Unbound Unconjugated Hyperbilirubinemia Is Associated with Central Apnea in Premature Infants

Objective To evaluate whether jaundice, indexed by unbound bilirubin (UB), is associated with central apnea in premature infants. Study design A prospective observational study was performed with 27-33 weeks' gestational age infants who were not requiring either mechanical ventilation or noninvasive ventilation with continuous positive airway pressure beyond 24 hours after birth. Infants with congenital infections, chromosomal disorders, craniofacial anomalies, and/or family history of hearing loss were excluded. Total serum bilirubin and UB were measured twice daily during the first postnatal week and then when clinically indicated. Central apnea was evaluated by visual inspection of continuous, electronic cardiorespiratory recordings until 2 weeks of age. Results One hundred infants were subdivided into 2 groups via median peak UB level: the high UB group (greater than median) and low UB group (less than median). The high UB group had an increased frequency of apnea events during the first 2 weeks compared with infants in the low UB group. After we controlled for confounders, the high UB group had more events of apnea during the first 2 postnatal weeks compared with the low UB group (incidence rate ratio: 1.9, 95% CI 1.2-3.2). Conclusions Our findings suggest that jaundice, as indexed by UB, is associated with central apnea in premature infants.