COVID-19 Vaccination in Pregnancy Cuts Preeclampsia Risk by 33%, Global Study Finds

Preeclampsia kills. It accounts for roughly 70,000 maternal deaths each year worldwide, and clinicians have very few tools to prevent it. That picture shifted slightly with data published in eClinicalMedicine, which found that COVID-19 vaccination - particularly when boosters are included - reduces the odds of developing preeclampsia by about one third.

The study drew on the INTERCOVID Consortium, a collaboration spanning more than 40 hospitals across 18 countries. Between 2020 and 2022, researchers enrolled 6,527 pregnant women and tracked outcomes across vaccination status and SARS-CoV-2 infection status, creating a four-way comparison that allowed them to separate the effects of the vaccine from the effects of the virus itself.

What the Numbers Show

COVID-19 infection during pregnancy was already known to raise preeclampsia risk. This study puts that increase at 45% overall - and 78% among unvaccinated women who contracted the virus. But the more striking finding concerns women who never tested positive at all: vaccination still appeared to offer protection, suggesting the vaccine's benefit operates through mechanisms beyond simply preventing infection.

Among women who received a booster dose, preeclampsia odds fell by 33%. For women with pre-existing conditions - diabetes, hypertension, or thyroid disorders - the benefit was even larger: a 42% reduction. Those figures held after statistical adjustment for age, body mass index, socioeconomic status, and other known confounders.

The booster's effects extended further. Compared with unvaccinated women, boosted participants showed a 33% lower rate of preterm delivery, 32% lower maternal morbidity and mortality, and 29% lower severe perinatal morbidity and mortality. All three figures reached statistical significance.

A Possible Vascular Mechanism

Why would a respiratory vaccine protect against a placental disorder? The honest answer is that no one is certain. Preeclampsia involves inflammation and vascular dysfunction - the placenta fails to implant properly, blood pressure spikes, and multiple organs can be affected. COVID-19 is known to trigger similar inflammatory and vascular pathways.

The leading hypothesis is that vaccination modulates immune and vascular signaling in ways that reduce the inflammatory cascade associated with preeclampsia development. Some vaccines are known to have so-called non-specific effects on immune regulation beyond their primary target. Whether the COVID-19 mRNA vaccines share this property is now a question researchers are actively investigating.

"We now have evidence that maternal vaccination may influence pathways involved in preeclampsia development, suggesting a broader immunological or vascular benefit of vaccination," said Professor Jose Villar, senior co-author and Principal Investigator of the INTERCOVID consortium at the University of Oxford's Nuffield Department of Women's and Reproductive Health.

Study Design Strengths and Constraints

The multinational scope is a genuine asset. Preeclampsia rates, vaccination uptake, and healthcare quality vary widely across countries, and drawing data from 18 nations reduces the risk of findings that only hold in specific healthcare contexts. That geographic breadth also means the results carry more weight for global policy discussions.

However, the study is observational. Women who chose to vaccinate may differ from those who did not in ways the researchers could not fully measure - health attitudes, access to prenatal care, socioeconomic stability. Randomizing pregnant women to receive or withhold a vaccine during a pandemic was not feasible, so residual confounding cannot be excluded. The data also span 2020-2022, when dominant SARS-CoV-2 variants, vaccine formulations, and booster schedules were all in flux, which complicates direct comparisons across the enrollment period.

The study examined outcomes at a single point in time and cannot track whether protective effects persist across subsequent pregnancies or change with different vaccine platforms.

Clinical and Policy Implications

Preeclampsia affects between 3% and 8% of pregnancies globally, depending on risk profile. It has no reliable screening test and no proven preventive treatment beyond low-dose aspirin in high-risk women. Any intervention that can reduce its incidence - particularly one as widely available as vaccination - carries significant clinical weight.

"Our results support the importance of strengthening COVID vaccination programs during pregnancy, emphasising boosters and ensuring that pregnant people across the world have equitable access to the vaccine," said study co-author Jagjit S. Teji, a neonatologist at Ann and Robert H. Lurie Children's Hospital of Chicago and Clinical Assistant Professor at Northwestern University Feinberg School of Medicine. "We offer evidence from the first large study suggesting that COVID vaccination may protect against one of the most serious pregnancy complications."

Current guidelines from major obstetric bodies already recommend COVID-19 vaccination during pregnancy for protection against severe infection. If the preeclampsia findings are confirmed in future mechanistic studies, those recommendations may gain an additional, independent rationale - one that applies even in populations where COVID-19 infection rates are low.