Assessment of Aminoglycoside-Induced Hearing Loss Risk in the Perinatal Period

Area of Science:

• Genetics and Genomics
• Mitochondrial DNA
• Auditory Science

Background:

• Mitochondrial ribosomal RNA (MT-RNR1) variants m.1555A>G and m.1494C>T are linked to aminoglycoside-induced hearing loss.
• Aminoglycoside antibiotics are commonly used in perinatal care, posing a risk for hearing impairment in infants.
• Understanding the prevalence of these variants is crucial for identifying at-risk individuals.

Purpose of the Study:

• To determine the prevalence and heteroplasmy levels of MT-RNR1 variants m.1555A>G and m.1494C>T in a general perinatal population.
• To investigate the association of these variants and their heteroplasmy with hearing loss outcomes.
• To assess the potential for universal prenatal or newborn screening for these hearing loss-associated variants.

Main Methods:

• Droplet digital polymerase chain reaction (ddPCR) was used to analyze 479 maternal DNA samples.
• Mitochondrial DNA variants m.1555A>G and m.1494C>T were specifically targeted.
• Retrospective chart review identified aminoglycoside exposures and hearing outcomes in maternal and neonatal subjects.

Main Results:

• No maternal samples tested positive for the MT-RNR1 variants m.1555A>G or m.1494C>T.
• High rates of aminoglycoside exposure were observed in both maternal (15.9%) and neonatal (13.9%) populations.
• No subjects with sensorineural or mixed hearing loss had documented aminoglycoside exposure.

Conclusions:

• A larger sample size is required to accurately determine the prevalence of MT-RNR1 variants in the perinatal population.
• Future research should focus on neonatal variant prevalence, heteroplasmy levels, and hearing outcomes.
• The reliability of maternal testing as a surrogate for neonatal testing warrants further investigation for potential universal screening.