Vaccines, Boosters, Pregnancy, and Risk

In the past few weeks, the CDC has made a big push to encourage vaccination among pregnant people. The agency noted higher risks for this group and much lower vaccination rates than the age-matched general population. It’s begging pregnant people to get vaccinated. Yet there remains a lot of fear and confusion; an article in The Guardian captures this well. Similar to with pediatric vaccination, there are people who would have no hesitation while not pregnant who have been more wary in pregnancy. On top of this push for more baseline vaccines in pregnant people, we now face another choice. If you’re pregnant and already vaccinated (with Pfizer), should you get a booster? I’m going to get into both questions below. (I’ve also written about vaccines in pregnancy before, when information was less available, back in December and April.) First-time vaccination in pregnancy I’ll start by talking through the first question. I’m pregnant and unvaccinated: Should I get vaccinated during pregnancy and, if so, when? Is it safe? Most (all?) decisions come down to weighing the costs and benefits. In thinking about this one, it makes sense to begin with the benefits. The fact is that the benefits of vaccination are higher in pregnancy than if one was not pregnant. We have increasing evidence that pregnant people are at somewhat higher risk for serious illness and hospitalization than comparable non-pregnant people. Some of these claims about excess risk are overstated. There is an oft-quoted statistic that 20% of pregnant women with COVID are hospitalized. But this is from early data and didn’t differentiate between hospitalized for COVID and hospitalized for other reasons (like, you know, childbirth). However: we now have better evidence showing that serious illness and death is more common in pregnancy. For example, an analysis of 400,000 people with symptomatic COVID-19 showed that those who were pregnant were three times as likely to be admitted to the ICU and 1.7 times as likely to die. Other, international data has shown serious risks to both mom and baby with COVID-19 infection. The U.K. is reporting this week that 20% of critically ill COVID patients are pregnant women. It is true that the magnitude of risk of serious illness is still small in this population, mostly because pregnant people are usually young. But that risk is higher among the unvaccinated. The most recent CDC report suggested that 97% of pregnant people hospitalized with COVID were unvaccinated. Vaccines do an excellent job of protecting against serious illness. That’s the benefit side. I think this is widely accepted, and probably not the main source of vaccine hesitancy. Instead, the concern is safety. How do we know the vaccines are safe in pregnancy? Pregnant people were not included in the original vaccine trials. This is standard practice for medical trials, but it’s frustrating, since it leaves us with less certainty and information than we could have. But this is different from saying we have no information. The first and probably most important thing to say is: all the data we do have is reassuring. At this point, millions of pregnant people have been vaccinated worldwide. That is perhaps the most reassuring thing to note. When we do millions and millions of vaccines and pay careful attention to safety data, we learn a lot about even rare complications. With the COVID-19 vaccine, for example, we’ve learned that there is a very rare complication of myocarditis in young men. But despite the millions of vaccines, we haven’t seen any such risks in pregnant people. Given the (appropriately) intense scrutiny, this is reassuring on its own. More systematically: we have early follow-up data from the v-safe pregnancy registry, and preliminary analysis points to no increased risk of complications. A paper in the New England Journal of Medicine in April indicated no increased risk of complications at birth. That paper also reported some data on miscarriage rates but, as I pointed out and the researchers later acknowledged, the data at the time wasn’t sufficient to draw conclusions about that outcome. However, an August update of these results was able to look at miscarriage, and more conclusively show that the miscarriage risk in the vaccinated group did not exceed the expected baseline risk. In other words, there wasn’t a link in the data between vaccination and pregnancy loss. This isn’t the only type of data we have to rely on, either. We have evidence from animals, evidence from lab studies of vaccines, small numbers of pregnancies in the vaccine trials, and so on. This article provides a full summary of what we know and what is underway. The bottom line is that everything we know is reassuring, and there are trials underway in pregnant people, so we’ll know more later. Vaccines have been given at all stages during pregnancy. People have sometimes expressed worry about getting a fever side effect during the first trimester, but the best data we have doesn’t point to a link there. If you want to get vaccinated, any time is a good time. Having said all this, it’s important to acknowledge what we do not and cannot know. We cannot with certainty rule out some long-term issue. To be clear, there is absolutely no reason to think such an issue would arise. But that’s different from saying we can rule it out. In recognizing this, we should also be clear that there is no data that would definitively rule out all concerns. Even if we had 10 years of randomized follow-up data, you could always worry about year 11. Fighting against this is the observation that we also cannot rule out any long-term complications of getting COVID during pregnancy. There will always, no matter what, be these “known unknowns.” What’s the bottom line? If you asked me for advice and you were an unvaccinated pregnant person, here is what I would say: You’re more at risk from COVID when pregnant than when not, so from the COVID-prevention standpoint, there is an additional benefit to being vaccinated now. And while we cannot ever be 100% sure we can rule out any complications from the vaccine, the same is true for ruling out complications from COVID. What we do know is that millions of pregnant people have been vaccinated, and all the data we have seen suggests that the vaccine doesn’t cause issues for mom or baby, and it protects you from COVID. For these reasons, I recommend you get vaccinated. Booster shots Now let’s turn to the other side. For pregnant people who are vaccinated, the next question is whether they should get a booster. It’s a question that is coming for us all, but it’s especially salient in pregnancy because (a) you may be at higher risk, (b) there are questions about protection of the fetus, and (c) pregnancy is considered a high-risk condition, so pregnant people are in the currently eligible booster group. To begin: We have no direct data or especially strong recommendations. Boosters are relatively recent, and at least in the U.S. we do not, so far, have systematic data on their use in pregnant people. The CDC recommendation includes pregnant people as a group that may get a booster, but they do not rise to the level of those who should (older or immunocompromised individuals). Any decision here is going to need to rely on inference from other areas. In terms of safety, there isn’t any reason to think a booster would have a different safety profile in this population than the initial vaccine, and, truth be told, anyone who is contemplating it is probably already sold on safety. For people in this group, the more salient question is probably whether there are benefits to doing so. One possible benefit is to address waning immunity. This is a complicated issue in general. It’s becoming clear that the protection afforded by vaccines against any infection wanes over time but that they remain extremely effective at preventing hospitalization and death. For the very elderly or immunocompromised, a third dose of the vaccine seems to be recommended to prompt a good immune response. Are pregnant people in this group? Is their risk sufficiently elevated that they should get a booster? Opinions differ, but even with an elevated risk, an otherwise healthy pregnant person has nowhere near the baseline risk of someone in their 80s or 90s. Their argument for a booster is more limited. Perhaps more interesting is the argument for a booster based on infant protection. Thinking this through, we consider the parallel to other illnesses. A Tdap booster shot is recommended for pregnant people between the 27th and 36th week of pregnancy, to protect their infant against whooping cough (the “p” is pertussis). This booster shot prompts the development of antibodies against pertussis in the mother, which are passed to the fetus during gestation. The immunity gained by infants in this way isn’t long-lasting; when antibodies decay, after about six months, they will no longer have this immunity. This is different from what happens when they are vaccinated themselves, when they develop both antibodies and T-cell and B-cell memory cells, which can produce new antibodies if needed. But in the case of whooping cough, the immunity from maternal antibodies is enough to tide them over until their own vaccines. There is a lot of reason to think that COVID vaccines would work the same way. If you were vaccinated in a first wave and are pregnant now, you probably have limited antibodies circling around (you’re still protected! just by the B- and T-cells). If you get a booster, you’ll re-up your antibodies. And then those antibodies could pass to your infant and provide them with some protection early in life. How much immunity? How important is that? Numerically, we do not know. This is based on inference and logic and the fact that we know infants can have COVID antibodies from vaccinated mothers. So we cannot be certain about any of it. More studies! Need more studies!! Any decisions about a booster should be made in consultation with your doctor; this feels like a complicated choice, where people will do things differently. I will say: if I were pregnant now (I’m not; the shop over here is decidedly closed), I would go to my doctor with a proposal of a booster in the same time frame as the Tdap booster. But that’s just me. A concluding thought As with vaccinating kids, I think it is natural that there is more hesitation about the COVID vaccine in pregnancy. It feels like a more fragile state, and there is the ever-present fear that you’ll make a choice that somehow, in some way, is damaging to your baby. The important difference between this group and kids is the level of risk from COVID infection itself, which elevates the benefit of vaccines. But even with such benefit, the fear can be hard to overcome, especially for people whose OBs are not encouraging vaccination. In the end, beyond the question of COVID, I think there is a lesson to learn about how we treat pregnant people in studies like these vaccine trials. There are concerns about the ethics of including this group in trials, but there are very clear risks in the other direction too. We’ve left pregnant people making this choice with information that many of them (and some of their doctors) find insufficient. And that’s wrong.

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