Document text
RSVpreF Vaccine, Preterm Birth, and
Small for Gestational Age at Birth
Preliminary Results from
The Vaccine Safety Datalink
Malini DeSilva, MD, MPH
ACIP
October 23, 20241
Vaccine Safety Datalink, 2024
•Collaborative project between
CDC and 13 integrated
healthcare organizations
•Monitors safety of vaccines
used in the U.S., primarily
through observational
multisite studies of rare and
serious events following
vaccination
•Includes data on ~15.5 million
individuals across all sites
annually (~3 -4% of U.S.
population)
•Annual birth Cohort ~ 115,000
•Data is organized using a
common data dictionary with
standardized coding systems
Prenatal RSV
Vaccine
2023 –2024 season
•ACIP recommendation 9/22/23:
•32–36 weeks gestation
•Seasonal administration
September – January
•Most VSD sites did not start
vaccinating until late October or
November 2023
•One VSD site did not administer
vaccine in health system
•Two VSD sites continued
administrations through
2/29/24
3
Evaluation of Preterm Birth and SGA at Birth
following prenatal RSV vaccine
•Perform a matched analysis comparing pregnant persons
exposed to RSV vaccine with pregnant persons unexposed at the
same gestational week to evaluate
•Preterm birth (<37 weeks gestation)
•Small for gestational age (SGA) at birth (<10th percentile)
4
Preterm birth
•Definition: live birth occurring prior to 37 weeks gestational age
•RSVpreF clinical trial identified an imbalance in preterm births in
vaccinated group compared to placebo group1
•Most were late preterm (34 –<37 weeks)
•Most occurred >30 days after vaccination
•Most prominent in a single country
•GSK RSV prenatal vaccine clinical trial halted due to imbalance in
preterm birth in vaccinated2
51Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.
N Engl J Med. 2023 Apr 20;388(16):1451 -1464. doi: 10.1056/NEJMoa2216480. Epub 2023 Apr 5. PMID: 37018474.
2Dieussaert I, Hyung Kim J, Luik S, et al. RSV Prefusion F Protein -Based Maternal Vaccine - Preterm Birth and Other
Outcomes. N Engl J Med. 2024 Mar 14;390(11):1009 -1021. doi: 10.1056/NEJMoa2305478. PMID: 38477988.
Small for Gestational Age (SGA) at birth
•Definition: Birthweight below 10% for gestational age and sex
•Causes
•Constitutionally small – parental genetics
•Intrauterine growth restriction (IUGR) –
•Placentation issues → decreased placental blood flow
•Maternal conditions (chronic heart or lung disease, HTN, CKD, DM,
infection, cigarette use, alcohol or drug use, malnutrition, infections)
•Genetic or structural abnormalities
•Early onset IUGR <32 weeks gestational age usually more severe
with higher morbidity/mortality
•SGA at birth not evaluated in clinical trial, but imbalance in low
birth weight (≤2500g) among RSVpreF vaccinated
6
Matched analysis methods
•Pregnant persons 16 –49 years with gestational age 30 –<37 weeks
during 9/22/2023 –1/31/24 (2/29/24 for two sites)
•Target trial emulation design to compare vaccinated and
unvaccinated persons at each gestational week
•Pregnant persons exposed to RSVpreF vaccine matched 1:1 on VSD site and
propensity to be vaccinated to unvaccinated pregnant persons during same
gestational week
•Unvaccinated index date = gestational day of vaccine
•Matched pair censored if unvaccinated person later vaccinated
•Propensity to be vaccinated calculated individually for 2 sites and for
all other sites combined
•Maternal age at pregnancy start, calendar week at pregnancy start, number of
weeks with prenatal care encounters, race/ethnicity, comorbidities
(hypertension, diabetes mellitus, gestational hypertension, gestational
diabetes, obesity, substance use), history of preterm labor, poor fetal growth,
supervision of high -risk pregnancy, enrollment, and VSD site
7
Analysis
•For SGA at birth, matched sets excluded if infant weight not
available for either infant in matched pair
•Log binomial model with robust variance to estimate risk
ratios with 95% confidence intervals
•Overall (30 –<37 weeks gestational age)
•Restricted to vaccines administered during 32 –<37 weeks
gestational age (ACIP recommendation)
8
Matched Cohort* characteristics, N = 14,099
9Age groupRSV Vaccinated,
n(%)Unvaccinated match,
n(%)
•16–24 years 1418 (10.1) 1607 (11.4)
•25–29 years 3180 (22.6) 3471 (24.6)
•30–34 years 5514 (39.1) 5325 (37.8)
•35–39 years 3320 (23.5) 3050 (21.6)
•40–49 years 667 (4.7) 646 (4.6)
Race/Ethnicity
•Asian 3061 (21.7) 2651 (18.8)
•Black 873 (6.2) 1007 (7.1)
•Hispanic 4488 (31.8) 4730 (33.5)
•White 4604 (32.7) 4595 (32.6)
•Other/Unknown 1073 (7.6) 1116 (7.9)
*Not unique individuals due to crossover from unvaccinated to vaccinated
Preterm birtha risk among pregnant persons receiving RSV
vaccine and unvaccinated matches, 30 –36 weeks GA
Matched
pairs, NRSV vaccinated Unvaccinated matchRisk Ratio
(95% CI)
N events*Preterm
birth %N events*Preterm
birth %
Overallb14,099 571 4.0 637 4.50.90
(0.80 –1.00)
32–36
weeks13,965 563 4.0 628 4.50.90
(0.80 –1.00)
10GA = gestational age
aPreterm birth = birth <37 weeks gestational age
bN RSV vaccines administered <32 weeks = 134 (0.95%)
*Events only included through date of censoring when unvaccinated pair crosses over to vaccinated
Preterm birth risk by GA* at vaccination or index
date for matched sets 32 –36 weeks GA*
11
Smoothed curve showing average preterm birth risk (line) by gestational age at vaccination or
index date with 95% confidence band (shading)
*GA = gestational age
Matched
pairs, NRSV vaccinated Unvaccinated matchRisk Ratio
(95% CI)
N
events*SGA at
birth %N
events*SGA at birth
%
Overall 11,920 800 6.7 781 6.61.02
(0.93 –1.13)
32–36
weeks11,819 799 6.8 774 6.51.03
(0.94 –1.14)
12SGAa at birth risk in infants born to RSV vaccinated pregnant
person or unvaccinated pregnant matches, 30 –36 weeks GAb
aSGA at birth = “Small for Gestational Age”; birthweight <10th percentile for gestational age compared
with a U.S. reference population1
bGA = gestational age
*Events only included through date of censoring when unvaccinated pair crosses over to vaccinated
Note: 11,920 matched pairs with complete infant weight data (85%)
1Talge NM, Mudd LM, Sikorskii A, Basso O. United States birth weight reference corrected for
implausible gestational age estimates. Pediatrics 2014;133:84453. PMID:24777216
Conclusions and next steps
•RSVpreF vaccine is not associated with increased risk for preterm
birth or SGA at birth
•Currently working on analysis for acute safety outcomes,
stillbirth, and preeclampsia/eclampsia/HELLP
•Chart review for stillbirths and some acute safety outcomes (i.e.,
anaphylaxis, Guillain -Barré syndrome, acute disseminated
encephalomyelitis, transverse myelitis, venous
thromboembolism, pulmonary embolism, and
myocarditis/pericarditis)
•Preeclampsia/eclampsia/HELLP – association with hypertensive
disorders of pregnancy in recent study1 and clinical trial
131Son M, Riley LE, Staniczenko AP , et al. Nonadjuvanted Bivalent Respiratory Syncytial Virus Vaccination and Perinatal
Outcomes. JAMA Netw Open. 2024;7(7):e2419268. doi:10.1001/jamanetworkopen.2024.19268
Our Team
HealthPartners
•Malini DeSilva
•Elyse Kharbanda
•Jacob Haapala
•Gabriela Vazquez -Benitez
•Leslie Kuckler
•Jingyi Zhu
•Sunita Thapa
•Nicole Trower
14Weill Cornell Medicine
•Heather Lipkind
Kaiser Northwest
•Kimberly Vesco
CDC
•Eric Weintraub
•Elizabeth QuincerOther VSD sites
•Acumen
•Denver Health
•Harvard Pilgrim
•Indiana University
•Kaiser Permanente Northwest
•Kaiser Permanente Colorado
•Kaiser Permanente Southern
California
•Kaiser Permanente Northern
California
•Kaiser Permanente Washington
•Kaiser Permanente Mid -Atlantic
States
•Marshfield Clinic
•OCHIN