Bedside tracking of functional autonomic age in preterm infants.

BACKGROUND: Preterm birth predisposes infants to adverse outcomes that, without early intervention, impacts their long-term health. To assist bedside monitoring, we developed a tool to track the autonomic maturation of the preterm by assessing heart rate variability (HRV) changes during intensive care. METHODS: Electrocardiogram (ECG) recordings were longitudinally recorded in 67 infants (26-38 weeks postmenstrual age (PMA)). Supervised machine learning was used to generate a functional autonomic age (FAA), by combining 50 computed HRV features from successive 5-minute ECG epochs (median of 23 epochs per infant). Performance of the FAA was assessed by correlation to PMA, clinical outcomes and the infant's functional brain age (FBA), an index of maturation derived from the electroencephalogram. RESULTS: The FAA was strongly correlated to PMA (r = 0.86, 95% CI: 0.83-0.93) with a mean absolute error (MAE) of 1.66 weeks and also accurately estimated FBA (MAE = 1.58 weeks, n = 54 infants). The relationship between PMA and FAA was not confounded by neurodevelopmental outcome (p = 0.18, n = 45), sex (p = 0.88, n = 56), patent ductus arteriosus (p = 0.08, n = 56), IVH (p = 0.63, n = 56) or body weight at birth (p = 0.95, n = 56). CONCLUSIONS: The FAA, an index derived from the ubiquitous ECG signal, offers direct avenues towards estimating autonomic maturation at the bedside during intensive care monitoring. IMPACT: The development of a tool to track functional autonomic age in preterm infants based on heart rate variability features in the electrocardiogram provides a rapid and specialized view of autonomic maturation at the bedside. Functional autonomic age is linked closely to postmenstrual age and central nervous system function response, as determined by its relationship to functional brain age from the electroencephalogram. Tracking functional autonomic age during neonatal intensive care unit monitoring offers a unique insight into cardiovascular health in infants born extremely preterm and their maturational trajectories to term age.

Electroencephalographic studies in growth-restricted and small-for-gestational-age neonates.

Foetal growth restriction (FGR) and being born small for gestational age (SGA) are associated with neurodevelopmental delay. Early diagnosis of neurological damage is difficult in FGR and SGA neonates. Electroencephalography (EEG) has the potential as a tool for the assessment of brain development in FGR/SGA neonates. In this review, we analyse the evidence base on the use of EEG for the assessment of neonates with FGR or SGA. We found consistent findings that FGR/SGA is associated with measurable changes in the EEG that present immediately after birth and persist into childhood. Early manifestations of FGR/SGA in the EEG include changes in spectral power, symmetry/synchrony, sleep-wake cycling, and the continuity of EEG amplitude. Later manifestations of FGR/SGA into infancy and early childhood include changes in spectral power, sleep architecture, and EEG amplitude. FGR/SGA infants had poorer neurodevelopmental outcomes than appropriate for gestational age controls. The EEG has the potential to identify FGR/SGA infants and assess the functional correlates of neurological damage. IMPACT: FGR/SGA neonates have significantly different EEG activity compared to AGA neonates. EEG differences persist into childhood and are associated with adverse neurodevelopmental outcomes. EEG has the potential for early identification of brain impairment in FGR/SGA neonates.

Modelling herd immunity requirements in Queensland: impact of vaccination effectiveness, hesitancy and variants of SARS-CoV-2.

Long-term control of SARS-CoV-2 outbreaks depends on the widespread coverage of effective vaccines. In Australia, two-dose vaccination coverage of above 90% of the adult population was achieved. However, between August 2020 and August 2021, hesitancy fluctuated dramatically. This raised the question of whether settings with low naturally derived immunity, such as Queensland where less than [Formula: see text] of the population is known to have been infected in 2020, could have achieved herd immunity against 2021's variants of concern. To address this question, we used the agent-based model Covasim. We simulated outbreak scenarios (with the Alpha, Delta and Omicron variants) and assumed ongoing interventions (testing, tracing, isolation and quarantine). We modelled vaccination using two approaches with different levels of realism. Hesitancy was modelled using Australian survey data. We found that with a vaccine effectiveness against infection of 80%, it was possible to control outbreaks of Alpha, but not Delta or Omicron. With 90% effectiveness, Delta outbreaks may have been preventable, but not Omicron outbreaks. We also estimated that a decrease in hesitancy from 20% to 14% reduced the number of infections, hospitalizations and deaths by over 30%. Overall, we demonstrate that while herd immunity may not be attainable, modest reductions in hesitancy and increases in vaccine uptake may greatly improve health outcomes. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Heart rate variability in hypoxic ischemic encephalopathy during therapeutic hypothermia.

BACKGROUND: Therapeutic hypothermia (TH) aims to ameliorate further injury in infants with moderate and severe hypoxic ischemic encephalopathy (HIE). We aim to assess the effect of TH on heart rate variability (HRV) in infants with HIE. METHODS: Multichannel video-electroencephalography (EEG) and electrocardiography were assessed at 6-72 h after birth in full-term infants with HIE, recruited prior to (pre-TH group) and following (TH group) the introduction of TH in our neonatal unit. HIE severity was graded using EEG. HRV features investigated include: mean NN interval (mean NN), standard deviation of NN interval (SDNN), triangular interpolation (TINN), high-frequency (HF), low-frequency (LF), very low-frequency (VLF), and LF/HF ratio. Linear mixed model comparisons were used. RESULTS: 118 infants (pre-TH: n = 44, TH: n = 74) were assessed. The majority of HRV features decreased with increasing EEG grade. Infants with moderate HIE undergoing TH had significantly different HRV features compared with the pre-TH group (HF: P = 0.016, LF/HF ratio: P = 0.006). In the pre-TH group, LF/HF ratio was significantly different between moderate and severe HIE grades (P = 0.002). In the TH group, significant differences were observed between moderate and severe HIE grades for SDNN: P = 0.020, TINN: P = 0.005, VLF: P = 0.029, LF: P = 0.010, and HF: P = 0.006. CONCLUSION: The HF component of HRV is increased in infants with moderate HIE undergoing TH.

Seizure burden and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy.

AIM: To examine the relationship between electrographic seizures and long-term outcome in neonates with hypoxic-ischemic encephalopathy (HIE). METHOD: Full-term neonates with HIE born in Cork University Maternity Hospital from 2003 to 2006 (pre-hypothermia era) and 2009 to 2012 (hypothermia era) were included in this observational study. All had early continuous electroencephalography monitoring. All electrographic seizures were annotated. The total seizure burden and hourly seizure burden were calculated. Outcome (normal/abnormal) was assessed at 24 to 48 months in surviving neonates using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales; a diagnosis of cerebral palsy or epilepsy was also considered an abnormal outcome. RESULTS: Continuous electroencephalography was recorded for a median of 57.1 hours (interquartile range 33.5-80.5h) in 47 neonates (31 males, 16 females); 29 out of 47 (62%) had electrographic seizures and 25 out of 47 (53%) had an abnormal outcome. The presence of seizures per se was not associated with abnormal outcome (p=0.126); however, the odds of an abnormal outcome increased over ninefold (odds ratio [OR] 9.56; 95% confidence interval [95% CI] 2.43-37.67) if a neonate had a total seizure burden of more than 40 minutes (p=0.001), and eightfold (OR: 8.00; 95% CI: 2.06-31.07) if a neonate had a maximum hourly seizure burden of more than 13 minutes per hour (p=0.003). Controlling for electrographic HIE grade or treatment with hypothermia did not change the direction of the relationship between seizure burden and outcome. INTERPRETATION: In HIE, a high electrographic seizure burden is significantly associated with abnormal outcome, independent of HIE severity or treatment with hypothermia.

Heart rate variability in hypoxic ischemic encephalopathy: correlation with EEG grade and 2-y neurodevelopmental outcome.

BACKGROUND: The study aims to describe heart rate variability (HRV) in neonatal hypoxic ischemic encephalopathy (HIE) and correlate HRV with electroencephalographic (EEG) grade of HIE and neurodevelopmental outcome. METHODS: Multichannel EEG and electrocardiography (ECG) were assessed at 12-48 h after birth in healthy and encephalopathic full-term neonates. EEGs were graded (normal, mild, moderate, and severe). Neurodevelopmental outcome was assessed at 2 y of age. Seven HRV features were calculated using normalized-RR (NN) interval. The correlation of these features with EEG grade and outcome were measured using Spearman's correlation coefficient. RESULTS: HRV was significantly associated with HIE severity (P < 0.05): standard deviation of NN interval (SDNN) (r = -0.62), triangular interpolation of NN interval histogram (TINN) (r = -0.65), mean NN interval (r = -0.48), and the very low frequency (VLF) (r = -0.60), low frequency (LF) (r = -0.67) and high frequency (HF) components of the NN interval (r = -0.60). SDNN at 24 and 48 h were significantly associated (P < 0.05) with neurodevelopmental outcome (r = -0.41 and -0.54, respectively). CONCLUSION: HRV is associated with EEG grade of HIE and neurodevelopmental outcome. HRV has potential as a prognostic tool to complement EEG.

Clinical outcome prediction with an automated EEG trend, Brain State of the Newborn, after perinatal asphyxia.

OBJECTIVE: To evaluate the utility of a fully automated deep learning -based quantitative measure of EEG background, Brain State of the Newborn (BSN), for early prediction of clinical outcome at four years of age. METHODS: The EEG monitoring data from eighty consecutive newborns was analyzed using the automatically computed BSN trend. BSN levels during the first days of life (a of total 5427 hours) were compared to four clinical outcome categories: favorable, cerebral palsy (CP), CP with epilepsy, and death. The time dependent changes in BSN-based prediction for different outcomes were assessed by positive/negative predictive value (PPV/NPV) and by estimating the area under the receiver operating characteristic curve (AUC). RESULTS: The BSN values were closely aligned with four visually determined EEG categories (p < 0·001), as well as with respect to clinical milestones of EEG recovery in perinatal Hypoxic Ischemic Encephalopathy (HIE; p < 0·003). Favorable outcome was related to a rapid recovery of the BSN trend, while worse outcomes related to a slow BSN recovery. Outcome predictions with BSN were accurate from 6 to 48 hours of age: For the favorable outcome, the AUC ranged from 95 to 99% (peak at 12 hours), and for the poor outcome the AUC ranged from 96 to 99% (peak at 12 hours). The optimal BSN levels for each PPV/NPV estimate changed substantially during the first 48 hours, ranging from 20 to 80. CONCLUSIONS: We show that the BSN provides an automated, objective, and continuous measure of brain activity in newborns. SIGNIFICANCE: The BSN trend discloses the dynamic nature that exists in both cerebral recovery and outcome prediction, supports individualized patient care, rapid stratification and early prognosis.

A growth chart of brain function from infancy to adolescence based on EEG.

BACKGROUND: In children, objective, quantitative tools that determine functional neurodevelopment are scarce and rarely scalable for clinical use. Direct recordings of cortical activity using routinely acquired electroencephalography (EEG) offer reliable measures of brain function. METHODS: We developed and validated a measure of functional brain age (FBA) using a residual neural network-based interpretation of the paediatric EEG. In this cross-sectional study, we included 1056 children with typical development ranging in age from 1 month to 18 years. We analysed a 10- to 15-min segment of 18-channel EEG recorded during light sleep (N1 and N2 states). FINDINGS: The FBA had a weighted mean absolute error (wMAE) of 0.85 years (95% CI: 0.69-1.02; n = 1056). A two-channel version of the FBA had a wMAE of 1.51 years (95% CI: 1.30-1.73; n = 1056) and was validated on an independent set of EEG recordings (wMAE = 2.27 years, 95% CI: 1.90-2.65; n = 723). Group-level maturational delays were also detected in a small cohort of children with Trisomy 21 (Cohen's d = 0.36, p = 0.028). INTERPRETATION: A FBA, based on EEG, is an accurate, practical and scalable automated tool to track brain function maturation throughout childhood with accuracy comparable to widely used physical growth charts. FUNDING: This research was supported by the National Health and Medical Research Council, Australia, Helsinki University Diagnostic Center Research Funds, Finnish Academy, Finnish Paediatric Foundation, and Sigrid Juselius Foundation.

Corrigendum: Building an open source classifier for the neonatal EEG background: a systematic feature-based approach from expert scoring to clinical visualization.

[This corrects the article DOI: 10.3389/fnhum.2021.675154.].

Inter-site generalizability of EEG based age prediction algorithms in the preterm infant.

Objective. To overcome the effects of site differences in EEG-based brain age prediction in preterm infants.Approach. We used a 'bag of features' with a combination function estimated using support vector regression (SVR) and feature selection (filter then wrapper) to predict post-menstrual age (PMA). The SVR was trained on a dataset containing 138 EEG recordings from 37 preterm infants (site 1). A separate set of 36 EEG recordings from 36 preterm infants was used to validate the age predictor (site 2). The feature distributions were compared between sites and a restricted feature set was constructed using only features that were not significantly different between sites. The mean absolute error between predicted age and PMA was used to define the accuracy of prediction and successful validation was defined as no significant differences in error between site 1 (cross-validation) and site 2.Main results. The age predictor based on all features and trained on site 1 was not validated on site 2 (p< 0.001; MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 2.1 weeks,n= 36). The MAE was improved by training on a restricted features set (MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 1.1 weeks,n= 36), resulting in a validated age predictor when applied to site 2 (p= 0.68). The features selected from the restricted feature set when training on site 1 closely aligned with features selected when trained on a combination of data from site 1 and site 2.Significance. The ability of EEG classifiers, such as brain age prediction, to maintain accuracy on data collected at other sites may be challenged by unexpected, site-dependent differences in EEG signals. Permitting a small amount of data leakage between sites improves generalization, leading towards universal methods of EEG interpretation in preterm infants.

Optimization of time series features to estimate brain age in children from electroencephalography.

Functional brain age measures in children, derived from the electroencephalogram (EEG), offer direct and objective measures in assessing neurodevelopmental status. Here we explored the effectiveness of 32 preselected 'handcrafted' EEG features in predicting brain age in children. These features were benchmarked against a large library of highly comparative multivariate time series features (>7000 features). Results showed that age predictors based on handcrafted EEG features consistently outperformed a generic set of time series features. These findings suggest that optimization of brain age estimation in children benefits from careful preselection of EEG features that are related to age and neurodevelopmental trajectory. This approach shows potential for clinical translation in the future.Clinical Relevance-Handcrafted EEG features provide an accurate functional neurodevelopmental biomarker that tracks brain function maturity in children.

The temporal evolution of electrographic seizure burden in neonatal hypoxic ischemic encephalopathy.

PURPOSE: Hypoxic ischemic encephalopathy (HIE) accounts for 60% of all neonatal seizures. There is emerging evidence that seizures cause additional injury to the developing brain that has sustained hypoxic ischemic injury. Temporal evolution of clinical seizure burden in HIE has been characterized, with maximum clinical seizure burden (the period of maximum seizure activity) being observed between 12 and 24 h of age. The purpose of our study was to investigate the distribution of electrographic seizure burden (the accumulated duration of seizures over a defined time period), following the initial hypoxic ischemic insult. METHODS: Fifteen full-term newborns with HIE and seizures, and a minimum of 48 h of continuous video-electroencephalography (EEG), were included in this retrospective study. Medical records of the infants were reviewed and details of clinical seizures and antiepileptic drugs were recorded. The time of maximum seizure burden was defined as the midpoint of an hour-long window, shifted in time by 1 s across the full EEG recording, which contained the maximum duration of seizures. The degree of temporal evolution of seizure burden within this period was tested. Temporal evolution was further analyzed by segmenting the time series into two periods; the time between the first recorded seizure and the maximum seizure burden (T(1)), and the time between the maximum seizure burden and the last recorded seizure (T(2)). Seizure burden, duration, and number of seizures per hour were analyzed within each time period. KEY FINDINGS: EEG was commenced at a median of 14 h of age. Maximum electrographic seizure burden was reached at a median age of 22.7 h. Time from first recorded seizure to maximum seizure burden (T(1)) was significantly shorter than time from maximum seizure burden to last recorded seizure (T(2)) (p-value = 0.01). Median seizure burden during T(1) was significantly higher than during T(2) (p-value = 0.007). There is temporal evolution of electrographic seizure burden in full-term newborns with HIE. There is a short period of high seizure burden (T(1)) followed by a longer period of lower seizure burden (T(2)). SIGNIFICANCE: Understanding the temporal evolution of seizure burden in HIE contributes further to our understanding of neonatal seizures, helps identify an optimal therapeutic window for seizure treatment, and provides a benchmark against which to measure the efficacy of new and innovative forms of neuroprotection and antiepileptic medication.

Sleep State Trend (SST), a bedside measure of neonatal sleep state fluctuations based on single EEG channels.

OBJECTIVE: To develop and validate an automated method for bedside monitoring of sleep state fluctuations in neonatal intensive care units. METHODS: A deep learning-based algorithm was designed and trained using 53 EEG recordings from a long-term (a)EEG monitoring in 30 near-term neonates. The results were validated using an independent dataset from 30 polysomnography recordings. In addition, we constructed Sleep State Trend (SST), a bedside-ready means for visualizing classifier outputs. RESULTS: The accuracy of quiet sleep detection in the training data was 90%, and the accuracy was comparable (85-86 %) in all bipolar derivations available from the 4-electrode recordings. The algorithm generalized well to a polysomnography dataset, showing 81% overall accuracy despite different signal derivations. SST allowed an intuitive, clear visualization of the classifier output. CONCLUSIONS: Fluctuations in sleep states can be detected at high fidelity from a single EEG channel, and the results can be visualized as a transparent and intuitive trend in the bedside monitors. SIGNIFICANCE: The Sleep State Trend (SST) may provide caregivers and clinical studies a real-time view of sleep state fluctuations and its cyclicity.

Validating an SVM-based neonatal seizure detection algorithm for generalizability, non-inferiority and clinical efficacy.

Neonatal seizure detection algorithms (SDA) are approaching the benchmark of human expert annotation. Measures of algorithm generalizability and non-inferiority as well as measures of clinical efficacy are needed to assess the full scope of neonatal SDA performance. We validated our neonatal SDA on an independent data set of 28 neonates. Generalizability was tested by comparing the performance of the original training set (cross-validation) to its performance on the validation set. Non-inferiority was tested by assessing inter-observer agreement between combinations of SDA and two human expert annotations. Clinical efficacy was tested by comparing how the SDA and human experts quantified seizure burden and identified clinically significant periods of seizure activity in the EEG. Algorithm performance was consistent between training and validation sets with no significant worsening in AUC (p > 0.05, n = 28). SDA output was inferior to the annotation of the human expert, however, re-training with an increased diversity of data resulted in non-inferior performance (Δκ = 0.077, 95% CI: -0.002-0.232, n = 18). The SDA assessment of seizure burden had an accuracy ranging from 89 to 93%, and 87% for identifying periods of clinical interest. The proposed SDA is approaching human equivalence and provides a clinically relevant interpretation of the EEG.

Facilitating early parent-infant emotional connection improves cortical networks in preterm infants.

Exposure to environmental adversities during early brain development, such as preterm birth, can affect early brain organization. Here, we studied whether development of cortical activity networks in preterm infants may be improved by a multimodal environmental enrichment via bedside facilitation of mother-infant emotional connection. We examined functional cortico-cortical connectivity at term age using high-density electroencephalography recordings in infants participating in a randomized controlled trial of Family Nurture Intervention (FNI). Our results identify several large-scale, frequency-specific network effects of FNI, most extensively in the alpha frequency in fronto-central cortical regions. The connectivity strength in this network was correlated to later neurocognitive performance, and it was comparable to healthy term-born infants rather than the infants receiving standard care. These findings suggest that preterm neurodevelopmental care can be improved by a biologically driven environmental enrichment, such as early facilitation of direct human connection.

An automated bedside measure for monitoring neonatal cortical activity: a supervised deep learning-based electroencephalogram classifier with external cohort validation.

BACKGROUND: Electroencephalogram (EEG) monitoring is recommended as routine in newborn neurocritical care to facilitate early therapeutic decisions and outcome predictions. EEG's larger-scale implementation is, however, hindered by the shortage of expertise needed for the interpretation of spontaneous cortical activity, the EEG background. We developed an automated algorithm that transforms EEG recordings to quantified interpretations of EEG background and provides simple intuitive visualisations in patient monitors. METHODS: In this method-development and proof-of-concept study, we collected visually classified EEGs from infants recovering from birth asphyxia or stroke. We used unsupervised learning methods to explore latent EEG characteristics, which guided the supervised training of a deep learning-based classifier. We assessed the classifier performance using cross-validation and an external validation dataset. We constructed a novel measure of cortical function, brain state of the newborn (BSN), from the novel EEG background classifier and a previously published sleep-state classifier. We estimated clinical utility of the BSN by identification of two key items in newborn brain monitoring, the onset of continuous cortical activity and sleep-wake cycling, compared with the visual interpretation of the raw EEG signal and the amplitude-integrated (aEEG) trend. FINDINGS: We collected 2561 h of EEG from 39 infants (gestational age 35·0-42·1 weeks; postnatal age 0-7 days). The external validation dataset included 105 h of EEG from 31 full-term infants. The overall accuracy of the EEG background classifier was 92% in the whole cohort (95% CI 91-96; range 85-100 for individual infants). BSN trend values were closely related to the onset of continuous EEG activity or sleep-wake cycling, and BSN levels showed robust difference between aEEG categories. The temporal evolution of the BSN trends showed early diverging trajectories in infants with severely abnormal outcomes. INTERPRETATION: The BSN trend can be implemented in bedside patient monitors as an EEG interpretation that is intuitive, transparent, and clinically explainable. A quantitative trend measure of brain function might harmonise practices across medical centres, enable wider use of brain monitoring in neurocritical care, and might facilitate clinical intervention trials. FUNDING: European Training Networks Funding Scheme, the Academy of Finland, Finnish Pediatric Foundation (Lastentautiensäätiö), Aivosäätiö, Sigrid Juselius Foundation, HUS Children's Hospital, HUS Diagnostic Center, National Health and Medical Research Council of Australia.

Risk of sustained SARS-CoV-2 transmission in Queensland, Australia.

We used an agent-based model Covasim to assess the risk of sustained community transmission of SARSCoV-2/COVID-19 in Queensland (Australia) in the presence of high-transmission variants of the virus. The model was calibrated using the demographics, policies, and interventions implemented in the state. Then, using the calibrated model, we simulated possible epidemic trajectories that could eventuate due to leakage of infected cases with high-transmission variants, during a period without recorded cases of locally acquired infections, known in Australian settings as "zero community transmission". We also examined how the threat of new variants reduces given a range of vaccination levels. Specifically, the model calibration covered the first-wave period from early March 2020 to May 2020. Predicted epidemic trajectories were simulated from early February 2021 to late March 2021. Our simulations showed that one infected agent with the ancestral (A.2.2) variant has a 14% chance of crossing a threshold of sustained community transmission (SCT) (i.e., > 5 infections per day, more than 3 days in a row), assuming no change in the prevailing preventative and counteracting policies. However, one agent carrying the alpha (B.1.1.7) variant has a 43% chance of crossing the same threshold; a threefold increase with respect to the ancestral strain; while, one agent carrying the delta (B.1.617.2) variant has a 60% chance of the same threshold, a fourfold increase with respect to the ancestral strain. The delta variant is 50% more likely to trigger SCT than the alpha variant. Doubling the average number of daily tests from ∼ 6,000 to 12,000 results in a decrease of this SCT probability from 43 to 33% for the alpha variant. However, if the delta variant is circulating we would need an average of 100,000 daily tests to achieve a similar decrease in SCT risk. Further, achieving a full-vaccination coverage of 70% of the adult population, with a vaccine with 70% effectiveness against infection, would decrease the probability of SCT from a single seed of alpha from 43 to 20%, on par with the ancestral strain in a naive population. In contrast, for the same vaccine coverage and same effectiveness, the probability of SCT from a single seed of delta would decrease from 62 to 48%, a risk slightly above the alpha variant in a naive population. Our results demonstrate that the introduction of even a small number of people infected with high-transmission variants dramatically increases the probability of sustained community transmission in Queensland. Until very high vaccine coverage is achieved, a swift implementation of policies and interventions, together with high quarantine adherence rates, will be required to minimise the probability of sustained community transmission.

Automated detection of artefacts in neonatal EEG with residual neural networks.

BACKGROUND AND OBJECTIVE: To develop a computational algorithm that detects and identifies different artefact types in neonatal electroencephalography (EEG) signals. METHODS: As part of a larger algorithm, we trained a Residual Deep Neural Network on expert human annotations of EEG recordings from 79 term infants recorded in a neonatal intensive care unit (112 h of 18-channel recording). The network was trained using 10 fold cross validation in Matlab. Artefact types included: device interference, EMG, movement, electrode pop, and non-cortical biological rhythms. Performance was assessed by prediction statistics and further validated on a separate independent dataset of 13 term infants (143 h of 3-channel recording). EEG pre-processing steps, and other post-processing steps such as averaging probability over a temporal window, were also included in the algorithm. RESULTS: The Residual Deep Neural Network showed high accuracy (95%) when distinguishing periods of clean, artefact-free EEG from any kind of artefact, with a median accuracy for individual patient of 91% (IQR: 81%-96%). The accuracy in identifying the five different types of artefacts ranged from 57%-92%, with electrode pop being the hardest to detect and EMG being the easiest. This reflected the proportion of artefact available in the training dataset. Misclassification as clean was low for each artefact type, ranging from 1%-11%. The detection accuracy was lower on the validation set (87%). We used the algorithm to show that EEG channels located near the vertex were the least susceptible to artefact. CONCLUSION: Artefacts can be accurately and reliably identified in the neonatal EEG using a deep learning algorithm. Artefact detection algorithms can provide continuous bedside quality assessment and support EEG review by clinicians or analysis algorithms.

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.