Background and Objectives: Predicting neurodevelopmental outcome for neonates with hypoxic-ischemic encephalopathy (HIE) is important for clinical decision-making, care planning, and parent communication. We examined the relationship between EEG background and neurodevelopmental outcome among children enrolled in a trial of erythropoietin (Epo) or placebo for neonates with HIE treated with therapeutic hypothermia. Methods: Participants had EEG recorded throughout hypothermia. EEG background was classified as normal, discontinuous, or severely abnormal (defined as burst suppression, low voltage suppressed, or status epilepticus) at five one-hour epochs: onset of recording, 24, 36, 48, and 72 hours after birth. The predominant background pattern during the entire cEEG recording was calculated using the arithmetic mean of the five EEG background ratings (normal=0; discontinuous=1; severely abnormal=2) as follows: “predominantly normal” (mean=0), “normal/discontinuous” (0<mean<1), “predominantly discontinuous” (mean=1), “discontinuous/severely abnormal” (1<mean<2), or “predominantly severely abnormal” (mean=2). Primary outcome was death or neurodevelopmental impairment (NDI) defined as cerebral palsy, Gross Motor Function Classification Score ≥1 or cognitive score <90 on Bayley Scales of Infant Toddler Development, 3rd edition at age two years. Neurodevelopment was also categorized into a 5-level ordinal measure: no, mild, moderate, or severe NDI, or death for secondary analysis. We used generalized linear regression models with robust standard errors to assess the relative risk of death or NDI by EEG background in both unadjusted and adjusted analyses controlling for effects of treatment group, sex, HIE severity, and study recruitment site. Results: Among 142 neonates, predominant background EEG pattern was predominantly normal in 35 (25%), normal/discontinuous in 68 (48%), predominantly discontinuous in 11 (7.7%), discontinuous/severely abnormal in 16 (11%), and predominantly severely abnormal in 12 (8.5%). Increasing severity of background across monitoring epochs was associated with increasingly worse clinical outcomes. Children with severe EEG background abnormality at any time point (n=36, 25%) were significantly more likely to die or have severe neurodevelopmental impairment at two years (adjusted relative risk: 7.95, 95% confidence interval 3.49–18.12). Discussion: EEG background is strongly associated with NDI at age two years. These results can be used to assist health care providers to plan follow-up care and counsel families for decision making related to goals of care. NCT02811263.

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

Objective To (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic hydrocephalus (PHH). Design Cohort study of the Children’s Hospitals Neonatal Database from 2010 to 2022. Setting 41 referral neonatal intensive care units (NICUs) in North America. Patients Infants born before 32 weeks’ gestation with PHH defined as acquired hydrocephalus with intraventricular haemorrhage. Interventions (1) No intervention, (2) temporising device (TD) only, (3) initial permanent shunt (PS) and (4) TD followed by PS (TD-PS). Main outcome measures Mortality and meningitis. Results Of 3883 infants with PHH from 41 centres, 36% had no surgical intervention, 16% had a TD only, 19% had a PS only and 30% had a TD-PS. Of the 46% of infants with TDs, 76% were reservoirs; 66% of infants with TDs required PS placement. The percent of infants with PHH receiving ventricular access device placement differed by centre, ranging from 4% to 79% (p<0.001). Median chronological and postmenstrual age at time of TD placement were similar between infants with only TD and those with TD-PS. Infants with TD-PS were older and larger than those with only PS at time of PS placement. Death before NICU discharge occurred in 12% of infants, usually due to redirection of care. Meningitis occurred in 11% of the cohort. Conclusions There was significant intercentre variation in rate of intervention, which may reflect variability in care or referral patterns. Rate of PS placement in infants with TDs was 66%.