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| Name | Class |
|---|---|
| Kaiser Permanente | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Exposed cohort women-on or after 1st day of 27th week of pregnancy | 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. |
| |
| Unexposed historical cohort women | 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. |
| |
| Exposed cohort women-before 1st day of 27th week of pregnancy | 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. |
| |
| Exposed cohort infants-on or after 1st day of 27th week of pregnancy | This group consisted of infants whose mothers belong to Exposed cohort women-on or after 1st day of 27th week of pregnancy group. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Safety assessment following routine immunization with Boostrix | Other | Subject-level data was collected for pregnant women and their infants through the Electronic Health Records. |
| 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. |
| 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. |
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Inclusion Criteria:
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:
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).
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.
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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 date
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Pasadena | California | 91101 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36520325 | Derived | Florea A, Sy LS, Ackerson BK, Qian L, Luo Y, Becerra-Culqui T, Lee GS, Tian Y, Zheng C, Bathala R, Tartof SY, Campora L, Ceregido MA, Kuznetsova A, Poirrier JE, Rosillon D, Valdes L, Cheuvart B, Mesaros N, Meyer N, Guignard A, Tseng HF. Investigating Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Congenital Anomalies. Infect Dis Ther. 2023 Feb;12(2):411-423. doi: 10.1007/s40121-022-00731-8. Epub 2022 Dec 15. |
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The study population for the first analysis includes pregnant women who received Tdap (Boostrix) vaccine on or after the first day of the 27th week of pregnancy (Exposed cohort-on or after 1st day of 27th week of pregnancy) and their infants, as well as the matched unexposed pregnant women and their infants (Unexposed historical cohort). A second analysis was performed on pregnant women who received the Tdap vaccine before the 1st day of the 27th week of pregnancy, and their infants.
Data was collected for both pregnant women and their infants from Kaiser Permanente Southern California (KPSC) Electronic Health Records (EHR).
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| ID | Title | Description |
|---|---|---|
| FG000 | Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy | 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 |
| FG001 | Unexposed Historical Cohort Women | 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 |
| FG002 | Exposed Cohort Women-before 1st Day of 27th Week of Pregnancy | 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 |
| FG003 | Exposed Cohort infants-on or After 1st Day of 27th Week of Pregnancy | This group consisted of infants whose mothers belong to Exposed cohort women-on or after 1st day of 27th week of pregnancy group |
| FG004 | Unexposed Historical Cohort Infants | This group consisted of infants whose mothers belong to the Unexposed historical cohort women group |
| FG005 | Exposed Cohort Infants-before 1st Day of 27th Week of Pregnancy | This group consisted of infants whose mothers belong to the Exposed cohort women-before 1st day of 27th week of pregnancy group |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The analysis was performed on all women from the Exposed cohort women-on or after 1st day of 27th week of pregnancy group and the Unexposed historical cohort women group, who met the eligibility criteria and for whom the event could be assessed. | Posted | Number | 95% Confidence Interval | Events per 1000 persons-year | 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 |
For each woman from date of Boostrix vaccination (Exposed cohort women-on or after 1st day of 27th week of pregnancy Group and Exposed cohort women-before 1st day of 27th week of pregnancy Group), and from an index date (Unexposed historical cohort women) until end of enrollment (up to 13 weeks) or pregnancy (up to 40 weeks). For infants, from birth through 6 months of age.
Classification of events as SAE/other AE is unknown, all events were reported in SAE section. SAEs data was collected from different analytic populations for whom the event could be evaluated. Therefore for: Preterm delivery, Preterm pre-labor rupture of membranes, Stillbirths/fetal deaths without congenital anomalies, Transfusion during delivery hospitalization, Small for gestational age, the number of participants at risk differs from total number at risk for SAEs reported in all Arms.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Preeclampsia/eclampsia | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
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Main limitation: difference in background rates and time periods for both cohorts. Other: confounding by indication possible for a less select historical unvaccinated population. The study wasn't designed to study safety of exposure before 27 weeks of gestation and was conducted in a prepaid health plan, so findings may not be generalized to uninsured populations. Congenital anomalies analysis performed by event code without adjustment for multiple testing.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 12, 2019 | Nov 30, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 2, 2019 | Nov 30, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D014917 | Whooping Cough |
| ID | Term |
|---|---|
| D001885 | Bordetella Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| ID | Term |
|---|---|
| C505143 | Boostrix |
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| Unexposed historical cohort infants | This group consisted of infants whose mothers belong to the Unexposed historical cohort women group. |
|
| Exposed cohort infants-before 1st day of 27th week of pregnancy | This group consisted of infants whose mothers belong to the Exposed cohort women-before 1st day of 27th week of pregnancy group. |
|
| From birth through 6 months of age |
| 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 |
| With unknown pregnancy outcome |
|
| Maternal death |
|
| Neonatal death |
|
| BG001 |
| Unexposed Historical Cohort Women |
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 |
| BG002 | Exposed Cohort Women-before 1st Day of 27th Week of Pregnancy | 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 |
| BG003 | Exposed Cohort infants-on or After 1st Day of 27th Week of Pregnancy | This group consisted of infants whose mothers belong to Exposed cohort women-on or after 1st day of 27th week of pregnancy group |
| BG004 | Unexposed Historical Cohort Infants | This group consisted of infants whose mothers belong to the Unexposed historical cohort women group |
| BG005 | Exposed Cohort Infants-before 1st Day of 27th Week of Pregnancy | This group consisted of infants whose mothers belong to the Exposed cohort women-before 1st day of 27th week of pregnancy group |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
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|
|
|
|
| Primary | 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. | The analysis was performed on all women from the Exposed cohort women-on or after 1st day of 27th week of pregnancy group and the Unexposed historical cohort women group, who met the eligibility criteria and for whom the event could be assessed. | Posted | Number | 95% Confidence Interval | Events per 1000 persons | 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 |
|
|
|
|
| Primary | 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. | The analysis was performed on live singleton infants for whom the event could be assessed and who born to women from Exposed cohort women-on or after 1st day of 27th week of pregnancy group and Unexposed historical cohort women group, who met eligibility criteria. | Posted | Number | 95% Confidence Interval | Events per 1000 persons | From birth through 6 months of age |
|
|
|
|
| Secondary | 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. | The analysis was performed on all women from the Exposed cohort women-on or after 1st day of 27th week of pregnancy group and the Unexposed historical cohort women group, who met the eligibility criteria and for whom the event could be assessed. Incidence rate of maternal death was not calculated for Unexposed Historical Cohort Women Group as none were reported in this group. | Posted | Number | 95% Confidence Interval | Events per 1000 persons-year | 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 |
|
|
|
|
| Secondary | 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. | The analysis was performed on all women from the Exposed cohort women-on or after 1st day of 27th week of pregnancy group and the Unexposed historical cohort women group, who met the eligibility criteria and for whom the specified event could be assessed. Incidence rate of stillbirth/fetal death with congenital anomalies was not calculated for Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Women Groups as none were reported in these groups. | Posted | Number | 95% Confidence Interval | Events per 1000 persons | 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 |
|
|
|
|
| Secondary | 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. | The analysis was performed on live singleton infants for whom the specified event could be assessed, and who born to women from Exposed cohort women-on or after 1st day of 27th week of pregnancy group and Unexposed historical cohort women group, who met the eligibility criteria. | Posted | Number | 95% Confidence Interval | Events per 1000 persons | From birth through 6 months of age |
|
|
|
|
| Secondary | 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. | The analysis was performed on women from Exposed cohort women-before 1st day of 27th week of pregnancy group who met the eligibility criteria and for whom the specified event could be assessed. Incidence rate of placental abruption and maternal death was not calculated for Exposed Cohort Women-before 1st Day of 27th Week of Pregnancy Group as none were reported in this group. | Posted | Number | 95% Confidence Interval | Events per 1000 persons-year | 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 |
|
|
|
| Secondary | 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. | The analysis was performed on women from Exposed cohort women-before 1st day of 27th week of pregnancy group who met the eligibility criteria and for whom the specified event could be assessed. Incidence rate of stillbirth/fetal death, stillbirth/fetal death with congenital anomalies, spontaneous abortion with congenital anomalies, therapeutic abortion, or therapeutic abortion with congenital anomalies was not calculated for the analyzed group as none were reported in this group. | Posted | Number | 95% Confidence Interval | Events per 1000 persons | 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 |
|
|
|
| Secondary | 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. | The analysis was performed on infants for whom the specified event could be assessed, who were born to women from Exposed cohort women-before 1st day of 27th week of pregnancy group, and who met the eligibility criteria. Incidence rate of neonatal death; clefts; congenital anomalies of: nervous system, respiratory system; lower gastrointestinal system, limb, or other and unspecified congenital anomalies was not calculated for the analyzed group as none were reported in this group. | Posted | Number | 95% Confidence Interval | Events per 1000 persons | From birth through 6 months of age |
|
|
|
| 2 |
| 16,606 |
| 3,733 |
| 16,606 |
| 0 |
| 0 |
| EG001 | Unexposed Historical Cohort Women | 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 | 0 | 16,606 | 3,679 | 16,606 | 0 | 0 |
| EG002 | Exposed Cohort Women-before 1st Day of 27th Week of Pregnancy | 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 | 0 | 65 | 18 | 65 | 0 | 0 |
| EG003 | Exposed Cohort infants-on or After 1st Day of 27th Week of Pregnancy | This group consisted of infants whose mothers belong to Exposed cohort women-on or after 1st day of 27th week of pregnancy group | 15 | 16,350 | 5,540 | 16,350 | 0 | 0 |
| EG004 | Unexposed Historical Cohort Infants | This group consisted of infants whose mothers belong to the Unexposed historical cohort women group | 17 | 16,088 | 4,211 | 16,088 | 0 | 0 |
| EG005 | Exposed Cohort Infants-before 1st Day of 27th Week of Pregnancy | This group consisted of infants whose mothers belong to the Exposed cohort women-before 1st day of 27th week of pregnancy group | 0 | 68 | 30 | 68 | 0 | 0 |
|
| Intra-uterine infections | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Small for gestational age | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Preterm delivery | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Transfusion during delivery hospitalization | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Poor fetal growth | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Placental abruption | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Preterm pre-labor rupture of membranes | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of nervous system | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of eye | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of ear, face or neck | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of cardiovascular system | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of respiratory system | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Clefts | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of upper gastrointestinal system | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of lower gastrointestinal system | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of genital organs | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of renal system | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of musculoskeletal system | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of limb | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Congenital anomalies of integument | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Other and unspecified congenital anomalies | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Spontaneous abortion | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Maternal deaths | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
| Stillbirths/fetal deaths without congenital anomalies | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
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| Neonatal deaths | General disorders | No vocabulary source | Systematic Assessment | No medical dictionary coding applied to this event |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D012140 | Respiratory Tract Diseases |
| Placental abruption |
|
|
| Preterm pre-labor rupture of membranes |
|
|
| Maternal death |
|
|
| Assessment of adjusted RR for placental abortion in Exposed women cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical women cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.31 | 2-Sided | 95 | 0.99 | 1.72 | Adjusted RR with 95% CI - Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. Superiority to be concluded if lower limit of the 95% CI for the adjusted RR is above 1. |
| Assessment of adjusted RR for preterm pre-labor rupture of membranes in Exposed women cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical women cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 0.76 | 2-Sided | 95 | 0.64 | 0.91 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. Superiority to be concluded if lower limit of the 95% CI for the adjusted RR is above 1. |
| Stillbirth/fetal death with congenital anomalies |
|
| Transfusion during delivery hospitalization |
|
|
| Assessment of adjusted RR for transfusion during delivery hospitalization in Exposed women cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical women cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.07 | 2-Sided | 95 | 0.86 | 1.33 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Congenital anomalies of eye |
|
| Congenital anomalies of ear, face, or neck |
|
| Congenital anomalies of cardiovascular system |
|
| Congenital anomalies of respiratory system |
|
| Clefts |
|
| Congenital anomalies of upper gastrointestinal system |
|
| Congenital anomalies of lower gastrointestinal system |
|
| Congenital anomalies of genital organs |
|
| Congenital anomalies of renal system |
|
| Congenital anomalies of musculoskeletal system |
|
| Congenital anomalies of limb |
|
| Congenital anomalies of integument |
|
| Other and unspecified congenital anomalies |
|
| Assessment of adjusted RR for congenital anomalies of nervous system in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.35 | 2-Sided | 95 | 0.81 | 2.24 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of eye in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.17 | 2-Sided | 95 | 1.06 | 1.29 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of ear, face or neck in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing. | Risk Ratio (RR) | 2.02 | 2-Sided | 95 | 1.59 | 2.55 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of cardiovascular system in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infant cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.12 | 2-Sided | 95 | 0.96 | 1.31 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of respiratory system in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.34 | 2-Sided | 95 | 1.07 | 1.68 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for clefts in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.41 | 95 | 0.78 | 2.57 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of upper gastrointestinal system in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.75 | 2-Sided | 95 | 1.57 | 1.95 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of lower gastrointestinal system in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 0.63 | 2-Sided | 95 | 0.36 | 1.12 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of genital organs in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.19 | 2-Sided | 95 | 1.01 | 1.42 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of renal system in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing. | Risk Ratio (RR) | 1.40 | 2-Sided | 95 | 1.04 | 1.88 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of musculoskeletal system in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.50 | 95 | 1.21 | 1.86 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of limb in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.13 | 2-Sided | 95 | 0.85 | 1.52 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for congenital anomalies of integument in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.98 | 2-Sided | 95 | 1.76 | 2.23 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
| Assessment of adjusted RR for other and unspecified congenital anomalies in Exposed infants cohort (on or after 1st day of 27th week of pregnancy) compared to Unexposed historical infants cohort was 1 or differed from 1 (superiority testing). | Risk Ratio (RR) | 1.09 | 2-Sided | 95 | 0.64 | 1.85 | Adjusted RR with 95% CI-Poisson regression model | Superiority | The objective was to explore differences (superiority testing) in the incidence rate of each of the maternal and infant adverse events, among vaccinated women with Boostrix and their infants as compared to the incidence in a matched cohort of unvaccinated women and their infants. The null hypothesis H0 RR=1 was rejected if lower limit of 95% CI for adjusted RR was above 1. |
|
| Poor fetal growth |
|
|
| Placental abruption |
|
| Preterm pre-labor rupture of membranes |
|
|
| Maternal death |
|
|
| Spontaneous abortion with congenital anomalies |
|
| Therapeutic abortion |
|
| Therapeutic abortion with congenital anomalies |
|
| Transfusion during delivery hospitalization |
|
|
| Preterm delivery |
|
|
| Clefts |
|
| Congenital anomalies of nervous system |
|
| Congenital anomalies of eye |
|
|
| Congenital anomalies of ear, face, or neck |
|
|
| Congenital anomalies of cardiovascular system |
|
|
| Congenital anomalies of respiratory system |
|
| Congenital anomalies of upper gastrointestinal system |
|
|
| Congenital anomalies of lower gastrointestinal system |
|
| Congenital anomalies of genital organs |
|
|
| Congenital anomalies of renal system |
|
|
| Congenital anomalies of musculoskeletal system |
|
|
| Congenital anomalies of limb |
|
| Congenital anomalies of integument |
|
|
| Other and unspecified congenital anomalies |
|