Clinical strategy for managing oxidative stress in premature infants, taking into account the sex of the newborn

Oxidative stress is present in preterm newborns born <30 weeks of gestation. This stress is an important trigger of several pathological complications related to prematurity, including bronchopulmonary dysplasia (BPD) which affects ≈ 50% of these infants. Supplemental oxygen and parenteral nutrition, inherently contaminated with peroxides, received by these neonates due to immaturity are associated with higher oxidative stress and the development of BPD. The gender of infants is another factor influencing the incidence of BPD, which is higher in baby boys. The association between pathological complications of prematurity and markers of oxidative stress has been widely studied in this population. From studies that have assessed the impact of sex, we learn that among the markers of oxidative stress measured in the extracellular compartments, only the plasma level of isoprostane differs according to sex, higher in males. From intracellular compartments, markers of oxidative stress such as carbonyl, peroxides and nitrotyrosine are higher in placenta of males while components of glutathione (antioxidant) metabolism measured in erythrocytes, leucocytes and placenta, favor girls. Thus, a higher incidence of BPD is observed in newborn males, who have lower levels of glutathione as measured in leucocytes isolated from pulmonary aspirations. Animal studies show that addition of glutathione in parenteral nutrition prevents pulmonary oxidative stress and alveolar loss (a main feature of BPD). Therefore, it has been proposed to supplement parenteral nutrition with glutathione to prevent the development of BPD. Such a phase I clinical trial is planned. Knowing that the sex difference in glutathione metabolism has been demonstrated in intracellular compartments and not in plasma, it will be important to take into account that the same dose of glutathione could lead to a similar correction of glutathione level in plasma (extracellular compartment) while the clinical outcome could differ depending on the sex of the preterm infant.