Brainstem size in extremely preterm infants: reference values and association with neurodevelopmental outcomes.

Abstract

Background and objectives: Extremely preterm infants are at high risk for neurodevelopmental impairment. The brainstem plays a critical role in early development. This study aimed to establish reference values for two-dimensional brainstem measurements on cerebral magnetic resonance imaging (cMRI) at term-equivalent age (TEA), assess the impact of severe neonatal brain injury, and examine associations with neurodevelopment.

Methods: In this retrospective cohort study, preterm infants underwent routine cMRI at TEA. Standardized midsagittal brainstem measurements were obtained. Reference values and z-scores were derived from infants without severe brain injury (high-grade IVH, CBH, or cystic WMI). In the reference cohort, associations with Bayley-III outcomes at 2 years' corrected age were evaluated using multivariable regression. Brainstem z-scores were compared between infants with and without severe brain injury.

Results: Reference values were established for 242 infants born between 22 + 1 and 27 + 6 weeks' gestation. Brainstem size increased with gestational age and was significantly smaller in infants with severe brain injury. Higher brainstem z-scores were independently associated with better cognitive (adjusted β = 3.56, 95% CI: 0.44-6.69) and motor (adjusted β = 2.80, 95% CI: 0.39-5.22) outcomes.

Conclusions: Brainstem size was associated with neonatal brain injury and later neurodevelopment, supporting its potential as a clinically applicable cMRI biomarker in extremely preterm infants.

Impact: Reference values and z-scores for two-dimensional brainstem measurements at term-equivalent age in extremely preterm infants without severe brain injury. Reduced brainstem size in infants with severe brain injury, and association with cognitive and motor outcomes at 2 years' corrected age. Brainstem size is a simple and reproducible MRI biomarker.