Safety of Tetanus, Diphtheria, Acellular Pertussis With 5 Acellular Pertussis Components (Tdap5) Vaccination During Pregnancy

Safety of Tetanus, Diphtheria, Acellular Pertussis With 5 Acellular Pertussis Components (Tdap5) Vaccination During Pregnancy: A Cohort Study Using US Electronic Medical Record Data

The purpose of this study is to evaluate the safety of Adacel vaccine among pregnant individuals exposed to Adacel at any point between the 1st day of the 27th week of gestation up to the end of pregnancy and their offspring (ie, Adacel-exposed cohort), in comparison with pregnant individuals not vaccinated with any Tdap vaccines during pregnancy and their offspring (ie, Tdap-unvaccinated comparator cohort).

The primary objectives are to estimate incidence rates and relative risks for each prespecified pregnancy outcome in Adacel-exposed and Tdap-unvaccinated comparator cohorts and for each prespecified adverse birth outcome in the offspring of both cohorts.

The secondary objectives are to estimate incidence rates and relative risks for each prespecified adverse fetal and neonatal outcome in the offspring of Adacel-exposed and Tdap unvaccinated comparator cohorts and for each prespecified adverse outcome for pregnant individuals in both cohorts.

Study Overview

• Status: Active, not recruiting
• Conditions: Pertussis (Whooping Cough)
• Intervention / Treatment: Other: Not applicable / database analysis

Detailed Description

This is a retrospective cohort study utilizing existing EHR data to identify eligible pregnant individuals, with an observation period spanning January 2016 through December 2024. Given this study design, follow-up for all pregnancies with documented deliveries is expected to be complete by December 2025.

The study report is expected to be completed by 31 December 2026.

• Study Type: Observational
• Enrollment (Estimated): 365000

Contacts and Locations

Study Locations

• France
  • Chilly-Mazarin, France, 91380
    • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population will be comprised of 2 cohorts of pregnant individuals with pregnancy onset from 01 January 2016 through 31 December 2024. Infants born from this study population of pregnant individuals with singleton gestation pregnancies will be eligible for inclusion in this study. Eligible live born infants must be born on 01 October 2025 or prior to this date, to allow adequate follow-up time

Description

Inclusion Criteria:

• For pregnant individuals:

  • Continuous enrollment, with no more than a 1-month administrative gap from 90 days prior to their last menstrual period (LMP)
  • Continuous enrollment for the duration of their pregnancy through delivery or termination of pregnancy (or 6 weeks postpartum for preeclampsia/eclampsia and 28 days for PPH) unless censored at death in order to capture study outcomes
  • At least 1 prenatal visit prior to 27 weeks of gestation during pregnancy

• For offspring:

  • Infants delivered by pregnant individuals who meet all the inclusion criteria above
  • With gestational age as calculated based on date of birth recorded in the EMR

Exclusion Criteria:

• For pregnant individuals:

  • Loss of pregnancy or with delivery before 27 weeks of gestation
  • Vaccinated with Boostrix® (Tdap vaccine, GSK), or with an unknown brand of Tdap vaccine, or Td (tetanus, diphtheria) vaccine during pregnancy
  • Vaccinated with any Tdap vaccine prior to the ACIP recommended optimal timeframe of ≥ 27 0/7 weeks of gestation
  • Received more than one Tdap vaccine during pregnancy
  • Vaccinated with one or more live vaccines during pregnancy
  • Pregnant individuals with multiple gestation pregnancies (eg, twins, triplets)

• For offspring:

  • Infants delivered by pregnant individuals who meet any of the exclusion criteria above

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adacel-Exposed Cohort; Cohort will include all pregnant individuals with a record of Adacel vaccination during the third trimester of pregnancy (ie, first day of 27th week of gestation up to the end of pregnancy) and their offspring	Other: Not applicable / database analysis; Not applicable / database analysis
Tdap-Unvaccinated Comparator Cohort; Cohort will include all pregnant individuals meeting eligibility criteria and with no record of any Tdap vaccination from pregnancy onset date until the end of pregnancy and their offspring	Other: Not applicable / database analysis; Not applicable / database analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy outcome: Live birth	Incidence rates of live births in Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation up to 42 weeks gestation
Pregnancy outcome: Still birth/fetal demise	Incidence rates of still birth/fetal demise in Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation up to 42 weeks gestation
Pregnancy outcome: Therapeutic abortion	Incidence rates of therapeutic abortion in Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation up to 42 weeks gestation
Birth outcome: Preterm birth	Incidence rates of preterm birth in live born infants of both Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation and less than 37 weeks gestation
Birth outcome: Low birth weight	Incidence rates of low birth weight in live born infants of both Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation up to 42 weeks gestation
Birth outcome: Small for gestational age	Incidence rates of small for gestational age in live born infants of both Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation up to 42 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse neonatal outcome: Neonatal death	Incidence rates of neonatal death in the offspring of Adacel-exposed and Tdap-unvaccinated comparator cohorts	From birth up to 28 days post-birth
Adverse neonatal outcome: Neonatal sepsis	Incidence rates of neonatal sepsis in the offspring of Adacel-exposed and Tdap-unvaccinated comparator cohorts	From birth up to 28 days post-birth
Adverse neonatal outcome: Neonatal respiratory distress	Incidence rates of neonatal respiratory distress in the offspring of Adacel-exposed and Tdap-unvaccinated comparator cohorts	From birth up to 28 days post-birth
Adverse neonatal outcome: Congenital anomalies	Incidence rates of congenital anomalies (major and minor) in the offspring of Adacel-exposed and Tdap-unvaccinated comparator cohorts	From birth up to 28 days post-birth
Adverse neonatal outcome: Neonatal/early infancy intensive care admissions for bronchopulmonary dysplasia	Incidence rates of neonatal/early infancy intensive care admissions for bronchopulmonary dysplasia in the offspring of Adacel-exposed and Tdap-unvaccinated comparator cohorts	From birth up to 28 days post-birth
Adverse fetal outcome: Fetal growth arrest (restriction)	Incidence rates of fetal growth arrest (restriction) in Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation up to 42 weeks gestation
Adverse outcomes in pregnant individuals: Preterm labor	Incidence rates of Preterm labor in Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation and less than 37 weeks gestation
Adverse outcomes in pregnant individuals: Preeclampsia/eclampsia	Incidence rates of preeclampsia/eclampsia in Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation up to 42 days postpartum
Adverse outcomes in pregnant individuals: Postpartum hemorrhage	Incidence rates of postpartum hemorrhage in Adacel-exposed and Tdap-unvaccinated comparator cohorts	Within 24 hours of delivery up to 28 days postpartum
Adverse outcomes in pregnant individuals: Placental abruption	Incidence rates of placental abruption in Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation up to 42 weeks gestation
Adverse outcomes in pregnant individuals: Premature rupture of membranes	Incidence rates of premature rupture of membranes in Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation up to 42 weeks gestation
Adverse outcomes in pregnant individuals: Chorioamnionitis	Incidence rates of chorioamnionitis in Adacel-exposed and Tdap-unvaccinated comparator cohorts	From 1st day of the 27th week of gestation up to 42 weeks gestation

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 12, 2024
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Bordetella Infections; Whooping Cough
• Other Study ID Numbers: TD500066 (Other Identifier: Sanofi Identifier); U1111-1290-9165 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No