Sleep During NICU Care Is Associated With Proportional Cerebellar Size at Term-Equivalent Age in Extrem Infantsmely Preter

Abstract

Background: Infants born extremely preterm (< 28 weeks’ gestation) are born during a phase of rapid cerebellar growth, when disturbances in brain maturation are common and reduced cerebellar size has been linked to unfavorable neurodevelopment. During late gestation, sleep is the dominant brain state and provides structured endogenous activity supporting circuit formation. In the neonatal intensive care unit (NICU), sleep may become fragmented at a developmental stage when the cerebellum is particularly vulnerable. We hypothesized that sleep quantity during late NICU care is associated with proportional cerebellar size at term-equivalent age (TEA). Methods: In a retrospective cohort of extremely preterm infants, continuous cardiorespiratory signals recorded at approximately 29–32 weeks postmenstrual age were analyzed using a validated algorithm to quantify sleep–wake states. All infants underwent 3 T MRI at TEA. The primary outcome was cerebellum-to-total brain volume ratio. Associations were tested using multivariable linear regression adjusted for age at MRI, birthweight, duration of mechanical ventilation, and sex. Results: Seventy-one infants contributed multi-day sleep recordings and TEA MRI. Higher total sleep percentage during late NICU monitoring was associated with a larger cerebellum-to-total brain volume ratio at TEA after adjustment for clinical covariates (p = 0.011). Sleep-state composition was not associated with absolute cerebellar volume, which was primarily related to clinical factors. Conclusions: Greater total sleep during late NICU care is associated with proportionally larger cerebellar size at term-equivalent age. Further studies are needed to determine whether sleep represents a modifiable factor influencing cerebellar development or a marker of overall physiological stability.