Preserved Limbic White Matter Predicts Favorable 2‐Year Outcomes in Neonatal Hypoxic‐Ischemic Encephalopathy

ABSTRACT Objective Accurate prediction of both favorable and unfavorable long‐term neurodevelopmental outcomes of neonatal hypoxic‐ischemic encephalopathy (HIE) is essential for clinical care, yet the brain structures underlying a favorable prognosis remain unclear. This study aimed to identify diffusion magnetic resonance imaging (MRI) measures that can predict the 2‐year outcomes in neonates with HIE. Methods We analyzed whole‐brain diffusion MRI scans from a retrospective cohort of 40 neonates with HIE, acquired within 14 days of birth. Diffusion measures were quantified across 16 cerebrum regions covering the whole cerebrum. We used the area under the Receiver Operating Characteristic curve (AUC) to evaluate the performance of regional fractional anisotropy (FA) and mean diffusivity (MD) values in predicting neurodevelopmental outcomes assessed at 2 years of age. Results Reduced FA in the thalamus (AUC = 0.990), basal ganglia (AUC = 0.961), basal forebrain (AUC = 0.951), and limbic white matter (AUC = 0.961) strongly predicted severe disability or death, whereas preserved limbic white matter FA uniquely predicted favorable outcomes (AUC = 0.811). Conclusion While FA reduction in the thalamus, basal ganglia, and basal forebrain is a robust marker for severe outcomes, the limbic white matter demonstrated sensitivity to mild hypoxic‐ischemic injury. Therefore, the preservation can be a potential marker for predicting favorable neurodevelopmental trajectories.