The risk of pregnancy-related adverse outcomes after COVID-19 vaccination: Propensity score-matched analysis with influenza vaccination

Introduction: Coronavirus 2019 (COVID-19) vaccination rates in pregnant women remain low owing to safety concerns. When evaluating vaccine safety, comparisons with unvaccinated individuals may lead to healthy vaccinee bias. This study aimed to investigate the association between mRNA-based COVID-19 vaccination and pregnancy-related adverse outcomes compared with influenza vaccination.

Methods: A propensity score-matched cohort study was conducted using the National Health Insurance Service insurance claims database, combined with COVID-19 and influenza vaccination registration data from the Korea Disease Control and Prevention Agency. Based on the age, comorbidities, insurance type, region, hospital type, gestational age at vaccination, and primiparity, the COVID-19 vaccination-only group and influenza vaccination-only group were matched in a 1:3 ratio, while both (COVID-19 and influenza) vaccination group and influenza vaccination-only group were also matched in a 1:3 ratio. Logistic regression analysis was used to calculate odds ratios (ORs) with 95 % confidence intervals (CIs) between the two groups.

Results: From October 18, 2021, to March 3, 2022, 71,902 pregnant women were identified, and the vaccination records of 67,522 individuals were verified. Among them, 610 received the COVID-19 vaccination only, 49,952 received the influenza vaccination only, and 2405 received both vaccines. In the COVID-19 vaccination-only group, the risk of large for gestational age was higher than in the influenza vaccination-only group (OR = 2.285, 95 % CI = 1.155-4.522, P = 0.018). In the group that received both vaccinations, the risk of premature birth was higher (OR = 1.365, 95 % CI = 1.124-1.656, P = 0.002) than that in the influenza vaccination-only group but lower than the domestic baseline incidence rates. No significant differences were observed in other maternal and neonatal outcomes.

Conclusion: mRNA-based COVID-19 vaccination in pregnant women is safe without a remarkable increase in adverse maternal and neonatal outcomes. Given the high morbidity and mortality rates of COVID-19 in pregnant women, it is reasonable to recommend COVID-19 vaccination for pregnant women.