Sometime between 27 and 36 weeks of pregnancy, every pregnant person in the US will be recommended by their obstetrician to receive the Tdap vaccine, which protects against tetanus, diphtheria and pertussis, or "whooping cough." The main reason for getting this vaccine in each pregnancy is to protect the newborn.
That's because some maternal antibodies can pass through the placenta to the fetus--what's called passive immunity. So some of the antibodies generated in response to the Tdap vaccine are transferred in this way. Passive immunity can also be conferred through breast milk.
The potential role that passive immunity might play is especially important since a newborn's immune system is not fully developed--it becomes capable of mounting a mature immune response around 4 to 6 months after birth.
In the context of the COVID-19 pandemic, passive immunity has received increased scientific attention. While questions remain, data are accumulating on the importance of vaccinating pregnant individuals against COVID-19, both to protect the health of the newborn and the mother or birthing parent.
The gold standard for looking at vaccine safety and efficacy is a randomized placebo-controlled clinical trial. But pregnant and lactating individuals were excluded from clinical trials of COVID-19 vaccines prior to authorization.
[Chambers:] We have traditionally done this and not allowed that information to be captured, and thus it falls in the postmarketing arena for us to try to capture this information in an observational setting.
Because of the initial lack of data, the earliest recommendations from the CDC and medical societies were that pregnant and lactating individuals should be offered COVID-19 vaccines, or that these vaccines should not be withheld, which led to confusion for many patients. But in summer 2021, these guidelines were strengthened to say that COVID-19 vaccines are recommended for these patients, based in large part on accumulating evidence on safety.
[Jamieson:] We know that the side effect profile in pregnant and nonpregnant persons is very similar, there's some subtle differences. And importantly, we know that there's similar pregnancy outcomes including no increased risk of spontaneous abortion or miscarriage.
Pregnancy and lactation represent unique immunological states--the immune systems of pregnant or lactating individuals don't function the same way as in nonpregnant individuals. And this may alter the effectiveness of vaccines. While some recent data suggest that the immune response to COVID-19 vaccines does differ for these groups, studies have consistently indicated that pregnant and lactating individuals do mount a robust immune response following two doses of the mRNA COVID-19 vaccines.
So what do we know about passively transferred antibodies?
Experience with other respiratory infections, such as pertussis, RSV and influenza, suggest that the presence of these SARS-CoV-2 antibodies could play a role in protecting a newborn against COVID-19.
And evidence is beginning to emerge confirming this. A case-control study published by the CDC in February estimated that maternal vaccination during pregnancy with two doses of mRNA vaccines was 61% effective in preventing COVID-19 hospitalizations in infants aged less than 6 months. In the study, 84% of the infants hospitalized with COVID-19 were born to those who were not vaccinated during pregnancy.
But more research is needed.
[Riley:] I think what is not known--what is the correlate of protection; i.e., how much, you know, antibody that we're measuring is consistent with enough antibody to protect from infection, I don't think we know the exact number, but I think it's pretty clear that having some antibody is certainly way better than having none.
And many additional questions remain unanswered. How long do passively-transferred antibodies persist? Which types of antibodies are transferred? What is the optimal vaccination timing? Are there any long-term neurobehavioral or growth differences in children born to those who were vaccinated versus unvaccinated?
Given these remaining questions, many individuals who are pregnant, lactating, or planning pregnancy, have been hesitant to be vaccinated.
[Chambers:] Sometimes the birthing parent says, you know, "I think I'm at low risk of infection," or "I don't believe there's enough data to be able to say that my fetus or my infant will not be harmed by this." There's the protection that you want to provide, and you want more information to be able to help you make those decisions. That being said, pregnant individuals have some of the lowest vaccination rates in the US.
About 33% of pregnant adults in the United States have not been fully vaccinated as of January 2022.
This brings us to an important point: while passive immunity transfer to the newborn is an important focus of scientific inquiry, the critical goal of COVID-19 vaccination before or during pregnancy is to protect the pregnant person themselves.
[Riley:] I think we should be really clear. The main reason that we want pregnant individuals to be vaccinated is because they are at high risk for severe complications if they become infected with COVID. It is an added benefit that that protection that is afforded the pregnant individual is also afforded to the newborn.
Evidence that pregnant individuals are at increased risk for complications from COVID-19 emerged early in the pandemic.
For example: in September 2020 the CDC published a report titled "Characteristics and Maternal and Birth Outcomes of Hospitalized Pregnant Women with Laboratory-Confirmed COVID-19." It detailed that among women of reproductive age hospitalized for COVID-19, more than 26 percent were pregnant. But in the general population, only about 5% of women of reproductive age are pregnant at any given time. This discrepancy signaled that pregnant individuals are disproportionately more likely to be hospitalized with COVID-19 compared to nonpregnant individuals.
Data have continued to confirm and elaborate on these findings.
Jamieson: We know that pregnant persons are more likely to have severe disease. They're more likely to need hospitalization, to require intensive care, require mechanical ventilation, and to die, compared to nonpregnant persons. We also know that COVID increases the risk of some adverse pregnancy outcomes, such as preeclampsia, pre-term birth, stillbirth.
Making the choice to receive a novel vaccine during pregnancy or lactation is not easy. When balancing the risks and benefits, the very low and predominantly theoretical safety risks of vaccination, in addition to the potential benefits of passive immunity for the newborn, have to be weighed against the well-documented risks of COVID-19 for pregnant individuals and their newborns. Importantly, remaining unvaccinated is not a risk-free choice.