Mitochondrial mutation m.1555A>G and aminoglycoside-induced hearing loss in neonates: an integrative review

Objective To evaluate the evidence related to the association between aminoglycoside-induced hearing loss and the mitochondrial mutation m.1555A>G, and to examine the potential clinical utility of pharmacogenetic prescription of aminoglycosides in neonates. Methods An integrative literature review of m.1555A>G mutation and aminoglycoside-induced hearing loss in neonates, analysed using the Wilson-Jungner framework of population-based preventive screening. Results The evidence base was observational and methodologically heterogeneous. Across population-based and epidemiological newborn cohorts, the study-level median frequency of m.1555A>G was 0.2% (range 0%–0.3%), with regional and ethnic variation. In a prospective multicentre study, aminoglycoside exposure was weakly associated with failed newborn hearing screen (NBHS) in carriers (OR: 1.26, 95% CI: 1.07–1.49, p = 0.0058). Pure tone hearing impairment was detected at 3 years in a very-low-birthweight carrier with prior exposure. Pilot data support both the analytical validity of prenatal screening using buccal swabs or blood samples and the feasibility of rapid NICU genotyping to inform aminoglycoside prescribing. Population-based genetic screening offers the potential for early carrier identification; however, long-term audiological surveillance, economic viability, and ethical considerations remain important areas for future investigation. Conclusion Aminoglycoside-induced hearing loss fulfills the criteria for preventive screening, including a latent preclinical period, available m.1555A>G genotyping tools, and an actionable aminoglycoside avoidance. Although screening appears feasible and early data support the validity of available tools, the clinical utility remains uncertain. Genetic screening may be considered as either a universal component of NBHS programmes or a targeted strategy informed by risk stratification. (family history, NICU admission, aminoglycoside predisposition). Further research on the clinical utility and effectiveness of screening methods is needed to inform neonatal aminoglycoside policy.