648 - Dysglycemia by 12 hours of life, neonatal resting state functional connectivity, and 36-month neurodevelopmental outcomes in survivors of neonatal encephalopathy

Publication Number: 648.4608

Daphne Kamino, The Hospital for Sick Children, Toronto, ON, Canada; Jessy Parokaran Varghese, The Hospital for Sick Children, Toronto, ON, Canada; Anwar S.. Shatil, The Hospital for Sick Children, Hockley, TX, United States; Elysa Widjaja, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Benjamin T. Dunkley, The Hospital for Sick Children, Toronto, ON, Canada; Eva G. Mamak, The Hospital for Sick Children, Toronto, ON, Canada; Vann Chau, The Hospital for Sick Children, Toronto, ON, Canada; Linh G. Ly, University of Toronto Temerty Faculty of Medicine, Toronto, ON, Canada; Emily W.Y.. Tam, The Hospital for Sick Children, Toronto, ON, Canada

Background: Dysglycemia is common in neonatal encephalopathy (NE) treated with therapeutic hypothermia, but its impact on outcomes requires further study.

Objective: To investigate the relationship between neonatal dysglycemia, neonatal resting state functional connectivity (rsFC), and 36-month neurodevelopmental outcomes after NE.

Design/Methods: A prospective cohort of cooled neonates ≥36 weeks postmenstrual age with NE had continuous glucose monitoring for 72 hours, brain MRI in the first week of life, and 36-month neurodevelopmental follow-up. NeoRs, a resting state functional MRI (rsfMRI) preprocessing pipeline for neonates, generated mean rsFC z-scores for 31 seeds representing 7 resting state networks (language, somatomotor, visual, default mode, dorsal attention, ventral attention, frontoparietal control). Mean rsFC z-scores represent seed-based functional connectivity and were calculated by averaging the Fisher z-transformed subject-wise Pearson correlations between each seed and the rest of the brain. Linear regression analyses assessed the relationship between minimum and maximum glucose levels by 12, 24, 48, and 72 hours of life (HOL) and mean rsFC z-scores. Based on linear regression findings, Spearman’s correlations assessed associations between mean rsFC z-scores of specific seeds and 36-month neurodevelopmental outcomes.

Results: Of 72 neonates, 58 (81%) had adequate quality rsfMRI data. Four (7%) neonates had basal ganglia, 1 (2%) had watershed, and 10 (17%) had both brain injury patterns. Fifty (86%) neonates had follow-up at 37±2 months. Means for Bayley-III composite scores were 97±14 for cognitive, 98±19 for language, and 94±14 for motor. Means for Child Behavior Checklist (CBCL) composite T-scores were 47±11 for internalizing and 46±10 for externalizing problems. Adjusting for umbilical artery pH, 5-min Apgar, and modified Sarnat score, minimum (Table 1) and maximum (Table 2) glucose by 12 HOL best predicted neonatal rsFC, with no further improvements when extending to 72 HOL. Correcting for multiple comparisons, mean rsFC z-score for the left supplementary motor area was positively correlated with Bayley-III language composite score (P=0.011), and mean rsFC z-score for the right temporoparietal junction was positively correlated with CBCL externalizing composite T-score (P=0.014) at 36 months.

Conclusion(s): Minimum and maximum glucose levels in the first 12 HOL best predicted neonatal rsFC after NE, while regional rsFC correlated with specific domains of outcomes. Early rsfMRI could provide meaningful clinical insight for understanding predictors and long-term outcomes after NE.

Table 1. Significant associations for adjusted linear regression analyses between minimum glucose levels during the first 12, 24, 48, and 72 hours of life and mean rsFC z-scores of 31 seeds


Table 2. Significant associations for adjusted linear regression analyses between maximum glucose levels during the first 12, 24, 48, and 72 hours of life and mean rsFC z-scores of 31 seeds


Table 1. Significant associations for adjusted linear regression analyses between minimum glucose levels during the first 12, 24, 48, and 72 hours of life and mean rsFC z-scores of 31 seeds


Table 2. Significant associations for adjusted linear regression analyses between maximum glucose levels during the first 12, 24, 48, and 72 hours of life and mean rsFC z-scores of 31 seeds