Respiratory syncytial virus (RSV) is a major cause of global newborn and infant morbidity and mortality. While usually not deadly in the U.S., RSV can in rare cases cause death for particularly vulnerable infants and is a serious burden on hospital systems both in the U.S. and globally.
In late August, Pfizer's bivalent RSV vaccine (Abrysvo) was approved by the FDA for use in pregnant individuals to protect newborns from serious RSV-related outcomes. In clinical trials, a single dose of the vaccine given at 24 weeks' gestational age or later demonstrated an efficacy of 81.8% against severe RSV-associated lower respiratory illness up to 90 days after birth and 69.4% efficacy up to 180 days, compared with placebo.
In May, prior to approval, an FDA advisory committee voted in favor of the new RSV vaccine for use in pregnancy, but several committee members expressed concerns about a potential signal that the vaccine is associated with a higher rate of preterm births. The study found a preterm birth rate of 5.7% in the vaccine group compared to 4.7% in the placebo group. However, this difference was not statistically significant. In an effort to reduce any potential risk, the FDA stipulated in its approval that the vaccine be given at 32 to 36 weeks' gestational age.
Two RSV vaccines have already been FDA-approved for older adults, and the CDC has advised that adults 60 and over talk to their clinicians about whether to get vaccinated. Meanwhile, for pregnant woman, the CDC's Advisory Committee on Immunization Practices () has two options to protect infants against serious RSV-related outcomes: they can get the RSV vaccine at 32 to 36 weeks' gestational age; or wait until their child is born, at which point babies entering or in their first RSV season can receive the monoclonal antibody nirsevimab (Beyfortus).
So where does this leave ob/gyns, who will inevitably be faced with patients raising questions about the new vaccine?
Background
We first need to understand that the notion of new vaccines in pregnancy is a very sensitive topic. For one thing, vaccines that involve live attenuated viruses (like the measles, mumps, and rubella vaccine, or MMR) are not recommended during pregnancy because they can cause illness on exceedingly rare occasions. This has led to some confusion that vaccines during pregnancy in general are .
This suspicion and confusion existed even before the COVID vaccine. After adding to the mix a vaccine with a new technology (mRNA) surrounded by an abundance of misinformation, it doesn't take much to understand why many pregnant people refused (and continue to refuse) the COVID vaccine. Perhaps the public health community could have been better prepared for these high rates of hesitancy, but many assumed the disease's immense threat would persuade most people to get vaccinated. This turned out to be wrong. We are already seeing the same pattern with regard to RSV: some are assuming vaccine acceptance will be high because many people know someone whose child ended up in intensive care with RSV. We should not be making this same assumption.
An Appropriate Communications Framework
Currently, little is being done to train clinicians to best communicate recommendations amidst the potential uncertainty surrounding the new RSV vaccine in pregnancy. Since CDC's recommendation leaves the communication up to clinicians and their patients, we must ensure ob/gyns feel adequately prepared to share information about the vaccine and nirsevimab, communicate wisely about uncertainties, answer questions, and manage potential hesitancy and misinformation.
There is actual uncertainty here, and communicating about that uncertainty to anxious patients is a skill that can be informed by evidence and honed through deliberate practice. It is true that the potential risk for preterm birth in the Pfizer vaccine trial was not statistically significant, and this relatively low risk compared to a higher risk of bad outcomes from RSV infection in newborns drove the FDA advisory committee to recommend the vaccine.
At the same time, "not statistically significant" may not be understood by individual patients. In the setting of scientific uncertainty, clinicians and patients must have frank discussions about the risks and benefits. Normally, this would take place through a process known as shared decision-making. But shared decision-making may prove difficult in this instance because: (1) the risk of severe outcomes from RSV in infants is unfamiliar to many people, so they may not truly understand the vaccine's benefit at a population level; (2) we do not yet fully understand the potential risks of this vaccine in populations at high risk for poor outcomes. The Pfizer vaccine was studied in an international population in 18 countries (45% of patients being in the U.S.). Black people made up 19-20% of the total study population, but the results were not broken down by Black African versus Black African American, even though the two groups have very different rates of preterm birth, with the latter having higher rates (for reasons that are not entirely clear). Moreover, the study population was healthier and probably less susceptible to preterm birth than the general population. We also cannot ignore that the monoclonal antibody nirsevimab offers another option to concerned patients.
We have an opportunity to get ahead of this difficult communication issue.
What would this look like in practice? Seeing that the shared decision-making framework might not directly apply here, we need to train clinicians specifically in communicating amidst uncertainty. This involves doctors being able to take stock of where their natural bias lies -- in favor of a "first do no harm" or a "better safe than sorry" attitude. The former would result in more conservative care and withholding the vaccine more frequently due to concerns about preterm birth (and perhaps suggesting the monoclonal antibody option instead). The latter would result in more vaccinations because of a fear of inaction leading to poor outcomes (e.g., RSV in newborns and infants). In this way, we might be dealing with a "values-based" decision-making framework as opposed to a "shared" decision-making framework. While these two are not necessarily diametrically opposed, the emphasis on understanding personal bias and communicating under uncertainty is unique to this "values-based" decision-making framework when compared to shared decision-making.
While there is still insufficient understanding about how medical professionals should handle uncertainty, we can borrow some insights from work by that uncovers the idea of physicians being in the camp of "interventionists" or "skeptics" when it comes to mammogram recommendations. In this view, the most important intervention is for physicians to understand and reflect on how they "lean," similar to uncovering unconscious bias. A relatively new from the American Board of Internal Medicine Foundation about building trustworthiness by addressing uncertainty in medicine is a good example of how these ideas about communicating uncertainty are being adapted by others in the medical field.
We must disseminate this kind of communication strategy soon. The RSV vaccine is only one of many emerging technologies that will pose challenges to traditional modes of communication and healthcare decision-making. Our population's trust in the medical field hinges on the right type of communication amidst uncertainty.
is CEO of Critica and executive director of Those Nerdy Girls. is an assistant professor of medicine at Weill Cornell Medical College in New York City and chief medical officer of Critica. is an ob/gyn in Albany, New York.