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Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
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Effectiveness of Maternal Influenza Vaccination during Pregnancy
against Influenza- associated Hospitalizations & ED Visits in Infants <6
Months of Age
Samantha M. Olson, MPH
NVSN Flu Lead/ EpidemiologistInfluenza Prevention and Control Team (IPACT)
Influenza Division
ACIP Meeting: Influenza Session
October 25, 2023
•Influenza virus infection during pregnancy is associated with severe disease and may be associated
with some adverse birth outcomes . Background
•Influenza vaccination during pregnancy can protect infants <6 months of age, who are not age -eligible
for vaccination.
•Randomized control trials conducted outside of the US showed a maternal vaccine efficacy against
laboratory -confirmed influenza in infants of 30-63%
•There is a lack of real -world, multi -center, multi -season, and US data on maternal vaccine effectiveness (VE)
against medically -attended influenza in infants•Receipt of inactivated influenza vaccine during pregnancy is safe and effective.
•Since the COVID -19 pandemic, influenza vaccination uptake during pregnancy is ~5-15% lower than pre -
pandemic seasons.
Current ACIP Wording (As of 2021- 2022 Influenza Season):
–Pregnant persons in the third trimester: Vaccination during July and August can be considered for
pregnant persons who are in the third trimester because vaccination might reduce risk for influenza
illness in their infants during the first months after birth, when they are too young to receive
influenza vaccine (33 –36). For pregnant persons in the first or second trimester during July and
August, waiting to vaccinate until September or October is preferable , unless there is concern that
later vaccination might not be possible.Prevention and Control of Seasonal Influenza with Vaccines:
Recommendations of the Advisory Committee on Immunization Practices
https://www.cdc.gov/mmwr/volumes/71/rr/rr7101a1.htm
https://www.cdc.gov/mmwr/volumes/70/rr/rr7005a1.htm?s_cid=rr7005a1_w
Influenza Division |NCIRDQuestion:
Does maternal influenza vaccination during pregnancy
reduce influenza -associated hospitalizations and
emergency department (ED) visits in infants <6 months
of age?
NVSN* Pediatric Inpatient & ED Network Sites
Seattle Children’s
Cincinnati
Children’sChildren’s Hospital of
Pittsburgh
Vanderbilt University
Nashville
Texas Children’s Hospital
Houston
Children’s Mercy Hospital
Kansas City
University of Rochester
*NVSN --New Vaccine Surveillance Network
•Enrollment: Infants <6 months of age admitted to the hospital or emergency department during 4 influenza seasons
(from Fall 2016 through Spring 2020) at 7 pediatric medical centers within the NVSN
•Cases:
•Tested positive for influenza by RT -PCR with acute respiratory illness (ARI) symptoms within 10 days of symptom
onset
•Controls: Tested negative for influenza with ARI symptoms
•Design: Test-negative design
•Odds of maternal influenza vaccination ≥14 days prior to delivery in case infants with influenza were compared
to control infants with non -influenza respiratory illness
•Vaccination status: Vaccination was defined as influenza vaccine received during pregnancy
•Documented (registry or providers) or self -reported vaccination with timing (date or trimester) during pregnancy
•Data on maternal influenza infection during pregnancy was not collected
•Analysis: VE= (1 – adjusted odds ratio) x 100%
•Adjusted for infant age, NVSN site, and calendar timeMethods
Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality
Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality
Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality
Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality
Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality
Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality
Influenza Division |NCIRDResults
4,049 infants <6 months of age enrolled
between the 2016- 2017 through the
2019- 2020 flu seasons from 7 pediatric
medical institutions
3,764 infants included
2,007 (53%) born to vaccinated mothers
1,757 (47%) born to unvaccinated
mothers285 Were excluded (21 cases, 264 controls)
92Born to mothers vaccinated <14 days
prior to delivery (8 cases, 84 controls)
193 Had unknown vaccination timing (13
cases, 180 controls)
223 case -infants tested positive for influenza
94 (42%) born to vaccinated mothers
129 (58%) born to unvaccinated mothers3,541 control -infants tested negative for influenza
1,913 (54%) born to vaccinated mothers
1,642 (46%) born to unvaccinated mothers
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Median age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)
Age group –no. (%)
0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)
3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)
Female sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)
Race and ethnic group –no./ total no. (%)
White, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)
Black, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)
Hispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)
Other21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)
At least one underlying condition in
infants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Median age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)
Age group –no. (%)
0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)
3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)
Female sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)
Race and ethnic group –no./ total no. (%)
White, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)
Black, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)
Hispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)
Other21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)
At least one underlying condition in
infants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)Case -infants and those born to unvaccinated mothers were older than control -
infants and those born to vaccinated mothers.
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Median age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)
Age group –no. (%)
0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)
3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)
Female sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)
Race and ethnic group –no./ total no. (%)
White, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)
Black, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)
Hispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)
Other21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)
At least one underlying condition in
infants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)Infant case status and maternal vaccination status differed by race and ethnic
group .
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Median age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)
Age group –no. (%)
0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)
3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)
Female sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)
Race and ethnic group –no./ total no. (%)
White, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)
Black, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)
Hispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)
Other21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)
At least one underlying condition in
infants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)More infants born to vaccinated mothers were breastfeeding on enrollment,
and more infants born to unvaccinated mothers had underlying conditions .
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Preterm birth (born <37 weeks gestation)
–no./ total no. (%)37/223 (17) 613/3535 (17) 315/2004 (16) 335/1754 (19)
35-<37 weeks 20/36 (56) 319/600 (53) 167/307 (54) 172/329 (52)
30-34 weeks 14/36 (39) 219/600 (37) 122/307 (40) 111/329 (34)
≤29 weeks 2/36 (6) 62/600 (10) 18/307 (6) 46/329 (14)
NVSN sites– no. (%)
Nashville 38 (17) 708 (20) 361 (18) 385 (22)
Rochester 14 (6) 358 (10) 213 (11) 159 (9)
Cincinnati 42 (19) 345 (10) 198 (10) 189 (11)
Seattle 26 (12) 359 (10) 281 (14) 104 (6)
Houston 39 (17) 797 (23) 391 (19) 445 (25)
Kansas City 35 (16) 317 (9) 174 (9) 178 (10)
Pittsburgh 29 (13) 657 (19) 389 (19) 297 (17)
Season of enrollment – no. (%)
2016- 2017 49 (22) 778 (22) 462 (23) 365 (21)
2017- 2018 60 (27) 829 (23) 429 (21) 460 (26)
2018- 2019 45 (20) 986 (28) 560 (28) 471 (27)
2019- 2020 69 (31) 948 (27) 556 (28) 461 (26)
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Preterm birth (born <37 weeks gestation)
–no./ total no. (%)37/223 (17) 613/3535 (17) 315/2004 (16) 335/1754 (19)
35-<37 weeks 20/36 (56) 319/600 (53) 167/307 (54) 172/329 (52)
30-34 weeks 14/36 (39) 219/600 (37) 122/307 (40) 111/329 (34)
≤29 weeks 2/36 (6) 62/600 (10) 18/307 (6) 46/329 (14)
NVSN sites– no. (%)
Nashville 38 (17) 708 (20) 361 (18) 385 (22)
Rochester 14 (6) 358 (10) 213 (11) 159 (9)
Cincinnati 42 (19) 345 (10) 198 (10) 189 (11)
Seattle 26 (12) 359 (10) 281 (14) 104 (6)
Houston 39 (17) 797 (23) 391 (19) 445 (25)
Kansas City 35 (16) 317 (9) 174 (9) 178 (10)
Pittsburgh 29 (13) 657 (19) 389 (19) 297 (17)
Season of enrollment – no. (%)
2016- 2017 49 (22) 778 (22) 462 (23) 365 (21)
2017- 2018 60 (27) 829 (23) 429 (21) 460 (26)
2018- 2019 45 (20) 986 (28) 560 (28) 471 (27)
2019- 2020 69 (31) 948 (27) 556 (28) 461 (26)More infants born to unvaccinated mothers were born preterm.
Preterm birth (born <37 weeks
gestation) –no./ total no. (%)35/216 (16) 612/3597 (17) 310/2051 (15) 337/1762 (19)
35-<37 weeks 19/34 (56) 318/602 (53) 166/305 (54) 171/331 (52)
30-34 weeks 14/34 (41) 219/602 (36) 120/305 (39) 113/331 (34)
≤29 weeks 1/34 (3) 65/602 (11) 19/305 (6) 47/331 (14)CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Preterm birth (born <37 weeks gestation)
–no./ total no. (%)37/223 (17) 613/3535 (17) 315/2004 (16) 335/1754 (19)
35-<37 weeks 20/36 (56) 319/600 (53) 167/307 (54) 172/329 (52)
30-34 weeks 14/36 (39) 219/600 (37) 122/307 (40) 111/329 (34)
≤29 weeks 2/36 (6) 62/600 (10) 18/307 (6) 46/329 (14)
NVSN sites– no. (%)
Nashville 38 (17) 708 (20) 361 (18) 385 (22)
Rochester 14 (6) 358 (10) 213 (11) 159 (9)
Cincinnati 42 (19) 345 (10) 198 (10) 189 (11)
Seattle 26 (12) 359 (10) 281 (14) 104 (6)
Houston 39 (17) 797 (23) 391 (19) 445 (25)
Kansas City 35 (16) 317 (9) 174 (9) 178 (10)
Pittsburgh 29 (13) 657 (19) 389 (19) 297 (17)
Season of enrollment – no. (%)
2016- 2017 49 (22) 778 (22) 462 (23) 365 (21)
2017- 2018 60 (27) 829 (23) 429 (21) 460 (26)
2018- 2019 45 (20) 986 (28) 560 (28) 471 (27)
2019- 2020 69 (31) 948 (27) 556 (28) 461 (26)Vaccination status differed by NVSN site and flu season of enrollment.
Maternal Vaccine Effectiveness against Influenza -associated
Hospitalizations and Emergency Department Visits in Infants <6 months
Overall maternal vaccine effectiveness against influenza hospitalizations
and emergency department visits in infants <6 months of age is 34%
Maternal vaccine effectiveness was higher among infants <3 months,
vaccinated during the third trimester , and against hospital admission
Maternal vaccine effectiveness was consistent with other VE estimates by
influenza type and subtype for the 2016 -17 through 2019 -20 flu seasons.
Maternal Vaccine Uptake
Influenza vaccine uptake during
pregnancy is nationally consistent
but suboptimal.
Benefits to Infants
Maternal vaccination was
associated with reduced odds of
influenza hospitalizations & ED
visits in infants <6 months of age.
Highest Vaccine Effectiveness
VE was greatest among infants <3
months of age , those born to
mothers vaccinated during their
third trimester of pregnancy, and
against influenza -associated
hospitalizations .
Summary Policy Implications
Currently, there are no anticipated
changes to vaccination timing
recommendations during
pregnancy.
Influenza Division |NCIRD
Acknowledgments
Leila C. Sahni
Natasha B. Halasa
Laura S. Stewart
Marian G. Michaels
John V. Williams
Janet A. Englund
Eileen J. Klein
Mary A. Staat
Elizabeth P . Schlaudecker
Jennifer E. SchusterRangaraj Selvarangan
Geoffrey A. Weinberg
Peter G. Szilagyi
Manish M. Patel
Julie A. Boom
Flor M. Muñoz
NVSN Research Teams & Study Participants