Neonatal sleep is a crucial state that involves endogenous driven brain activity, important for neuronal survival and guidance of brain networks. Sequential EEG-sleep analysis in preterm infants provides insights into functional brain integrity and can document deviations of the biologically pre-programmed process of sleep ontogenesis during the neonatal period. Visual assessment of neonatal sleep-EEG, with integration of both cerebral and non-cerebral measures to better define neonatal state, is still considered the gold standard. Electrographic patterns evolve over time and are gradually time locked with behavioural characteristics which allow classification of quiet sleep and active sleep periods during the last 10weeks of gestation. Near term age, the neonate expresses a short ultradian sleep cycle, with two distinct active and quiet sleep, as well as brief periods of transitional or indeterminate sleep. Qualitative assessment of neonatal sleep is however challenged by biological and environmental variables that influence the expression of EEG-sleep patterns and sleep organization. Developing normative EEG-sleep data with the aid of automated analytic methods, can further improve our understanding of extra-uterine brain development and state organization under stressful or pathological conditions. Based on those developmental biomarkers of normal and abnormal brain function, research can be conducted to support and optimise sleep in the NICU, with the ultimate goal to improve therapeutic interventions and neurodevelopmental outcome.

This is the first study to present a successful method for the automated staging of four states in term-age sleep using multichannel EEG. Results suggested a benefit in incorporating transition information using an HMM, and correcting for inter-recording variability through personalized feature scaling. Determining the timing and quality of these states are indicative of developmental delays in both preterm and term-born babies that may lead to learning problems by school age.

Sleep state development in preterm neonates can provide crucial information regarding functional brain maturation and give insight into neurological well being. However, visual labeling of sleep stages from EEG requires expertise and is very time consuming, prompting the need for an automated procedure. We present a robust method for automated detection of preterm sleep from EEG, over a wide postmenstrual age (PMA = gestational age + postnatal age) range, focusing first on Quiet Sleep (QS) as an initial marker for sleep assessment. Our algorithm, CLuster-based Adaptive Sleep Staging (CLASS), detects QS if it remains relatively more discontinuous than non-QS over PMA. CLASS was optimized on a training set of 34 recordings aged 27-42 weeks PMA, and performance then assessed on a distinct test set of 55 recordings of the same age range. Results were compared to visual QS labeling from two independent raters (with inter-rater agreement Kappa = 0.93), using Sensitivity, Specificity, Detection Factor (DF = proportion of visual QS periods correctly detected by CLASS) and Misclassification Factor (MF = proportion of CLASS-detected QS periods that are misclassified). CLASS performance proved optimal across recordings at 31-38 weeks (median DF = 1.0, median MF 0-0.25, median Sensitivity 0.93-1.0, and median Specificity 0.80-0.91 across this age range), with minimal misclassifications at 35-36 weeks (median MF = 0). To illustrate the potential of CLASS in facilitating clinical research, normal maturational trends over PMA were derived from CLASS-estimated QS periods, visual QS estimates, and nonstate specific periods (containing QS and non-QS) in the EEG recording. CLASS QS trends agreed with those from visual QS, with both showing stronger correlations than nonstate specific trends. This highlights the benefit of automated QS detection for exploring brain maturation.

A convolutional neural network outperforming state-of-the-art sleep staging algorithms for both preterm and term infantsAccepted for publication in Journal of neural engineering, 2019.

Premature babies are subjected to environmental stresses that can affect brain maturation and cause abnormal neurodevelopmental outcome later in life. Better understanding this link is crucial to developing a clinical tool for early outcome estimation. We defined maturational trajectories between the electroencephalography (eeG)-derived 'brain-age' and postmenstrual age (the age since the last menstrual cycle of the mother) from longitudinal recordings during the baby's stay in the neonatal Intensive Care Unit. Data consisted of 224 recordings (65 patients) separated for normal and abnormal outcome at 9-24 months follow-up. Trajectory deviations were compared between outcome groups using the root mean squared error (RMSE) and maximum trajectory deviation (δ max). 113 features were extracted (per sleep state) to train a data-driven model that estimates brain-age, with the most prominent features identified as potential maturational and outcome-sensitive biomarkers. RMSE and δ max showed significant differences between outcome groups (cluster-based permutation test, p < 0.05). RMSE had a median (IQR) of 0.75 (0.60-1.35) weeks for normal outcome and 1.35 (1.15-1.55) for abnormal outcome, while δ max had a median of 0.90 (0.70-1.70) and 1.90 (1.20-2.90) weeks, respectively. Abnormal outcome trajectories were associated with clinically defined dysmature and disorganised EEG patterns, cementing the link between early maturational trajectories and neurodevelopmental outcome.