Research Professor School of Pharmacy, Sungkyunkwan University, South Korea Suwon, Republic of Korea
Background: Influenza vaccination during pregnancy has shown benefits on influenza-related health outcomes for mothers and their infants. Safety evidence on maternal influenza vaccination has been well established in the Caucasian population, but few studies have investigated on maternal influenza vaccination in the Asian population.
Objectives: To investigate whether maternal influenza vaccination is associated with the risk of gestational outcomes and adverse events.
Methods: We conducted a nationwide cohort study using Korea’s linkage healthcare database between vaccination registry data and claims data. All live birth pregnancies between September 2019 and April 2022 were included, with follow-up until June 2022. We defined vaccination as intention-to-treat approach for gestational outcomes and time-varying approach for adverse events, respectively. Study outcomes were gestational outcomes (preeclampsia, gestational diabetes, antenatal bleeding, postpartum haemorrhage) and adverse events (lymphadenitis, thrombocytopenia, anaphylaxis, Guillain-Barré syndrome, convulsive seizure, neuropathy, facial nerve palsy, thromboembolism, vasculitis). We calculated relative risks (RRs) using generalized linear model for gestational outcomes and hazard ratios (HRs) using Cox hazard model for adverse events with 95% confidence intervals (CIs) after propensity score (PS) matching.
Results: We included 286,389 PS-matched pairs with well-balanced characteristics across vaccinated and unvaccinated groups. For the risk of gestational outcomes, the RRs were 0.84 (95% CI 0.81-0.88) for preeclampsia, 0.98 (0.97-0.99) for gestational diabetes, 0.97 (0.95-1.00) for antenatal bleeding, and 1.08 (1.04-1.11) for postpartum haemorrhage. For the risk of adverse events, the HRs were 1.00 (0.87-1.14) for lymphadenitis, 0.97 (0.86-1.10) for thrombocytopenia, 1.74 (0.51-5.93) for anaphylaxis, 1.90 (0.28-12.66) for Guillain-Barré syndrome, 0.63 (0.39-1.03) for convulsive seizure, 0.79 (0.74-0.84) for neuropathy, 1.02 (0.81-1.29) for facial nerve palsy, 1.12 (1.11-1.34) for thromboembolism, and 0.98 (0.86-1.11) for vasculitis. Stratified analyses according to trimester of vaccination, number of doses, and type of vaccine were not largely different from main findings.
Conclusions: We did not find any association between influenza vaccination during pregnancy and the risk of gestational outcomes and adverse events, but an increased risks of postpartum haemorrhage and thromboembolism were observed. Our findings suggest no ethnic difference in safety evidence of maternal vaccination and support the recommendation of influenza vaccination at any stage of pregnancy; however, in-depth monitoring for observed adverse events should be conducted.
