The first studies of COVID vaccines didn’t include pregnant people or lactating mothers. That left a big gap in knowledge. Now, there’s a rapidly growing body of research on COVID vaccination and infection during pregnancy.
“The vaccines are very efficacious, very safe,” said Andrea Edlow, an obstetrician at Massachusetts General Hospital and a professor at Harvard Medical School. “And we know that not getting these vaccines predisposes you to blood clots, preterm birth, stillbirth, maternal death and severe morbidity [if you contract COVID while pregnant].”
Edlow’s team has made some fascinating discoveries. They found the sex of a fetus may affect how a pregnant person responds to a COVID infection. And, in a recently published study in the Journal of the American Medical Association (JAMA), Edlow and her colleagues show antibodies from COVID vaccination can linger in a newborn baby, offering some degree of protection months after delivery.
WBUR asked Edlow for an overview of the latest research on COVID and pregnancy. The following conversation has been edited for length and clarity.
Bring us up to speed on what we know about getting COVID while pregnant.
It's very dangerous for a pregnant person to get COVID. That's been well established in large population-level studies. So the pregnant person with COVID would be more likely than someone else their same age and with their same comorbidities [or health conditions] to have severe illness, for example, requiring an ICU stay or intubation or a heart lung bypass machine.
Another thing that's been well established is that it's relatively rare for a fetus to be infected in utero from a maternal COVID-19 infection. We have really good data on this up to the point of the delta and omicron variants emerging. The reason that's important to note is that there have been new studies showing that maternal morbidity and mortality is even worse in delta compared to pre-delta.
You said pregnant people are at a higher risk, but how much higher?
Compared to non-pregnant counterparts of similar age, pregnant people with COVID-19 have a 1.7-fold increased risk for death, approximately 3-fold increased risk of ICU stay and intubation, and 2.4-fold increased risk for needing a heart-lung bypass machine.
COVID-19 is also associated with increased risk for stillbirth, hypertensive disorders of pregnancy like preeclampsia and postpartum hemorrhage. Preterm delivery and cesarean delivery were also found to be significantly increased.
Several months ago, there was news about pregnant people having a different response to COVID depending on the sex of their fetus. Where does that research stand now?
What we found is, if [unvaccinated] mothers had a male fetus, they made a significantly lower level of antibody against SARS-CoV-2 [the virus that causes COVID], and they also transferred fewer antibodies to their male fetus. The reduced transfer was not surprising because they had less to start with, but the reduced maternal production of antibody in the setting of a male fetus was striking.
That speaks to potentially more vulnerability of the mother carrying a male fetus — and to increased vulnerability of the male fetus and neonate [or newborn]. Caveats include that this work was conducted in a relatively small number of patients and done prior to when COVID vaccines became available. We need more research to be performed in this area — both sex differences and pregnancy immunity are understudied areas.
Do you have a sense of why pregnant people are at increased risk? Is it that the immune system is weaker in pregnancy?
Our understanding of the immune system in pregnancy has evolved beyond a blanket concept of, “your immune system is weaker in pregnancy” to it really being trimester specific and, in some regards, pathogen specific. Different aspects of the immune system may be tuned up or down at different points in pregnancy.
So, for example, early in pregnancy inflammation at the maternal interface where [embryo] implantation is taking place can actually be advantageous to a pregnancy surviving.
Then, during periods of rapid fetal growth in pregnancy [such as the second trimester], the fetus really needs to grow and develop unencumbered by any immune attacks. The fetus is half non-self. So, the mom's body could, in theory, recognize that other component and make an immune response. So, it is especially advantageous to tone down immune responses during periods of rapid fetal growth.
Even this understanding of pregnancy immunity is overly simplistic.
Apart from immune system differences, though, pregnant people are at increased risk from respiratory viral infections in particular due to specific changes that occur in the pulmonary [or lung] and cardiovascular [or heart and blood vessel] systems in pregnancy.
Pregnant women often feel that they can't breathe. That is in part because your uterus really is taking up a lot more space and pushing other organs out of the way. Your diaphragm can't drop as deeply when you inhale. And so that's part of what makes people more prone to severe lung disease.
The other important aspect is changes that occur in your heart and blood vessels. The cardiovascular demands of pregnancy are huge. The pregnant heart has to pump approximately 1 liter of blood per minute to the placenta, in part to oxygenate blood for the fetus. And so, your heart is doing a lot of extra work and can easily become overtaxed if additional demands are added, such as in the setting of infection.
What is known about vaccines and boosters in pregnancy?
Originally, when the COVID vaccines were studied, pregnant individuals and lactating individuals were left out of those initial trials. That, unfortunately, led to a lot of vaccine hesitancy because it created a temporary information vacuum.
Our group and other groups have tried to step in and fill that vacuum. We published a large study looking primarily at pregnant health care workers who, given their job risks, had elected to take the COVID vaccines. And we showed that they produce a strong immune response that's comparable to non-pregnant individuals, showing that the vaccines are effective in pregnancy and when lactating.
Since then, people have gone on to show that in larger groups of lactating individuals, the mRNA in the vaccine is not transmitted in breast milk, but the antibodies that it produces are transmitted. We suspect that these breast milk antibodies will be protective to some extent to the breastfed infant. And how protective probably depends on the amount of breastfeeding, whether it’s exclusive breastfeeding, the duration of breastfeeding, the time from when the mom was vaccinated and other considerations.
Right now, we're still at that phase in the pandemic where, unfortunately, all pregnant individuals are vulnerable, so the right time to get vaccinated is now. It doesn't matter what trimester you're in. I think the conversation about boosters is a little more nuanced, and that's an important area for future study.
People have been able to show that maybe getting vaccinated between 20 and 32 weeks gestation provides excellent transfer of antibodies to the newborn. If people are vaccinated for the first time in the third trimester, very close to delivery, it gives less time for the transfer of antibodies.
Our group has also shown that the antibodies produced by a third trimester COVID infection — as compared to vaccination — have different kinds of sugar attachments on them. And these sugars made the antibodies less able to be transferred to the fetus. So, there’s yet another reason to be vaccinated.
How long does a baby have protection from these antibodies?
We didn’t have a great answer for our patients when they were asking us that question. So, we did a study where we asked moms who were already enrolled in our vaccine study if we could draw a little bit of blood from their babies at two months and six months of age.
We found – in a study published in JAMA – that at two months, 48 of 49 babies had detectable levels of the kind of maternal antibodies that can cross the placenta. At six months of age, 16 of 28 babies [more than 50%] still had detectable antibodies. We also looked at babies at six months of age whose mothers had COVID while pregnant, and only one of those babies still had antibodies against SARS-CoV-2.
This is important because even though trials for the COVID vaccines are ongoing in children who are aged six months to five years, there aren't plans currently to vaccinate babies younger than six months of age against SARS-CoV-2. So knowing that protective antibodies from [a vaccinated] mom can last up to six months is valuable.
What do we know about how high the levels of antibodies need to be in order to provide protection?
Even in adults, and certainly in infants, the absolute level of antibody at which you're “protected” against severe COVID-19 disease is not known. Our knowledge is evolving, and we know that antibodies definitely protect you from severe disease and death. But for some variants of concern, they don't protect you from testing positive for SARS-CoV-2 or from transmitting it.
What are the treatment options for people who get COVID while pregnant? Do pregnant people count as high-risk enough to get the limited supply of treatments?
Right now, unfortunately, there's a shortage of the one monoclonal antibody that's active against omicron. We've had our pregnant patients calling around, trying to get that treatment and trying to go to different sites all over the state to get it.
Certainly, if there was an unlimited amount, we would likely say that all pregnant individuals should receive it. But right now, it is mostly going to pregnant individuals who are unvaccinated and test positive. Or if you are pregnant and vaccinated but have other health or immune conditions.
At Mass. General, we are trialing outpatient remdesivir. And that's very novel and cutting edge — and not available at most hospitals across the country.
There are also newly available oral COVID treatments. But I think they may create a false sense of security. People might say, “Oh, now there's a treatment that I can take if I get COVID, I don't need to be vaccinated.” I strongly advocate against that approach.
We have so much more data about the safety and efficacy of all the COVID vaccines in pregnancy than we do on any of the newer COVID therapies at this point. So if you want to take the intervention with the most data behind it, you would take the COVID vaccines every time.