Early Life Resting-State Network Functional Connectivity and Long-Term Neurodevelopmental Outcomes after Neonatal...

Neonatal encephalopathy (NE) is a risk factor for long-term neurodevelopmental impairments, and early measures of brain function may help understand which survivors are most at risk. This study investigates the relationship between resting-state network (RSN) functional connectivity (FC) in the first week of life and long-term neurodevelopmental outcomes after NE.

A prospective cohort of therapeutic hypothermia-treated neonates ≥36 weeks gestational age with NE had resting-state functional MRI (rs-fMRI) in the first week of life, and follow-up at 18 and 36 months. Subject-wise Pearson correlations between each pair of 27 seeds (seed-to-seed correlation matrix) that represent 6 RSNs of interest (Language, Somatomotor, Default Mode, Frontoparietal, Dorsal attention, Ventral Attention), and subject-wise seed-based mean z scores for each seed were generated. Spearman correlations assessed the associations between 6 intra-RSN FC strength values (averaged subject-wise z-transformed seed-to-seed correlations within each RSN) and 18- and 36-month neurodevelopmental outcomes. Based on primary analyses findings, Spearman correlations also assessed the associations between seed-based mean z scores for specific RSNs and neurodevelopmental outcomes at 36 months.

Of 72 neonates, 52 (72%) had adequate quality rs-fMRI data. Based on Barkovich scoring, 3 (6%) neonates had basal ganglia, 2 (4%) had watershed, and 10 (19%) had both brain injury patterns. Of 52, 47 (90%) neonates had follow-up at 19 ± 1.7 months, and 45 (87%) at 36.8 ± 1.5 months. Correcting for multiple comparisons, intra-RSN FC strength was not correlated with 18- or 36-month outcomes. Correcting for multiple comparisons, mean z scores for the right motor, and the right and left supplementary motor area within the Somatomotor RSN were positively correlated with Bayley-III language composite score, and mean z scores for the right temporoparietal junction within the Ventral Attention RSN were positively correlated with Child Behavior Checklist Externalizing Problems composite T-score at 36 months.

RSN FC in the first week of life is correlated with 36-month neurodevelopmental outcomes after NE. Early rs-fMRI could provide meaningful clinical insight for predicting long-term neurodevelopmental outcomes after NE.