Neonatal inflammation predicts adolescent brain volume and neurologic outcomes in children born extremely prematurely.

Children born extremely preterm (< 28 weeks gestation) are at increased risk for neurodevelopmental disorders and reduced brain volumes. This study examined whether neonatal inflammation predicts adolescent brain volume and whether associations differ by sex or presence of major neurologic disorders. Data were drawn from the Extremely Low Gestational Age Newborns (ELGAN) Study. Inflammatory protein levels measured during the first two postnatal weeks were used to classify neonates into low, moderate, or high inflammation groups. At age 15, participants underwent 3T MRI, and total and regional brain volumes were quantified using FreeSurfer. Neurologic status was assessed at ages 2, 10, and 15. Higher neonatal inflammation was associated with reduced volumes in the cerebellum cortex, brainstem, and subcortical gray matter, including the ventral diencephalon, thalamus, and amygdala. Sex-specific effects were observed: females with moderate inflammation showed reduced volumes in total brain, cerebellum cortex and white matter, ventral diencephalon, and thalamus, while males with moderate or high inflammation had reductions in the cerebellum cortex, corpus callosum, and brainstem. Among adolescents with major neurologic disorders, higher inflammation was linked to smaller cerebellum cortex, cerebellum white matter, and brainstem volumes. These findings suggest lasting effects of neonatal inflammation on brain development in extremely preterm individuals.