Hearing loss at 6-monthly assessments from age 12 to 36 months: secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules.

Introduction: In remote communities, Australian First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance, compared to those with normal hearing. Our objective was to compare two pneumococcal conjugate vaccine (PCV) formulations and mixed schedules (the PREVIX trials) designed to broaden protection and reduce conductive hearing loss to age 36 months. Methods: In two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 at age 28-38 days to standard or mixed PCV primary schedules, then at age 12 months to a booster dose (1:1) of PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S). Here we report secondary hearing outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. Findings: From March 2013 to September 2018, 461 hearing assessments were performed. Prevalence of mild- moderate hearing loss declined in both groups from ~75% at age 12 months to ~53% at 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% and 41% in the +P and +S groups, respectively (difference -19% [95% confidence interval -38, -1], p=0.07) and prevalence of normal hearing was 36% and 16%, respectively (difference 19% [95%CI 2, 37], p=0.05). At subsequent timepoints prevalence of moderate hearing loss remained lower in the +P group at -3% [95% CI -23, 18] at age 24 months, -12% [95%CI -30, 6] at 30 months, and -9% [95%CI -23, 5] at 36 months. Interpretation: This study provides first evidence of the high prevalence and persistence of mild and moderate hearing loss throughout early childhood. A lower prevalence of moderate (disabling) hearing loss in the +P group may have substantial benefits for high-risk children and warrants further investigation.