Transient bilirubin encephalopathy and apnea of prematurity in 28 to 32 weeks gestational age infants

Objective: Apnea of prematurity (AoP) is, in part, a reflection of brainstem-mediated respiratory control system maturation. We previously demonstrated changes in brainstem function in relation to hyperbilirubinemia (bilirubin encephalopathy, (BE)) as evaluated by auditory brainstem evoked responses (ABR) in infants 28 to 32 weeks gestational age (GA). We hypothesized that in this population, as bilirubin increases and causes auditory brainstem dysfunction, respiratory control system may also be adversely affected leading to increased frequency of AoP. Study design: We studied 100, 28 to 32 weeks GA infants and identified 66 with normal and 34 with abnormal ABR progression in temporal relation to hyperbilirubinemia (BE). The abnormal ABR progression was associated with elevated bilirubin, specifically elevated unbound bilirubin levels. A blinded, retrospective chart review quantified the amount of weekly apnea and bradycardia events during the hospital stay, total duration of methylxanthine treatment, total duration of mechanical ventilation, CPAP, and/or nasal cannula, and risk factors for apnea (sepsis, IVH grade >II, asphyxia). Since mechanical ventilation confounds the identification of apnea, infants requiring mechanical ventilation were excluded from further review (n = 60; 21 with BE and 39 with normal ABR progression). Data from the remaining 40 infants were analyzed. Student's t-test was used to analyze continuous variables if the distribution was normal otherwise Wilcoxon-ranked-sum test was used. χ2 was used to analyze nominal variables. A p≤0.05 was considered significant. Results: There was no difference in risk factors between infants with and without BE, BE was identified on day 3 (median; range 1 to 6 days). Patents with BE had significantly more apneic events (15 vs 2, p = 0.0009), bradycardic events (14 vs 1, p = 0.02), and required more prolonged treatment with CRAP (2.2 vs 0.5 days, p = 0.007), nasal cannula (6.6 vs 2.2 days, p = 0.02), and methylxanthines (9.5 vs. 1.9 days, p = 0.002) than those with normal ABR progression. The difference in the incidence of apnea and bradycardia between infants with and without BE was most pronounced during the first week. Conclusions: Premature infants with transient bilirubin encephalopathy as defined by abnormal ABR progression in relation to hyperbilirubinemia have more concurrent apneic events and require more prolonged respiratory support and medications. © 2005 Nature Publishing Group All rights reserved.