The placenta as a window into neonatal brain injury

The placenta serves as an essential communicative organ between a mother and fetus throughout gestation. The placenta is critical in the development and maintenance of pregnancy while serving as a hub for immune signaling. In the context of an ever-changing microenvironment, the placenta responds dynamically to infection, inflammation, and other potentially harmful exposures. As in chorioamnionitis and preterm birth, a placental inflammatory response can impart harm to the developing fetal brain and facilitate the presentation of perinatal brain injury. Through various functional and structural disruptions, including changes to neural networks and complex neural immune interactions, neurodevelopmental disorders can manifest. In this review, we utilize chorioamnionitis as a platform for understanding immune signaling and inflammatory cell communication along the maternal-placental-fetal axis. We delineate how immune dysfunction changes neurodevelopment and explore cellular and molecular mechanisms associated with adverse clinical outcomes after birth. Together with discussion of unique inflammatory pathophysiology and triggers of perinatal brain injury, we explore avenues for neuroimmunomodulation, novel biomarker discovery, and precision medicine approaches for clinical practice.