COVID-19 vaccination status during pregnancy and preeclampsia risk: the pandemic-era cohort of the INTERCOVID consortium

Background We tested whether COVID-19 vaccination affects the risk of preeclampsia (PE) given the well-documented association between COVID-19 and PE, and their overlapping risk factors and pathophysiological pathways. Methods We analysed individual level data from pregnant women prospectively enrolled from 18 countries in two consecutive cohorts between 2020 and 2022 during the COVID-19 pandemic using identical methodology. Pregnant women were recruited either with a COVID-19 diagnosis or as concomitant, consecutive, non-diagnosed controls from the same hospitals. Following vaccine availability, vaccination status was documented to define a vaccine-exposed subgroup. Multivariable logistic regression models assessed the odds of PE adjusting for confounders and cohort as a proxy for viral strain, stratifying by pre-existing morbidities and SARS-CoV-2 infection. Survival analyses estimated PE incidence according to vaccination status and pre-existing morbidities. Findings Of 6527 pregnant women, 2166 (33.2%) were diagnosed with COVID-19 and 3753 (57.5%) were unvaccinated. Of the 2774 vaccinated women, 1795 (64.7%) received mRNA vaccines; 848 (30.6%) received the initial regimen plus a booster dose, of whom 66.6% received a booster with an mRNA vaccine. We confirmed an independent association between COVID-19 and PE (aOR: 1.45; 95% CI: 1.15–1.84), particularly in unvaccinated women (aOR: 1.78; 95% CI: 1.31–2.42). Overall, after adjusting for confounders, any vaccination gave a protective effect against PE during the index pregnancy (aOR: 0.85; 95% CI: 0.65–1.10), that was stronger with a booster dose (aOR: 0.67; 95% CI: 0.45–0.99). Among women with pre-existing morbidities who received a booster dose the odds were reduced by 58% (aOR: 0.42; 95% CI: 0.20–0.87) – an effect mainly observed in women diagnosed with COVID-19. Adjustment for study site and cohort year did not alter the magnitude of the effect. Vaccination amongst women who received a booster dose was also associated with decreased odds of maternal (aOR: 0.68; 95% CI: 0.55–0.83) and perinatal (aOR: 0.71; 95% CI: 0.54–0.95) morbidity and mortality, and preterm birth (aOR: 0.67; 95% CI: 0.53–0.85). Interpretation COVID-19 vaccination with a booster reduces the odds of PE by 30% approaching 60% reduction among women with pre-existing morbidities. Funding The original INTERCOVID study was supported in Oxford by the COVID-19 Research Response Fund from the University of Oxford (Ref 0009083).