As a maternal-fetal medicine specialist, Jacqueline Parchem, an assistant professor at the McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth), cares for many people with high-risk pregnancies. But before the COVID-19 pandemic, she had rarely seen the kind of illness that has since become a devastating part of her practice: young patients, who would otherwise have uneventful pregnancies, requiring oxygen, being intubated or even put on an extracorporeal membrane oxygenation (ECMO) machine, which temporarily replaces the function of the heart and lungs.

“I was training when the H1N1 pandemic happened, and that was the most similar time that I can remember,” Parchem says. “This is an order of magnitude worse.”

About 19 months into the COVID pandemic, there is mounting evidence that pregnant people are more vulnerable than the general population to severe disease. Having COVID while pregnant considerably increases the risk of dying or having several pregnancy-related complications. Yet despite a growing number of studies demonstrating that the COVID vaccines are safe during pregnancy, only about 32 percent of pregnant people aged 18 to 49 in the U.S. had been fully vaccinated as of September 25. This figure is especially concerning now that “some data suggest the Delta variant might cause more severe illness than previous variants in unvaccinated people,” as noted by the CDC.  On September 29 the CDC issued a health advisory strongly recommending COVID-19 vaccination "either before or during pregnancy," citing evidence that the benefits of vaccination outweigh potential risks for both pregnant people and their fetuses.

How COVID Affects Pregnant People

Because previous outbreaks caused by other coronaviruses were especially dangerous for pregnant individuals, the medical community was closely watching this group early on in the COVID pandemic, says Aris Papageorghiou, a professor of fetal medicine and director of research at the Oxford Maternal & Perinatal Health Institute at the University of Oxford.

Testing was not widely available then, though, so it took time for scientists to properly investigate the question. An initial small study in China suggested pregnant people were not at an increased risk from COVID, but larger studies subsequently started to show otherwise. An analysis of women of reproductive age who had been diagnosed with the disease showed that those who were pregnant were significantly more likely to be admitted to the intensive care unit (ICU) and receive invasive ventilation than those who were not.

Comparing pregnant and non-pregnant women, however, does not provide a full picture of the impact of the virus on pregnancy. “You cannot have premature birth or preeclampsia in a nonpregnant woman,” Papageorghiou notes. To overcome that limitation, he and his colleagues in 18 countries conducted a cohort study to compare the outcomes of pregnant people with and without COVID. They enrolled 706 pregnant women with COVID. For each of these subjects, about two other pregnant individuals without COVID were recruited immediately after, at the same medical center, to form a comparison group with similar characteristics.

Among pregnant women with COVID in this study, the risk of developing preeclampsia—a pregnancy complication characterized by high blood pressure—was 76 percent higher, and the risk of preterm birth was 59 percent higher. They were five times more likely to be admitted to an ICU and 22 times more likely to die than those without COVID. Papageorghiou thinks these results contributed to tipping the balance of risks versus benefits in favor of vaccinating pregnant individuals. “At the same time, you have evidence emerging that the vaccine was not risky and that COVID in pregnancy is a significant burden,” he says.

Research has also determined which risk factors make pregnant individuals even more susceptible to severe COVID. A U.S. Centers for Disease Control and Prevention study found that pregnant women who were 25 years of age and older, were employed as health care workers or had underlying medical conditions—including obesity, chronic lung disease, chronic hypertension or diabetes—were at increased risk.

“We also found, interestingly, that the risk for severe COVID-19 increased with the number of underlying conditions. That information may be helpful for pregnant people in the understanding of their own individual risk for getting severe COVID-19,” says Romeo Galang, an obstetrician-gynecologist at the CDC and the study’s lead author.

The impact of COVID in pregnant people has also varied across countries, amplifying disparities. In Mexico, maternal mortality increased more than 60 percent in one year during the pandemic, according to a study coordinated by Genny Carrillo, an associate professor at the Texas A&M University School of Public Health. Prior to that, maternal mortality was decreasing in the country. “Everybody was surprised by the number of pregnant women affected,” she says. In addition to the deaths directly linked to COVID, Carrillo says that the disruption in health services also contributed to the increase.

Delta Variant: “Alarm Bells Are Really Going Off”

The Delta variant, currently the predominant SARS-CoV-2 strain, seems to be particularly bad for pregnant people, notes Linda Eckert, a professor of obstetrics and gynecology at the University of Washington. According to preliminary data that the CDC presented during the Advisory Committee on Immunization Practices (ACIP) meeting on September 22, the number of pregnant individuals who were admitted to an ICU or died because of COVID this year has spiked.

“Death rates in pregnant women have been the highest they have ever been at any time during the pandemic, and they are on the increase. So, I think our alarm bells are really going off for just how dangerous COVID is to pregnant individuals,” says Eckert, who is the American College of Obstetricians and Gynecologists’ (ACOG’s) liaison at the ACIP.

According to the CDC, through September 27, there were a total of 161 COVID deaths in pregnant women, of which 22 occurred in the month of August alone. “That represents the highest number of deaths [in pregnant individuals] in a single month of the pandemic,” Galang says.

How Scientists Know Vaccines Are Safe

Pregnant people were not included in the COVID vaccines’ phase 3 clinical trials, so there were little safety data for this group at first. ACOG’s initial recommendation was that eligible pregnant individuals should make an informed decision with their doctor weighing the risks and benefits.

This scenario has changed. Preliminary real-world data on the mRNA vaccines suggest they are safe both for pregnant individuals and their unborn children. Data from more than 3,900 pregnant people who received these vaccines indicated that they did not have increased rates of miscarriages, birth defects or preterm births. And another analysis also did not show an increased risk among more than 2,000 vaccinated pregnant people. The most recent ACOG practice advisory now recommends that all eligible people receive a COVID vaccine, including pregnant and lactating individuals.

“The groups that were previously being more cautious,” such as ACOG and the Society for Maternal-Fetal Medicine, “now believe that the information that has been provided about safety really changes the calculus,” says Sonja Rasmussen, a professor in the departments of pediatrics and epidemiology at the University of Florida. In addition, evidence suggests that vaccinated people’s COVID antibodies are transferred to their babies during pregnancy.

Low Vaccination Rates

Experts agree that the 32 percent vaccination rate among pregnant people in the U.S. is incredibly low for a higher-risk group (for comparison, 83.6 percent of people aged 65 and older had been fully vaccinated as of October 4).

It is important to acknowledge that decision-making during pregnancy can be complicated, notes UTHealth’s Parchem. “People are generally more risk averse because they’re thinking about two people,” she says.

Parchem was pregnant with her third child last year. When the vaccine became available for her as a frontline health care provider, she was happy and relieved. Her trust in science and experience seeing pregnant people severely ill with COVID made the decision to get the vaccine easy, she says. But she remembers having to deal with strong reactions from people who thought the vaccine was dangerous.

“It inserts doubt into your mind when people that you know have this reaction to what you’re doing,” she says. “I had to take a step back and say, ‘Hold on, this is actually my exact area [of expertise]. I’m a scientist first, I’m a high-risk pregnancy specialist, and I’ve gone to school for a very long time to help other people make these decisions. I’m capable of making this decision for myself.’”

Whenever Parchem has conversations with patients who are on the fence about getting the vaccine, she tries not to focus so much on the data. Instead she acknowledges that pregnancy is a hard time to make decisions and focuses on how pregnant people not only can protect themselves with the vaccine but can also protect their babies. “I try to focus on that messaging because there’s not a single pregnant person whose priority isn’t protecting their baby,” she says.

For Parchem, seeing pregnant people severely ill with COVID now is even worse than it was earlier in the pandemic because the disease is preventable. “The regret of those families for not having done everything possible to protect themselves, to protect their babies and their loved ones is so deep,” she says. “It’s devastating.”