Safety of COVID-19 vaccines in pregnancy: a Canadian National Vaccine Safety (CANVAS) Network study

Background Pregnant individuals have been receiving COVID-19 vaccines following pre-authorization clinical trials in non-pregnant people. This study aimed to determine significant health events amongst pregnant females after COVID-19 vaccination, compared with unvaccinated pregnant controls and vaccinated non-pregnant individuals. Methods Study participants were pregnant and non-pregnant females aged 15-49 years who had received any COVID-19 vaccine, and pregnant unvaccinated controls. Participants reported significant health events occurring within seven days of vaccination. We employed multivariable logistic regression to examine significant health events associated with mRNA vaccines. Findings Overall 226/5,597(4.0%) vaccinated pregnant females reported a significant health event after dose one of an mRNA vaccine, and 227/3,108(7.3%) after dose two, compared with 11/339(3.2%) pregnant unvaccinated females. Pregnant vaccinated females had an increased odds of a significant health event after dose two of mRNA-1273 (aOR 4.4,95%CI 2.4-8.3) compared to pregnant unvaccinated controls, but not after dose one of mRNA-1273 or any dose of BNT162b2. Pregnant females had decreased odds of a significant health event compared to non-pregnant females after both dose one (aOR 0.63,95%CI 0.55-0.72) and dose two (aOR 0.62,95%CI 0.54-0.71) of mRNA vaccination. There were no significant differences in any analyses when restricted to events which led to medical attention. Interpretation COVID-19 mRNA vaccines have a good safety profile in pregnancy. Rates of significant health events were higher after dose two of mRNA-1273 compared with unvaccinated controls, with no difference when considering events leading to medical consultation. Rates of significant health events were lower in pregnant females than similarly aged non-pregnant individuals. Funding This work was supported by the COVID-19 Vaccine Readiness funding from the Canadian Institutes of Health Research and the Public Health Agency of Canada CANVAS grant number CVV-450980 and by funding from the Public Health Agency of Canada, through the Vaccine Surveillance Reference Group and the COVID-19 Immunity Task Force.