Lessons Learned From the COVID-19 Vaccines International Pregnancy Exposure Registry: Insights for Designing and Implementing Global Pregnancy Safety Studies.

BACKGROUND

Pregnant women are at increased risk of severe illness from COVID-19, yet they were excluded from the initial clinical trials of COVID-19 vaccines, resulting in limited pregnancy-specific safety data. The COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) was established to prospectively collect safety and birth outcome data following COVID-19 vaccination during pregnancy. This article summarizes key operational, methodological, and scientific lessons from implementation of the registry.

METHODS

The C-VIPER was designed as an international, noninterventional, postmarketing cohort study using a web-based platform to enroll pregnant women exposed to COVID-19 vaccines and collect longitudinal maternal, pregnancy, birth, neonatal, and infant outcome data. Registry implementation, recruitment, retention, questionnaire design, comparator selection, data completeness, and evolving vaccination patterns were reviewed to identify lessons relevant to future pregnancy safety studies.

RESULTS

Implementation during a global pandemic presented substantial challenges, including uncertainty regarding vaccine acceptance and study participation among pregnant women, widespread misinformation and vaccine hesitancy, evolving vaccination regimens, recruitment and long-term retention difficulties, and limitations in questionnaire design and data completeness. Despite these challenges, the C-VIPER demonstrated the feasibility of conducting a large-scale multinational, web-based pregnancy registry under emergency conditions and highlighted important methodological considerations for future postmarketing vaccine safety studies in pregnancy.

CONCLUSIONS

The C-VIPER contributed to the broader evidence base evaluating COVID-19 vaccination during pregnancy and provided important lessons for the design and implementation of future pregnancy registries. Future studies should prioritize early planning, flexible protocol design, robust recruitment and retention strategies, careful comparator selection, and mechanisms to improve data completeness and quality.

TRIAL REGISTRATION: NCT04705116, EUPAS39096.