Covid-19 vaccines are likely safe during pregnancy. When will we know for sure?

People who are pregnant or breastfeeding in the US could choose to get the vaccines, or wait until more data comes out this spring.

People who are pregnant should be able to decide if they want to get the coronavirus vaccine, US health agencies and medical organizations resoundingly agree. And in the first couple months of vaccine rollout, many pregnant health care workers have already chosen to do so:

Israel also recently added higher-risk pregnant women to its vaccine priority list. But other countries, such as the UK, and the World Health Organization are saying most should wait.

Why the disagreement? The clinical trials of the new Covid-19 vaccines explicitly excluded pregnant people, and we don’t yet have enough follow-up data from individuals who have opted to get the shots to say for sure they are safe during pregnancy. And so some governments and the WHO are being extra cautious about greenlighting the vaccine for all pregnant people.

The US and many national medical groups — including the American College of Obstetrics and Gynecology, the Society for Maternal-Fetal Medicine, and the Academy of Breastfeeding Medicine — say the vaccine should be offered to this group in large part because there’s strong evidence that pregnancy elevates the risk for severe Covid-19 and death. (Given this data, the American Society for Reproductive Medicine goes so far as to say the vaccine is “recommended” for those who are pregnant or considering pregnancy.)

“If a pregnant patient gets infected during pregnancy, her risk of intensive care admission is around 5 percent,” says David Baud, chief of obstetrics at Le Centre hospitalier universitaire vaudois in Switzerland, where he studies infections during pregnancy. “I do not know of any disease that put a 30-year-old woman at such high risk to be admitted to the ICU.” Furthermore, if the infection happens late in pregnancy, it also increases the risk of preterm birth and the baby needing intensive care.

These groups also have good reason to think the vaccines should be safe for pregnancy, including the lack of major adverse events in pregnancy reported so far, solid studies in animals, and a good understanding of how the vaccines work in the body (they don’t contain live virus, and they are quickly broken down). “The data that we’re collecting on it so far has no red flags,” Anthony Fauci, the top US infectious disease doctor, said at a press event Monday.

But we just don’t have the data to prove it yet. Add to this the persistent misinformation swirling around the Covid-19 vaccines and pregnancy and fertility, and it is little wonder many people are confused or worried. And most organizations still stop short of advising all pregnant people to definitely get the vaccine.

These information gaps should start to fill in soon, however. Numerous studies are planned or just starting — by vaccine manufacturers and outside researchers — to follow the outcomes of pregnant and breastfeeding people and their offspring after immunization.

But until we have more solid data, a growing number of people will have to make this decision, with the optional help of their care provider, with some uncertainty. And no one needs an extra thing to stress about during a pandemic pregnancy.

So additional information about the coronavirus vaccines in pregnancy can’t come soon enough.

4 reasons the coronavirus vaccine should be okay to get while pregnant — but why not everyone is recommending it

One of the big reasons why, despite Covid-19’s known risks in pregnancy, not everyone has unequivocally recommended the vaccines that currently have emergency approval in the US for pregnant people is that the way they work is fairly new. We don’t have any other approved vaccines that are designed this way. But we do have a few key pieces of information now:

1) These vaccines don’t contain live virus. The only vaccines that are contraindicated in pregnancy contain live virus that has been weakened, such as the chickenpox vaccine. (Even fewer immunizations, such as the smallpox vaccine, are not recommended during lactation.) While these types of vaccines don’t pose a risk to most people, there is a small chance they could cross the placenta and infect the fetus.

The two US–authorized coronavirus vaccines, Pfizer/BioNTech and Moderna, on the other hand, contain just a fragment of genetic material, called messenger RNA, that can tell human cells to build just a tiny part of the virus’s outer shell, which the immune system learns to recognize and fight off. So there is no way the vaccine can cause a Covid-19 infection.

2) The coronavirus vaccines are very fragile. Once the mRNA enters the body, it likely only reaches local arm muscle cells before the body breaks it down. This means it is very unlikely to reach the bloodstream, and even less likely to make it as far as the placenta. Even if it does get that far, “one of the placenta’s main functions is to be an immune barrier to the fetus,” which adds another layer of protection, says Stephanie Gaw, a maternal-fetal medicine specialist at the University of California San Francisco Medical Center. And although it contains genetic material, it doesn’t enter our cells’ nuclei, meaning that it doesn’t cause any mutations to our cells — or those of a developing fetus.

Experts also expect it unlikely for the mRNA to make its way intact into breastmilk. And even if a small amount of it were to be transferred to a feeding baby, they think it would get broken down by their stomach acids.

3) Animal studies look promising. Before giving shots to pregnant humans, vaccine companies have been gathering safety data in other pregnant mammals. None of these developmental and reproductive toxicity (DART) studies from Pfizer/BioNTech or Moderna suggest any safety concerns for use during pregnancy.

Rats, of course, are not humans, and DART study results do not always translate identically into humans. “Some results are similar to humans and some are very different,“ Gaw says. Nevertheless, they are a good starting point — when combined with strong safety data in the other adult clinical trials and vaccine rollout so far.

4) We haven’t seen adverse events in pregnant people who have gotten it so far. For the Covid-19 vaccine trials, those of “childbearing potential” were screened for pregnancy before each shot, and those with positive tests were removed from the studies. However, a handful of people (12 who got the vaccine in Pfizer/BioNTech’s study and six who got the vaccine in Moderna’s study) ended up having been pregnant at the time of vaccination — and companies haven’t reported any negative outcomes from these individuals. Although they are also still waiting for the babies to be born. The Centers for Disease Control and Prevention is also following pregnant people who sign up for its tracking app after being vaccinated.

“From a scientific perspective, there’s no specific reason to think that pregnant individuals would have more adverse reactions to the vaccine or that there would be a risk to the fetus with the vaccine, while we know that there is risk with the Covid infection,” says Alisa Kachikis, an assistant professor of obstetrics and gynecology at the University of Washington.

A January study published in JAMA Internal Medicine, for example, analyzed the outcomes of more than 406,000 people who gave birth in hospitals between April and November 2020 and found that a significantly higher rate of those with Covid-19 had major complications. “The higher rates of preterm birth, preeclampsia, thrombotic [blood clotting] events, and death in women giving birth with Covid-19 highlight the need for strategies to minimize risk,” noted the authors.

So why are some, such as the WHO and the UK, saying most pregnant people should not get the coronavirus vaccine yet? They are waiting for more data.

There are also other coronavirus vaccines in the works that don’t rely on the new mRNA approach. Many employ more familiar techniques that have a longer history of use. For example, protein-based vaccines (which is the basis for Novavax’s shots) have been used for years — including for pertussis and hepatitis B — “and we are very comfortable with [their] safety profile,” Gaw says. Viral vector vaccines (which is how shots by AstraZeneca/Oxford and Johnson & Johnson work) have also been used safely in pregnancy, such as for the Ebola and Zika vaccines, although there is less data on these.

So, says Kachikis, if what’s hanging people up about getting a Covid-19 vaccine in pregnancy is the novelty of the mRNA vaccines, having other types to choose from — as long as they’re just as effective — could be a good option in the future.

What studies are happening, and what will they help us learn about the Covid-19 vaccine in pregnancy?

Pfizer/BioNTech has yet to start enrolling pregnant participants in a clinical trial of its vaccine and declined to say when it will begin. For its part, Moderna is creating a registry to track those who received their vaccine while pregnant. These studies will help answer some key questions, including: What is the best way to space out doses for pregnant people? Are there any additional side effects? How effective are the vaccines in this population given that the immune system shifts throughout pregnancy? Are there are any negative outcomes for the individuals, their fetuses, or the babies down the line once they’re born?

In the meantime, other researchers are racing to collect and study data from the natural experiment that started in December, when many pregnant people began electing to get vaccines as they became eligible because of their high-risk work in hospitals or long-term care centers.

The CDC has an app that any vaccine recipient can sign up for, called V-Safe, which is allowing the organization to follow the outcomes of people who are pregnant when they get vaccinated. About 15,000 people who are pregnant and received the vaccines have signed up so far, the New York Times reported in late January.

In more targeted research at the University of Washington, Kachikis is leading a new study to also follow vaccination in people who are pregnant. More than 15,000 people have signed up for their tracking registry from around the US and the world, she says, thousands of whom have already received the vaccine while pregnant. (People who are pregnant or lactating but have not yet gotten vaccinated can also sign up, as can people who are considering becoming pregnant within the next two years.) This research will help them track any adverse outcomes, as well as gather additional data, such as whether any vaccinated individuals (or their newborns) later get Covid-19.

An additional large-scale clinical trial, which has not started enrolling participants, aims to track 5,000 women and their offspring over the course of 21 months. As is one at Duke University. Others are in the works as well.

Over at the University of California San Francisco, Gaw and her team are preparing to launch a separate observational study. This one will more closely follow a smaller group of participants — 100 or so who are pregnant and roughly 50 who are lactating — “to determine whether the Covid vaccines are equally effective in pregnant and lactating women, how long antibody responses last, and whether immunity is transferred to the baby,” Gaw explains.

“Based on our experience with other vaccinations in pregnancy, such as pertussis, we expect that the antibodies will transfer to the baby, and we hope that they will be protective,” Gaw says.

A new study published in JAMA found that the majority of women who were positive for Covid-19 at delivery had transferred antibodies across the placenta, potentially helping to protect their newborn.

If this benefit holds true for vaccines as well, it could be especially helpful, as newborns and infants will likely be among the last to have an authorized vaccine — and have the highest rates for complications and death from the virus among children.

More nuanced research might also eventually help advise on optimal timing for the Covid-19 vaccine during pregnancy. For example, Gaw notes, “there needs to be sufficient time for the mom to develop a robust antibody response, and then pass [this] to the baby.” After extensive research, the Tdap vaccine is recommended around 27 weeks of gestation so as to provide the best protection for the infant after birth. Without such information for the Covid-19 vaccine, many experts are recommending those who decide to get the shot treat it like the flu shot — getting it as soon as it’s available to them, regardless of where they are in their pregnancy.

People who are lactating were also excluded from the vaccine trials. So researchers at a number of institutions are now working to study how the vaccine might impact breast milk contents and a nursing child. (A study from October 2020 showed that most people who had recovered from Covid-19, as well as those suspected of being infected, passed on protective antibodies to the virus in their breast milk.)

At the University of Massachusetts Amherst, one team is planning a study to collect frozen breast milk from people at various times after they receive the second dose of vaccine, to see how antibodies and other components in the breast milk might help educate the baby’s immune system.

Wait, why weren’t pregnant people included in the early research to begin with?

Pregnancy has, for decades, been considered a “vulnerable” condition when it comes to researching new medical treatments and preventions, meaning people who are pregnant have been excluded from general trials in much the same way as have those who are unable to give informed consent, like children and those with severe mental disabilities.

Part of the reason for this might be due to the damaging legacy of thalidomide. This drug was given to pregnant women around the world starting in the 1950s as a way to ease nausea (although it was never approved specifically for use in pregnancy in the US). Soon, thousands of these babies were being born with devastating birth defects. This hammered home for scientists and the public that, when it comes to pregnant women and their fetuses, much more care ought to be taken in giving medications or vaccines.

But this conclusion, many are now saying, has it backward, as the oft-repeated phrase indicates: Protect pregnant people “through research, not from research.” If thalidomide had been carefully and systematically studied for pregnancy, it likely never would have been approved for use (or used unofficially) in this population, preventing the majority of these tragic outcomes.

“It can’t be emphasized enough that pregnant women should be included in vaccine trials from the get-go,” Kachikis says.

Johannes EiseleI/AFP via Getty Images

Gaw agrees: “We actually cause harm by not including [pregnant people] in early research, as they have to wait longer for good data to be published.”

Only in 2019, as NPR recently reported, was pregnancy removed as a “vulnerable” condition for clinical trials. But it remains a common criterion for excluding participants, as in the major Covid-19 vaccine trials.

So when will we have more data about the coronavirus vaccine in pregnancy and lactation?

One big challenge with researching anything to do with pregnancy is that it takes a long time: nine months, plus follow-up time to monitor infant outcomes. And subsequent study during lactation while you’re at it, and maybe preconception research, too.

Consider that it took vaccine makers just 10 months to develop the Covid-19 vaccines and ensure they were safe and effective in adults. But with experts expecting Moderna and Pfizer/BioNTech to only begin enrolling pregnant people in trials early this spring, it could be early 2022 or beyond until we have comprehensive, robust safety data for all stages of pregnancy. And even later to assess long-term outcomes for babies.

We will likely, however, learn whether these vaccines are equally effective in pregnancy sooner than that. Vaccine company researchers will be able to use the shorthand of existing immune response data from the earlier trials — and not have to wait for pregnant people to get sick from the virus.

And independent studies are aiming to have data even sooner. At UCSF, Gaw hopes to have preliminary information about at least efficacy in participants (by looking at their antibody count after the shots) a few months after they are able to start the study. Further data will take “at least six to nine months, as we have to wait for a sufficient number of babies to deliver,” she says.

Kachikis and her team at the University of Washington plan to follow the outcomes of people who sign up for their list for about a year, with hopes to continue more long-term follow-up.

But they don’t want to wait that long to start sharing what they learn. “The focus is on getting any data out,” Kachikis says. And “if multiple groups can get some data out, that will be better than having absolutely nothing,” which is essentially the current situation, she notes.

For now, much of the official guidance stresses the need for people to conduct their own analysis of the known risks of Covid-19 with the unknown risks of the vaccine. And this calculus is not the same for everyone.

“Ultimately, the decision to get vaccinated in pregnancy should consider the individual’s risk of getting Covid-19 (for example, if you are a front-line worker), the known risk of more severe disease with Covid-19 in pregnancy (which is harmful for both the mom and the fetus), with the unknown (but most likely low) risk of the vaccine to the pregnancy and baby,” Gaw advises.

Additionally, even those who are reluctant to offer the vaccine for all pregnant people just yet, such as the WHO, do suggest it should be available to those with high risk of exposure to the virus or underlying health conditions that increase their risk of severe Covid-19.

Might the CDC eventually even make pregnancy a criterion for earlier access to the vaccine? It already lists pregnancy as a risk factor for severe Covid-19, along with other conditions, such as obesity and heart disease, that could help people get priority access to doses. The agency will likely wait for additional preliminary data to come in first, and then it will ultimately be up to states to determine how they high prioritize pregnant people for limited shots.

How soon could that information arrive? Baud, who also helps run an international registry for pregnant people exposed to Covid-19 (and now also those vaccinated against it), expects we will start seeing early data about the vaccines during pregnancy this spring.

So to help move along the plodding process, people who are pregnant and considering getting the vaccine can contribute to getting more and better guidance sooner by opting into registries and studies.