Abstract
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).