A Post-marketing, Observational, Retrospective Study to Assess the Safety of RefortrixTM (Tdap) When Administered During Pregnancy in a Maternal Immunization Program in Brazil.

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety of RefortrixTM (Tdap) when administered during pregnancy in a maternal immunization program in Brazil.

Detailed Description
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In this retrospective cohort study the safety of RefortrixTM (Tdap) administered during pregnancy as part of the National immunization program in Brazil will be assessed by comparing the risk of pre-defined adverse events before and after introduction of the RefortrixTM (Tdap) maternal immunization program.

Official Title
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A Post-marketing, Observational, Retrospective, Cohort Study to Assess the Safety of RefortrixTM (Tdap) When Administered During Pregnancy in a Maternal Immunization Program in Brazil.

Conditions
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Diphtheria

Intervention / Treatment
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* Biological: Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects between 18 and 45 years of age at the time of pregnancy under consideration for the study, who deliver in the study centre. Residents of the study area Subjects who were compliant with the routine antenatal care including at least one ultrasound assessment report early in the pregnancy. Subjects with the complete and relevant medical records available. Inclusion criteria for the Exposed cohort: Subjects who received one dose of Refortrix vaccine in the recommended time period between 27 and 36 completed weeks of pregnancy (or as late as 20 days before delivery due date) as part of the maternal immunization program in Brazil, and according to the program recommendations from May 2015 onwards. Subjects with appropriate vaccination records. Inclusion criteria for the Unexposed cohort: Subjects who had delivered in the same hospital (study centre) before 01 September 2014 (September 2012-August 2014) and who did not receive Tdap vaccination during pregnancy to the best knowledge of the investigator. Exclusion Criteria: Subjects who have been transferred to other specialised centres, where their medical records would be inaccessible for the study (private clinics, psychiatric or prison hospitals, other state hospitals, etc).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Exposed cohort<br>Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) from May 2015 and who received one dose of Refortrix during 27 to 36 weeks of pregnancy (or as late as 20 days before delivery due date). | Biological: Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]<br>* Subjects were included in the Exposed cohort if they received Refortrix as part of the maternal immunization program in Brazil.<br>|
| Unexposed cohort<br>Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) before implementation of the maternal immunization program in Brazil in September 2014 and who did not receive Tdap vaccination during pregnancy. | Biological: Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]<br>* Subjects were included in the Exposed cohort if they received Refortrix as part of the maternal immunization program in Brazil.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Gestational Diabetes | Gestational diabetes was defined as: Onset or first recognition of abnormal glucose tolerance during pregnancy (the diagnosis is based on administration of glucose challenge test at 24-28 weeks of gestation). Includes Class A1: Euglycaemia achieved with diet and/or exercise and Class A2: Euglycaemia achieved with medication. | After week 27 of pregnancy | 
| Number of Subjects Reporting Pregnancy-related Hypertension, Pre-eclampsia, Eclampsia, and HELLP Syndrome | Pregnancy-related hypertension is defined as: Blood pressure systolic higher than (>) 140 and/or diastolic > 90 millimetre of mercury (mmHg), documented in at least two separate measurements after 20 weeks of gestation, without proteinuria or other stigmata of pre-eclampsia, and returning to normal post-partum. Hypertension usually resolves by 12 weeks post-partum, included pre-eclampsia, eclampsia and haemolysis elevated liver enzymes low platelet (HELLP) Syndrome for this study. | After week 27 of pregnancy | 
| Number of Subjects Reporting Pregnancy Hemorrhage | Pregnancy vaginal hemorrhage is defined as: excessive blood loss after delivery i.e. estimated blood loss in excess of 500 milliliters (ml) after vaginal delivery and estimated blood loss in excess of 1000 ml after Caesarean delivery. The other symptoms are higher than or equal to (≥) 10 percent (%) drop in hematocrit, need for blood transfusion, symptomatic hypotension, dizziness, pallor and oliguria. Vaginal or intrauterine hemorrhage that encompasses antepartum (i.e. bleeding from the genital tract after 24 weeks of gestation), intrapartum, and postpartum bleeding (i.e. within 24 hours post-delivery). A major obstetric hemorrhage is defined as blood loss from uterus or genital tract >1500 ml or a decrease. | After week 27 of pregnancy | 
| Number of Subjects With Pre-specified Neonate-related Outcomes Resulting in Preterm Birth | Preterm birth is defined as: Birth before 37 weeks of gestation. | From week 27 up to week 37 of pregnancy | 
| Number of Subjects With Pre-specified Neonate-related Outcomes, Resulting in Neonates Small for Their Gestational Age | Small for gestational age is defined as: Birth weight less than (<) 10% for infants of same gestational age and gender in same population. | After week 27 of pregnancy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery | Pregnancy-related AEs of interest and neonate-related events are defined as: premature rupture of membranes, preterm premature rupture of membranes, premature uterine contraction, neonatal death, maternal death, still birth, neonatal hypoxic ischaemic encephalopathy. | After week 27 of pregnancy | 
| Number of Subjects Reporting Cases of Congenital Anomalies in the Neonates | Congenital anomalies include morphological, functional, chromosomal or genetic anomalies, regardless of whether detected at birth or not, the foetus is delivered dead or alive, or defects are identified by prenatal ultrasound, amniocentesis or examination of the products of conception. | From week 27 of pregnancy up to birth | 
| Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year | Pregnancy related AEs include: gestational diabetes, pregnancy-related hypertension, pre-eclampsia, eclampsia, HELLP Syndrome and pregnancy hemorrhage. Birth outcomes include: preterm birth and small for gestational age. | After week 27 of pregnancy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exposed and unexposed cohorts, post-marketing, maternal immunization, neonate related Adverse Events, Congenital anomaly, RefortrixTM, Pregnancy related Adverse Events