Meningococcal Quadrivalent CRM-197 Conjugate Vaccine Pregnancy Registry

Study Overview
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Brief Summary
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The GlaxoSmithKline's Meningococcal quadrivalent CRM-197 conjugate vaccine pregnancy registry is established to meet a post marketing commitment agreed upon with CBER to prospectively collect data on pregnancy exposures to Meningococcal quadrivalent CRM-197 conjugate vaccine. It is an observational study of women inadvertently immunized with the Meningococcal quadrivalent CRM-197 conjugate vaccine within 28 days prior to conception or at any time during pregnancy as part of routine care. The objective of the pregnancy registry is to evaluate pregnancy outcomes among women immunized with the Meningococcal quadrivalent CRM-197 conjugate vaccine within 28 days prior to conception or at any time during pregnancy. The primary outcomes of interest include major congenital malformation, preterm birth, and low birth weight. Other pregnancy outcomes will be collected, including spontaneous abortions and stillbirths.

Official Title
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MENVEO Pregnancy Registry: an Observational Study on the Safety of MENVEO Exposure in Pregnant Women and Their Offspring

Conditions
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Meningococcal Disease, Pregnancy, Infections, Meningococcal

Intervention / Treatment
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* Biological: Meningococcal quadrivalent CRM-197 conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sufficient evidence to confirm that MENVEO exposure occurred within 28 days prior to conception or at any time during pregnancy Sufficient information to determine whether the pregnancy is prospectively or retrospectively registered (ie, whether the outcome of pregnancy was known at the time of first contact with the registry) Date the pregnancy exposure is registered Full reporter (ie, HCP) contact information to allow for follow-up (name, address, etc.) Exclusion Criteria:
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 |
| --- | --- |
| Exposure group<br>Pregnant women who were exposed to ≥1 dose of Menveo vaccine within 28 days prior to conception or at any time during pregnancy were included. | Biological: Meningococcal quadrivalent CRM-197 conjugate vaccine<br>* This pregnancy registry is strictly observational. Decisions of vaccination are made by health care providers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Live Births Reported With Major Congenital Malformations (MCM) on Exposure to Menveo Within 28 Days Prior to Conception | The pregnancy registry defined an MCM as any major structural or chromosomal defect or combination of 2 or more conditional defects in live-born infants, stillbirths, or fetal losses of any gestational age. This outcome measure was analyzed on live births reported with MCM, for subjects who were exposed to Menveo vaccine within 28 days prior to conception. The prevalence estimate of MCM was calculated as proportions of live births with MCM from the total number of live births | From the time of enrolment until the date of pregnancy outcome documentation (i.e. From registration upon Menveo exposure within 28 days prior to conception until the estimated delivery date) | 
| Percentage of Live Births Reported With Major Congenital Malformations (MCM) on Exposure to Menveo Vaccine During the First Trimester | The pregnancy registry defined an MCM as any major structural or chromosomal defect or combination of 2 or more conditional defects in live-born infants, stillbirths, or fetal losses of any gestational age. This outcome measure was analyzed on live births reported with MCM, for subjects who were exposed to Menveo vaccine during the first trimester of pregnancy.The prevalence estimate of MCM was calculated as proportions of live births with MCM from the total number of live births. | From the time of enrolment until the date of pregnancy outcome documentation (i.e.From registration upon Menveo exposure during first trimester of pregnancy [0-13 weeks] until the estimated delivery date) | 
| Percentage of Live Births Reported With Major Congenital Malformations (MCM) on Exposure to Menveo Vaccine During the Second Trimester | The pregnancy registry defined an MCM as any major structural or chromosomal defect or combination of 2 or more conditional defects in live-born infants, stillbirths, or fetal losses of any gestational age. This outcome measure was analyzed on live births reported with MCM, for subjects who were exposed to Menveo vaccine during the second trimester of pregnancy.The prevalence estimate of MCM was calculated as proportions of live births with MCM from the total number of live births | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure during second trimester of pregnancy [14-27 weeks] until the estimated delivery date) | 
| Percentage of Live Births Reported With Major Congenital Malformations (MCM) on Exposure to Menveo Vaccine During Third Trimester | The pregnancy registry defined an MCM as any major structural or chromosomal defect or combination of 2 or more conditional defects in live-born infants, stillbirths, or fetal losses of any gestational age. This outcome measure was analyzed on live births reported with MCM, for subjects who were exposed to Menveo vaccine during the third trimester of pregnancy.The prevalence estimate of MCM was calculated as proportions of live births with MCM from the total number of live births | From the time of enrolment until the date of pregnancy outcome documentation (i.e.From registration upon Menveo exposure during third trimester of pregnancy [>27 weeks] until the estimated delivery date) | 
| Percentage of Live Births Reported With Major Congenital Malformations (MCM) on Exposure to Menveo Within 28 Days Prior to Conception or at Any Time During the Pregnancy | The pregnancy registry defined an MCM as any major structural or chromosomal defect or combination of 2 or more conditional defects in live-born infants, stillbirths, or fetal losses of any gestational age. This outcome measure was analyzed on live births reported with MCM, for subjects who were exposed to Menveo vaccine within 28 days prior to conception or at any time during the pregnancy.The prevalence estimate of MCM was calculated as proportions of live births with MCM from the total number of live births | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon exposure to Menveo within 28 days prior to conception or at any time during pregnancy until the estimated delivery date) | 
| Percentage of Preterm Births Reported on Exposure to Menveo Vaccine Within 28 Days Prior to Conception | A pregnancy outcome that is reported with a preterm birth represents an infant born at a gestational age under (<) 37 weeks. The prevalence rate of preterm birth was calculated as a proportion, with the number of preterm births as the numerator and the number of live births as the denominator. Because MCMs are often associated with preterm birth and LBW, infants with MCMs were excluded from analyses of this outcome measure and were not counted in the numerator or denominator when prevalence rate was determined. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure within 28 days prior to conception until the estimated delivery date) | 
| Percentage of Preterm Births Reported on Exposure to Menveo Vaccine During the First Trimester | A pregnancy outcome that is reported with a preterm birth represents an infant born at a gestational age under (<) 37 weeks. The prevalence rate of preterm birth was calculated as a proportion, with the number of preterm births as the numerator and the number of live births as the denominator. Because MCMs are often associated with preterm birth and LBW, infants with MCMs were excluded from analyses of this outcome measure and were not counted in the numerator or denominator when prevalence rate was determined. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure during first trimester of pregnancy [0-13 weeks] until the estimated delivery date) | 
| Percentage of Preterm Births Reported on Exposure to Menveo Vaccine During the Second Trimester | A pregnancy outcome that is reported with a preterm birth represents an infant born at a gestational age under (<) 37 weeks. The prevalence rate of preterm birth was calculated as a proportion, with the number of preterm births as the numerator and the number of live births as the denominator. Because MCMs are often associated with preterm birth and LBW, infants with MCMs were excluded from analyses of this outcome measure and were not counted in the numerator or denominator when prevalence rate was determined. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure during second trimester of pregnancy [14-27 weeks] until the estimated delivery date) | 
| Percentage of Preterm Births Reported on Exposure to Menveo Vaccine During the Third Trimester | A pregnancy outcome that is reported with a preterm birth represents an infant born at a gestational age under (<) 37 weeks. The prevalence rate of preterm birth was calculated as a proportion, with the number of preterm births as the numerator and the number of live births as the denominator. Because MCMs are often associated with preterm birth and LBW, infants with MCMs were excluded from analyses of this outcome measure and were not counted in the numerator or denominator when prevalence rate was determined. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure during third trimester of pregnancy (>27 weeks) until the estimated delivery date) | 
| Percentage of Preterm Births Reported on Exposure to Menveo Vaccine Within 28 Days Prior to Conception or at Any Time During the Pregnancy | A pregnancy outcome that is reported with a preterm birth represents an infant born at a gestational age under (<) 37 weeks. The prevalence rate of preterm birth was calculated as a proportion, with the number of preterm births as the numerator and the number of live births as the denominator. Because MCMs are often associated with preterm birth and LBW, infants with MCMs were excluded from analyses of this outcome measure and were not counted in the numerator or denominator when prevalence rate was determined. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon exposure to Menveo within 28 days prior to conception or at any time during pregnancy until the estimated delivery date) | 
| Percentage of Low Birth Weight (LBW) Live Births Reported on Exposure to Menveo Vaccine Vaccine Within 28 Days Prior to Conception | A pregnancy outcome that is reported as a LBW birth represents an infant whose birth weight is <2500 g. The prevalence rate of LBW was calculated as a proportion, with the number of LBW infants as the numerator and the number of live births as the denominator. Infants with MCMs were excluded from the analysis of this outcome measure as MCMs are often associated with LBW. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure within 28 days prior to conception until the estimated delivery date) | 
| Percentage of LBW Live Births Reported on Exposure to Menveo Vaccine During the First Trimester | A pregnancy outcome that is reported as a LBW birth represents an infant whose birth weight is <2500 g. The prevalence rate of LBW was calculated as a proportion, with the number of LBW infants as the numerator and the number of live births as the denominator. Infants with MCMs were excluded from the analysis of this outcome measure as MCMs are often associated with LBW. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure during first trimester of pregnancy [0-13 weeks] until the estimated delivery date) | 
| Percentage of LBW Live Births Reported on Exposure to Menveo Vaccine During the Second Trimester | A pregnancy outcome that is reported as a LBW birth represents an infant whose birth weight is <2500 g. The prevalence rate of LBW was calculated as a proportion, with the number of LBW infants as the numerator and the number of live births as the denominator. Infants with MCMs were excluded from the analysis of this outcome measure as MCMs are often associated with LBW. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure during second trimester of pregnancy [14-27 weeks] until the estimated delivery date) | 
| Percentage of LBW Live Births Reported on Exposure to Menveo Vaccine During the Third Trimester | A pregnancy outcome that is reported as a LBW birth represents an infant whose birth weight is <2500 g. The prevalence rate of LBW was calculated as a proportion, with the number of LBW infants as the numerator and the number of live births as the denominator. Infants with MCMs were excluded from the analysis of this outcome measure as MCMs are often associated with LBW. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure during third trimester of pregnancy (>27 weeks) until the estimated delivery date) | 
| Percentage of LBW Live Births Reported on Exposure to Menveo Vaccine Within 28 Days Prior to Conception or at Any Time During the Pregnancy | A pregnancy outcome that is reported as a LBW birth represents an infant whose birth weight is <2500 g. The prevalence rate of LBW was calculated as a proportion, with the number of LBW infants as the numerator and the number of live births as the denominator. Infants with MCMs were excluded from the analysis of this outcome measure as MCMs are often associated with LBW. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon exposure to Menveo within 28 days prior to conception or at any time during pregnancy until the estimated delivery date) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Pregnancy Outcomes Reported for Subjects Exposed to Menveo Within 28 Days Prior to Conception | The pregnancy outcomes assessed were: live births, stillbirths, SABs, IABs, ectopic pregnancy, molar pregnancy and others. Spontaneous abortions (SABs) are defined as fetal death or expulsion of products of conception prior to 20 weeks gestation. Induced abortions (IABs) are defined as voluntary interruption of pregnancy, including pregnancy termination that occurs electively, to preserve maternal health, or due to fetal abnormalities. Stillbirths are defined as fetal death occurring at 20 weeks gestation or greater, or if gestation age is unknown, a fetus weighing 500 g or more. Ectopic pregnancy is defined as implantation of a conception outside of the uterus. Molar pregnancy is defined as a conception that results in a gestational trophoblastic tumor. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure within 28 days prior to conception until the estimated delivery date) | 
| Number of Pregnancy Outcomes Reported for Subjects Exposed to Menveo During the First Trimester | The pregnancy outcomes assessed were: live births, stillbirths, SABs, IABs, ectopic pregnancy, molar pregnancy and others. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure during first trimester of pregnancy [0-13 weeks] until the estimated delivery date) | 
| Number of Pregnancy Outcomes Reported for Subjects Exposed to Menveo Vaccine During the Second Trimester | The pregnancy outcomes assessed were: live births, stillbirths, SAB, IAB, ectopic pregnancy, molar pregnancy and others | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure during second trimester of pregnancy [14-27 weeks] until the estimated delivery date) | 
| Number of Pregnancy Outcomes Reported for Subjects Exposed to Menveo Vaccine During the Third Trimester | The pregnancy outcomes assessed were: Live births, stillbirths, SAB,IAB, ectopic pregnancy, molar pregnancy and others. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon Menveo exposure during third trimester of pregnancy (>27 weeks) until the estimated delivery date) | 
| Number of Pregnancy Outcomes Reported for Subjects Exposed to Menveo Vaccine Within 28 Days Prior to Conception or at Any Time During the Pregnancy | The pregnancy outcomes assessed were: Live births,stillbirths, SAB, IAB, ectopic pregnancy, molar pregnancy and others. | From the time of enrolment until the date of pregnancy outcome documentation (i.e. from registration upon exposure to Menveo within 28 days prior to conception or at any time during pregnancy until the estimated delivery date) |