Early Glycemic State and Outcomes of Neonates With Hypoxic-Ischemic Encephalopathy

Abstract

Objectives: In infants with hypoxic-ischemic encephalopathy (HIE), conflicting information on the association between early glucose homeostasis and outcome exists. We characterized glycemic profiles in the first 12 hours after birth and their association with death and neurodevelopmental impairment (NDI) in neonates with moderate or severe HIE undergoing therapeutic hypothermia.

Methods: This post hoc analysis of the High-dose Erythropoietin for Asphyxia and Encephalopathy trial included n = 491 neonates who had blood glucose (BG) values recorded within 12 hours of birth. Newborns were categorized based on their most extreme BG value. BG >200 mg/dL was defined as hyperglycemia, BG <50 mg/dL as hypoglycemia, and 50 to 200 mg/dL as euglycemia. Primary outcome was defined as death or any NDI at 22 to 36 months. We calculated odds ratios for death or NDI adjusted for factors influencing glycemic state (aOR).

Results: Euglycemia was more common in neonates with moderate compared with severe HIE (63.6% vs 36.6%; P < .001). Although hypoglycemia occurred at similar rates in severe and moderate HIE (21.4% vs 19.5%; P = .67), hyperglycemia was more common in severe HIE (42.3% vs 16.9%; P < .001). Compared with euglycemic neonates, both, hypo- and hyperglycemic neonates had an increased aOR (95% confidence interval) for death or NDI (2.62; 1.47-4.67 and 1.77; 1.03-3.03) compared to those with euglycemia. Hypoglycemic neonates had an increased aOR for both death (2.85; 1.09-7.43) and NDI (2.50; 1.09-7.43), whereas hyperglycemic neonates had increased aOR of 2.52 (1.10-5.77) for death, but not NDI.

Conclusions: Glycemic profile differs between neonates with moderate and severe HIE, and initial glycemic state is associated death or NDI at 22 to 36 months.

FIGURE 1

Distribution (A) and combined trajectory (B) of all blood glucose levels (n = 2541) obtained in the first 12 hours of life for 491 babies with moderate and severe hypoxic-ischemic encephalopathy (HIE).

FIGURE 2

Association of primary outcome (death or NDI) with lowest (A) and highest (B) blood glucose level in the first 12 hours of life. NDI, neurodevelopmental impairment.

FIGURE 3

Combined glucose profile during the first 12 hours after birth displayed by outcome category: survival without NDI (purple) vs any NDI (gold) or death (black). NDI, neurodevelopmental impairment.

FIGURE 4

Outcome by glucose status within the first 12 hours of life, using euglycemic state as reference. (A) Combined primary outcome of death and any NDI for each glycemic state. (B) Survival versus nonsurvival by glycemic state. (C) Outcome in survivors by glycemic state. 95% CI, 95% confidence interval; aOR, adjusted odds ratio; NDI, neurodevelopmental impairment.