The developing auditory system as a window into bilirubin neurotoxicity

Neonatal hyperbilirubinemia is one of the most common conditions in infancy and a cause of potentially preventable neurodevelopmental injury worldwide. Auditory impairment is a well-known consequence of bilirubin neurotoxicity, with effects ranging from hearing loss in severe cases to more subtle processing problems with mild to moderate exposure. Several cellular mechanisms can shed light on how these impairments arise and when physiological dysfunction might be reversible before permanent injury. Current clinical tools provide excellent information about bilirubin-induced changes related to hearing thresholds. Emerging methods in this field, including the frequency-following response (FFR), are promising candidates to include more subtle, suprathreshold measures of auditory processing. Our work has shown that the FFR reflects deficits in neonates with moderate hyperbilirubinemia despite conventional measures within normal limits, and rebounds as bilirubin levels improve with treatment. Future studies are needed to better characterize the pattern of auditory deficits, determine when testing is most informative, and establish the extent to which emerging measures can predict later developmental outcomes.