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

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.