Persistent sleep-disordered breathing independently contributes to metabolic syndrome in prepubertal children.

BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor for metabolic syndrome (MetS) in adults, but its association in prepubertal children is still questionable due to the relatively limited cardiometabolic data available and the phenotypic heterogeneity. OBJECTIVE: To identify the role of OSA as a potential mediator of MetS in prepubertal children. METHODS: A total of 255 prepubertal children from the Childhood Adenotonsillectomy Trial were included, with standardized measurements taken before OSA treatment and 7 months later. MetS was defined if three or more of the following criteria were present: adiposity, high blood pressure, elevated glycemia, and dyslipidemia. A causal mediation analysis was conducted to assess the effect of OSA treatment on MetS. RESULTS: OSA treatment significantly impacted MetS, with the apnea-hypopnea index emerging as mediator (p = .02). This mediation role was not detected for any of the individual risk factors that define MetS. We further found that the relationship between MetS and OSA is ascribable to respiratory disturbance caused by the apnea episodes, while systemic inflammation as measured by C-reactive protein, is mediated by desaturation events and fragmented sleep. In terms of evolution, patients with MetS were significantly more likely to recover after OSA treatment (odds ratio = 2.56, 95% confidence interval [CI] 1.20-5.46; risk ratio = 2.06, 95% CI 1.19-3.54) than the opposite, patients without MetS to develop it. CONCLUSION: The findings point to a causal role of OSA in the development of metabolic dysfunction, suggesting that persistent OSA may increase the risk of MetS in prepubertal children. This mediation role implies a need for developing screening for MetS in children presenting OSA symptoms.

A deep learning model based on the combination of convolutional and recurrent neural networks to enhance pulse oximetry ability to classify sleep stages in children with sleep apnea.

Characterization of sleep stages is essential in the diagnosis of sleep-related disorders but relies on manual scoring of overnight polysomnography (PSG) recordings, which is onerous and labor-intensive. Accordingly, we aimed to develop an accurate deep-learning model for sleep staging in children suffering from pediatric obstructive sleep apnea (OSA) using pulse oximetry signals. For this purpose, pulse rate (PR) and blood oxygen saturation (SpO2) from 429 childhood OSA patients were analyzed. A CNN-RNN architecture fed with PR and SpO2 signals was developed to automatically classify wake (W), non-Rapid Eye Movement (NREM), and REM sleep stages. This architecture was composed of: (i) a convolutional neural network (CNN), which learns stage-related features from raw PR and SpO2 data; and (ii) a recurrent neural network (RNN), which models the temporal distribution of the sleep stages. The proposed CNN-RNN model showed a high performance for the automated detection of W/NREM/REM sleep stages (86.0% accuracy and 0.743 Cohen's kappa). Furthermore, the total sleep time estimated for each children using the CNN-RNN model showed high agreement with the manually derived from PSG (intra-class correlation coefficient = 0.747). These results were superior to previous works using CNN-based deep-learning models for automatic sleep staging in pediatric OSA patients from pulse oximetry signals. Therefore, the combination of CNN and RNN allows to obtain additional information from raw PR and SpO2 data related to sleep stages, thus being useful to automatically score sleep stages in pulse oximetry tests for children evaluated for suspected OSA.Clinical Relevance-This research establishes the usefulness of a CNN-RNN architecture to automatically score sleep stages in pulse oximetry tests for pediatric OSA diagnosis.

An explainable deep-learning model to stage sleep states in children and propose novel EEG-related patterns in sleep apnea.

Automatic deep-learning models used for sleep scoring in children with obstructive sleep apnea (OSA) are perceived as black boxes, limiting their implementation in clinical settings. Accordingly, we aimed to develop an accurate and interpretable deep-learning model for sleep staging in children using single-channel electroencephalogram (EEG) recordings. We used EEG signals from the Childhood Adenotonsillectomy Trial (CHAT) dataset (n = 1637) and a clinical sleep database (n = 980). Three distinct deep-learning architectures were explored to automatically classify sleep stages from a single-channel EEG data. Gradient-weighted Class Activation Mapping (Grad-CAM), an explainable artificial intelligence (XAI) algorithm, was then applied to provide an interpretation of the singular EEG patterns contributing to each predicted sleep stage. Among the tested architectures, a standard convolutional neural network (CNN) demonstrated the highest performance for automated sleep stage detection in the CHAT test set (accuracy = 86.9% and five-class kappa = 0.827). Furthermore, the CNN-based estimation of total sleep time exhibited strong agreement in the clinical dataset (intra-class correlation coefficient = 0.772). Our XAI approach using Grad-CAM effectively highlighted the EEG features associated with each sleep stage, emphasizing their influence on the CNN's decision-making process in both datasets. Grad-CAM heatmaps also allowed to identify and analyze epochs within a recording with a highly likelihood to be misclassified, revealing mixed features from different sleep stages within these epochs. Finally, Grad-CAM heatmaps unveiled novel features contributing to sleep scoring using a single EEG channel. Consequently, integrating an explainable CNN-based deep-learning model in the clinical environment could enable automatic sleep staging in pediatric sleep apnea tests.

Effect of Hypertonic Saline on Lung Function as Add-on Treatment in People With Cystic Fibrosis Receiving Dornase Alfa: A Cystic Fibrosis Foundation Patient Registry Analysis.

BACKGROUND: Introduction of novel therapies for cystic fibrosis (CF) raises the question of whether traditional treatments can be withdrawn. Nebulized hypertonic saline (HS) potentially could be discontinued in patients receiving dornase alfa (DA). RESEARCH QUESTION: In the era before modulators, did people with CF who are F508del homozygous (CFF508del) and who received DA and HS have better preserved lung function than those treated with DA only? STUDY DESIGN AND METHODS: Retrospective analysis of the Cystic Fibrosis Foundation Patient Registry data (2006-2014). Among 13,406 CFF508del with data for at least 2 consecutive years, 1,241 CFF508del had spirometry results and were treated with DA for 1 to 5 years without DA or HS during the preceding (baseline) year. Absolute FEV1 % predicted change while receiving DA and HS, relative to treatment with DA only, was the main outcome. A marginal structural model was applied to assess the effect of 1 to 5 years of HS treatment while controlling for time-dependent confounding. RESULTS: Of 1,241 CFF508del, 619 patients (median baseline age, 14.6 years; interquartile range, 6-53 years) received DA only and 622 patients (median baseline age, 14.55 years; interquartile range, 6-48.1 years) were treated with DA and HS for 1 to 5 years. After 1 year, patients receiving DA and HS showed FEV1 % predicted that averaged 6.60% lower than that in patients treated with DA only (95% CI, -8.54% to -4.66%; P < .001). Lower lung function in the former relative to the latter persisted throughout follow-up, highlighting confounding by indication. After accounting for baseline age, sex, race, DA use duration, baseline and previous year's FEV1 % predicted, and time-varying clinical characteristics, patients treated with DA and HS for 1 to 5 years were similar to those treated with DA only regarding FEV1 % predicted (year 1: mean FEV1 % predicted change, +0.53% [95% CI, -0.66% to +1.71%; P = .38]; year 5: mean FEV1 % predicted change, -1.82% [95% CI, -4.01% to +0.36%; P = .10]). INTERPRETATION: In the era before modulators, CFF508del showed no significant difference in lung function when nebulized HS was added to DA for 1 to 5 years.

Pediatric sleep apnea: Characterization of apneic events and sleep stages using heart rate variability.

Heart rate variability (HRV) is modulated by sleep stages and apneic events. Previous studies in children compared classical HRV parameters during sleep stages between obstructive sleep apnea (OSA) and controls. However, HRV-based characterization incorporating both sleep stages and apneic events has not been conducted. Furthermore, recently proposed novel HRV OSA-specific parameters have not been evaluated. Therefore, the aim of this study was to characterize and compare classic and pediatric OSA-specific HRV parameters while including both sleep stages and apneic events. A total of 1610 electrocardiograms from the Childhood Adenotonsillectomy Trial (CHAT) database were split into 10-min segments to extract HRV parameters. Segments were characterized and grouped by sleep stage (wake, W; non-rapid eye movement, NREMS; and REMS) and presence of apneic events (under 1 apneic event per segment, e/s; 1-5 e/s; 5-10 e/s; and over 10 e/s). NREMS showed significant changes in HRV parameters as apneic event frequency increased, which were less marked in REMS. In both NREMS and REMS, power in BW2, a pediatric OSA-specific frequency domain, allowed for the optimal differentiation among segments. Moreover, in the absence of apneic events, another defined band, BWRes, resulted in best differentiation between sleep stages. The clinical usefulness of segment-based HRV characterization was then confirmed by two ensemble-learning models aimed at estimating apnea-hypopnea index and classifying sleep stages, respectively. We surmise that basal sympathetic activity during REMS may mask apneic events-induced sympathetic excitation, thus highlighting the importance of incorporating sleep stages as well as apneic events when evaluating HRV in pediatric OSA.

Single-cell RNA-seq uncovers cellular heterogeneity and provides a signature for paediatric sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a highly prevalent disease and a major cause of systemic inflammation leading to neurocognitive, behavioural, metabolic and cardiovascular dysfunction in children and adults. However, the impact of OSA on the heterogeneity of circulating immune cells remains to be determined. METHODS: We applied single-cell transcriptomics analysis (scRNA-seq) to identify OSA-induced changes in transcriptional landscape in peripheral blood mononuclear cell (PBMC) composition, which uncovered severity-dependent differences in several cell lineages. Furthermore, a machine-learning approach was used to combine scRNAs-seq cell-specific markers with those differentially expressed in OSA. RESULTS: scRNA-seq demonstrated OSA-induced heterogeneity in cellular composition and enabled the identification of previously undescribed cell types in PBMCs. We identified a molecular signature consisting of 32 genes, which distinguished OSA patients from various controls with high precision (area under the curve 0.96) and accuracy (93% positive predictive value and 95% negative predictive value) in an independent PBMC bulk RNA expression dataset. CONCLUSION: OSA deregulates systemic immune function and displays a molecular signature that can be assessed in standard cellular RNA without the need for pre-analytical cell separation, thereby making the assay amenable to application in a molecular diagnostic setting.

Nocturnal oximetry parameters as predictors of sleep apnea severity in resource-limited settings.

Nocturnal oximetry is an alternative modality for evaluating obstructive sleep apnea syndrome (OSAS) severity when polysomnography is not available. The Oxygen Desaturation (≥3%) Index (ODI3) and McGill Oximetry Score (MOS) are used as predictors of moderate-to-severe OSAS (apnea-hypopnea index-AHI >5 episodes/h), an indication for adenotonsillectomy. We hypothesised that ODI3 is a better predictive parameter for AHI >5 episodes/h than the MOS. All polysomnograms performed in otherwise healthy, snoring children with tonsillar hypertrophy in a tertiary hospital (November 2014 to May 2019) were analysed. The ODI3 and MOS were derived from the oximetry channel of each polysomnogram. Logistic regression was applied to assess associations of ODI3 or MOS (predictors) with an AHI >5 episodes/h (primary outcome). Receiver operating characteristic (ROC) curves and areas under ROC curves were used to compare the ODI3 and MOS as predictors of moderate-to-severe OSAS. The optimal cut-off value for each oximetry parameter was determined using Youden's index. Polysomnograms of 112 children (median [interquartile range] age 6.1 [3.9-9.1] years; 35.7% overweight) were analysed. Moderate-to-severe OSAS prevalence was 49.1%. The ODI3 and MOS were significant predictors of moderate-to-severe OSAS after adjustment for overweight, sex, and age (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.19-1.51); and OR 4.10, 95% CI 2.06-8.15, respectively; p < 0.001 for both). Area under the ROC curve was higher for the ODI3 than for MOS (0.903 [95% CI 0.842-0.964] versus 0.745 [95% CI 0.668-0.821]; p < 0.001). Optimal cut-off values for the ODI3 and MOS were ≥4.3 episodes/h and ≥2, respectively. The ODI3 emerges as preferable or at least a complementary oximetry parameter to MOS for detecting moderate-to-severe OSAS in snoring children when polysomnography is not available.

Slow EEG Oscillation to Characterize Pediatric Sleep Apnea and Associated Cognitive Impairments.

Previous studies have suggested that the typical slow oscillations (SO) characteristics during sleep could be modified in the presence of pediatric obstructive sleep apnea (OSA). Here, we evaluate whether these modifications are significant and if they may reflect cognitive deficits. We recorded the overnight electroencephalogram (EEG) of 294 pediatric subjects (5-9 years old) using eight channels. Then, we divided the cohort in three OSA severity groups (no OSA, mild, and moderate/severe) to characterize the corresponding SO using the spectral maximum in the slow wave sleep (SWS) band δ1: 0.1-2 Hz (Maxs o), as well as the frequency where this maximum is located (FreqMaxso). Spectral entropy (SpecEn) from δ1 was also included in the analyses. A correlation analysis was performed to evaluate associations of these spectral measures with six OSA-related clinical variables and six cognitive scores. Our results indicate that Maxso could be used as a moderate/severe OSA biomarker while providing useful information regarding verbal and visuo-spatial impairments, and that FreqMaxso emerges as an even more robust indicator of visuospatial function. In addition, we uncovered novel insights regarding the ability of SpecEn in δ1 to characterize OSA-related disruption of sleep homeostasis. Our findings suggest that the information from SO may be useful to automatically characterize moderate/severe pediatric OSA and its cognitive consequences. Clinical Relevance- This study contributes towards reaching an objective quantifiable and automated assessment of the potential cognitive consequences of pediatric sleep apnea.

A 2D convolutional neural network to detect sleep apnea in children using airflow and oximetry.

The gold standard approach to diagnose obstructive sleep apnea (OSA) in children is overnight in-lab polysomnography (PSG), which is labor-intensive for clinicians and onerous to healthcare systems and families. Simplification of PSG should enhance availability and comfort, and reduce complexity and waitlists. Airflow (AF) and oximetry (SpO2) signals summarize most of the information needed to detect apneas and hypopneas, but automatic analysis of these signals using deep-learning algorithms has not been extensively investigated in the pediatric context. The aim of this study was to evaluate a convolutional neural network (CNN) architecture based on these two signals to estimate the severity of pediatric OSA. PSG-derived AF and SpO2 signals from the Childhood Adenotonsillectomy Trial (CHAT) database (1638 recordings), as well as from a clinical database (974 recordings), were analyzed. A 2D CNN fed with AF and SpO2 signals was implemented to estimate the number of apneic events, and the total apnea-hypopnea index (AHI) was estimated. A training-validation-test strategy was used to train the CNN, adjust the hyperparameters, and assess the diagnostic ability of the algorithm, respectively. Classification into four OSA severity levels (no OSA, mild, moderate, or severe) reached 4-class accuracy and Cohen's Kappa of 72.55% and 0.6011 in the CHAT test set, and 61.79% and 0.4469 in the clinical dataset, respectively. Binary classification accuracy using AHI cutoffs 1, 5 and 10 events/h ranged between 84.64% and 94.44% in CHAT, and 84.10%-90.26% in the clinical database. The proposed CNN-based architecture achieved high diagnostic ability in two independent databases, outperforming previous approaches that employed SpO2 signals alone, or other classical feature-engineering approaches. Therefore, analysis of AF and SpO2 signals using deep learning can be useful to deploy reliable computer-aided diagnostic tools for childhood OSA.

Increased incidence of pediatric narcolepsy following the 2009 H1N1 pandemic: a report from the pediatric working group of the sleep research network.

This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multicenter retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and its relationship to historical H1N1 influenza data. A total of 950 participants were included in the analysis; 487 participants were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6  ±â€… 3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (p  <  .0001) occurred over the 1998-2016 period, peaking in 2010, reflecting a 1.6-fold increase in narcolepsy incidence. In addition, there was significant seasonal variation in narcolepsy incident cases, with increased cases in spring (p  <  .05). Cross-correlation analysis demonstrated a significant correlation between monthly H1N1 infection and monthly narcolepsy incident cases (p  =  .397, p  <  .0001) with a lag time of 8 months. We conclude that there is a significant increase in pediatric narcolepsy incidence after the 2009 H1N1 pandemic in the United States. However, the magnitude of increase is lower than reported in European countries and in China. The temporal correlation between monthly H1N1 infection and monthly narcolepsy incidence, suggests that H1N1 infection may be a contributing factor to the increased pediatric narcolepsy incidence after the 2009 H1N1 pandemics.

Heart rate variability as a potential biomarker of pediatric obstructive sleep apnea resolution.

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) affects cardiac autonomic regulation, altering heart rate variability (HRV). Although changes in classical HRV parameters occur after OSA treatment, they have not been evaluated as reporters of OSA resolution. Specific frequency bands (named BW1, BW2, and BWRes) have been recently identified in OSA. We hypothesized that changes with treatment in these spectral bands can reliably identify changes in OSA severity and reflect OSA resolution. METHODS: Four hundred and four OSA children (5-9.9 years) from the prospective Childhood Adenotonsillectomy Trial were included; 206 underwent early adenotonsillectomy (eAT), while 198 underwent watchful waiting with supportive care (WWSC). HRV changes from baseline to follow-up were computed for classical and OSA-related frequency bands. Causal mediation analysis was conducted to evaluate how treatment influences HRV through mediators such as OSA resolution and changes in disease severity. Disease resolution was initially assessed by considering only obstructive events, and was followed by adding central apneas to the analyses. RESULTS: Treatment, regardless of eAT or WWSC, affects HRV activity, mainly in the specific frequency band BW2 (0.028-0.074 Hz). Furthermore, only changes in BW2 were specifically attributable to all OSA resolution mediators. HRV activity in BW2 also showed statistically significant differences between resolved and non-resolved OSA. CONCLUSIONS: OSA treatment affects HRV activity in terms of change in severity and disease resolution, especially in OSA-related BW2 frequency band. This band allowed to differentiate HRV activity between children with and without resolution, so we propose BW2 as potential biomarker of pediatric OSA resolution. CLINICAL TRIAL REGISTRATION: Childhood Adenotonsillectomy Trial, NCT00560859, https://sleepdata.org/datasets/chat.

Reliability of machine learning to diagnose pediatric obstructive sleep apnea: Systematic review and meta-analysis.

BACKGROUND: Machine-learning approaches have enabled promising results in efforts to simplify the diagnosis of pediatric obstructive sleep apnea (OSA). A comprehensive review and analysis of such studies increase the confidence level of practitioners and healthcare providers in the implementation of these methodologies in clinical practice. OBJECTIVE: To assess the reliability of machine-learning-based methods to detect pediatric OSA. DATA SOURCES: Two researchers conducted an electronic search on the Web of Science and Scopus using term, and studies were reviewed along with their bibliographic references. ELIGIBILITY CRITERIA: Articles or reviews (Year 2000 onwards) that applied machine learning to detect pediatric OSA; reported data included information enabling derivation of true positive, false negative, true negative, and false positive cases; polysomnography served as diagnostic standard. APPRAISAL AND SYNTHESIS METHODS: Pooled sensitivities and specificities were computed for three apnea-hypopnea index (AHI) thresholds: 1 event/hour (e/h), 5 e/h, and 10 e/h. Random-effect models were assumed. Summary receiver-operating characteristics (SROC) analyses were also conducted. Heterogeneity (I 2 ) was evaluated, and publication bias was corrected (trim and fill). RESULTS: Nineteen studies were finally retained, involving 4767 different pediatric sleep studies. Machine learning improved diagnostic performance as OSA severity criteria increased reaching optimal values for AHI = 10 e/h (0.652 sensitivity; 0.931 specificity; and 0.940 area under the SROC curve). Publication bias correction had minor effect on summary statistics, but high heterogeneity was observed among the studies.

Automatic Sleep Staging in Children with Sleep Apnea using Photoplethysmography and Convolutional Neural Networks.

Sleep staging is of paramount importance in children with suspicion of pediatric obstructive sleep apnea (OSA). Complexity, cost, and intrusiveness of overnight polysomnography (PSG), the gold standard, have led to the search for alternative tests. In this sense, the photoplethysmography signal (PPG) carries useful information about the autonomous nervous activity associated to sleep stages and can be easily acquired in pediatric sleep apnea home tests with a pulse oximeter. In this study, we use the PPG signal along with convolutional neural networks (CNN), a deep-learning technique, for the automatic identification of the three main levels of sleep: wake (W), rapid eye movement (REM), and non-REM sleep. A database of 366 PPG recordings from pediatric OSA patients is involved in the study. A CNN architecture was trained using 30-s epochs from the PPG signal for three-stage sleep classification. This model showed a promising diagnostic performance in an independent test set, with 78.2% accuracy and 0.57 Cohen's kappa for W/NREM/REM classification. Furthermore, the percentage of time in wake stage obtained for each subject showed no statistically significant differences with the manually scored from PSG. These results were superior to the only state-of-the-art study focused on the analysis of the PPG signal in the automated detection of sleep stages in children suffering from OSA. This suggests that CNN can be used along with PPG recordings for sleep stages scoring in pediatric home sleep apnea tests.

Erratum: Martín-Montero et al. Bispectral Analysis of Heart Rate Variability to Characterize and Help Diagnose Pediatric Sleep Apnea. Entropy 2021, 23, 1016.

The author wishes to make the following correction to this paper [...].

Pediatric Sleep Apnea: The Overnight Electroencephalogram as a Phenotypic Biomarker.

Pediatric obstructive sleep apnea (OSA) is a prevalent disorder that disrupts sleep and is associated with neurocognitive and behavioral negative consequences, potentially hampering the development of children for years. However, its relationships with sleep electroencephalogram (EEG) have been scarcely investigated. Here, our main objective was to characterize the overnight EEG of OSA-affected children and its putative relationships with polysomnographic measures and cognitive functions. A two-step analysis involving 294 children (176 controls, 57% males, age range: 5-9 years) was conducted for this purpose. First, the activity and irregularity of overnight EEG spectrum were characterized in the typical frequency bands by means of relative spectral power and spectral entropy, respectively: δ1 (0.1-2 Hz), δ2 (2-4 Hz), θ (4-8 Hz), α (8-13 Hz), σ (10-16 Hz), ß1 (13-19 Hz), ß2 (19-30 Hz), and γ (30-70 Hz). Then, a correlation network analysis was conducted to evaluate relationships between them, six polysomnography variables (apnea-hypopnea index, respiratory arousal index, spontaneous arousal index, overnight minimum blood oxygen saturation, wake time after sleep onset, and sleep efficiency), and six cognitive scores (differential ability scales, Peabody picture vocabulary test, expressive vocabulary test, design copying, phonological processing, and tower test). We found that as the severity of the disease increases, OSA broadly affects sleep EEG to the point that the information from the different frequency bands becomes more similar, regardless of activity or irregularity. EEG activity and irregularity information from the most severely affected children were significantly associated with polysomnographic variables, which were coherent with both micro and macro sleep disruptions. We hypothesize that the EEG changes caused by OSA could be related to the occurrence of respiratory-related arousals, as well as thalamic inhibition in the slow oscillation generation due to increases in arousal levels aimed at recovery from respiratory events. Furthermore, relationships between sleep EEG and cognitive scores emerged regarding language, visual-spatial processing, and executive function with pronounced associations found with EEG irregularity in δ1 (Peabody picture vocabulary test and expressive vocabulary test maximum absolute correlations 0.61 and 0.54) and ß2 (phonological processing, 0.74; design copying, 0.65; and Tow 0.52). Our results show that overnight EEG informs both sleep alterations and cognitive effects of pediatric OSA. Moreover, EEG irregularity provides new information that complements and expands the classic EEG activity analysis. These findings lay the foundation for the use of sleep EEG to assess cognitive changes in pediatric OSA.

Bispectral Analysis of Heart Rate Variability to Characterize and Help Diagnose Pediatric Sleep Apnea.

Pediatric obstructive sleep apnea (OSA) is a breathing disorder that alters heart rate variability (HRV) dynamics during sleep. HRV in children is commonly assessed through conventional spectral analysis. However, bispectral analysis provides both linearity and stationarity information and has not been applied to the assessment of HRV in pediatric OSA. Here, this work aimed to assess HRV using bispectral analysis in children with OSA for signal characterization and diagnostic purposes in two large pediatric databases (0-13 years). The first database (training set) was composed of 981 overnight ECG recordings obtained during polysomnography. The second database (test set) was a subset of the Childhood Adenotonsillectomy Trial database (757 children). We characterized three bispectral regions based on the classic HRV frequency ranges (very low frequency: 0-0.04 Hz; low frequency: 0.04-0.15 Hz; and high frequency: 0.15-0.40 Hz), as well as three OSA-specific frequency ranges obtained in recent studies (BW1: 0.001-0.005 Hz; BW2: 0.028-0.074 Hz; BWRes: a subject-adaptive respiratory region). In each region, up to 14 bispectral features were computed. The fast correlation-based filter was applied to the features obtained from the classic and OSA-specific regions, showing complementary information regarding OSA alterations in HRV. This information was then used to train multi-layer perceptron (MLP) neural networks aimed at automatically detecting pediatric OSA using three clinically defined severity classifiers. Both classic and OSA-specific MLP models showed high and similar accuracy (Acc) and areas under the receiver operating characteristic curve (AUCs) for moderate (classic regions: Acc = 81.0%, AUC = 0.774; OSA-specific regions: Acc = 81.0%, AUC = 0.791) and severe (classic regions: Acc = 91.7%, AUC = 0.847; OSA-specific regions: Acc = 89.3%, AUC = 0.841) OSA levels. Thus, the current findings highlight the usefulness of bispectral analysis on HRV to characterize and diagnose pediatric OSA.