COVID-19 Vaccines International Pregnancy Exposure Registry

Rationale and background: COVID-19 vaccines will be used in pregnant populations. Scientific evidence regarding their safety for pregnant women and the developing fetus is lacking.

Objective: The objective of the COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) is to estimate the risk of obstetric outcomes (spontaneous abortion, antenatal bleeding, gestational diabetes, gestational hypertension, intrauterine growth restriction, postpartum hemorrhage, fetal distress, uterine rupture, placenta previa, chorioamnionitis, Caesarean delivery, COVID-19), neonatal outcomes (major congenital malformations, low birth weight, neonatal death, neonatal encephalopathy, neonatal infections, neonatal acute kidney injury, preterm birth, respiratory distress in the newborn, small for gestational age, stillbirth, COVID-19), and infant outcomes (developmental milestones \[motor, cognitive, language, social-emotional, and mental health skills\], height, weight, failure to thrive, medical conditions during the first 12 months of life, COVID-19) among pregnant women exposed to single (homologous) or mixed (heterologous) COVID-19 vaccine brand series from 30 days prior to the first day of the last menstrual period (LMP) to end of pregnancy and their offspring relative to a matched reference group who received no COVID-19 vaccines during pregnancy.

Study design: The C-VIPER is an international, non-interventional, post-marketing cohort study designed to collect prospective safety data among women vaccinated with a COVID-19 vaccine during pregnancy or within 30 days prior to the first day of the LMP.

Population: The study population includes 2 cohorts of pregnant women 18 years of age and older matched by country and gestational age (±2 weeks):

* Cohort 1: pregnant women exposed from 30 days prior to the first day of the LMP to end of pregnancy to at least one dose of a COVID-19 vaccine. These participants are enrolled as part of the C-VIPER. * Cohort 2: pregnant women unexposed to a COVID-19 vaccine during pregnancy. These participants are enrolled through the Pregistry International Exposure Registry (PIPER) with the same methods as those in Cohort 1. Women vaccinated before 30 days prior to the first day of the LMP are eligible for inclusion.

Registration and participation via a website especially developed for the C-VIPER are voluntary. Eligible women can enroll at any time during pregnancy.

Data collection: Pregnancy data are collected at enrollment, monthly, and at the end of pregnancy. Liveborn infants are followed-up and data are collected at birth and then every three months until 12 months of age. Information is obtained directly from the participant. The C-VIPER collects data on potential confounding factors (such as maternal sociodemographic characteristics, occupation, behaviors, reproductive history, chronic conditions, results of SARS-CoV-2 tests before and during this pregnancy, new COVID-19 vaccinations, use of medications and other vaccinations, and measures of healthcare utilization), and information related to obstetric, neonatal, and infant outcomes. Given the international nature of the C-VIPER, the questionnaires are available in the languages spoken where it is conducted. Participant confidentiality and anonymity are strictly upheld.