The shifting landscape of the preterm brain

Preterm birth remains a significant global health concern despite advancements in neonatal care. While survival rates have increased, the long-term neurodevelopmental consequences of preterm birth persist. Notably, the profile of the preterm infant has shifted, with infants at earlier gestational ages surviving and decreased rates of gross structural injury secondary to intracranial hemorrhage. However, these infants are still vulnerable to insults, including hypoxia-ischemia, inflammation, and disrupted in utero development, impinging on critical developmental processes, which can lead to neuronal and oligodendrocyte injury and impaired brain function. Consequently, preterm infants often experience a range of neurodevelopmental disorders, such as cognitive impairment and behavioral problems. Here, we address mechanisms underlying preterm brain injury and explore existing and new investigational therapeutic strategies. We discuss how gestational age influences brain development and how interventions, including pharmacological and non-pharmacological approaches, mitigate the effects of preterm birth complications and improve the long-term outcomes of preterm infants.