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/ Epidemiologist

Influenza 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 prepandemic 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 | NCIRD

Question:

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’s Children’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 time

Methods
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 | NCIRD

Results
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 

mothers

285 Were excluded (21 cases, 264 controls)

92 Born 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 mothers

3,541 control-infants tested negative for influenza 

1,913 (54%) born to vaccinated mothers

1,642 (46%) born to unvaccinated mothers
Characteristic

Case 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-Hispanic 69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)

Black, non-Hispanic 69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)

Hispanic 64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)

Other 21/223 (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)
Characteristic

Case 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-Hispanic 69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)

Black, non-Hispanic 69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)

Hispanic 64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)

Other 21/223 (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 controlinfants and those born to vaccinated mothers.
Characteristic

Case 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-Hispanic 69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)

Black, non-Hispanic 69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)

Hispanic 64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)

Other 21/223 (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.
Characteristic

Case 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-Hispanic 69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)

Black, non-Hispanic 69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)

Hispanic 64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)

Other 21/223 (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. 
Characteristic

Case 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)
Characteristic

Case 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)

Characteristic

Case 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. Schuster

Rangaraj Selvarangan

Geoffrey A. Weinberg

Peter G. Szilagyi

Manish M. Patel

Julie A. Boom

Flor M. Muñoz

NVSN Research Teams & Study Participants