Building an Open Source Classifier for the Neonatal EEG Background: A Systematic Feature-Based Approach From Expert Scoring to Clinical Visualization

Neonatal brain monitoring in the neonatal intensive care units (NICU) requires a continuous review of the spontaneous cortical activity, i.e., the electroencephalograph (EEG) background activity. This needs development of bedside methods for an automated assessment of the EEG background activity. In this paper, we present development of the key components of a neonatal EEG background classifier, starting from the visual background scoring to classifier design, and finally to possible bedside visualization of the classifier results. A dataset with 13,200 5-minute EEG epochs (8–16 channels) from 27 infants with birth asphyxia was used for classifier training after scoring by two independent experts. We tested three classifier designs based on 98 computational features, and their performance was assessed with respect to scoring system, pre- and post-processing of labels and outputs, choice of channels, and visualization in monitor displays. The optimal solution achieved an overall classification accuracy of 97% with a range across subjects of 81–100%. We identified a set of 23 features that make the classifier highly robust to the choice of channels and missing data due to artefact rejection. Our results showed that an automated bedside classifier of EEG background is achievable, and we publish the full classifier algorithm to allow further clinical replication and validation studies.Peer reviewe

Glucose Derangements and Brain Function in Neonatal Encephalopathy

Hypoglycemia and hyperglycemia are common in neonates with encephalopathy and may be independently associated with unfavourable outcomes. This thesis describes how glucose derangements detected with continuous interstitial glucose monitoring commenced soon after birth are associated with brain function on amplitude-integrated electroencephalography (aEEG) and continuous EEG (cEEG) in the context of neonatal encephalopathy. We hypothesize that hypoglycemia, hyperglycemia and glucose variability in neonatal encephalopathy are associated with abnormal brain background activity and increased electrographic seizures on aEEG and cEEG. In neonates with encephalopathy, epochs of hyperglycemia, but not hypoglycemia, were common and temporally associated with worse aEEG background scores, less sleep-wake cycling, and more electrographic seizures, including after adjusting for clinical markers of hypoxia-ischemia. Epochs of hyperglycemia also were associated with worse cEEG background scores, including after adjusting for hypoxia-ischemia severity. Our data support the hypothesis that proactive avoidance of hyperglycemia may be a neuroprotective strategy in infants with neonatal encephalopathy.M.Sc

Nutrition and management of glycemia in neonates with neonatal encephalopathy treated with hypothermia.

Adequate nutrition and glycemic homeostasis are increasingly recognized as potentially neuroprotective for the developing brain. In the context of hypoxia-ischemia, evidence is scarce regarding optimal nutritional support and administration route, as well as the short- and long-term consequences of such interventions. In this review, we summarize current knowledge on disturbances of brain metabolism of glucose and substrates by hypoxia-ischemia, and compound effects of these mechanisms on brain injury characterized by specific patterns on EEG and MRI. Risks and benefits of nutrition delivery via parenteral or enteral routes are examined. Nutrition could mitigate adverse neurodevelopmental outcomes, and the impact of nutritional strategies and specific nutritional interventions are reviewed. Limited literature highlights the need for further studies to understand the changes in energy metabolism during and after hypoxic-ischemic injury, to optimize nutritional regimens and glucose management, and to inform the neuroprotective role of nutrition

Distal 22q11.2 Microduplication

Distal chromosome 22q11.2 microduplications are associated with a wide range of phenotypes and unclear pathogenicity. The authors report on a 3-year-old girl with global developmental delay harboring a de novo 1.24 Mb distal chromosome 22q11.2 microduplication and a paternally inherited 0.25 Mb chromosome 4p14 microduplication. The authors review clinical features of 30 reported cases of distal 22q11.2 duplications. Common features include developmental delay (93%), neuropsychiatric features (26%), and nonspecific facial dysmorphisms (74%). In 70% of cases, the distal 22q11.2 duplications were inherited, and the majority of the carrier parents were phenotypically normal. Furthermore, 30% of probands carried an additional copy number variant. Review of the phenotype in individuals carrying microduplications involving similar low copy repeats (LCR) failed to establish any clear genotype–phenotype correlations. Distal 22q11.2 duplications represent a major challenge for genetic counseling and prediction of clinical consequences. Our report suggests a pathogenic role of distal 22q11.2 duplications and supports a “multiple hit” hypothesis underlying its variable expressivity and phenotypic severity

Long-term consequences of neonatal encephalopathy in the hypothermia era: protocol for a follow-up cohort study at 9 years of age

Introduction Therapeutic hypothermia (TH) became the standard of care treatment for neonates with moderate and severe neonatal encephalopathy (NE) in most industrialized countries about 10 years ago. Although TH is effective in reducing mortality and the incidence of severe developmental disabilities, the recent literature converges in reporting frequent cognitive and behavioural difficulties at school entry in children with NE-TH. Although these challenges are deemed minor compared with cerebral palsy and intellectual disability, their impacts on a child’s self-determination and family’s well-being are quite significant. Therefore, the nature and extent of these difficulties need to be comprehensively described so that appropriate care can be offered.Methods and analysis The current study will be the largest follow-up study of neonates with NE treated with TH to characterize their developmental outcomes and associated brain structural profiles at 9 years of age. Specifically, we will compare executive function, attention, social cognition, behaviour, anxiety, self-esteem, peer problems, brain volume, cortical features, white matter microstructure and myelination between children with NE-TH and matched peers without NE. Associations of perinatal risk factors and structural brain integrity with cognitive, behavioural and psycho-emotional deficits will be evaluated to inform about the potential aggravating and protective factors associated with function.Ethics and dissemination This study is supported by the Canadian Institute of Health Research (202203PJT-480065-CHI-CFAC-168509), and received approval from the Pediatric Ethical Review Board of the McGill University Health Center (MP-37-2023-9320). The study findings will be disseminated in scientific journals and conferences and presented to parental associations and healthcare providers to inform best practices.Trial registration number NCT05756296