1st day of 27th week of pregnancy<br>This group consisted of pregnant women who received the Tdap vaccine (Boostrix) before the 1st day of the 27th week of pregnancy during the period January 1, 2018-January 31, 2019 who were not vaccinated with any other Tdap vaccine at any other time during the pregnancy. | Other: Safety assessment following routine immunization with Boostrix<br>* Subject-level data was collected for pregnant women and their infants through the Electronic Health Records.<br>|
| Exposed cohort infants-on or after 1st day of 27th week of pregnancy<br>This group consisted of infants whose mothers belong to Exposed cohort women-on or after 1st day of 27th week of pregnancy group. | Other: Safety assessment following routine immunization with Boostrix<br>* Subject-level data was collected for pregnant women and their infants through the Electronic Health Records.<br>|
| Unexposed historical cohort infants<br>This group consisted of infants whose mothers belong to the Unexposed historical cohort women group. | Other: Safety assessment following routine immunization with Boostrix<br>* Subject-level data was collected for pregnant women and their infants through the Electronic Health Records.<br>|
| Exposed cohort infants-before 1st day of 27th week of pregnancy<br>This group consisted of infants whose mothers belong to the Exposed cohort women-before 1st day of 27th week of pregnancy group. | Other: Safety assessment following routine immunization with Boostrix<br>* Subject-level data was collected for pregnant women and their infants through the Electronic Health Records.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence Rate (Per 1000 Person-years) of Pre-specified Maternal Adverse Events for Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort-women Groups | The incidence rate (per 1000) of maternal adverse events was calculated as the total number of adverse events in the numerator and the total person-years at risk in the denominator. Every unexposed woman was assigned an index date that is determined by the number of days from pregnancy start to the Boostrix vaccination date of her matched exposed woman. The same number of days calculated in the exposed woman was added to the pregnancy start of the unexposed woman to identify her index date. The pre-specified maternal adverse events assessed were pre-eclampsia and eclampsia; Intra-uterine infections. | From date of Boostrix vaccination (Exposed cohort women-on or after 1st day of 27th week of pregnancy) or from an index date (Unexposed historical cohort women) until end of enrollment or pregnancy, whichever came first, up to 13 weeks | 
| Incidence Rate (Per 1000 Persons) of Prespecified Maternal Adverse Events for Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Women Groups | Incidence rate (per 1000) consisted of the total number of adverse events in the numerator and the number of persons at risk in the denominator. Every unexposed woman was assigned an index date that is determined by the number of days from pregnancy start to the Boostrix vaccination date of her matched exposed woman. The same number of days calculated in the exposed woman was added to the pregnancy start of the unexposed woman to identify her index date. The pre-specified maternal adverse event assessed was preterm delivery. | From date of Boostrix vaccination (Exposed cohort women-on or after 1st day of 27th week of pregnancy) or from an index date (Unexposed historical cohort women) until end of enrollment or pregnancy, whichever came first, up to 13 weeks | 
| Incidence Rate (Per 1000 Persons) of Pre-specified Infant Adverse Events for Exposed Cohort infants-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Infants Groups | The incidence rate (per 1000) of adverse events was calculated as the total number of adverse events in the numerator and the total of persons at risk in the denominator. The pre-specified infant adverse event assessed was small for gestational age. | From birth through 6 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence Rate (Per 1000 Person-years) of Other Maternal Adverse Events for Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Women Groups | The incidence rate (per 1000) of other maternal adverse events was calculated as the total number of adverse events in the numerator and the total person-years at risk in the denominator. Every unexposed woman was assigned an index date that is determined by the number of days from pregnancy start to the Boostrix vaccination date of her matched exposed woman. The same number of days calculated in the exposed woman was added to the pregnancy start of the unexposed woman to identify her index date. The analysis was used for hypothesis generation/signal detection, hence without adjustment for multiple comparisons. The other maternal adverse events assessed were poor fetal growth; placental abruption; preterm pre-labor rupture of membranes; maternal death. | From date of Boostrix vaccination (Exposed cohort women-on or after 1st day of 27th week of pregnancy) or from an index date (Unexposed historical cohort women) until end of enrollment or pregnancy, whichever came first, up to 13 weeks | 
| Incidence Rate (Per 1000 Persons) of Other Maternal Adverse Events for Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Women Groups | The incidence rate (per 1000) consisted of the total number of adverse events in the numerator and the number of persons at risk in the denominator. Every unexposed woman was assigned an index date that is determined by the number of days from pregnancy start to the Boostrix vaccination date of her matched exposed woman. The same number of days calculated in the exposed woman was added to the pregnancy start of the unexposed woman to identify her index date. The analysis was used for hypothesis generation/signal detection, hence without adjustment for multiple comparisons. The other maternal adverse events assessed were stillbirth/fetal death; stillbirth/fetal death with congenital anomalies; transfusion during delivery hospitalization. | From date of Boostrix vaccination (Exposed cohort women-on or after 1st day of 27th week of pregnancy) or from an index date (Unexposed historical cohort women) until end of enrollment or pregnancy, whichever came first, up to 13 weeks | 
| Incidence Rate (Per 1000 Persons) of Other Infant Adverse Events for Exposed Cohort infants-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Infants Groups | The incidence rate (per 1000) of other infant adverse events was calculated as the total number of adverse events in the numerator and the total of persons at risk in the denominator. The analysis was used for hypothesis generation/signal detection, hence without adjustment for multiple comparisons. The other infant adverse events assessed were neonatal death, congenital anomalies of: nervous system; eye; ear, face, or neck; cardiovascular system; respiratory system; clefts; upper gastrointestinal system; lower gastrointestinal system; genital organs; renal system; musculoskeletal system; limb; integument; other and unspecified. | From birth through 6 months of age | 
| Incidence Rate (Per 1000 Person-years) of Women Adverse Events for Exposed Cohort Women-before 1st Day of 27th Week of Pregnancy Group | The incidence rate (per 1000) was calculated as the total number of adverse events in the numerator and the total person-years at risk in the denominator. Due to the small sample size, the analysis of these women adverse events was descriptive. The women adverse events assessed were pre-eclampsia and eclampsia; intra-uterine infections; poor fetal growth; placental abruption; preterm pre-labor rupture of membranes; maternal death. | For the Exposed cohort women-before 1st day of 27th week of pregnancy: from date of Boostrix vaccination until end of enrollment or pregnancy, whichever came first, up to 40 weeks | 
| Incidence Rate (Per 1000 Persons) of Women Adverse Events Presented for Exposed Cohort Women-before 1st Day of 27th Week of Pregnancy Group | The incidence rate (per 1000) consisted of the total number of adverse events in the numerator and the number of persons at risk in the denominator. The adverse events of this analysis include the adverse events presented in the above outcomes as well as spontaneous and therapeutic abortion with or without congenital anomalies in pregnant women vaccinated with Boostrix before the 27th week of gestation. Due to the small sample size, the analysis of these women adverse events was descriptive. The women adverse events assessed were stillbirth/fetal death; stillbirth/fetal death with congenital anomalies; spontaneous abortion; spontaneous abortion with congenital anomalies; therapeutic abortion; therapeutic abortion with congenital anomalies; transfusion during delivery hospitalization; preterm delivery. | For the Exposed cohort women-before 1st day of 27th week of pregnancy: from date of Boostrix vaccination until end of enrollment or pregnancy, whichever came first, up to 40 weeks | 
| Incidence Rate (Per 1000 Persons) of Infant Adverse Events for Exposed Cohort Infants-before 1st Day of 27th Week of Pregnancy Group | The incidence rate (per 1000) was calculated as the total number of adverse events in the numerator and the total of persons at risk in the denominator. The adverse events of this analysis include adverse events presented in the above outcomes, among the infants whose mothers were vaccinated with Boostrix before the 27th week of gestation. Due to the small sample size, the analysis of these infant adverse events was descriptive. The infant adverse events assessed were: small for gestational age; neonatal death; congenital anomalies of: nervous system; eye; ear, face, or neck; cardiovascular system; respiratory system; clefts; upper gastrointestinal system; lower gastrointestinal system; genital organs; renal system; musculoskeletal system; limb; integument; other and unspecified. | From birth through 6 months of age | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
whooping cough, Boostrix, Tdap, safety, pregnancy, infants