1. Unbound bilirubin (UB) was significantly associated with neonatal chronic auditory toxicity.
2. Total serum bilirubin (TSB) and bilirubin albumin molar ratio (BAMR) were not significantly associated with chronic neonatal auditory toxicity.
Evidence Rating: 1 (Excellent)
Study Rundown: High serum levels of unconjugated bilirubin are neurotoxic and can produce kernicterus. Recent literature also suggests that significant hyperbilirubinemia (SHB ≥20mg/dL, or TSB that meet criteria for exchange transfusion) is a poor discriminator of bilirubin toxicity. In healthy term neonates, kernicterus may rarely occur with a TSB of <25mg/dL. Few studies have assessed the relationship between SHB and auditory toxicity. The purpose of this investigation was to assess TSB, BAMR, UB and their association with chronic auditory toxicity in neonates through auditory neuropathy spectrum disorder (ANSD) and/or chronic auditory toxicity (SNHL) in neonates with SHB. Researchers found that peak UB (but not peak TSB or BAMR) was significantly associated with auditory toxicity. Peak UB and TSB (but not BAMR) were significantly higher in infants found to have chronic auditory toxicity compared to those without. When stratifying for TSB<20mg/dL versus TSB≥25mg/dL, only peak UB was significantly associated with chronic auditory toxicity. This study demonstrates that chronic auditory toxicity is common among infants ≥34 weeks gestational age with SHB, and that UB is associated with chronic auditory toxicity through either SNHL and/or ANSD. Limitations of this study include insufficient power to appropriately adjust for the role of hypoxia, acidosis, and asphyxia as risk factors for bilirubin toxicity. This study supports the need for close auditory monitoring of infants with SHB as well as the possibility of using UB over TSB and BAMR for predicting chronic auditory toxicity.
In-Depth [prospective cohort]: A total of 93 of 100 infants ≥34 weeks gestational age with SHB during the first 2 postnatal weeks across 2 academic medical centers in India were enrolled in this study. Infants with conditions that may be associated with auditory disorders were excluded. Auditory brainstem response tympanometry was performed at 2-3 months to assess for ANSD, and visual reinforcement audiometry testing was performed at 9-12 months to assess for SNHL. Approximately 13% (12 of 93) infants had auditory toxicity, 3 with ANSD, 4 with SNHL and 5 with both. Among the 9 neonates with SNHL, 4 had severe to profound SNHL (>70 dB). Regression analyses showed peak UB (but not peak TSB or peak BAMR) was associated with auditory toxicity (OR=2.41;95% CI=1.43-4.07; P=0.001). Peak TSB and peak UB (but not peak BAMR) were significantly higher in infants with chronic auditory toxicity compared to those without. In subgroup analyses, peak UB in neonates with TSB<25mg/dL was significantly higher in infants with auditory toxicity compared to those without (1.99 vs. 1.19, aOR=3.31; P=0.03), the same holding true for infants with TSB≥25mg/dL (2.07 vs. 6.69; aOR=7.09; P=0.03). From a clinical standpoint, neonates who developed chronic auditory toxicity received exchange transfusion more compared to those without (75% vs 31%, P=0.02). Additionally, the positive and negative predictive value for neonatal auditory evaluations for subsequent chronic auditory toxicity during infancy were 0.3 (95%CI=0.20-0.59) and 0.97 (95%CI-0.90-0.99), respectively.
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