Changes in bilirubin in infants with hypoxic–ischemic encephalopathy

Antioxidant properties of bilirubin have been reported in many studies. We hypothesized that bilirubin might be involved in neuroprotection mechanisms against oxidative stress in infants with hypoxic–ischemic encephalopathy (HIE) and that total serum bilirubin (TSB) might increase in these patients. We retrospectively studied infants with gestational age ≥ 35 weeks and birth weight ≥ 1800 g who were admitted to the neonatal intensive care unit (NICU) with a diagnosis of moderate-to-severe HIE and received or did not receive therapeutic hypothermia. We evaluated peak TSB and changes of mean TSB in these patients in comparison with a control group of infants admitted to the NICU with diagnoses other than HIE. Peak and mean TSB values were lower in the no hypothermia and hypothermia groups in comparison with the control group, while differences were not noted between infants who received hypothermia or did not. Regression analysis showed that HIE and hypothermia significantly reduced the risk of developing TSB values higher than median value (> 8.4 mg/dL) in our population.

Conclusion: Peak and mean TSB values were lower in infants with moderate-to-severe HIE than in control infants. HIE and hypothermia independently decreased TSB. These results exclude a TSB increase as a neuroprotective mechanism in infants with HIE. We speculated that low TSB values in infants with HIE could be due to hypoxic repression of HO expression and represent a defensive strategy for limiting brain injuries in these patients.