Hyperglycemia and Glucose Variability Are Associated with Worse Brain Function and Seizures in Neonatal Encephalopathy: A Prospective Cohort Study

Abstract

To investigate how glucose abnormalities correlate with brain function on amplitude-integrated electroencephalography (aEEG) in infants with neonatal encephalopathy. Neonates born at full term with encephalopathy were enrolled within 6hours of birth in a prospective cohort study at a pediatric academic referral hospital. Continuous interstitial glucose monitors and aEEG were placed soon after birth and continued for 3days. Episodes of hypoglycemia (≤50mg/dL; ≤2.8mmol/L) and hyperglycemia (>144mg/dL; >8.0mmol/L) were identified. aEEG was classified in 6-hour epochs for 3 domains (background, sleep-wake cycling, electrographic seizures). Generalized estimating equations assessed the relationship of hypo- or hyperglycemia with aEEG findings, adjusting for clinical markers of hypoxia-ischemia (Apgar scores, umbilical artery pH, and base deficit). Forty-five infants (gestational age 39.5±1.4weeks) were included (24 males). During aEEG monitoring, 16 episodes of hypoglycemia were detected (9 infants, median duration 77.5, maximum 220minutes) and 18 episodes of hyperglycemia (13 infants, median duration 237.5, maximum 3125minutes). Epochs of hypoglycemia were not associated with aEEG changes. Compared with epochs of normoglycemia, epochs of hyperglycemia were associated with worse aEEG background scores (B 1.120, 95% CI 0.501-1.738, P<.001), less sleep-wake cycling (B 0.587, 95% CI 0.417-0.757, P<.001) and more electrographic seizures (B 0.433, 95% CI 0.185-0.681, P=.001), after adjusting for hypoxia-ischemia severity. In neonates with encephalopathy, epochs of hyperglycemia were temporally associated with worse global brain function and seizures, even after we adjusted for hypoxia-ischemia severity. Whether hyperglycemia causes neuronal injury or is simply a marker of severe brain injury requires further study.