If pregnant women need another push to get a COVID vaccine, consider this: The vaccine plus a booster dose reduces the odds of preeclampsia by 30% and by as much as 58% in those with preexisting morbidities, according to new research.

Investigators from the international INTERCOVID consortium reviewed records from over 6000 participants in two cohorts and found an association between SARS-CoV-2 infection and preeclampsia, with an increased risk of 45% for those vaccinated during the pandemic and 78% among unvaccinated women. COVID vaccines provided additional benefits related to maternal and perinatal morbidity and mortality and preterm birth. 

A description of the work was published online in eClinicalMedicine, a Lancet journal. 

Researchers were surprised by the strong protective effect of the vaccine for preeclampsia, said corresponding author José Villar, MD, MPH, MSc, professor of perinatal medicine and co-director of the Oxford Maternal and Perinatal Health Institute, Oxford, England. With other interventions for preeclampsia, including aspirin, the effects are between 10% and 20%, he told Medscape Medical News. “This is a clean, straightforward intervention,” he said.

Recent research has shown a positive association between COVID and preeclampsia, with a more than 60% increased risk in infected vs noninfected pregnancies, researchers wrote. COVID and preeclampsia share endothelial and inflammatory mechanisms, Villar explained. “SARS-CoV-2-induced vascular injury may amplify the prothrombotic, anti-angiogenic milieu of preeclampsia, increasing hypertensive and placental complications,” he said.

Villar and colleagues reviewed health records from 6527 women previously enrolled in two INTERCOVID studies from 40 hospitals in 18 countries that took place in 2020 and 2022. Participants were enrolled at any time during pregnancy or childbirth, and most diagnosed COVID cases had laboratory evidence of SARS-CoV-2 infection by real-time PCR or rapid test. Two unmatched, consecutive, uninfected women were recruited after each case at each study site to serve as the control group.

Investigators used multivariable logistic regression models to assess the odds of preeclampsia, adjusting for confounders and cohort, stratifying by preexisting morbidities and SARS-CoV-2 infections. Survival analyses estimated preeclampsia incidence according to vaccination status and preexisting morbidities.

Overall, 2166 (33.2%) participants were diagnosed with COVID, and 3753 (57.5%) were unvaccinated. Among the 2774 vaccinated women, 1795 (64.7%) received mRNA vaccines, and 848 (30.6%) received the initial vaccine plus a booster dose, of whom 66.6% received a booster dose with an mRNA vaccine. A COVID diagnosis during pregnancy was given to 2166 (33.2%) women and 330 (5.1%) were diagnosed with preeclampsia.

Researchers evaluated the association of preeclampsia with COVID diagnosis during pregnancy for vaccinated women compared to no diagnosis, adjusting for maternal age, tobacco use, previous pregnancies, overweight/obesity, cohort, antenatal aspirin prophylaxis, nonsteroidal anti-inflammatories, history of cardiac disease, hypertension, kidney disease and diabetes, and study site. They also evaluated the association in unvaccinated women. 

They found an independent association between COVID and preeclampsia (aOR, 1.45; 95% CI, 1.15-1.84), particularly in unvaccinated women (aOR, 0.67; 95% CI, 0.45-0.99). After adjusting for confounders, any vaccination was found to protect against preeclampsia 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).

In women with preexisting morbidities who received a booster dose, the odds of preeclampsia were reduced by 58% (aOR, 0.42; 95% CI, 0.20-0.87) — an effect mainly observed in women diagnosed with COVID. Vaccination among women who received a booster dose also was 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, as well as preterm birth (aOR, 0.67; 95% CI, 0.53-0.85). 

“All pregnant women, and more specifically, those with preexisting medical conditions or preeclampsia risk, must follow the recommendations for vaccination during pregnancy for COVID, and any other infections that are included in local protocols,” Villar said.

The trend noted in this paper of a complication in pregnancy being exacerbated by COVID and being reduced by the vaccine “all fits with the general global literature as it’s coming out,” commented Deborah Money, CM, MD, professor and head of the Department of Obstetrics and Gynecology at the University of British Columbia, Vancouver, British Columbia, Canada. Money co-authored a recent study in JAMA that also found benefits from COVID vaccines, demonstrating that vaccination against the SARS-CoV-2 virus prior to and during pregnancy, before a COVID diagnosis, was associated with a lower risk for severe maternal disease and preterm birth. 

“We saw significant protective effects in a very, very large-scale study, and no adverse effects, either,” she said. “We hoped that paper was a significant reassurance to patients and care providers to say, yes, it’s not only safe to take a vaccine in pregnancy, but it is of benefit to you and your baby.”

COVID and other infections in pregnancy have more consequences than just the infection itself, Money said, potentially causing a higher rate of preterm birth, adverse outcomes, or preeclampsia, so screening for those conditions in prenatal care remains critically important, as well as counseling pregnant women to make “wise choices around vaccination.”

“Primary care providers are huge influencers in affecting pregnant women’s decisions,” she said. “If they come out strongly in support, that is a key factor.”

The study was supported by the Alumbra Innovations Foundation. Villar reported having no relevant financial disclosures. Money reported receiving vaccine and in-kind support for studies from Merck. 

Karen Blum is a freelance medical/science writer in the Baltimore area.