Screening for Hearing Impairment in Newborns Using Targeted Genomic Sequencing: A Large Pilot Cohort Study

Area of Science:

• Genetics
• Audiology
• Genomic Medicine

Background:

• State-run newborn hearing screening (NBHS) programs often miss mild or late-onset sensorineural hearing impairment (SNHI).
• Genetic factors account for over 50% of pediatric SNHI cases.
• Advancements in genomic sequencing offer a potential solution to enhance NBHS.

Purpose of the Study:

• To assess the feasibility of integrating next-generation sequencing (NGS)-based genomic screening into NBHS.
• To evaluate the benefits and challenges of this combined screening approach.
• To identify infants at risk for SNHI missed by conventional screening methods.

Main Methods:

• A prospective study involving 8,261 newborns who underwent simultaneous NBHS and NGS-based genomic screening.
• Targeted sequencing of 46 known deafness genes.
• Genotyping and audiological assessments for subjects with confirmed genetic diagnoses.

Main Results:

• Conclusive genetic diagnoses were established in 164 newborns (1.97%).
• 126 infants (1.5%) with genetic SNHI risk passed conventional NBHS, highlighting a gap in physiological screening.
• Familial screening identified undiagnosed genetic syndromes in relatives, demonstrating broader diagnostic utility.

Conclusions:

• Targeted genomic sequencing complements NBHS by identifying infants at risk for SNHI.
• This integrated approach enables earlier diagnosis, particularly for non-syndromic genetic hearing loss.
• Genomic screening offers significant familial benefits through early detection of genetic conditions.