PC1096: Brainstem Auditory Evoked Response Abnormalities in a Rodent Model of Preterm Infant Hyperbilirubinemia

Background: Hyperbilirubinemia is a common disorder among premature infants and is a significant risk factor for neonatal hearing loss. Brainstem auditory evoked response (BAER) is the primary hearing test performed on infants in the neonatal intensive care unit and is a clinically informative test to evaluate bilirubin neurotoxicity. The Gunn rat model has been used to study the effects of acute preterm bilirubin encephalopathy. Gunn rats carry an autosomal recessive mutation in the gene that codes for uridine diphosphate glucoronyl transferase enzyme. Homozygous animals (jj) acutely increase free bilirubin following administration of a sulfa drug (sulfadimethoxine, SDMX). Our prior results show that this treatment given on postnatal day (P) 5 (24 – 28-week human equivalent) results in cerebellar-mediated behavior perturbation and decreased cerebellar weights on P30, in jj but not heterozygous animals (Nj). In these experiments, we hypothesize that SDMX given to jj rat pups on P5 alters hearing as measured by BAER.

Methods: On P5, Nj and jj Gunn rats were injected with 200 mg/kg SDMX or saline (n=6 per group). BAER recordings were obtained on P17-20. BAER responses were band-pass filtered at 300-3000 Hz and averaged 1024 times. The duration of each stimulus was 31.1 µs and the rate of stimuli presented was 21.1/s. Apparatus from Intelligent Hearing System (Miami, FL) was used to record BAERs.

Results: Mean peak 1 latencies at 80 dB SPL for Nj saline, Nj SDMX, jj Saline, and jj SDMX were 1.415 ± 0.04, 1.44 ± 0.05, 1.41 ± 0.07, and 1.54 ± 0.1 milliseconds (msec), respectively. There was a significant delay in peak 1 latency in the jj SDMX group in comparison to Nj saline (p=0.044) and jj saline (p=0.037) when tested using a two-way ANOVA followed by a Sidak's multiple comparisons test. Consistent with the delay in peak 1 latency, peaks 2 and 3 were also delayed in the jj SDMX group. There were no significant differences in BAER thresholds between any group (p>0.05, paired t-test) indicating no overt hearing loss originating from the sensory hair cells of the cochlea at P17-P20.

Conclusion: We conclude that the induction of acute elevation in free bilirubin on P5 results in changes in the BAER. This model may be used in future studies to determine effective interventions to preserve hearing in preterm infants.