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Neonatal inflammation predicts adolescent brain volume and neurologic outcomes in children born extremely prematurely
Carmen A Marable1, Kyle Roell2, Lei Zhang2
1Curriculum in Neuroscience, School of Medicine, University of North Carolina, Chapel Hill, NC, United States of America.
Insights
Neonatal inflammation in extremely preterm infants is linked to reduced adolescent brain volumes, particularly in the cerebellum and brainstem. These effects vary by sex and the presence of neurological disorders, indicating lasting impacts on brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatric Neurology
Background:
- Infants born extremely preterm (< 28 weeks gestation) face heightened risks for neurodevelopmental issues and diminished brain volumes.
- Neonatal inflammation is a potential factor influencing long-term neurodevelopmental outcomes in this vulnerable population.
Purpose of the Study:
- To investigate the predictive relationship between neonatal inflammation and adolescent brain volumes in extremely preterm children.
- To explore potential sex-specific differences and the impact of major neurologic disorders on these associations.
Main Methods:
- Utilized data from the Extremely Low Gestational Age Newborns (ELGAN) Study.
- Classified neonates into low, moderate, or high inflammation groups based on early postnatal inflammatory protein levels.
- Assessed adolescent brain volumes at age 15 using 3T MRI and quantified regional volumes with FreeSurfer, alongside neurological assessments.
Main Results:
- Higher neonatal inflammation correlated with reduced volumes in the cerebellum cortex, brainstem, and subcortical gray matter (including ventral diencephalon, thalamus, amygdala).
- Observed sex-specific effects: females with moderate inflammation showed reductions in total brain and specific regions, while males exhibited reductions in cerebellum cortex, corpus callosum, and brainstem.
- In adolescents with major neurologic disorders, higher inflammation was associated with smaller volumes in the cerebellum cortex, cerebellum white matter, and brainstem.
Conclusions:
- Neonatal inflammation has persistent, detrimental effects on brain development in extremely preterm individuals.
- The impact of inflammation on brain structure is influenced by sex and the presence of neurological disorders.
- Findings highlight the importance of monitoring and potentially mitigating neonatal inflammation to improve long-term neurodevelopmental outcomes.
Abstract:
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.
