PROJECT SUMMARY
Respiratory Syncytial Virus (RSV) can cause severe illness in young children and is the leading cause of infant
hospitalization in the United States. Prenatal RSV prefusion F protein−based (RSVpreF) vaccine efficacy is
69% for severe RSV-associated lower respiratory tract illness in infants through 6 months. In August 2023, the
Food and Drug Administration approved the vaccine for use at 32 through 36 gestational weeks with a
Prescribing Information warning about preterm birth given an imbalance in preterm birth risk observed between
the vaccine and placebo groups in the clinical trial. However, pregnant people at high risk for preterm birth
were excluded from the trial, the trial did not assess the effect of the vaccination on lactation-related outcomes,
and there are limited safety data on neonatal outcomes and longer-term infant and child outcomes including
growth, neurodevelopment, and allergic conditions.
On September 22, 2023, the Advisory Committee on Immunization Practices (ACIP) recommended seasonal
administration of either prenatal RSVpreF vaccine or nirsevimab, a long-acting monoclonal antibody
administered to infants, to prevent severe RSV infection. Lack of safety data decreases vaccine confidence
and could contribute to poor uptake of RSVpreF during pregnancy. Though there is little biologic plausibility of
harmful effects of prenatal RSVpreF vaccination on neonatal, lactation, and child health outcomes, rigorous
real-world safety data are needed to guide informed decision-making.
To address the need for comprehensive safety data on prenatal RSVpreF, we propose to study the effects of
RSVpreF vaccination on neonatal, lactation, and child health outcomes in up to 20,000 mother-infant dyads
using electronic health record data supplemented with vaccinations from state immunization information
systems across four large health systems in Hawaii, Oregon, Washington, Minnesota, and Wisconsin. We will
use rigorous epidemiologic methods, including propensity scores to address confounding, inverse probability of
censoring weighting (IPCW) to address selection bias, and target trial emulation to address immortal time bias.
For associations suggesting harm, we will explore the direct effects of RSVpreF independent of preterm birth
and infant nirsevimab exposure. The exploratory mediation analysis will use a causal inference approach.
We will build on the data structure and methods that we developed through a National Institutes of Health
(NIH)-funded study of COVID-19 vaccination and lactation outcomes and expertise developed through Centers
for Disease Control and Prevention-funded research on antenatal vaccination safety. We are uniquely
positioned to study lactation and child health outcomes and overcome reporting and volunteer bias in other
studies by using routinely collected information on breastfeeding, growth, and developmental screening at well-
child visits for a defined population as we have done in prior NIH-funded research. The study will provide timely
real-world evidence to inform clinical guidelines and decision making regarding prenatal RSV vaccination.
