For people who are pregnant, the rollout of COVID-19 vaccines is prompting agonizing questions about whether it’s safer to get the vaccine or risk infection. Despite emerging evidence that the vaccines are generally safe and effective, there is virtually no data as to whether that’s true for those who are expecting, even though they are at higher risk of complications from the disease.
The world’s regulatory bodies have at times issued contradictory advice about pregnancy and COVID-19 vaccines. The Centers for Disease Control and Prevention (CDC) has said that the vaccines should be available to pregnant people but ultimately leaves the decision up to expectant parents and their doctors. The World Health Organization (WHO) recommends against it unless the pregnant person is at high risk.
So how does someone make an evidence-based decision about whether it’s safe to get the vaccine in the absence of any safety data? “It all turns on the features of your life,” says Ruth Faden, founder of the Johns Hopkins Berman Institute of Bioethics in Maryland. Each person must balance what is known about the vaccine with what is known about their own risk of getting infected.
Although experts suggest talking through these decisions with a medical provider, here's a look at the facts available, what’s still being sorted out, and why there’s reason to be optimistic.
What we know about past vaccines
Scientists generally know quite a lot about vaccines and pregnancy—although historically it has taken longer to get that evidence than general safety data. Because of the ethical complexities of pregnancy—in which parents and their fetuses face interconnected risks—and fears of legal liability, pregnant people are typically excluded from the randomized clinical trials that are required to obtain approval for a drug or vaccine.
In the past, it has taken years after vaccines are approved for general use to gather enough data to show how they work during pregnancy. Many of these follow-on studies are observational and involve fewer participants. As a result, women who are pregnant may be hesitant to get a vaccine, and doctors may hold off on recommending them.
“What has resulted from this has been decades of essentially unfairness to pregnant women,” says Faden, who also leads the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) project. Although at times it might make sense to not include expectant parents in early trials, she says, “we’ve been protecting pregnant women to death.”
But scientists have accumulated incontrovertible evidence that certain vaccines are safe, effective and, in some cases, direly needed. Today, the CDC highly encourages pregnant people to get vaccinations against influenza, which is known to cause severe complications in pregnant women. Medical experts also advise getting the vaccine for pertussis (or whooping cough), which can be fatal to newborns. Expectant people can also receive immunizations for a handful of other diseases, including hepatitis and meningitis.
Lessons from those vaccines have shown that there’s no reason to worry about the types of shots that use an inactivated virus to elicit an immune response, since they cannot infect either the parent or the baby, says Geeta Swamy, associate professor of obstetrics and gynecology at the Duke University School of Medicine in North Carolina and a leading maternal immunization researcher.
On the other hand, vaccines using a small amount of live virus—such as the one for measles, mumps, and rubella and the one for chickenpox—can cause low-grade infections that some scientists worry could harm a fetus. But, Swamy says, “even that is based on theoretical risk concerns,” not on evidence that it occurs.
What’s different about the COVID-19 vaccines
The Moderna and Pfizer-BioNTech vaccines for COVID-19 pose a new challenge. Until now, the messenger RNA platform they use had not been licensed for human use. As such, the only pregnancy-related data available are from preclinical studies in laboratory animals and a handful of clinical trial participants who later discovered they were pregnant. (Here's the latest on COVID-19 vaccines.)
But we do know a fair amount about how the mRNA technology works. Instead of using inactivated or live virus, these vaccines contain snippets of genetic code encased in lipids, or fat globules, that protect the code from degrading. Once injected, the mRNA instructs cells to produce the SARS-CoV-2 spike protein, which triggers the body’s immune response.
Theoretically, all of this is promising because, like past vaccines, it does not involve a live virus. “Everything that is understood to be biologically the case about mRNA vaccines is incredibly reassuring,” Faden says. “It shouldn’t have any impact on pregnancy or pregnancy outcomes.”
Anthony Fauci, White House chief medical adviser, has also said that the data “so far has no red flags” for pregnant people.
Still, scientists have raised questions about how the mRNA vaccines will work in reality. The biggest concern is whether mRNA can cross the placenta and generate the spike protein in the fetus. It wouldn’t necessarily be harmful if it did—and would not cause birth defects—but the worry is that the fetus could experience side effects including pain, swelling, and fever. Swamy says the animal studies showed no signs of physical side effects, but that is yet to be tested in humans.
Side effects in the mother may also be an issue. Christina Chambers, a perinatal epidemiologist at the University of California, San Diego, is conducting a study of COVID-19 vaccinated pregnant women. She notes that it can be harmful to the baby when a pregnant woman runs a high fever. “If that is a side effect, you’d want to pay attention to that and talk to your provider about taking something to reduce the fever,” she says.
There are clinical trials in the pipeline to investigate the effects of the vaccines in pregnant women. Faden wishes these trials had started as soon as the vaccines received FDA approval, but she points out that the process is still moving more rapidly than it has in the past.
“We used to feel like one or two lonely drums out there, beating our drums in this vast silence,” she says. “Now we’ve got like a whole percussion section calling for more data and the inclusion of pregnant women in the rollout of the vaccine. And that’s a really good thing.”
The risks of infection
On the flip side, we do know plenty about the risks getting COVID-19 poses to expectant parents. “There’s no question at all that pregnant women fare worse than not-pregnant people,” Swamy says.
Studies have shown that pregnant people with COVID-19 are at an increased risk for hospitalization, ICU admission, and mechanical ventilation. In January, a study published in the journal JAMA Internal Medicine found that COVID-19 was associated with higher odds of blood pressure problems and premature birth, though there weren’t greater chances of stillbirth. And a study in October found that one in four pregnant people may be COVID-19 “long-haulers,” whose symptoms can linger for weeks or even months.
But the risk of severe illness is lower for the expecting than for other high-risk groups, such as the elderly or those with heart disease. So it’s critical to look at individual factors that increase a person’s individual risks—including numbers of daily contacts, access to testing and high-quality PPE, and comorbidities such as asthma or obesity—and whether there’s anything that can be done to reduce them.
Timing has to be taken into consideration, too. Swamy says there’s no evidence that a vaccine can cause developmental problems or miscarriage in the first trimester. But women at lower risk of infection may choose not to get vaccinated during that period, which is vital for fetal organ development and is when miscarriages typically occur. (The influenza vaccine is safe at any point during pregnancy.)
For pregnant women who are at high risk of exposure and who don’t have the option of reducing that risk, it may make sense to consider getting the vaccine as soon as they’re eligible. But to find out for sure, Chambers says, “the urgency is to get the data on people who are getting vaccinated.”
What we’re still trying to find out
There’s reason to hope that scientists will soon have a better understanding of how the COVID-19 vaccines work during pregnancy. In the near term, scientists are looking forward to the data from pregnant health-care workers who began taking the vaccines in December. Faden says that data should be robust, since more than 15,000 pregnancies among the vaccinated were reported to the CDC as of January 20.
Beyond the mRNA vaccines, there are some new options on the horizon. Johnson & Johnson submitted its vaccine for FDA approval on February 4, while AstraZeneca and Novavax have recently released critical phase three trial data. All three vaccines rely on technologies that have been studied in pregnant women in the past, which Swamy says could provide further reassurance. (Should people take more than one type of COVID-19 vaccine?)
Recent studies have also suggested that there could be extra benefits to vaccination while pregnant. One study published in the journal JAMA Pediatrics showed that women who have been infected with COVID-19 efficiently transfer protective antibodies to their babies—particularly if infected earlier in the pregnancy. The study does not suggest this transfer will happen after vaccination, notes co-author Karen Puopolo, attending neonatologist at Pennsylvania Hospital. But Swamy says it’s good news that antibodies are regularly crossing the placenta in natural infection, and that she expects vaccination would have a similar response.
“It tells us that vaccinating women could have that kind of two-for-the-price of-one,” she says, “that by vaccinating women we’re also providing some benefit during early childhood.”