10 - Automated EEG background and outcomes in neonates with mild hypoxic-ischemic encephalopathy

Publication Number: 1008.10

Emily S. Taketa, University of California, San Francisco, School of Medicine, San Francisco, CA, United States; Adam L. Numis, University of California, San Francisco, School of Medicine, San Francisco, CA, United States; Natalie Chan, UCSF Benioff Children's Hospital San Francisco, San Francisco, CA, United States; Hannah Glass, University of California, San Francisco, School of Medicine, San Francisco, CA, United States; Tiana Nguyen, UCSF, San Francisco, CA, United States; Mark A. Petersen, University of California, San Francisco, School of Medicine, San Francisco, CA, United States; Marie-Coralie Cornet, UCSF Benioff Children's Hospital San Francisco, San Francisco, CA, United States

Background: Assessing neonatal brain function following an acute perinatal event is a clinical challenge. Neurologic examinations are limited by both inter- and intra-rater variability. EEG background patterns, identified by automated EEG background analysis, predict outcomes in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE). Still, their utility for evaluating outcomes in mild HIE has yet to be established.

Objective: To determine whether EEG background quantified by the Brain State of the Newborn (BSN) in neonates with mild HIE is associated with neurodevelopmental outcomes at 2 years of age.

Design/Methods: Retrospective cohort study of neonates ≥ 35 weeks GA (01/2017 - 01/2024) born in a level IV neonatal intensive care unit and treated with therapeutic hypothermia (TH) for mild encephalopathy ( < 3 moderate findings on modified Sarnat exam) with EEG started < 12 hours of age. BSN, ranging from 0 (no brain activity) to 100 (normal brain activity), was extracted from continuous EEG. We calculated the median BSN after 20 minutes and 1 hour of recording, and at 6-12 and 12-24 hours of age. The primary outcome, moderate to severe neurodevelopmental impairment (NDI) or death, was defined as a cognitive, motor, or language score < 80 on Bayley Scale for Infant Development III or IV at 12-36 months or death. The secondary outcome was acute brain injury on MRI. We used descriptive statistics, chi-squared, and the Wilcoxon rank-sum test for statistical analysis. This study was approved by UCSF IRB and was exempt from individual patient consent.

Results: Among 114 infants treated with TH for mild encephalopathy 62 (54%) had follow-up available at age 2, 5/62 (8%) had moderate to severe NDI or death. BSN at all studied timepoints was associated with moderate to severe NDI or death (Table 1). Among the 28/62 (45%) infants with a median BSN>75 at 1hour of recording, none had moderate to severe NDI or death compared to 5/34 (15%) when BSN was < 75 (Figure 1). All 114 infants had brain MRI and 12/114 (10%) had HI brain injury. BSN starting at 1 hour of recording was associated with the presence of HI brain injury on MRI (Table 2- Figure 1).

Conclusion(s): Moderate to severe NDI or death occurred in less than 1 in 10 infants with a history of mild HIE. BSN was associated with neurodevelopmental outcome, suggesting a possible utility in early risk stratification. Further studies, including detailed phenotyping and rigorous follow-up, are needed to understand the potential role of BSN in patient selection for TH in mild HIE.

Table 1: Maternal and infant clinical and EEG characteristics stratified by the presence of moderate to severe neurodevelopmental impairment or death in a cohort of 62 infants with mild HIE and follow-up at age 2 (18-36 months) available
Data is displayed as median (IQR) and N (%)
HI: Hypoxic ischemic; BSN: Brain state of the newborn
1. The Sarnat score was calculated by using the modified Sarnat neurologic examination and assigning for each of the six categories (level of consciousness, activity, tone, posture, reflex and autonomic features) a score of 0 for normal, 1 for mild, 2 for moderate or 3 for severe.
2. Other non-HI-related findings included hemorrhages, brain malformation, and small punctate lesions.
3. P-value was obtained by chi-squared for categorical variables, Wilcoxon rank sum test for continuous non normally distributed variables, and linear regression for ordered variables.

Table 2: Maternal and infant clinical and EEG characteristics stratified by the presence of hypoxic-ischemic (HI) brain injury on MRI in a cohort of 114 infants with mild HIE
Data is displayed as median (IQR) and N(%)
HI: Hypoxic ischemic; BSN: Brain state of the newborn
1. The Sarnat score was calculated by using the modified Sarnat neurologic examination and assigning for each of the six categories (level of consciousness, activity, tone, posture, reflex and autonomic features) a score of 0 for normal, 1 for mild, 2 for moderate or 3 for severe.
2. Outcome at 12-36 months; The degree of NDI was defined as the lowest score across cognitive, motor, or language on the Bayley Scale of Infant Development III or IV. Mild was defined as any score between 80-90, moderate 75-80, and severe <75.
3. P-value was obtained by chi-squared for categorical variables, Wilcoxon rank sum test for continuous non normally distributed variables, and linear regression for ordered variables.

Figure 1: Presence of hypoxic ischemic injury and outcomes by timepoint and BSN category in a cohort of neonates with mild HIE
Outcome at 12-36 months; The degree of NDI was defined as the lowest score across cognitive, motor, or language on the Bayley Scale of Infant Development III or IV. Mild was defined as any score between 80-90, moderate 75-80, and severe <75.