The Yield of a Systematic Advanced Etiologic Approach within the Activity of the UNHS Program and Childhood Hearing Surveillance (CHS) Program in Friuli Venezia Giulia Region, Italy

Most universal newborn hearing screening (UNHS) programs lack a systematic etiologic focus with reported percentage of permanent hearing loss (PHL) of uncertain etiology ranging from 30% to 60%.

The aim of this study was to obtain data on the diagnostic yield of a systematic etiologic approach within the activity of the UNHS program and childhood hearing surveillance (CHS) program in Friuli-Venezia-Giulia region, Italy. All newborns and children aged 0-3 screened or monitored during the period July 2012-June 2014 (19.468 subjects) were included in the study. The diagnostic data were further revisited in 2017.

UNHS is performer with A-TEOAE and A-ABR while CHS is performed by High Risks Registry (JCIH 2007). Neonates failing the screening or having an audiologic risk undergo complete audiologic diagnostic evaluation that includes: ABR, admittance testing, DPOAE, questionnare of auditory development. Children with permanent hearing loss (PHL) undertake 1.level (ENT examination, ophtalmology, TORCH, ECG, GJB2/GJB6 mutation analysis) and 2. level etiologic assessment (Imaging, clinical genetic evaluation, Targeted Sequencing Panel including 96 genes). Results are discussed by a multidisciplinary team and cases are further classified into 4 etiologic grouping: (1) PHL of exogenous origin (2) defined syndrome that includes PHL (3) GJB2/GJB6 biallelic PHL (4) putative non-syndromic PHL. The latter group of subjects was identified for targeted re-sequencing by Ion Torrent PGM (Life Technologies) to analyze coding and UTR regions of 96 genes related to PHL and hearing function.

An etiologic diagnosis has been achieved in 90% of examined bilateral PHL cases. The Targeted Sequencing panel clarified etiology in 50% of subjects for whom the putative genetic aetiology was not characterized by the standard etiologic protocol. It is important to underline the high number of loss to follow up subjects in the articulated path of audiological and etiological investigation of an identified neonate or child.