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. ### Competing Interest Statement The authors have declared that no competing interests exist. ### Clinical Trial ClinicalTrials.gov [NCT01735084][1] and [NCT01174849][2] ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval has been obtained from Human Research Ethics Committees of the Northern Territory Department of Health and Menzies School of Health Research (NHMRC Reg no: EC00153), the Central Australian HREC (NHMRC Reg no: EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Parents or guardians provided signed informed consent for their infant’s participation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Availability of data/Data sharing Data collected for the study that underlie the results reported in this Article, including individual participant data and a data dictionary defining each field in the set, will be made available after deidentification. No additional, related documents will be available, and the study protocols have been published. Data will be available up to 3 years after publication of this Article, upon request to the corresponding author. Data will be shared with investigators whose proposed use of the data has been approved by the ethics committees of NT Health, Menzies School of Health Research, WA Department of Health, and WA Aboriginal Health Ethics Committee, and approved by the Menzies’ Child Health Division’s Australian First Nations Reference Group, for analyses that meet criteria for excellence in research with Aboriginal and Torres Strait Islander people, and with an institutional-signed and investigator signed data sharing research agreement. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01735084&atom=%2Fmedrxiv%2Fearly%2F2024%2F03%2F15%2F2024.03.13.24304198.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01174849&atom=%2Fmedrxiv%2Fearly%2F2024%2F03%2F15%2F2024.03.13.24304198.atom