350 - Evaluating Bilirubin-Related Neurotoxicity Using Auditory Brainstem Responses in Very Preterm Infants

Poster Number: 350
Publication Number: 350.123

Santosh Parab, Richmond University Medical Center, Staten Island, NY, United States; Ha T. Phan, NYS Institute for Basic Research in Developmental Disabilities, Staten island, NY, United States; Phyllis M. Kittler, NYS Institute for Basic Research, JACKSON HEIGHTS, NY, United States; Catherine A. McDonough, Richmond University Medical Center, Staten Island, NY, United States; Anne Gordon, IBR, Staten Island, NY, United States; Michael J. Flory, NYState Institute for Basic Research, BROOKLYN, NY, United States; Thomas Hegyi, Rutgers, Robert Wood Johnson Medical School, Englewood, NJ, United States

Background: Auditory Brainstem Responses (ABRs) have been used to detect various perturbations in brainstem functioning and may serve as an early biomarker for neurodevelopmental disorders. Abnormalities are indicated by prolongation of the absolute wavelengths and inter-wave latencies. Because bilirubin has a specific preference for the auditory neural pathways, ABRs are especially useful in detecting bilirubin-induced neuronal injury. Reports of ABR alterations include prolongation of the absolute wave latencies and inter-wave intervals (e.g., Amin et al, 2001;Jiang et al, 2007). 
Preterm infants are at increased risk for bilirubin neurotoxicity, even at moderate or low total serum bilirubin (TSB) levels (Watchko, 2016). Changes in ABR waveforms have been observed in very preterm infants at much lower TSB levels than recommended phototherapy thresholds for full-term infants (e.g., 10 vs 20 mg/dL). Thus, accurate assessment of bilirubin-induced neurologic damage is very important in very preterm infants.

Objective: To examine the relationship between TSB levels and auditory neural integrity as assessed by ABR in very preterm infants. 

Design/Methods: Data from a subset of participants in a longitudinal study of NICU infants was analyzed (Nf105; BW=1284±411g; GA=29.7±2.6 weeks; 57% male). The peak TSB levels ranged from 2.5 to 12.1 mg/dL. 85% of infants received phototherapy. A bilirubin risk/deviation score, delta, was calculated based upon a BW-adjusted threshold for hyperbilirubinemia (delta = peak TSB – (BW/200)). The effects of bilirubin level (expressed as delta and also peak TSB) on ABR waveforms were evaluated using linear regression models, with post-menstrual age at ABR as a covariate.

Results: Prolonged wave I, III, and V absolute latencies and the I-III inter-wave interval were significantly associated with higher delta scores (all ps < 0.02). No relationship between ABR latencies and peak TSB levels was observed.Conclusion(s): In very preterm infants prolonged click-evoked ABR latencies were associated with higher bilirubin levels, which replicates other studies in term infants. This relationship was only observed for birthweight adjusted bilirubin risk scores, but not for peak TSB levels. This suggests that TSB levels alone, in very preterm infants, are insufficient for predicting bilirubin neurotoxicity levels, assessed by ABRs. In addition to transmission delays through the brainstem nuclei, the cochlear nerve, represented by wave I, appears to be affected as well. These findings suggest that very preterm infants are highly susceptible to bilirubin toxicity, which should be monitored closely.