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

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.

Fig. 1

Timing of modules for collection of key variables. B baseline module, C-VIPER COVID-19 Vaccines International Pregnancy Registry, COVID-19 coronavirus disease 2019, D delivery module, F follow-up modules during pregnancy, LMP last menstrual period, PIPER Pregistry International Pregnancy Exposure Registry, V Vaccination module; 3, 6, 9, 12: maternal and infant outcomes modules at 3, 6, 9, and 12 months of age