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Principal Investigator: Kristin Palmsten
Organization: HEALTHPARTNERS INSTITUTE
Fiscal Year: 2024
Award: $732,591
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
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.
Terms: <0-11 years old><0-4 weeks old><Address><Admission><Admission activity><Advisory Committees><Age Months><Allergic><Allergic to food><Allergy to food><Apgar Score><Atopic Dermatitis><Atopic Eczema><Atopic Neurodermatitis><Biological><Birth><Breast Feeding><Breast fed><Breastfed><Breastfeeding><COVID-19 vaccination><Centers for Disease Control><Centers for Disease Control and Prevention><Centers for Disease Control and Prevention (U.S.)><Child><Child Health><Child Youth><Children (0-21)><Chronologic Fetal Maturity><Clinical><Clinical Treatment Moab><Clinical Trials><Complement><Complement Proteins><Conduct Clinical Trials><Convulsions><Data><Data Systems><Decision Making><Development><Diagnosis><Disseminated Neurodermatitis><Electronic Health Record><Epidemiologic Methods><Epidemiological Methods><Epidemiological Techniques><Exclusion><FDA approved><Fetal Age><Food><Food Allergy><Food Hypersensitivity><Food and Drug Administration><Funding><Generalized Growth><Gestation><Gestational Age><Goals><Growth><Growth and Development><Growth and Development function><Guidelines><Hawaii><Health system><Hospital Admission><Hospitalization><IT Systems><IgE><Immunization><Immunoglobulin E><Infant><Information Systems><Information Technology Systems><Lactation><Lower respiratory tract structure><Mediating><Mediation><Medical><Methods><Methods Epidemiology><Minnesota><Monoclonal Antibodies><Mothers><NIH><National Institutes of Health><Negotiating><Negotiation><Neonatal><Neonatal Intensive Care Units><Neonatal Jaundice><Neural Development><Newborn Infant><Newborn Intensive Care Units><Newborns><Oregon><Outcome><Parturition><Patients><Persons><Phase><Pneumonia><Population><Position><Positioning Attribute><Postpartum Period><Pregnancy><Premature Birth><Prematurely delivering><Preterm Birth><Probability><Proctocolitis><Proteins><RSV Vaccines><RSV infection><Recommendation><Rectocolitis><Reporting><Research><Research Design><Respiratory Syncytial Virus Infections><Respiratory Syncytial Virus Vaccines><Respiratory syncytial virus><Risk><SARS-CoV-2 vaccination><Safety><Screening Result><Seasons><Selection Bias><Sepsis><Severe acute respiratory syndrome coronavirus 2 vaccination><Small for Gestational Age Infant><Study Type><Survey Instrument><Surveys><Task Forces><Time><Tissue Growth><USFDA><United States><United States Centers for Disease Control><United States Centers for Disease Control and Prevention><United States Food and Drug Administration><United States National Institutes of Health><Vaccination><Vaccinee><Vaccines><Washington><Well Child Visits><Well child checks><Well child checkups><Well child exam><Wisconsin><accept vaccination><accept vaccine><advisory team><age associated><age correlated><age dependent><age linked><age related><age specific><allergic dermatitis><allergic eczema><antenatal><antepartum><biologic><blood infection><bloodstream infection><child routine wellness visits><child wellness visit><complementation><coronavirus disease 2019 vaccination><data structure><developmental><electronic health care record><electronic health medical record><electronic health plan record><electronic health registry><electronic medical health record><high risk><kids><lactating><lactational><lower respiratory tract><mAbs><monoclonal Abs><neonatal ICU><neonatal health><neonatal hyperbilirubinemia><neonatal outcome><neurodevelopment><newborn child><newborn children><newborn health><newborn wet lung disease><non vaccinated><not vaccinated><ontogeny><pediatric preventive visit><pediatric well visit><placebo group><post-partum><pregnant><premature childbirth><premature delivery><prenatal><preterm delivery><prevent><preventing><respiratory distress syndrome><routine child health visit><screening><screenings><sham group><small for gestational age><study design><transient tachypnea><unborn><unvaccinated><uptake><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination acceptability><vaccination acceptance><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccination confidence><vaccination uptake><vaccination willingness><vaccine acceptability><vaccine acceptance><vaccine confidence><vaccine efficacy><vaccine safety><vaccine uptake><vaccine willingness><volunteer><youngster>