Early-Life Clinical Factors Shape Cerebellar Structure in Preterm-Born Children.

Objective: Preterm birth alters typical brain development due to complex exposures related to neonatal illness, pain management, and brain injury. Despite an increased understanding of neonatal brain injury on developmental outcomes, the association of cerebellar maturation with school-age motor and cognitive function remains incompletely understood. The current study evaluated neonatal clinical factors associated with regionally specific cerebellar volumes and white matter pathways at 8 years of age in children born preterm (24-32 weeks of gestational age). Methods: Neuroimaging, clinical, and behavioral data were collected from 130 children born very preterm (24-32 weeks' gestational age) at BC Women's Hospital. Cerebellar subregions were automatically segmented using CerebNet, and cerebellar white matter connectivity was assessed using tractography. The relationships between cerebellar subregion volumes and neonatal clinical factors were examined using constrained principal component analysis. Cognitive and motor neurodevelopmental outcomes related to cerebellar volume and connectivity were also investigated. Results: Neonatal clinical factors including mechanical ventilation, number of invasive procedures, and opioid exposures were associated with reduced cerebellar volumes in specific subregions. Acute neonatal mortality risk (i.e., SNAPPE-II) was negatively associated with cerebellar connectivity at 8 years. Reduced cerebellar volumes and structural connectivity were related to poorer cognitive and motor outcomes. Interpretation: In very preterm children, neonatal illness severity and exposure to invasive procedures and opioids are associated with reduced cerebellar volumes, connectivity, and poorer neurodevelopmental outcomes at 8 years.