Effectiveness of COVID-19 mRNA primary and booster vaccination against infection and hospitalisation during pregnancy: a target trial emulation and meta-analysis of data from 4 European countries

ObjectiveTo estimate vaccine effectiveness (VE) of COVID-19 mRNA vaccines administered during pregnancy. Primary (2-dose) vaccination was compared with unvaccinated women; and 1st booster (3rd dose) with primary (2-dose) vaccination. DesignTarget trial emulation cohort study. SettingRoutinely collected health data from UK, Sweden, Spain, and Norway. All had complete vaccine exposure data and were mapped to the OMOP common data model. ParticipantsPregnant women (aged 12-55) with [≤]34 weeks of gestation, no history of COVID-19 in the 90 days prior and [≥]1 year of data visibility. Women were matched 1:1 to those with no dose and 2-dose vaccination, respectively, using weekly sequential matching from vaccination roll-out to 2023 (Swedish data: 2024). Main outcome measuresThe main outcomes were COVID-19 infection, hospitalisation and Intensive Care Unit (ICU) admission (COVID-related, excluding delivery-related care). Hazard ratios (HR) were estimated with Cox regression from 15 days post-vaccination, and VE was reported as 100 x (1-HR). Analyses were stratified by pregnancy trimester and vaccine brand. Database-specific results were pooled using a random-effects meta-analysis. ResultsWe included 62,061 and 41,096 pregnant women at date of vaccination with a first and third dose, respectively. Median follow-up across databases ranged from 42 to 55 days for primary vaccination and 73 to 116 days for boosters. For primary vaccination, the meta-analysis showed a VE of 26.2% (16.2 to 35.1; I2 =0.7) against infection and 55.6% (44.1 to 64.8; I2 =0) against hospitalisation. For boosters, corresponding figures were 33.6% (-1.6 to 56.6; I2=1) and 34.1% (0.6 to 56.4; I2 =0.5). Event counts were insufficient to analyse VE against ICU admission. Results were consistent across pregnancy trimesters and vaccine brands. ConclusionsVaccination with a primary (2-dose) or a 1st booster (3rd dose) during pregnancy was effective in preventing COVID-19 hospitalisation, with modest and heterogeneous VE against infection across 4 European countries. SummaryO_ST_ABSWhat is already known on this topicC_ST_ABS- Pregnant women are at increased risk of severe complications from COVID-19, which can affect both mothers and their infants. - Vaccination during pregnancy has been shown to be safe and effective, with benefits of vaccination outweighing any potential risks. - Studies examining the effectiveness of COVID-19 vaccines during pregnancy have primarily focused on primary vaccination with BNT162b2, with limited follow-up, sample size and representativeness. What this study adds- This study provides evidence on the effectiveness of COVID-19 mRNA vaccines administered during pregnancy using routinely collected data of over 124,122 pregnancies from 4 European countries. - Primary (2-dose) vaccination against COVID-19 during pregnancy was effective in preventing infection during pregnancy with a vaccine effectiveness of 26%, and 55% for preventing COVID-19 related hospitalisations. - A 1st booster (3rd dose) had a vaccine effectiveness of 30-35% against COVID-19 infection and COVID-19-related hospitalisation compared to primary (2-dose) vaccination.