The analysis, based on medical records of nearly 14 million US patients since coronavirus immunization became available, found that pregnant people who are vaccinated have the greatest risk of developing covid among a dozen medical states, including being an organ transplant recipient and having cancer.
The findings come on top of research showing that people who are pregnant or gave birth recently and became infected are especially prone to getting seriously ill from covid-19. And covid has been found to increase the risk of pregnancy complications, such as premature births.
The Centers for Disease Control and Prevention has been urging people to get coronavirus shots before or during pregnancy, seeking to dispel fear — widespread in some communities, without scientific basis — that those vaccinations could be harmful. As of March, nearly 70 percent of people who were pregnant had been vaccinated before or during their pregnancy, according to federal data, though disparities persist among racial and ethnic groups.
The new study goes beyond what has previously been understood, suggesting that even pregnant people who are fully vaccinated tend to have less protection from the virus than many other patients with significant medical problems.
“If you are fully vaccinated, that’s magnificent,” said a lead author of the study, David R. Little, a physician who is a researcher at Epic, a Wisconsin company that maintains electronic patient records for nearly 1,000 hospitals and more than 20,000 clinics across the country. “But if you are fully vaccinated and become pregnant, you remain at a higher risk of acquiring covid.”
Little said the findings buttress CDC recommendations that additional precautions against the virus should be taken during pregnancy, such as wearing masks and maintaining safe distances. He said the study also suggests that health-care workers should “be on the lookout” for symptoms and encourage testing to detect the virus early, when it is easier to treat.
The data also raises scientific questions that warrant further research into how best to protect pregnant individuals and their babies from infection, according to public health leaders and specialists in pregnancy.
“To me, the most important question the new study raises is, is there an increased rate of severe illness and death in pregnant patients after a certain period of time” following vaccination, said Brenna L. Hughes, vice chair for obstetrics and quality at the Duke University School of Medicine Department of Obstetrics and Gynecology.
“I have not admitted a single vaccinated patient to the ICU. Every one has been unvaccinated,” Hughes said. “Of course, we worry the wane boosters.” There is no research evidence on whether the protection conferred by coronavirus shots lasts as long for pregnant people as it does for others.
The study did not assess how sick the patients became when they were infected with covid after having been vaccinated.
Georges C. Benjamin, executive director of the American Public Health Association, said the Epic findings point to a need to understand whether it is most helpful to be vaccinated before becoming pregnant or soon afterward, the most useful time interval between shots and what dosage is best. Those questions apply, he said, to the well-being of pregnant patients and their babies.
“There’s lots of good science to be had here,” Benjamin said. But for now, he added, “people shouldn’t panic. You are not getting sick because of the vaccine. It argues that you probably need a little more of the vaccine.”
The analysis was based on Epic medical records from 13.8 million patients between January 2021, when the first people in the United States were fully vaccinated and had enough time to develop immunity, and late January this year. Little and colleagues analyzed the risk from 12 comorbidities throughout that period. The study included the delta and omicron variant surges but did not differentiate the rate of breakthrough infections during those waves or other times.
The researchers measured the risk by analyzing the records of pairs of fully vaccinated patients from the same part of the country. In each pair, one patient had the condition that was being measured, and the other did not. The patients were not matched by age, and the pregnant people could have been matched in the analysis with a man or a woman.
The analysis found that the 110,000 pregnant individuals included in the study were 90 percent more likely to have been infected with coronavirus than the same number of people who were not pregnant. The next-highest risk — 80 percent greater — was among organ transplant recipients. The elevated risk among those two groups was higher than among patients with compromised immune systems, who had 60 percent greater odds of coronavirus infection.
The fact pregnancy appears to pose a greater risk than having a weakened immune system is striking, because public health officials have been warned that being immunocompromised can render coronavirus vaccines significantly less effective. Federal regulators allowed people with immunity troubles to get a fourth shot substantially before guidance shifted this week to allow the extra vaccine doses for Americans who are 50 or older.
Hughes predicted that federal health officials will eventually add pregnancy to the list of factors that are grounds for extra booster shots.
The study found that several conditions pose only a slightly greater risk of vaccinated people experiencing infections compared with people without those conditions. They include kidney, liver and blood disorders. Patients with lung diseases had a slightly higher risk — 30 percent greater than patients without those diseases. On the other hand, cardiovascular diseases appear to create no added risk, and patients with cancers had slightly lower odds of breakthrough cases than those who are cancer-free.
The findings do not explain the reason behind the risk levels. Denise Jamieson, a specialist in infectious diseases during pregnancy, called the high risk of infection among vaccinated pregnant people an “interesting and intriguing finding.”
Jamieson, chair of gynecology and obstetrics at Emory University School of Medicine in Atlanta, said the finding could reflect that such people are more likely to get tested, because they are receiving prenatal care, putting them in unusually frequent contact with a health-care provider .
And Hughes noted that coronavirus testing has become routine when pregnant patients are admitted to labor and delivery centers. As a result, she said, it is possible that more positive tests may be detected among such patients, even when they lack symptoms, compared with people whose medical conditions do not lead to routine tests.
Jamieson said the finding could also suggest that people of childbearing age tend to be in jobs, such as teaching or nursing, that put them at uncommonly high risk of exposure to the virus. At the same time, she said, the apparently high risk of a breakthrough case during pregnancy could be a result of the way the study matched its pairs of patients.
Or, Jamieson said, the study could actually reveal that pregnant individuals are more susceptible to becoming infected with the coronavirus, even when vaccinated.
“It’s definitely interesting,” Jamieson said. “This study asks this question but doesn’t answer it.”