Systematic review of COVID-19 vaccine effectiveness and safety in 930,556 pregnancies

Pregnant and recently pregnant women with SARS-CoV-2 infection are at an increased risk of severe infection with associated mortality and morbidity than non-pregnant women of reproductive age. Vaccines have been the most important intervention in preventing covid-19.

We conducted a living systematic review to identify comparative cohort studies reporting the effects of covid-19 vaccines on maternal infection-related and pregnancy outcomes until 25 October 2022. We also included non-comparative studies reporting on side effects. A random effects meta-analysis was performed and the findings were summarized as odds ratios (OR) and rates with 95% confidence intervals (CI). We undertook subgroup and sensitivity analysis by vaccine type and dose. Heterogeneity was reported as I².

We included 43 comparative cohort studies (930,556 women) and 16 non-comparative cohort studies (74,692 women). Pregnant women who received at least one dose of any covid-19 vaccine had a reduction in the odds of SARS-CoV-2 infection (OR 0.59, 95% CI 0.48 to 0.73), severe covid-19 infection (OR 0.10, 95% CI 0.02 to 0.62) and all-cause maternal death (OR 0.24, 95% CI 0.11 to 0.49). Covid-19 vaccination was also associated with a significant reduction in preterm birth, miscarriage and admission to the neonatal intensive care unit. There were no differences in the outcomes between the vaccine type, except for SARS-CoV-2 infection and NICU admission, which were lower for m-RNA only vaccine group. In fully vaccinated women (women receiving two doses of a two-dose regimen vaccine or one dose of a one-dose regimen vaccine), the reduction in SARS-CoV-2 infection, severe covid-19, maternal death, preterm birth and NICU admission remain similar. The most common side effect after partial and full vaccination was pain at the injection site. 

Covid-19 vaccines reduce the odds of SARS-CoV-2 infection, severe covid-19 and maternal death in pregnant and recently pregnant women. There are no safety concerns regarding maternal and perinatal outcomes or systemic side effects. These results should be interpreted with caution as we only included observational and non-randomised studies.