Target trial emulation of effectiveness of COVID-19 mRNA vaccination during pregnancy in four European countries

Evidence on real-world effectiveness of COVID-19 vaccination during pregnancy remains limited. Using health data from the UK, Sweden, Spain, and Norway, we emulated two target trials to estimate vaccine effectiveness (VE) of mRNA COVID-19 vaccines administered during pregnancy against COVID-19 infection, hospitalisation, and admission to an Intensive Care Unit (ICU). The first trial compares initiation of a primary (two-dose) vaccination with unvaccinated, and the second compares the receipt of a first booster (third dose) with unboosted after primary vaccination. Pregnant women receiving a first or booster vaccination were matched weekly to comparable unexposed pregnant women. A total of 62,061 and 41,096 pregnant women were included in the first and second trial, respectively. Meta-analysis across the four databases showed a VE for primary vaccination of 26·2% (95% CI 16·2–35·1) against infection and 55·6% (95% CI 44·1–64·8) against hospitalisation. For boosters, the VE was 33.6% (95% CI 1·6–56·6) against infection and 34·1% (95% CI 0·6–56·4) against hospitalisation. ICU admission outcomes were too rare to analyse. In this work, we show that primary and first-booster mRNA vaccination during pregnancy is associated to a lower risk of COVID-19-related hospitalisation, while protection against infection is more modest and heterogeneous across databases. This study of over 100,000 pregnancies in four European countries found that both initial and booster COVID-19 mRNA vaccination during pregnancy were linked to lower risks of infection and related hospital admission.