Sex-related and postnatal development of the glutathione antioxidant system in extremely preterm infants: laboratory findings from a randomized controlled trial

Preterm birth disrupts in utero antioxidant system maturation, including glutathione metabolism, and forces infants’ transition to a relatively oxidative extrauterine environment, leading to multiple devastating complications. This study aims to describe sex-related differences and the postnatal evolution of the glutathione antioxidant system in extremely preterm infants. In a cohort of extremely preterm infants participating in the parenteral nutrition photoprotection randomized controlled study C-SMART-PN (25.8 ± 0.2 weeks of gestation; n = 30), blood samples were collected at one week of life and 36 weeks postmenstrual age. Erythrocyte glutathione peroxidase and reductase activities were measured. Female infants had higher glutathione peroxidase activity at all study time points ( p < 0.05; n = 28). Glutathione reductase activity significantly increased between one week of life and 36 weeks postmenstrual age in all infants ( p < 0.001; n = 25). This increase in glutathione reductase activity resulted in a significant decrease in glutathione peroxidase / glutathione reductase ratio between the two timepoints in all participants ( p < 0.001; n = 26). The protective profile of higher glutathione peroxidase activity observed in female infants provides a possible mechanism for the well-documented sex-related outcome differences in extremely preterm infants. Glutathione antioxidant system continues its overall maturation during the postnatal period in this population.