Monitoring the safety of COVID-19 vaccines in pregnancy in the US

Figures & data

Table 1. Mechanisms for CDC COVID −19 vaccine safety monitoring among pregnant persons

System/Project	Vaccine Adverse Event Reporting System (VAERS)	V-safe	V-safe pregnancy registry	Vaccine Safety Datalink (VSD)
Collaboration	CDC and FDA	CDC	CDC	CDC and 9 Integrated Healthcare Plans
Description	VAERS is the U.S. frontline spontaneous reporting system that detects potential vaccine safety problems. It serves as the nation’s early warning system; can rapidly detect concerns and generate hypotheses for further safety studies. Anyone can report possible vaccine adverse events to VAERS. Enhanced monitoring, involving review of all reports and associated medical records, is being conducted to review adverse events reported following COVID-19 vaccines administration to pregnant people.	V-safe is a new CDC smartphone-based active surveillance system developed for the COVID-19 vaccination program; enrollment is voluntary. V-safe sends text messages to participants with weblinks to online surveys that assess for adverse reactions and health status during a post-vaccination follow-up period Surveys also include questions about pregnancy status at time of vaccination and about whether there has been a positive pregnancy test result following vaccination	Persons self-identifying as pregnant in v-safe may then be contacted by phone, and if they meet inclusion criteria, offered enrollment in the v-safe pregnancy registry. For persons who choose to enroll, the pregnancy registry phone-based survey collects detailed information about the participant, including medical and obstetric history, pregnancy complications, birth outcomes, and obstetric and pediatric healthcare provider contact information for medical records; infants are followed through the first three months of life. Data are analyzed in near real-time and include descriptive analyses and clinical and medical record review of adverse pregnancy and birth outcomes.	VSD is a large linked electronic health record-based database system used for epidemiologic research on vaccine safety and for active, near real-time monitoring of new vaccines and seasonal influenza vaccines. Both near real-time monitoring and traditional epidemiologic studies are being used to monitor the safety of COVID-19 vaccines in pregnancy.
Strengths	National data; accepts reports from anyone Rapid signal detection Able to detect rare adverse events Collects information about vaccine, characteristics of vaccine, and adverse event (AE) Data available to the public†	National active surveillance system Can calculate rates of adverse events Availability of control groups	National active surveillance system Can calculate proportions of adverse pregnancy and birth outcomes Detailed clinical/data on participants	Outpatient and inpatient medical encounters are available for the duration of a person’s enrollment in the participating health plan allowing for capture of prior pregnancies and medical conditions Datasets include information from state vaccine registries and birth and death certificates Can calculate background rates of AEs in the VSD population Unvaccinated comparison group to determine risk of an AE Electronic data is supplemented with medical records Validated algorithm to identify pregnancies and pregnancy outcomes Large annual birth cohort = 100,000
Limitations	Reporting bias Inconsistent data quality and completeness Lack of unvaccinated comparison group Generally, cannot assess if vaccine caused an AE Pregnancy status inconsistently reported	Participation is voluntary V-safe registration information not uniformly available in all vaccination locations Resource intensive Misclassification of participants as pregnant due to mistakes in completion of v-safe health surveys	V-safe registration information not uniformly available in all vaccination locations Participation is voluntary Sample size may be inadequate for very rare events Resource intensive Potential for lack of socioeconomic diversity Might not reflect true post-vaccination proportions of spontaneous abortions because participants might have been vaccinated after the period of greatest risk as well as because very early pregnancy losses might not be recognized.	Sample size may be inadequate for very rare events May take time to accumulate doses to power important outcomes of interest Vaccines administered outside of medical home may not be captured Potential for lack of socioeconomic diversity

† https://wonder.cdc.gov/vaers.html

Figure 1. Part of a VAERS form showing specific question on pregnancy status (inside red rectangle).

Figure 2. V-safe surveillance system reporting structure.

Figure 3. Relative pregnancy timing inclusion criteria for v-safe pregnancy registry enrollment.

Figure 4. Vaccine safety datalink sites.