Document text
Pedro L. Moro, MD, MPH
Division of Healthcare Quality Promotion
Centers for Disease Control and Prevention (CDC)NATIONAL CENTER FOR EMERGING AND ZOONOTIC INFECTIOUS DISEASES
Maternal RSV vaccine safety surveillance
Advisory Committee on Immunization Practices (ACIP)
June 28, 2024
▪The findings and conclusions in this presentation are those of the author
and do not necessarily represent the official position of the CDC
▪The use of product trade names is for identification purposes onlyDisclaimer
2
▪Background
▪CDC vaccine safety monitoring for Pfizer RSV vaccines in pregnancy:
•Vaccine Adverse Event Reporting System (VAERS)
•V-Safe
•Vaccine Safety Datalink (VSD)
▪SummaryTopics
3
▪In clinical trials among pregnant persons at 24 –36 weeks’ gestation, more preterm births were noted
among Pfizer RSV vaccine recipients compared to placebo (differences not statistically significant)
▪Post -licensure safety surveillance of the Pfizer RSV vaccine in pregnant persons was initiated during
the 2023 -2024 season
▪The patterns of reported local and systemic (e.g., headache) symptoms in V -safe and VAERS after
maternal P fizer RSV vaccine were consistent with its pre -licensure safety profile
▪Among reports received in VAERS after maternal Pfizer RSV vaccine, the most frequent adverse
events reported were p regnancy -specific conditions (e.g., preterm delivery) , as expected for a vaccine
recommended at 32 -36 weeks’ gestational age
▪Preliminary findings in the VSD observed that the incidence of preterm births is 4.1% among pregnant
persons who received Pfizer RSV vaccine during the 2023 -2024 respiratory season. This was within
the expected range of the incidence of preterm births at 32 -36 weeks’ gestation (3.1 - 6.1%) before
introduction of this vaccine
▪CDC and FDA will continue to monitor maternal RSV vaccine safety in VAERS, V-safe and VSDKey points up front
4
▪In clinical trials among pregnant persons at 24 –36 weeks’ gestation, more preterm
births were noted among Pfizer RSV vaccine recipients compared to placebo, but the
differences were not statistically significant
•To avoid the potential risk of preterm birth before 32 weeks’ gestation, FDA approved the
maternal Pfizer RSV vaccine ( Abrysvo ) for use in pregnant persons at 32 through 36 weeks’
gestational age1
▪The label for Pfizer RSV vaccine notes potential risk of preterm birth under warnings
and precautions section1
▪In addition, more hypertensive disorders of pregnancy were observed among vaccine
recipients compared to placebo recipients, but the differences were not statistically
significant
▪Post -licensure safety surveillance of the new Pfizer RSV vaccine in pregnant persons is
of great importance to ensure maternal Pfizer RSV safety at the population level and
the benefits of using the vaccine in pregnant persons to protect infants from RSV LRTD
outweigh possible risksBackground
RSV: respiratory syncytial virus; LRTD: lower respiratory tract disease
1 https://www.fda.gov/media/168889/download 5
VAERS is the nation’s early warning system for vaccine safety
Co-managed by
CDC and FDA
https://vaers.hhs.gov/
6
VAERS ADVERSE EVENT REPORTING SYSTEM (VAERS)
Strengths
▪National data
▪Accepts reports from anyone
▪Rapidly detects safety signals
▪Can detect rare adverse events
▪Data available to publicLimitations
▪Reporting bias
▪Inconsistent data quality and
completeness
▪Lack of unvaccinated comparison
group
▪Generally cannot assess causality
•VAERS accepts all reports from all reporters without making judgments on
causality or judging clinical seriousness of the event
•As a hypothesis generating system, VAERS identifies potential vaccine safety
concerns that can be studied in more robust data systems7
Approaches to analyzing VAERS data
▪For more than a decade VAERS has been used as part of vaccine safety surveillance
for vaccines used in pregnancy (e.g., influenza, Tdap, COVID -19)1,2
• Descriptive analysis
•Clinical review of individual reports
•Aggregate descriptions of automated data (e.g., counts of reported adverse
events)
•Calculation of reporting rates for pregnancy outcomes (if doses of a vaccine
administered in pregnancy or vaccination coverage data are available)
▪Clinical review of infant’s medical records at birth and for the first 3 months of life
(enhanced surveillance)
1Moro et al. Obstetrics & Gynecology 140(3):p 421 -427, September 2022. https://journals.lww.com/greenjournal/Fulltext/2022/09000/Safety_of_Booster_Doses_of_Coronavirus_Disease.11.aspx
2Moro et al. Vaccine. 34(20):p2349 -2353, April 2016. https://www.sciencedirect.com/science/article/pii/S0264410X16300329?via%3Dihub 8
Characteristics of maternal Pfizer RSV vaccine reports submitted to VAERS
(as of June 3, 2024)
Characteristics N (%)
Number of reports 121
Maternal deaths 0
Pregnancy -specific adverse event(s) reports 52 (43)
Maternal age in years, median (range) 1 32 (21 -41)
Maternal age ≥ 35 years 24 (20)
Onset interval in days from vaccination to adverse event, median (interquartile range) 1 (0,4)
Gestational age2 in weeks at time of vaccination, median (range) 34 (9,37)
Type of reporter
Patient/relative3 60 (50)
Provider 36 (30)
Vaccine manufacturer 19 (16)
Other 6 (5)
1 Age not provided in 15 reports; 2 Gestational age at vaccination available for 90 reports; unknown for 31 reports
3 Pregnant persons represented 70% of those who reported a preterm delivery
From October 2023 through March 2024 an estimated 320,400 pregnant persons received RSV vaccine (Peacock. Implementation and Uptake of Nirsevimab and Maternal RSV Vaccine.
Advisory Committee on Immunization Practices. June 28, 2024.9
Most frequently reported MedDRA Preferred Terms1 among reports (n=121)
to VAERS following Pfizer RSV vaccination in pregnant persons (as of June 3,
2024)
Rank MedDRA PT (not mutually exclusive) N (%)
1 Premature delivery 29 (24)
2 Premature labor 18 (15)
3 Caesarean section 18 (15)
4 Uterine contractions during pregnancy 16 (13)
5 Headache 15 (12)
6 Nausea 13 (11)
7 Fever 13 (11)
8 Vomiting 12 (10)
9 Pain 11 (9)
10 Preterm premature rupture of membranes 10 (8)
1 Medical Dictionary for Regulatory Activities Preferred Terms ( https://www.meddra.org/how -to-use/basics/hierarchy ); MedDRA PTs not mutually exclusive
From October 2023 through March 2024, an estimated 320,400 pregnant persons received RSV vaccine (Peacock. Implementation and Uptake of Nirsevimab and
Maternal RSV Vaccine. Advisory Committee on Immunization Practices. June 28, 2024.10
Adverse events among pregnant persons following Pfizer RSV vaccination in VAERS
(as of June 3, 2024)
Adverse event N (%)
Pregnancy specific 52 (43)
Premature delivery (< 37 weeks' gestation) 37 (31)
High blood pressure/gestational hypertension1 4 (3)
Infant death2 1 (1)
Stillbirth (≥ 20 weeks' gestation) 3 (2)
Delivery/labor/contractions 3 (2)
Premature rupture of membranes 2 (2)
Other3 2 (2)
Non -pregnancy specific 69 (57)
General disorders and administration site conditions
(mostly injection site and systemic reactions)41 (34)
Vaccination errors4 21 (17)
Infections and infestations 3 (2)
Neurological disorders (Bell’s palsy)6 2 (2)
Other4 5 (4)
1 One report of thrombocytopenia that met Brighton level 2 criteria was reported in a patient with elevated blood pressure foll owing vaccination
2 35-week infant with anoxic brain injury and neonatal death after emergent C -section, resuscitation, and hospital transfer 4 days after vaccination
3 Other includes one report each of premature infant incorrectly classified as preterm (37w), a patient who underwent labor at 37 weeks, 6 days
4 Vaccination errors included: eight reports of vaccine given outside recommended gestational period, six given outside season, three reports
of an additional dose of RSV given during same season, before approval in two, subcutaneous route in one, storage issue for
Covid -19 vaccine, not RSV. Three reports of adverse events with vaccination errors
5 Other includes two reports of no adverse event, and one each of diarrhea, infant with jaundice, and a report of rash
From October 2023 through March 2024, an estimated 320,400 pregnant persons received RSV vaccine (Peacock. Implementation
and Uptake of Nirsevimab and Maternal RSV Vaccine. Advisory Committee on Immunization Practices. June 28, 2024.
6 No verified cases of Guillain -Barre Syndrome reported11
12Preterm deliveries (as of June 3, 2024)
Risk factors and clinical information2
▪ 22 reported a medical condition or
complication that increased risk for preterm
delivery (e.g., elevated blood pressure, history
of preterm delivery)
▪ 12 had insufficient information (no medical
records)
▪ 3 uncomplicated pregnancies (no reported
factors)
▪ 8 deliveries were inducedClassification1N
Late preterm (34 -36 weeks) 27
Early preterm (≥ 32 - <34 weeks) 7
Very preterm (28 - < 32 weeks) 0
Extremely preterm (< 28 weeks) 0
Unknown gestational age 3
Total 37**
1 Based on ACOG and WHO definitions
2 Median maternal age at vaccination was 33 years (range 25 -40 years); median onset interval from vaccination to preterm birth
was 3 days (range 0 -31 days)
From October 2023 through March 2024, an estimated 320,400 pregnant persons received RSV vaccine (Peacock.
Implementation and Uptake of Nirsevimab and Maternal RSV Vaccine. Advisory Committee on Immunization Practices. June 28, 2024 .
13Characteristics and outcomes of infants born to Pfizer RSV recipients
Characteristics N (%)
Number of infants175
Premature at birth (< 37 weeks)238 (51)
Gestational age at birth (weeks) 3, median (range) 36 (32 – 41)
Infants at term 33 (44)
Sex
Male 32 (43)
Female 34 (45)
Unknown sex 9 (12)
Infant deaths41
Infant born with low birth weight (< 2,500 g) 16 (21)
NICU admission524
Condition or reason for admission in NICU (not mutually exclusive)
Respiratory distress
Prematurity
Fetal distress
Unknown10 (42)
7 (29)
1 (4)
9 (38)
1 66 infants born of a single pregnancy; 6 from 3 twin pregnancies; 3 data not reported
2 Includes 6 infants from three twin pregnancies
3 Gestational age at birth unknown for 4 reports
4 35-week infant with anoxic brain injury and neonatal death after emergent C -section, resuscitation, and hospital transfer 4 day s after vaccination
5 NICU admission unknown in 20 (39%) reports
From October 2023 through March 2024, an estimated 320,400 pregnant persons received RSV vaccine (Peacock. Implementation
and Uptake of Nirsevimab and Maternal RSV Vaccine. Advisory Committee on Immunization Practices. June 28, 2024.
▪Among reports received, local and systemic symptoms (e.g., headache) were
frequently reported in VAERS after Pfizer RSV vaccine consistent with pre -licensure
studies in pregnant persons
▪In clinical trials among pregnant persons at 24 –36 weeks’ gestation, more preterm
births were noted among Pfizer RSV vaccine recipients compared to placebo
▪The label for Pfizer RSV vaccine notes potential risk of preterm birth under warnings
and precautions section
▪Patients (pregnant persons) were the most common reporters (50%) overall and
represented 70% of those who reported a preterm delivery
▪Reports of pregnancy specific conditions (e.g., preterm delivery) were not
unexpected for the Pfizer RSV vaccine, which is recommended at 32 -36 weeks’
gestation in pregnancyVAERS Summary
14
V-safe
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▪Surveys sent daily during the first week after vaccination, then weekly through week 6
▪Daily surveys solicit adverse events and health impacts after vaccination
•Local reactions (e.g., pain, redness, swelling)
•Systemic reactions (e.g., fatigue, headache, muscle pain)
•Health impacts (e.g., unable to perform normal daily activities, missed school or
work, or received medical care)
•Additional questions for persons who reported immunocompromise at vaccination
▪Weekly surveys solicit new symptoms or conditions after vaccination
▪Maternal RSV protocol includes additional questions about current and prior
pregnanciesIn Fall 2023 V-safe expanded to include RSV vaccine
16
Characteristics of persons aged 16 -49 years with
reported RSV vaccination during pregnancy*
* For 1,116 V -safe participants aged 16 -49 years enrolled in the maternal RSV protocol with ≥1 completed daily survey during Aug ust 21, 2023 – May 20,
202417
Reactions and health impacts reported for persons aged 16 -49
years with reported RSV vaccination during pregnancy (n=1,116)*
0102030405060708090100
Any symptoms Injection site
reactionSystemic reaction Unable to complete
daily activitiesUnable to work or
attend schoolGot medical care
Pfizer
* For 1,116 V -safe participants aged 16 -49 years enrolled in the maternal RSV protocol with ≥1 completed daily survey
during August 21, 2023 – May 20, 202418
Vaccine Safety Datalink
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Vaccine Safety Datalink (VSD) 2024
▪Collaborative project between CDC and
integrated healthcare organizations
▪Monitors safety of vaccines used in the
US, primarily through real -world data of
rare and serious events following
vaccination
▪Includes data on ~15.5 million
individuals across all sites annually
▪~ 115,000 annual live births
▪Data is organized using a common data
model with standardized coding
systems
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▪Determine cumulative historical incidence rates of preterm birth among
singleton pregnancies in the VSD reaching specified gestational ages from
22–36 weeks during 2017 –2022
▪Determine incidence of preterm births in RSV vaccinated pregnant
persons1,2VSD Prenatal RSV Vaccine Surveillance
1For RSV vaccines administered at 30 to less than 37 weeks’ gestation
2Pfizer RSV should be administered at 32 through 36 weeks’ gestation
https://www.fda.gov/media/168889/download21
Preterm births in VSD – Historical incidence of preterm births and preterm
births following RSV vaccine during pregnancy at 9 VSD sites
Incidence of preterm births among singleton pregnancies in the VSD reaching
specified gestational ages from 22 –36 weeks during 2017 –2022
▪In VSD, 10,295 RSV vaccines were administered at 30 to less than 37 weeks gestational age among
pregnant persons during 2023 –2024 respiratory season with 427 preterm births among vaccinees.
▪The preterm birth incidence was 4.1% which is within the expected range (3.1–6.1%) based on
historical data.
22
▪Pregnant persons, RSV vaccinated: unexposed at same gestational week
▪Create propensity scores to account for confounding
▪Outcomes
•Acute safety outcomes (e.g., anaphylaxis, Guillain -Barré syndrome)
•Preterm birth
•Stillbirth
•Preeclampsia/eclampsia/HELLP*
▪2023 -2024 analysis pending, data available later this yearVSD 1:1 Matched analysis (ongoing)1
*Hemolysis, elevated liver enzymes, low platelet count
1https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -09-22/02 -Mat-Peds -DeSilva -508.pdf 23
▪Local and systemic symptoms were reported to V -safe following Pfizer RSV vaccine in
pregnant persons, with a frequency similar to that observed in pre -licensure trials;
few pregnant people in V -safe reported medical care for symptoms1
▪Among reports received in VAERS after maternal Pfizer RSV vaccine, the most
frequent adverse events reported were local and systemic symptoms (e.g., headache)
and pregnancy specific conditions (e.g., preterm delivery), as expected for a vaccine
recommended for pregnant persons at 32 -36 weeks’ gestation
▪Post -licensure vaccine safety data from VAERS and V -safe during first season after
maternal Pfizer RSV vaccine are consistent with the pre -licensure safety profile
▪Preliminary findings in the VSD observed that the incidence of preterm births is 4.1%
among pregnant persons who received Pfizer RSV vaccine during the 2023 -2024
respiratory season. This was within the expected range of the incidence of preterm
births at 32 -36 weeks’ gestation (3.1 - 6.1%) before introduction of this vaccine
▪CDC and FDA will continue to monitor maternal RSV vaccine safety in VAERS, V -safe
and VSDSummary
24 1 https://www.fda.gov/vaccines -blood -biologics/abrysvo
Acknowledgements
▪CDC Immunization Safety Office
•VAERS Team
•V-safe Team
•Clinical Immunization Safety Assessment (CISA) Project
•Vaccine Safety Datalink (VSD)
▪Food and Drug Administration
•Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation and
Research
▪National Center for Immunization and Respiratory Diseases
•Coronavirus and Other Respiratory Viruses Division
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For more information, contact CDC/ATSDR
1-800-CDC-INFO (232 -4636)
TTY: 1 -888-232-6348 www.cdc.gov www.atsdr.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry.
Closing Slide / Disclaimer
The findings and conclusions in this presentation are those of the authors
and not necessarily represent the official position of CDC