Pregnant women who received COVID-19 vaccines had a 42% lower chance of developing preeclampsia, a life-threatening hypertensive condition, according to a multinational study from the INTERCOVID consortium led by University of Oxford researchers. The finding, drawn from data on 6,527 pregnant women across 18 countries enrolled between 2020 and 2022, adds to a growing body of evidence that vaccination during pregnancy carries protective benefits beyond preventing severe COVID-19 illness. With preeclampsia responsible for tens of thousands of maternal deaths worldwide each year, the results carry direct clinical weight for obstetricians and expectant mothers weighing vaccine decisions.
New INTERCOVID Data Links Vaccines to Preeclampsia Reduction
The INTERCOVID consortium’s latest analysis, published in the journal eClinicalMedicine, is the first large prospective multinational study to directly measure the relationship between COVID-19 vaccination status, including booster receipt, and preeclampsia risk in pregnant women. The 42% reduction in preeclampsia odds among vaccinated participants was statistically significant, according to the University of Oxford team that coordinated the work, and the effect remained after adjusting for maternal age, comorbidities, and socioeconomic factors. That effect size is notable because preeclampsia has few proven preventive interventions beyond low-dose aspirin, which itself only reduces risk by roughly 10 to 20% in high-risk populations and is not universally effective.
This new analysis builds on the consortium’s earlier prospective longitudinal work, which established that SARS-CoV-2 infection during pregnancy is strongly associated with preeclampsia and adverse maternal and perinatal outcomes, independent of preexisting risk factors such as chronic hypertension or diabetes. The logical next question was whether preventing or blunting infection through vaccination could interrupt that pathway. The new data suggests the answer is yes, though the mechanism remains an open question. One plausible explanation is that vaccination reduces the systemic inflammatory response and endothelial damage that SARS-CoV-2 can trigger in the placental vasculature, a process that mirrors the vascular dysfunction at the root of preeclampsia itself. No direct mechanistic study has confirmed this hypothesis, but the consistent direction of the effect across 18 countries strengthens the case that the association is real rather than an artifact of regional health system differences or selective recruitment.
Large Cohorts Confirm Safety and Signal Protective Effects
The INTERCOVID results do not exist in isolation. A population-based cohort analysis of 865,654 pregnancies in England and Wales evaluated both COVID-19 diagnosis and vaccination during pregnancy against a range of adverse outcomes, including preeclampsia, stillbirth, and neonatal death. That study found that vaccination was not associated with higher risks of adverse pregnancy outcomes and identified patterns consistent with protection against hypertensive disorders when compared with unvaccinated women who developed COVID-19. The sheer scale of the English and Welsh dataset, more than 130 times the size of the INTERCOVID cohort, provides strong reassurance on the safety side even if its design was not specifically powered to isolate preeclampsia prevention as a primary endpoint.
Separately, a systematic review and meta-analysis that synthesized results from 67 observational studies involving approximately 1.8 million pregnant women reported pooled estimates showing a reduced risk of hypertensive disorders in pregnancy among vaccinated women in adjusted cohorts. The review also found no increased risk for miscarriage, congenital anomalies, preterm birth, or neonatal intensive care admission, reinforcing the safety profile of COVID-19 vaccines in pregnancy across diverse health systems and vaccine platforms. When three independent lines of evidence (a prospective multinational cohort, a national population registry, and a meta-analysis aggregating dozens of studies) all point in the same direction, the signal becomes difficult to dismiss as coincidence or residual confounding, particularly given the biological plausibility of an anti-inflammatory benefit.
U.S. Safety Data Addressed Early Concerns
Early in the vaccine rollout, limited data on pregnant populations fueled hesitancy among patients and caution among clinicians. In the United States, a CDC retrospective cohort analysis using Vaccine Safety Datalink data examined 46,079 live births between December 15, 2020, and July 22, 2021, comparing outcomes for women vaccinated during pregnancy with those who remained unvaccinated. Investigators found no association between COVID-19 vaccination and increased risk of preterm birth or small-for-gestational-age outcomes, two key markers of fetal well-being. The study used time-dependent exposure methods and adjusted hazard ratios to account for the timing of vaccination relative to delivery, a methodological safeguard that reduced bias from women being vaccinated later in pregnancy when adverse outcomes are less likely to manifest.
These U.S. data, combined with similar findings from other high-income settings, helped establish the baseline safety case that later studies, including the INTERCOVID analysis, could build upon. As more pregnant women were vaccinated and followed over time, registries and pharmacovigilance systems did not detect new safety signals related to hypertensive disorders, placental complications, or neonatal outcomes. This absence of harm, while never definitive on its own, created a backdrop against which the emerging protective signal against preeclampsia became more compelling. For many obstetric providers, the conversation has shifted from whether vaccines are safe in pregnancy to how best to communicate the balance of benefits, which now appears to include both reduced risk of severe maternal COVID-19 and a meaningful reduction in a major obstetric complication.
Guidance, Communication, and Equity Considerations
Current CDC recommendations for pregnant or breastfeeding individuals state that COVID-19 vaccination has not been linked to increased health risks for pregnant women or babies and can be given at any trimester. Rather than issuing a rigid directive, the 2025-2026 guidance emphasizes shared decision-making between patients and clinicians, reflecting both accumulated safety evidence and the complex political environment around vaccination. For clinicians, the new INTERCOVID data may shift those conversations: a 42% reduction in preeclampsia risk is a concrete, quantifiable benefit that can be weighed alongside the already established protection against severe respiratory disease, hospitalization, and intensive care admission in pregnant patients who contract COVID-19.
Effective communication of these findings also requires attention to language access and health equity. The CDC hosts translated vaccine information across multiple languages through its multilingual resources portal, which includes patient-facing materials that can be used in prenatal clinics serving diverse communities. Ensuring that information about both the safety and potential protective benefits of COVID-19 vaccination reaches women who speak languages other than English is critical, given that preeclampsia and severe COVID-19 disproportionately affect marginalized and minority populations. Culturally adapted counseling, community health worker engagement, and collaboration with trusted local leaders can help bridge gaps in trust and understanding that simple data summaries cannot overcome on their own.
What the Evidence Does Not Yet Show
Several gaps remain despite the encouraging data. No published primary cohort has yet reported detailed long-term neurodevelopmental or cardiometabolic outcomes in children born to vaccinated mothers, leaving open questions about child development in the first years of life. Existing studies have largely focused on perinatal endpoints such as birth weight, gestational age, and neonatal intensive care unit admission, which are important but do not capture subtler developmental trajectories. In addition, while the INTERCOVID study and the large English and Welsh cohort adjusted for many confounders, residual differences in healthcare access, baseline health status, and health-seeking behavior between vaccinated and unvaccinated women could still influence the magnitude of the observed risk reduction.
Researchers also have not conclusively disentangled how much of the protective effect against preeclampsia stems from preventing symptomatic COVID-19 infection versus modulating immune and vascular pathways more directly. It remains possible that different vaccine platforms or dosing intervals could vary in their impact on hypertensive disorders, a question that current observational designs are not well powered to answer. Future work combining clinical cohorts with biomarker studies of placental function and maternal vascular health may clarify mechanisms and identify subgroups who benefit most. Until then, the available evidence supports a reassuring message: for pregnant women, COVID-19 vaccination appears not only safe but also potentially protective against one of pregnancy’s most feared complications, even as scientists continue to refine the details of that protection.
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*This article was researched with the help of AI, with human editors creating the final content.
