Effect of blue LED phototherapy on oxidative stress and DNA damage in term and preterm infants with hyperbilirubinemia

Phototherapy is the first-line treatment for neonatal hyperbilirubinemia. Despite its widespread use, concerns persist regarding the potential biological effects of phototherapy beyond bilirubin reduction, particularly in vulnerable populations such as preterm infants. Comparative data evaluating oxidative stress and DNA damage (8-OHdG) in response to phototherapy in term versus preterm neonates are limited. This study evaluated the association between blue LED phototherapy and oxidative stress and 8-OHdG in both term and preterm newborns. This study was a prospective exploratory cohort study with repeated measurements of oxidative stress markers before and after phototherapy. We included 20 term and 20 preterm infants receiving phototherapy as study group and 17 term and 19 preterm as reference group without phototherapy. Blood samples were collected before (pre) and 24 h after (post) phototherapy to assess total antioxidant capacity (TAC), total oxidative status (TOS), and 8-OHdG in the study group while the reference group had single initial measurements. Multivariable adjustment for baseline differences (gestational age and baseline total bilirubin) and an adjusted repeated-measures analysis were performed. Before phototherapy, there was no significant difference in TAC, TOS, or 8-OHdG between the term study and reference groups or between the preterm study and reference groups after adjustment for gestational age and baseline total bilirubin. Similar to the univariate analysis, in term study group there was no significant difference in pre and post TAC, TOS, and 8-OHdG, while in preterm study group, pre and post TAC, TOS, 8-OHdG levels were significantly decreased after adjustment analysis for gestational age and baseline total bilirubin. Preterm study group had lower pre and post TOS and 8-OHdG and post TAC than term study group, whereas pre TAC was similar. Blue LED phototherapy was associated with lower oxidative stress and DNA damage markers in preterm newborns but not in term newborns. These findings suggest a gestational age–dependent biochemical response to phototherapy, potentially mediated by bilirubin-related redox balance.