The COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER): Protocol and Methodological Considerations

Diego F Wyszynski; Mondira Bhattacharya; Oscar Martínez-Pérez; Anthony R Scialli; Melissa Tassinari; Naor Bar-Zeev; Cheryl Renz; Sonia Hernández-Díaz

doi:10.1007/s40264-022-01271-3

The COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER): Protocol and Methodological Considerations

Drug Saf. 2023 Mar;46(3):297-308. doi: 10.1007/s40264-022-01271-3. Epub 2023 Jan 22.

Authors

Diego F Wyszynski¹, Mondira Bhattacharya², Oscar Martínez-Pérez³, Anthony R Scialli⁴, Melissa Tassinari⁵, Naor Bar-Zeev⁶, Cheryl Renz⁷, Sonia Hernández-Díaz⁸

Affiliations

¹ Pregistry, London, Cheshire, UK. diegow@pregistry.com.
² , Chicago, IL, USA.
³ Maternal-Fetal Medicine Unit, Department of Gynecology and Obstetrics, Puerta de Hierro University Hospital of Majadahonda, Madrid, Spain.
⁴ Reproductive Toxicology Center, A Non-Profit Foundation, Washington, DC, USA.
⁵ , Boston, MA, USA.
⁶ Department of International Health, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁷ , Pregistry, Los Angeles, CA, USA.
⁸ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Abstract

Introduction: The advent of the coronavirus disease 2019 (COVID-19) pandemic has led to the development of vaccines against severe acute respiratory syndrome coronavirus 2. Prospective evidence regarding safety for pregnant people and their developing fetuses is lacking. The aim of the COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) is to estimate the relative risk of obstetric, neonatal, and infant outcomes by comparing participants vaccinated against COVID-19 during pregnancy to a reference group of people enrolled in the Pregistry International Pregnancy Exposure Registry (PIPER) who remained unvaccinated during pregnancy.

Methods: The C-VIPER and the PIPER are international, non-interventional, real-world cohort studies. Participants receiving a COVID-19 vaccine during pregnancy will be matched in the analyses by country and gestational age at enrollment to unvaccinated individuals. Self-enrolled and self-consented participants complete online questionnaires at enrollment, during pregnancy, and for 12 months after the delivery of a live infant. Where possible, outcomes are verified by medical records. The study aims to recruit at least 500 pregnancies for each approved or authorized vaccine and will last for 5 years for each product.

Conclusions: By collecting data for each vaccine brand, the C-VIPER will be able to determine individual safety profiles. The study design allows for analysis of the effects of exposure to COVID-19 vaccines during specific etiologically relevant periods of gestation. Although the sample size may be too small to detect associations with rare outcomes, the study will be used to generate hypotheses for future research. Ultimately, the C-VIPER should provide data that will allow pregnant people and their healthcare providers to make informed decisions about COVID-19 vaccination.

Clinical trial registration: ClinicalTrials.gov NCT04705116. Registered on 12 January, 2021. EU PAS EUPAS39096. Registered on 20 January, 2021.

MeSH terms

COVID-19 Vaccines / adverse effects
COVID-19* / epidemiology
COVID-19* / prevention & control
Female
Humans
Infant, Newborn
Pregnancy
Prospective Studies
Treatment Outcome
Vaccines*

Substances

COVID-19 Vaccines
Vaccines

Associated data

ClinicalTrials.gov/NCT04705116