Manufacturing influenza vaccines in eggs can lead to mutations that reduce antigenicity. The inactivated quadrivalent influenza vaccine (IIV4c) made from mammalian cells may be more effective than vaccinations made from eggs. This study aimed to compare the efficacy of the egg-based inactivated quadrivalent influenza vaccine (IIV4e) with that of the inactivated trivalent influenza vaccine (IIV3c) in preventing influenza-related medical encounters (IRME) in children and adolescents in the United States during the 2019-2020 flu season. Children in the United States aged 4 through 17 who received an IIV4c or IIV4e vaccine in preparation for the 2019-2020 flu season were included in a retrospective cohort research that linked electronic medical records from general and specialty care with data from medical and pharmacy claims. Adjusting for age, sex, race/ethnicity/location, index week, health status, and two surrogate variables for healthcare access and use, odds ratios (ORs) were calculated using a doubly robust inverse probability of treatment-weighted technique. Exploratory analysis assessed IRMEs differently in outpatient and inpatient settings, with adjusted rVE computed as (1-ORadjusted)*100. There were a total of 1,240,990 people who received the IIV4e vaccine and 60,480 people who received the IIV4c vaccine. Subjects vaccinated with IIV4c had a lower incidence of IRMEs compared to those immunized with IIV4e. For any IRME, the rVE for IIV4c versus IIV4e was 12.2% [95% CI: 7.5-16.6], while for outpatient IRMEs it was 14.3% (9.3-19.0). Inpatient IRMEs were significantly less common, and effectiveness estimates were close to the null. Immunization with IIV4c reduced the incidence of IRMEs in children compared to vaccination with IIV4e. These findings suggested that during the 2019-2020 flu season in the United States, IIV4c will be more effective than IIV4e among this demographic.
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