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. 2024 Feb 1;178(2):176-184.
doi: 10.1001/jamapediatrics.2023.5639.

Maternal Vaccine Effectiveness Against Influenza-Associated Hospitalizations and Emergency Department Visits in Infants

Leila C Sahni  1 , Samantha M Olson  2 , Natasha B Halasa  3 , Laura S Stewart  3 , Marian G Michaels  4 , John V Williams  4 , Janet A Englund  5 , Eileen J Klein  5 , Mary A Staat  6 , Elizabeth P Schlaudecker  6 , Rangaraj Selvarangan  7 , Jennifer E Schuster  7 , Geoffrey A Weinberg  8 , Peter G Szilagyi  9 , Julie A Boom  1 , Manish M Patel  2 , Flor M Muñoz  1 ; New Vaccine Surveillance Network Collaborators
Collaborators, Affiliations

Maternal Vaccine Effectiveness Against Influenza-Associated Hospitalizations and Emergency Department Visits in Infants

Leila C Sahni et al. JAMA Pediatr. .

Abstract

Importance: Influenza virus infection during pregnancy is associated with severe maternal disease and may be associated with adverse birth outcomes. Inactivated influenza vaccine during pregnancy is safe and effective and can protect young infants, but recent evidence, particularly after the 2009 novel influenza A (H1N1) pandemic, is limited.

Objective: To evaluate the effectiveness of influenza vaccination during pregnancy against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits in infants younger than 6 months.

Design, setting, and participants: This was a prospective, test-negative case-control study using data from the New Vaccine Surveillance Network from the 2016 to 2017 through 2019 to 2020 influenza seasons. Infants younger than 6 months with an ED visit or hospitalization for acute respiratory illness were included from 7 pediatric medical institutions in US cities. Control infants with an influenza-negative molecular test were included for comparison. Data were analyzed from June 2022 to September 2023.

Exposure: Maternal influenza vaccination during pregnancy.

Main outcomes and measures: We estimated maternal vaccine effectiveness against hospitalizations or ED visits in infants younger than 6 months, those younger than 3 months, and by trimester of vaccination. Maternal vaccination status was determined using immunization information systems, medical records, or self-report. Vaccine effectiveness was estimated by comparing the odds of maternal influenza vaccination 14 days or more before delivery in infants with influenza vs those without.

Results: Of 3764 infants (223 with influenza and 3541 control infants), 2007 (53%) were born to mothers who were vaccinated during pregnancy. Overall vaccine effectiveness in infants was 34% (95% CI, 12 to 50), 39% (95% CI, 12 to 58) against influenza-associated hospitalizations, and 19% (95% CI, -24 to 48) against ED visits. Among infants younger than 3 months, effectiveness was 53% (95% CI, 30 to 68). Effectiveness was 52% (95% CI, 30 to 68) among infants with mothers who were vaccinated during the third trimester and 17% (95% CI, -15 to 40) among those with mothers who were vaccinated during the first or second trimesters.

Conclusions and relevance: Maternal vaccination was associated with reduced odds of influenza-associated hospitalizations and ED visits in infants younger than 6 months. Effectiveness was greatest among infants younger than 3 months, for those born to mothers vaccinated during the third trimester, and against influenza-associated hospitalizations.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Sahni reported grants from the US Centers for Disease Control and Prevention (CDC; paid to institution) during the conduct of the study and for participation in the Overcoming COVID-19 network outside the submitted work. Dr Halasa reported grants from the CDC during the conduct of the study and grants from Sanofi, Quidel, and Merck outside the submitted work. Dr Stewart reported grants from the CDC during the conduct of the study. Dr Michaels reported grants from the CDC during the conduct of the study and grants from the National Institutes of Health (NIH) (paid to institution), nonfinancial support from Viracor, and grants from Merck (paid to institution) not related to this work outside the submitted work. Dr Williams reported grants from the CDC during the conduct of the study; personal fees from Quidel (scientific advisory board) and personal fees from GSK (independent data monitoring committee) outside the submitted work. Dr Englund reported grants from the CDC (research support) during the conduct of the study and personal fees from AbbVie, AstraZeneca, Ark Biopharma, Meissa, Moderna, GSK, Pfizer, Shinogi, and SanofiPasteur and grants from AstraZeneca, Pfizer, and GSK outside the submitted work. Dr Staat reported grants from the CDC during the conduct of the study and grants from the NIH, Cepheid, Pfizer, and Merck outside the submitted work. Dr Schlaudecker reported grants from the CDC during the conduct of the study and grants from Pfizer and personal fees from Sanofi Pasteur outside the submitted work. Dr Schuster reported grants from the CDC during the conduct of the study and grants from the CDC (paid to my institution) and the NIH (paid to my institution) and personal fees from the American Association of Medical Colleges outside the submitted work. Dr Weinberg reported grants from the CDC during the conduct of the study and personal fees from Merck (honoraria for writing textbook chapters in Merck Manual) outside the submitted work. Dr Szilagyi reported grants from the CDC during the conduct of the study. Dr Boom reported grants from the CDC New Vaccine Surveillance Network during the conduct of the study. Dr Patel reported personal fees from AbbVie outside the submitted work. Dr Munoz reported grants from Pfizer (paid to institution) and other from Pfizer and Moderna (data and safety monitoring boards) outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram of Participant Inclusion
Infants younger than 6 months were enrolled between the 2016 to 2017 and 2019 to 2020 influenza seasons from 7 pediatric institutions to evaluate the association between maternal vaccination status and influenza illness in infants. Mothers were considered vaccinated if they received an influenza vaccine during pregnancy and were considered unvaccinated if they did not. Because protective immunity is not achieved until approximately 2 weeks after vaccination, we excluded infants born to mothers vaccinated less than 14 days before delivery. The remaining 223 infants had the following influenza subtypes: influenza A/H1N1 (n = 53), influenza A/H3N2 (n = 87), influenza A, unspecified (n = 15), influenza B (n = 66), and influenza coinfection (n = 2).
Figure 2.
Figure 2.. Effectiveness of Maternal Influenza Vaccination During Pregnancy Against Influenza Hospitalizations and Emergency Department (ED) Visits in Infants
Maternal vaccine effectiveness was calculated as (1 − adjusted odds ratio) × 100%, where the odds ratio is the odds of maternal vaccination among mothers of infants with influenza compared with mothers of control infants. Models were adjusted a priori for infant age (by month), hospital site, and calendar time (by month of enrollment). Firth penalized regression was used for all subgroup analyses. Among those with verified vaccination in the first or second trimester of pregnancy, gestational age at vaccination was a median (IQR) of 20 (12-24) weeks, and among those vaccinated in the third trimester, gestational age at vaccination was a median (IQR) of 31 (30-34) weeks.
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