Two studies examined the effects of COVID-19 vaccination in pregnancy, with one estimating that full vaccination and a booster dose reduce the risk of preeclampsia (PE) by 15% and 33%, respectively, and the other finding no elevated risk of miscarriage before 20 weeks’ gestation among pregnant or soon-to-be-pregnant recipients of the Pfizer/BioNTech or Moderna vaccines.
Lower odds of disease, death, and preterm birth
For the first study, published yesterday in eClinicalMedicine, an international roster of researchers in the INTERCOVID consortium mined data from 6,527 pregnant women with and without a COVID-19 diagnosis from 18 countries in two consecutive cohorts in 2020 and 2022.
Preeclampsia is a serious complication of pregnancy that may include high blood pressure, high concentrations of protein in the urine that flag kidney damage, or other signs of organ damage. The condition typically begins after 20 weeks’ gestation in women whose blood pressure had previously been in the healthy range. Untreated preeclampsia may lead to life-threatening complications for both mothers and babies.
“If vaccination mitigates the risk of PE, this will not only reinforce current vaccination strategies in pregnancy but also provide insight into shared pathogenic mechanisms between infection-related inflammation and hypertensive disorders of pregnancy,” the study authors wrote. “Such findings may also contribute to the broader understanding of PE pathophysiology beyond COVID-19.”
Although the PE odds reduction provided by vaccination remained significant after adjusting for SARS-CoV-2 infection, it was greater among women diagnosed with COVID-19.
Of all participants, 33.2% tested positive for COVID-19, and 57.5% were unvaccinated. Among the 2,774 vaccinated women, 64.7% received an mRNA vaccine, and 30.6% received the initial regimen followed by a booster dose (66.6% of whom received an mRNA booster).
COVID-19 was independently tied to COVID-19 infection (adjusted odds ratio [aOR], 1.45), especially in unvaccinated women (aOR, 1.78). After adjusting for potential confounders, overall, any vaccine protected against PE (aOR, 0.85), and a booster dose even more so (aOR, 0.67).
Among women with underlying medical conditions who received a booster dose, the risk of PE dropped by 58% (aOR, 0.42)—an effect primarily seen in women who had COVID-19. Adjustment for study site and cohort year didn’t change the degree of the effect. Vaccination in women who received a booster dose was also tied to lower odds of maternal and perinatal disease, death, and preterm birth (aORs, 0.68, 0.71, and 0.67, respectively).
“Although the PE odds reduction provided by vaccination remained significant after adjusting for SARS-CoV-2 infection, it was greater among women diagnosed with COVID-19,” the researchers wrote.
“These results go beyond the known benefits of COVID-19 vaccination in pregnancy,” senior co-author Jose Villar, MD, MPH, of the University of Oxford, said in a press release from Children’s Hospital of Chicago. “We now have evidence that maternal vaccination may influence pathways involved in preeclampsia development, suggesting a broader immunological or vascular benefit of vaccination.”
The authors called for strengthening COVID-19 vaccination programs during pregnancy and research into PE etiology, with a focus on the immune system’s interaction with infections, with and without vaccination.
Risks were below or within prepandemic estimates
The second study, led by researchers from the US Centers for Disease Control and Prevention (CDC), involved the assessment of miscarriage risk during 6 to 20 weeks’ gestation among women who received at least one dose of the monovalent (single-strain) mRNA COVID-19 vaccine up to a month before their last menstrual period or during pregnancy.
The researchers analyzed data from the CDC’s COVID-19 Vaccine Pregnancy Registry on 12,907 pregnancies among women aged 18 to 54 years from December 2020 to June 2021. Participants were interviewed at different intervals based on when vaccination and pregnancy outcome were reported.
Most participants were White (79.1%), in their 30s (77.3%), and had received two doses of an mRNA COVID-19 vaccine (93.7%), 58.5% of whom received the Pfizer vaccine.
Understanding risk for adverse pregnancy outcomes after COVID-19 vaccination can inform decisions and recommendations about vaccination in pregnancy.
“A qualitative analysis of pregnant women’s hesitation about COVID-19 vaccines reported hesitancy due to lack of research about safety in pregnancy,” the authors wrote. “Understanding risk for adverse pregnancy outcomes after COVID-19 vaccination can inform decisions and recommendations about vaccination in pregnancy.”
The findings, published yesterday in Vaccine, are an update on a 2021 preliminary report based on early, incomplete data.
The cumulative risk of miscarriage was 10.8%, with similar risk in both Moderna and Pfizer vaccine recipients (adjusted hazard ratio [aHR], 0.92). A sensitivity analysis that included miscarriages occurring at less than 6 weeks’ gestation estimated a cumulative risk of 13.5%, and a sensitivity analysis that excluded participants who received all COVID-19 vaccines before their last menstrual period showed a cumulative risk of 9.7%.
Estimated risks were below or within pre-pandemic parameters. The authors cautioned that the generalizability of the study may be limited because the study cohort was fairly homogenous.
“Acknowledgement of limitations in comparing contemporary data to historical data can be used to inform future emergency response public health safety monitoring programs that aim to assess risk of early pregnancy outcomes,” the researchers concluded.
