Acquired Brain Injuries Across the Perinatal Spectrum: Pathophysiology and Emerging Therapies.

The development of the central nervous system can be directly disrupted by a variety of acquired factors, including infectious, inflammatory, hypoxic-ischemic, and toxic insults. Influences external to the fetus also impact neurodevelopment, including placental health, maternal comorbidities, adverse experiences, environmental exposures, and social determinants of health. Acquired perinatal brain insults tend to affect the developing brain in a stage-specific manner that reflects the susceptible cell types, developmental processes, and risk factors present at the time of the insult. In this review, we discuss the pathophysiology, neurodevelopmental outcomes, and management of common acquired perinatal brain conditions. In the fetal brain, we divide insults based on trimester, and in the postnatal brain, we focus on common pathologies that have a presentation dependent on gestational age at birth: white matter injury and germinal matrix hemorrhage/intraventricular hemorrhage in preterm infants and hypoxic-ischemic encephalopathy in term infants. Although specific treatments for fetal and newborn brain disorders are currently limited, we emphasize therapies in preclinical or early clinical phases of the development pipeline. The growing number of novel cell type- and stage-specific emerging therapies suggests that in the near future we may have a dramatically improved ability to treat acquired perinatal brain disorders and to mitigate the associated neurodevelopmental consequences.