Rationale and background: Respiratory syncytial virus (RSV) vaccine is approved for use
in pregnant individuals during late pregnancy (32 weeks, 0 days through 36 weeks, 6 days
of gestation) to prevent RSV-related severe lower respiratory tract disease in infants
from birth through 6 months of age.
Research question and objectives: This work is intended to answer the question regarding
what is the risk of adverse pregnancy outcomes, including preterm birth, hypertensive
disorders, and other maternal and neonatal/infant outcomes, following exposure to RSV
vaccine between 32 weeks, 0 days and 36 weeks, 6 days of gestation? The primary study
objective is to estimate the risk of (1) preterm birth and (2) hypertensive disorders of
pregnancy following exposure to RSV vaccine between 32 weeks, 0 days and 36 weeks, 6 days
of gestation.
The secondary study objective is to estimate the risk of other safety outcomes of
interest following exposure to RSV vaccine between 32 weeks, 0 days and 36 weeks, 6 days
of gestation, including:
Pregnancy-related outcomes: stillbirth, premature labor, premature rupture of
membranes (PROM), preterm premature rupture of membranes (PPROM), cesarean delivery,
prolonged maternal duration of hospital stay
Maternal outcomes: thrombocytopenia, Guillain-Barré syndrome (GBS), other
immune-mediated demyelinating conditions, polyneuropathies, atrial fibrillation,
maternal death
Neonatal/infant outcomes: small for gestational age (SGA), large for gestational
age, low birth weight (LBW), admission to a neonatal intensive care unit (NICU),
NICU duration of stay, mechanical ventilation in neonatal period, neonatal death,
postnatal growth deficiency at 1 year of age The exploratory study objective is to
describe the most frequently reported maternal adverse events (AEs) occurring within
42 days of RSV vaccine administration between 32 weeks, 0 days and 36 weeks, 6 days
of gestation.
Outcomes occurring before 32 weeks, 0 days of gestation, including but not limited to
spontaneous abortion and major congenital malformations, will not be evaluated.
Study design: This US-based observational cohort study is designed to evaluate RSV
vaccine exposure during weeks 32 through 36 of pregnancy (i.e., 32 weeks, 0 days through
36 weeks, 6 days) and the risk of subsequent pregnancy, maternal, and neonatal/infant
outcomes. For this study, the index date will be the date of RSV vaccine administration
for the exposed cohort and the date of enrollment for the unexposed cohort. The risks of
pregnancy-related outcomes, maternal outcomes, and neonatal/infant outcomes for
participants exposed and unexposed to RSV vaccine during pregnancy will be estimated.
Population: The study population will include 2 cohorts of individuals enrolled in the
Respiratory Syncytial Virus Vaccine Pregnancy Registry (RSV-PR): (1) those exposed to RSV
vaccine between 32 weeks, 0 days and 36 weeks, 6 days and (2) those unexposed to RSV
vaccine during pregnancy.
Variables: Exposure to RSV vaccine will be defined as receipt of RSV vaccine at any time
between 32 weeks, 0 days and 36 weeks, 6 days of gestation. The primary outcomes are
preterm birth and hypertensive disorders of pregnancy. Secondary pregnancy outcomes of
interest include stillbirth, premature labor, PROM, PPROM, cesarean delivery, and
prolonged maternal duration of hospital stay. Maternal outcomes of interest include
thrombocytopenia, GBS, other immune-mediated demyelinating conditions, polyneuropathies,
atrial fibrillation, and maternal death. The neonatal/infant outcomes of interest are
SGA, large for gestational age, LBW, admission to a NICU, prolonged infant duration of
hospital stay, mechanical ventilation in neonatal period, neonatal death, and postnatal
growth deficiency at 1 year of age. Maternal AEs occurring within 42 days of RSV vaccine
administration will be captured for the cohort of RSV vaccine-exposed pregnant
individuals.
Information on covariates (including demographics, risk factors for the study outcomes,
comorbidities, concomitant medications, and predictors of RSV vaccine use) will be
incorporated into the analyses.
Data source: This study will collect data from participants and the healthcare providers
(HCPs) involved in their care or the care of their infants via concise data collection
forms at pre-defined timepoints during pregnancy, at pregnancy outcome, and up to 1 year
of infant age.
Study Size: The study will aim to include 2,062total participants (1,031 per cohort) to
detect a minimum risk ratio of 1.5 or greater for the primary outcome of preterm birth
(fewer participants are required to detect hypertensive disorders of pregnancy), assuming
equal accrual (1:1) of RSV vaccine-exposed and -unexposed participants, and accounting
for exclusions from the analysis population and loss of effective sample size due to
inverse probability of treatment weighting.
Data analysis: Participant characteristics will be summarized with descriptive statistics
for each cohort. Comparative analyses will be conducted for each outcome if sample size
permits. Supplementary analyses will be conducted that include pregnant individuals who
were excluded from the analysis population (i.e., those lacking HCP confirmation of RSV
vaccine exposure, pregnancy, or outcomes of interest). If sample size permits, subgroup
and sensitivity analyses will be performed to examine the extent to which changes in
certain methods or assumptions affect the results.
Milestones: Start of data collection is planned for 30 September 2024, and the end of
data collection is planned for 30 September 2030. The final study report and analysis is
projected for 30 September 2031.