Disrupted sleep patterns and atypical electroencephalograms in children admitted to the pediatric intensive care unit: an observational cohort study

Disrupted sleep patterns and atypical electroencephalograms in children admitted to the pediatric intensive care unit: an observational cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Disrupted sleep patterns and atypical electroencephalograms in children admitted to the pediatric intensive care unit: an observational cohort study Eris van Twist, Arnout B.G. Cramer, Sascha C.A.T. Verbruggen, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8174098/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose : To describe sleep (disruptions) in critically ill and non-critically ill hospitalized children, by comparing sleep parameters to reference ranges of healthy children. Methods: Observational cohort study in a tertiary, university children’s hospital. Twenty-five critically ill children with expected PICU stay ≥ 48 hours who underwent 24-hour polysomnography (PSG) and 120 non-critically ill children who underwent diagnostic PSG between May 2017 and June 2021 for suspected sleep disordered breathing (SDB) were included. In both groups, nighttime sleep parameters were determined and compared to age-specific reference ranges obtained from literature. Results: Among critically ill children, comparison to reference ranges showed reduced rapid-eye-movement (REM) sleep (24, 96%) and, in those with discernable non-REM stages, reduced non-REM 3 sleep (4 of 6, 67%). Median nighttime sleep accounted for 50.9% (interquartile range (IQR) 49.5–55.5) of total 24-hour sleep. Moreover, EEG abnormalities were prominent (19, 76%), including abundant slow-wave activity (9, 36%), lacking sleep spindles (6, 24%) and/or K-complexes (2, 8%) and abnormal background EEG with persistent theta and delta activity (2, 8%). In non-critically ill children with suspected SDB, comparison to reference ranges showed reductions in REM sleep (age ≤ 6 months), reduced mean sleep period duration (age ≥ 1 year), and low sleep efficiency and high awakening index in older children. Conclusions: Critically ill children exhibit disrupted sleep architecture, loss of day-night variation and atypical EEG. Non-critically ill children mainly exhibit fragmented and reduced sleep. These findings foster better understanding of how critical illness and the hospital environment affect sleep in children. pediatric intensive care unit critically ill children sleep polysomnography electroencephalogram What is Known – What is New Sleep in the PICU is frequently disrupted, but detailed PSG data in critically ill children are limited, often exclude young infants and patients with CNS injury, and lack EEG assessment. This study compares sleep parameters of critically ill and non-critically ill hospitalized children to reference ranges of healthy controls. Critically ill children show reduced REM and N3 sleep, sleep fragmentation, loss of day-night variation and EEG abnormalities. Introduction Sleep may play a pivotal role in recovery from illness, considering its essential roles in tissue repair, immune function, cognitive function, pain management and hormonal regulation.[ 1 – 3 ] However, critically ill children admitted to the pediatric intensive care unit (PICU) are at risk of disrupted and even abnormal sleep due to pathological, environmental and pharmacological factors.[ 4 – 6 ] While these children may frequently exhibit the behavioural state of sleep on account of continuous sedation, this apparent sleep may restorative qualities.[ 7 ] Unfortunately, detailed understanding of what sleep during critical illness and sedation in a hospital environment entails in children is currently lacking.[ 7 , 8 ] Only five studies have described sleep in the PICU using gold standard overnight polysomnography (PSG) testing, reporting sleep fragmentation, reduced rapid-eye-movement (REM) sleep and a loss of circadian rhythm.[ 9 – 13 ] However, these studies typically excluded infants under three months of age and children with central nervous system (CNS) injuries, who comprise a substantial portion of PICU admissions. Such exclusions may be motivated by the difficulty of sleep scoring in the presence of atypical electroencephalogram (EEG) patterns, although none of the studies reported on this.[ 14 – 16 ] Previously published automated sleep scoring algorithms using EEG also performed poorly in critically ill children as compared to non-critically ill children, suggesting fundamental differences in sleep and EEG patterns.[ 17 – 19 ] Relative contributions of critical illness, sedation and the hospital environment to these differences are yet to be disentangled. The present study describes sleep (disruptions) in critically ill children, including young infants and patients with CNS injury, and in non-critically ill hospitalized children, by comparing parameters of sleep quality and quantity with age-specific reference ranges. Underlying EEG patterns are assessed for atypical features to determine sleep scoring feasibility. The findings provide insight into how critical illness and the hospital environment may contribute to sleep disruptions. Methods Study design Observational cohort study conducted at Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands in accordance with the 1975 Helsinki Declaration and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.[ 20 ] Two populations were studied: critically ill children and non-critically ill children with suspected sleep disordered breathing (SDB), hereafter referred to as PICU and SDB group, respectively. Sleep measurements in the PICU group were obtained during two clinical studies: the Critical Clock study (Netherlands Trial Register (NTR): NL8533) investigating circadian rhythm; and the ContInNuPIC study (NTR NL7877) investigating intermittent feeding with overnight fasting. Both studies were approved by the appropriate review committees (NL72302.000.19, “ContInNuPIC”, 2020; NL72597.078.20, “Critical Clock”, 2020). Written informed consent was obtained from patients and/or parents or legal guardians. Separate consent was obtained for PSG. In the SDB group, sleep measurements were obtained from a retrospective database, with consent waived by the Erasmus MC Medical Ethics Committee (MEC-2021-0121, “Sleep studies”, 2021). Study population PICU group In the PICU group, eligible patients were critically ill children (aged term to 18 years) admitted to the PICU with expected stay ≥ 48 hours. Exclusion criteria for ContInNuPIC mainly concerned contra-indications for prolonged fasting.[ 21 ] Exclusion criteria for Critical Clock were the diagnosis of a syndrome associated with severe mental retardation (trisomy 21 was not an exclusion criterion), hydrocortisone use in the three days prior to admission, melatonin use within 24 hours prior to admission, weight < 2.0 kg and patients expected not to receive an arterial line. The criteria were intended to exclude pre-existent circadian rhythm disruptions and to minimize the burden of blood sampling. Both studies also excluded patients transferred from another PICU, patients participating in trials with conflicting study procedures and previously included patients. In addition to sleep measurements, medical records were screened for the following: age, gender, private room or ward, diagnosis upon admission, Pediatric Index of Mortality 3 (PIM3) score, Pediatric Logistic Organ Dysfunction 2 (PELOD-2) score from the day of PSG, CNS injury, sedative and norepinephrine dosage during the PSG (cumulative dose from noon to noon), ventilator support and duration of PICU stay. Duration of mechanical ventilation and PICU stay were counted from the day of PSG and censored on study day 31 as this was the follow-up limit. Duration of PICU stay was only counted when patients required critical care, i.e. not when they were awaiting transfer. Death was treated as a competing risk factor and also censored on day 31. SDB group In the SDB group, sleep measurements were obtained from non-critically ill children who underwent PSG for diagnostic purposes between May 2017 and June 2021. Age categories were established: 0–2 months, 2–6 months, 6–12 months, 1–2 years, 3–4 years, 5–8 years, 9–12 years and 13–18 years.[ 22 ] Fifteen recordings of distinct patients were randomly collected per age category (120 in total). If patients had undergone multiple PSGs, the last one was used. In addition, medical records were screened for age, gender, PSG indication and possible diagnosis of epilepsy or neurocognitive impairment. Sleep measurement All PSGs were recorded at 250 or 256 Hz (Brain RT, OSG, Rumst, Belgium or Morpheus, Micromed S.p.A., Treviso, Italy) and scored conform the American Academy of Sleep Medicine (AASM) criteria.[ 23 ] In the PICU group, patients underwent sleep measurement with 24-hour PSG using optional EEG derivations.[ 23 ] Sleep scoring was performed by a European Sleep Research Society certified and experienced sleep technologist (KB) and reviewed by a clinical neurophysiologist (DS). Both were blinded to subject characteristics other than age and gender. In the SDB group, sleep measurements were conducted with recommended EEG derivations in a high or medium care unit.[ 23 ] Scoring was performed by sleep technicians under supervision of a clinical neurophysiologist. All sleep was scored into REM and non-REM (NREM) stages 1–3 (N1-3). The transitional sleep stage for young infants (age < 2 months) is not used in our center. Epochs meeting criteria for transitional sleep were instead scored as NREM sleep. If abnormalities affected EEG features used for sleep scoring, scoring was based on remaining features. Not scoring or scoring epochs as unclassified NREM sleep (N) was minimized. Scored sleep measurements were extracted for analysis from RT Software Suite v4.05.00. Sleep characteristics Parameters of sleep quality and quantity were derived from scored PSGs. Total sleep time (TST) was calculated for the entire recording in the SDB group and for both the entire recording and for nighttime in the PICU group. Other parameters were calculated for nighttime only for maximal comparability to reference ranges. Nighttime was defined as 21:00 to 07:00 for the PICU group, and as mean PSG start time until mean PSG end time for the SDB group. Sleep parameters included the proportion of sleep stages for REM, NREM, N1, N2 and N3 relative to nighttime TST; sleep proportion (nighttime TST as a proportion of TST in entire recording, corrected for daytime and nighttime measurement duration); sleep period (continuous sleep between two wake epochs); sleep period duration (time from first to last sleep epoch), awakening index (number of awakenings per hour of TST of entire recording) and sleep efficiency (nighttime TST as a proportion of sleep period duration). Reference ranges of sleep parameters were obtained from studies with PSG-based sleep measurement, as detailed in Supplemental Methods A. [ 24 – 27 ] Statistical analysis Descriptive statistics were reported as count (percentage) and mean (standard deviation (SD)) or median (first quartile, third quartile (Q1-Q3)). The primary outcome was the deviation from normal sleep during critical illness, assessed by comparing the PICU group to reference ranges.[ 24 – 27 ] The secondary outcome was deviation from normal sleep in the SDB population, assessed by comparison of mean (SD) sleep parameters per age group to the reference ranges. Sleep parameter values were considered abnormal when exceeding the mean with 2 SD, the 5th to 95th percentile or the range, whichever was reported. Nighttime sleep proportion ≥ 50% of total sleep signified no day-night variation. Analyses were conducted in python (version 3.11) and R (version 4.3.0), with packages listed in Supplemental Methods B . Results Study population Between May 2020 and July 2022, 140 and 25 PICU patients were included in the ContInNuPIC and Critical Clock study respectively. Sleep measurements were feasible in 34 patients and ultimately 25 measurements conducted in distinct patients were included ( Supplemental Figure S1 ) . Characteristics of the PICU and SDB group are reported in Table 1 . In the PICU group, age varied between 3 days and 17 years, with median 3.6 (1.0, 20.4) months. Six patients (24.0%) had CNS injury and five (20.0%) encephalopathy. Most PICU patients received sedative medication, primarily midazolam (16, 64.0%) and various opioids (18, 72.0%). In the SDB group, characteristics varied across age categories (Table 2 ). In total, 35 children (29.2%) had neurocognitive impairment and eight (6.7%) had a history of epilepsy. PSG was mainly indicated for suspected airway obstruction (62, 51.7%). Fifteen children (12.5%) were already asleep when PSG recordings started. Twelve (10.0%) children had obstructive sleep apnea (OSA) during PSG, of which five severe, three moderate and four mild. Table 1 Patient characteristics of the PICU and SDB group Characteristic PICU group SDB group Sample size 25 120 Female gender 13 (52.0%) 59 (49.2%) Age (months) 3.6 (1.0, 20.4) 36.7 (6.1–107.7) Indication of PICU admission/PSG recording N/A Cardiac/cardiothoracic surgery 8 (32.0%) 0 (0.0%) Abdominal surgery 1 (4.0%) 0 (0.0%) Respiratory/pulmonary 7 (28.0%) 11 (9.2%) Infectious 4 (16.0%) 0 (0.0%) Neurological/neuromuscular 3 (12.0%) 16 (13.3%) Metabolic 1 (4.0%) 0 (0.0%) Oncological 1 (4.0%) 0 (0.0%) Airway obstruction 0 (0.0%) 62 (51.7%) Central sleep apnea 0 (0.0%) 15 (12.5) Day of sleep measurement 3 (2, 7) N/A Type of room (multi-patient ward) 17 (68.0%) 7 (5.0%) Study group ContInNuPIC: intervention (nighttime fasting) 7 (28.0%) N/A ContInNuPIC: control (day and night feeding) 14 (56.0%) N/A Critical Clock 4 (16.0%) N/A PIM3 score -3.57 (-4.45, -1.87) N/A PIM3 mortality risk 0.03 (0.01, 0.13) N/A PELOD-2 score 7 (6, 9) N/A Mechanical ventilation during measurement (including non-invasive BiPAP) 20 (80.0%) N/A Sedative use 3 n Dose Esketamine (mg/kg/day) 7 6.05 (4.03, 9.80) N/A Fentanyl (µg/kg/day) 2 (3.85, 4.22) N/A Midazolam (µg/kg/day) 16 3.53 (2.33, 4.57) N/A Morphine (µg/kg/day) 14 229 (137, 242) N/A Propofol (mg/kg/day) 1 2,97 N/A Remifentanil (µg/kg/day) 4 167 (108, 223) N/A Norepinephrine 3 (mg/kg/day) 4 3.80 (2.01, 223) N/A Length of PICU stay (days) 12.5 (5, 26.25) N/A Data are presented as n (%) or median (Q, Q3) where applicable (N/A indicates not applicable). BiPAP = Bilevel Positive Airway Pressure; CNS = central nervous system; PELOD = Paediatric Logistic Organ Dysfunction; PICU = pediatric intensive care unit; PIM3 = Paediatric Index of Mortality 3. Table 2 Demographic characteristics of the control group Age category Neurocognitive impairment History of epilepsy PSG indication OSA Airway obstruction Neuromuscular disease Pulmonary disease Central sleep apnea 0–2 months 5 (33.3%) 2 (13.3%) 10 (66.7%) 4 (26.7%) 0 (0.0%) 4 (26.7%) 2 (13.3%) 2–6 months 8 (53.3%) 1 (6.7%) 5 (33.3%) 3 (20.0%) 2 (13.3%) 4 (26.7%) 2 (13.3%) 6–12 months 3 (20.0%) 0 (0.0%) 4 (26.7%) 1 (6.7%) 5 (33.3%) 2 (13.3%) 1 (6.7%) 1–3 years 4 (26.7%) 0 (0.0%) 12 (80.0%) 3 (20.0%) 1 (6.7%) 1 (6.7%) 3 (20.0%) 3–5 years 3 (20.0%) 3 (20.0%) 12 (80.0%) 1 (6.7%) 0 (0.0%) 1 (6.7%) 1 (6.7%) 5–9 years 6 (40.0%) 1 (6.7%) 9 (60.0%) 2 (13.3%) 0 (0.0%) 0 (0.0%) 2 (13.3%) 9–13 years 3 (20.0%) 1 (6.7%) 4 (26.7%) 0 (0.0%) 2 (13.3%) 1 (6.7%) 0 (0.0%) 13–18 years 3 (20.0%) 0 (0.0%) 6 (40.0%) 2 (13.3%) 1 (6.7%) 2 (13.3%) 1 (6.7%) Total 35 (29.2%) 8 (6.7%) 62 (51.7%) 16 (13.3%) 11 (9.2%) 15 (12.5%) 12 (10%) Data are presented as n (%). Note that there are 15 children per age category and 120 children in total. PSG = polysomnography; OSA = obstructive sleep apnea. Sleep characteristics in critically ill children Results of primary analysis showed deviations from normal sleep during critical illness (Table 3 and Supplemental Table S2 ). Nighttime TST appeared normal, with only four (16.0%) children sleeping less, but day-night variation was absent as median nighttime sleep was only 50.9% (49.5, 55.5) of 24-hour TST. This led to high TST over 24 hours. REM sleep was considerable reduced in nearly all (24, 96.0%) patients and occasionally (6, 24.0%) absent, while NREM sleep was increased (20, 80.0%). In nine patients where NREM stages were discernable we observed more N1 (5 of 9, 55.6%) and N2 (4 of 9, 44.4%) but less N3 sleep (6 of 9, 66.7%). Reduced N3 sleep was prominent in patient with CNS injury (3 of 6, 50.0%), alongside reduced REM (6 of 6, 100.0%) and increased NREM or N1 and N2 sleep (4 of 6, 66.7%). In young infants up to one month, similar patterns in REM and NREM sleep were observed, with normal (4 of 6, 66.7%) to high (2 of 6, 33.3%) sleep efficiency. In patients older than one month, sleep efficiency was mainly reduced (10 of 19, 53.0%). Table 3 Selection of sleep parameters of critically ill children compared to literature reference ranges Participant/Age Nighttime TST min (%24h TST) REM %TST NREM %TST N1 %TST N2 %TST N3 %TST SE % SPT 1. 0–1 months 378 (49.0) 44.8 55.2 0.0 0.0 0.0 63.1 2. 0–1 months 413.5 (49.5) 17.9 82.1 0.0 0.0 0.0 69.0 3. 0–1 months 545.5 (49.4) 37.5 62.5 0.0 0.0 0.0 91.0 4. 0–1 months 534 (50.9) 0.7 99.3 0.0 0.0 0.0 89.9 5. 0–1 months 435 (57.0) 29.4 70.6 0.0 0.0 0.0 72.6 6. 0–1 months 393 (51.1) 30.8 69.2 0.0 0.0 0.0 65.6 7. 1–2 months 405 (54.5) 24.0 76.0 0.0 0.0 0.0 71.0 8. 1–2 months 357.5 (65.8) 36.1 63.9 0.0 0.0 0.0 60.1 9. 1–2 months 437 (48.5) 25.3 74.7 0.0 0.0 0.0 72.9 10. 2–6 months 260.5 (50.6) 18.2 81.8 0.0 0.0 0.0 43.5 11. 2–6 months 543.5 (50.6) 8.5 91.5 0.0 0.0 0.0 91.0 12. 2–6 months 433 (55.7) 10.3 89.7 0.0 0.0 0.0 85.6 13. 2–6 months 385.5 (49.4) 8.7 91.3 0.0 0.0 0.0 64.3 14. 2–6 months 223.5 (44.1) 5.4 0.0 11.4 4.0 79.2 38.5 15. 2–6 months 517 (55.2) 13.7 39.1 0.0 13.4 33.8 86.2 16. 2–6 months 83 (29.2) 0.0 100.0 0.0 0.0 0.0 14.1 17. 6–12 months 366.5 (55.5) 0.0 2.9 38.6 47.1 11.5 62.3 18. 1–3 years 578.5 (51.3) 4.5 0.0 14.6 52.5 28.4 96.5 19. 1–3 years 459.5 (56.5) 11.3 0.0 16.2 53.2 19.3 77.4 20. 5–9 years 390 (50.6) 8.5 0.0 26.7 57.7 7.2 67.5 21. 9–13 years 342.5 (59.0) 0.0 0.0 42.2 54.2 3.6 57.1 22. 13–18 years 552 (50.3) 0.0 73.9 0.0 21.8 4.3 92.1 23. 13–18 years 261 (44.5) 3.8 0.0 11.1 54.4 30.7 43.5 24. 13–18 years 323 (56.4) 0.0 0.0 46.1 50.6 3.3 53.9 25. 13–18 years 575 (51.8) 0.0 100.0 0.0 0.0 0.0 95.9 Selection of nighttime sleep characteristics (columns) of individual patients (rows, in order of increasing age) and the corresponding values which are either in range (black), below range (blue) or above range (red) with regard to reference ranges of healthy controls. Grey values represent values for which no valid reference range was found. Up two months of age, we assumed differentiation of different NREM stages is not yet present in healthy children. The complete table is available in the supplements. NREM = non-rapid-eye-movement sleep (N); REM = rapid-eye-movement sleep; SE = Sleep efficiency; SPT = sleep period time; TST = total sleep time Sleep scoring in critically ill children Among PICU patients, 19 (76.0%) had abnormalities in the underlying EEG. Nine (36.0%) patients exhibited excessive slow wave activity during wake. In these patients, epochs with a marked increase in slow waves were scored N3, while remaining epochs were scored based on the presence of other features. Eight patients (32.0%) lacked specific EEG features expected for their age. Sleep spindles, expected after nine weeks, were absent in six out of seventeen patients in this age category; and K-complexes, expected after six months, were absent in two out of nine patients in this age category.[ 23 ] In four (16.0%) patients, EEG abnormalities precluded distinction of NREM sleep stages, although these should have been discernible at their age. Two of these patients, both with severe CNS injuries, displayed atypical EEG patterns with abundant theta and delta activity without sleep spindles or K-complexes. All hypnograms are available in Supplemental Figure S2 , the last hypnogram showing an older patient (patient Y) in whom NREM stages could not be distinguished. Sleep characteristics in non-critically ill children Results of secondary analysis, deviations from normal sleep in non-critically ill hospitalized children, are presented in Table 4 and Supplemental Table S3 . Children in the SDB group showed reduced proportions of REM sleep up to six months of age, lower sleep efficiency and higher awakening index above the age of nine years and shorter mean sleep period duration in all age groups for which reference values were available. Table 4 Selection of mean sleep parameters in the control group compared to literature reference ranges Age group TST min REM %TST NREM %TST N1 %TST N2 %TST N3 %TST SE % SPT 0–2 months 498.7 34.4 59.5 0.5 0.0 5.6 71.7 2–6 months 524.6 32.0 20.1 5.4 14.0 28.5 81.7 6–12 months 535.0 28.7 0.0 11.5 27.5 32.2 85.5 1–3 years 493.3 22.6 0.0 15.1 28.9 33.4 83.9 3–5 years 540.5 21.6 0.0 9.5 27.3 41.6 89.6 5–9 years 507.0 21.5 0.0 9.0 35.6 33.9 86.0 9–13 years 408.8 16.2 0.0 14.9 32.7 36.3 77.1 13–18 years 412.7 17.9 0.0 13.2 38.0 30.8 82.2 Selection of sleep characteristics (in columns) per age category (in rows, in order of increasing age) and the corresponding values which are either in range (black), below range (blue) or above range (red) with regard to reference ranges of healthy controls. Grey values represent values for which no valid reference range was found. Values were considered abnormal when they exceeded either mean with 2 standard deviations, the 5th to 95th percentile range or the range, whichever was reported in the respective article. AI = awakening index; NREM = non-rapid-eye-movement sleep (N); REM = rapid-eye-movement sleep; SE = Sleep efficiency; SPD = average sleep period duration; SPT = sleep period time; TST = total sleep time Discussion This observational study describes sleep (disruptions) in critically ill and non-critically ill hospitalized children aged 0 to 18 years. Through inclusion of young infants and children with CNS injury, and by reporting on the underlying EEG, this study addresses critical gaps in pediatric sleep research. Critical illness was associated with disrupted sleep, specifically reduced duration, high fragmentation and reduced REM and N3 sleep. Underlying EEGs showed frequent abnormalities, with abundant slow waves, absence of prominent sleep features and non-discernible NREM sleep. In non-critically ill children with suspected SDB, sleep was mainly disrupted by high fragmentation and occasionally reduced REM sleep. The findings obtained here align with previous sleep studies in critically ill PICU patients, reporting higher 24-hour TST, loss of day-night variation and reduced REM sleep.[ 9 – 13 ] Our study adds that young infants in the PICU tend to experience higher sleep efficiency and fewer awakenings, whilst CNS injured patients experienced less REM and N3 sleep, as compared to healthy reference ranges. Sleep efficiency is rarely reported in the PICU as it requires clearly defined sleep onset and wake periods. Yet, it was included here as a measure of sleep continuity. To account for disrupted circadian rhythm, we calculated sleep efficiency from the first to last sleep epoch during nighttime. Despite its limitations in critically ill populations, our findings of low sleep efficiency and high awakening index, particularly in children over one year, align with adult literature and one pediatric study.[ 8 , 13 ] In contrast, findings on NREM sleep and in particular N3 sleep in critically ill children deviate from previous studies. While generally N3 sleep was reduced when NREM stages were discernable, there was considerable interpatient variability (e.g. one patient spent almost 80.0% of TST in N3 sleep). Dervan et al. reported normal mean proportions of N3 sleep with similar interpatient variability as observed here, while Zhao et al. reported means of 61.1% and 83.1%.[ 12 , 13 ] These discrepancies may reflect the challenge in distinguishing pathological slow wave activity from physiological N3 sleep, potentially leading to mislabeling.[ 23 ] Therefore, the present study uniquely reported on underlying EEGs. Slow waves were in abundance among critically ill children, requiring an adaptation of sleep scoring, and may reflect sedation or analgesics, hypercapnia and/or encephalopathy.[ 28 – 31 ] Importantly, sedatives may reduce environmental sensitivity, lowering the awakening index and prolonging mean sleep periods, even for increased illness severity.[ 12 ] The observed abnormalities in underlying brain activity and overall difficulty experienced during sleep scoring in critically ill children raises concern whether the observed sleep was truly restorative sleep. The abnormal EEG patterns observed in two older patients with CNS injuries resembled non-typical sleep stages At1 and At2 described by Watson et al., which are associated with encephalopathy.[ 16 ] While their classification offers guidance for handling the most abnormal EEG patterns, it remains difficult to distinguish restorative sleep from sedation induced or pathological states. Perhaps more importantly, findings of the present study raise the question whether critically ill patients retain the capacity for healthy (restorative) sleep, and whether the hospital environment harbors modifiable targets to improve this. The hospital environment and iatrogenic factors likely contribute to sleep disruptions.[ 32 , 33 ] In non-critically ill children exposed to a high or medium care unit, we observed reduced REM sleep up to six months of age. Normally, REM sleep typically reduces from around 50.0% in the neonatal period to a stable 20.0% at two years of age.[ 34 ] In non-critically ill children aged one year and older, mean sleep period durations were reduced and in the ages nine to eighteen years sleep efficiency was reduced due to high fragmentation. While these disruptions may be due to underlying sleep disorders, such as SDB/OSA, the influence of the hospital setting and/or PSG cannot be dismissed. Disrupted sleep can exacerbate the stress response, impair cognition and weaken the immune system, potentially prolonging admission and increasing complication risk.[ 12 , 35 – 38 ] Increased illness severity may also enhance the homeostatic process driving sleep, creating a vicious cycle in which critical illness and sleep disruption reinforce one another. It seems imminent that strategies to optimize sleep in the PICU may contribute to individual recovery trajectories and, potentially, outcomes. The present study has several strengths. Firstly, our study is the first to include patients of all ages and a wide variety of (critical) illnesses. Including a non-critically ill group provided insight into relative contributions of illness and the hospital environment to sleep disruption. Finally, the use of 24-hour PSG enabled evaluation of day-night variation, reflecting circadian rhythm. However, several limitations must be acknowledged. First, sleep is a dynamic process that changes as children grow and mature, which we aimed to describe as comprehensively as possible. The study was designed to be longitudinal, but logistical constraints resulted in single sleep measurements per patient, obtained on day 1, 3, 7 or 14 of the study. The SDB group is not a healthy population, but was nonetheless selected for methodological and ethical reasons. As fifteen children in the SDB group were already asleep when PSG started, their sleep efficiency and sleep period duration may not be accurate, therefore we averaged across age categories. Furthermore, the small sample size and heterogeneity of the cohort did not permit statistical analysis. Lastly, reference ranges were limited by differential measurement conditions and reporting standards. The present study provides valuable insight into how critical illness and the hospital environment disrupt sleep in children, which may bear implications for the standard of pediatric (critical) care. Much work remains to clarify the exact role of sleep in short- and long-term recovery from critical illness. An important step in future research is the development of patient-friendly, automated sleep measurement tools.[ 39 – 41 ] Such tools would facilitate larger, longitudinal sleep studies in the PICU, enable bedside monitoring and support personalized interventions. However, these tools require understanding and consensus on how to interpret atypical EEG patterns in critically ill children. Finally, establishing comprehensive pediatric reference values is essential, by including all sleep characteristics and preferably obtaining them over 24 hours to assess sleep disruptions. Conclusion This observational study describes sleep in critically ill and non-critically ill hospitalized children, as compared to healthy reference ranges. Critically ill children in the PICU, including young infants and CNS injured patients, exhibited EEG abnormalities, loss of REM and N3 sleep, high fragmentation and absent day-night variation. Non-critically ill children mainly showed high fragmentation and reduced sleep efficiency. Findings suggest underlying illness and sedative medications disrupt sleep, with the hospital environment likely contributing. Further research is needed to clarify how sleep affects both short- and long-term recovery from critical illness. Abbreviations AASM American Academy of Sleep Medicine AI Awakening index CNS Central nervous system EEG Electroencephalography IQR Interquartile range (Q1, Q3) MEC Medical Ethics Committee NREM Non-rapid-eye-movement OSA Obstructive sleep apnea PELOD-2 Pediatric Logistic Organ Dysfunction 2 PICU Pediatric intensive care unit PIM3 Pediatric Index of Mortality 3 PSG Polysomnography REM Rapid-eye-movement SDB Sleep disordered breathing SE Sleep efficiency SD Standard deviation SPD Sleep period duration SPT Sleep period time STROBE Strengthening the Reporting of Observational Studies in Epidemiology TST Total sleep time Declarations Authorship statement The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding statement This study was funded by the Sophia Research Foundation under grant number S19-33 and the Department of Neonatal and Pediatric Intensive Care, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands. Competing interest statement The authors have nothing to disclose. Ethics approval statement This study was performed in line with the principles of the Declaration of Helsinki. The ContInNuPIC trial was approved by the Dutch national review board, the Central Committee on Research Involving Human Subjects (NL72302.000.19). The Critical Clock study and the use of diagnostic and follow-up polysomnograms were approved by the Erasmus MC Medical Ethics Review Committee (NL72597.078.20, MEC-2020-0333 and MEC-2021-0121, respectively). Patient consent statement All ContInNuPIC and Critical Clock trial participants and/or their parents or legal guardians provided written informed consent to participate in this study and to publish individual data. Given the potential discomfort of the application and removal of the electrodes, separate consent was asked for the PSG on the day of measurement. Consent for the use of diagnostic and follow-up polysomnograms was waived due to the retrospective nature. Data availability statement Individual patient data reported in this article can be shared in the context of a collaboration, after de-identification, to researchers who provide a methodologically sound proposal and after approval by the internal scientific committee. Proposals should be addressed to the corresponding author. Data requestors must sign a data transfer agreement to gain access. References Stremler R et al (2021) Objective Sleep Characteristics and Factors Associated With Sleep Duration and Waking During Pediatric Hospitalization. JAMA Netw Open 4(4):e213924 Davis KF, Parker KP, Montgomery GL (2004) Sleep in infants and young children: Part one: normal sleep. J Pediatr Health Care 18(2):65–71 Patel AK, Shumway RV (2023) KR et al., Physiology, Sleep Stages. StatPearls, Treasure Island (FL) Kudchadkar SR, Aljohani OA, Punjabi NM (2014) Sleep of critically ill children in the pediatric intensive care unit: a systematic review. Sleep Med Rev 18(2):103–110 Cooper AB et al (2000) Sleep in critically ill patients requiring mechanical ventilation. Chest 117(3):809–818 Ambrogio C et al (2008) Assessment of sleep in ventilator-supported critically III patients. Sleep 31(11):1559–1568 Carno MA, Connolly HV (2005) Sleep and sedation in the pediatric intensive care unit. Crit Care Nurs Clin North Am 17(3):239–244 Kakar E et al (2022) Sleep assessment in critically ill adults: A systematic review and meta-analysis. J Crit Care 71:154102 Carno MA et al (2004) Sleep monitoring in children during neuromuscular blockade in the pediatric intensive care unit: a pilot study. Pediatr Crit Care Med 5(3):224–229 Gottschlich MM et al (1997) Lack of Effect of Sleep on Energy Expenditure and Physiologic Measures in Critically Ill Burn Patients. J Am Diet Assoc 97(2):131–139 Al-Samsam RH, Cullen P (2005) Sleep and adverse environmental factors in sedated mechanically ventilated pediatric intensive care patients. Pediatr Crit Care Med 6(5):562–567 Dervan LA, Wrede JE, Watson RS (2022) Sleep Architecture in Mechanically Ventilated Pediatric ICU Patients Receiving Goal-Directed, Dexmedetomidine- and Opioid-based Sedation. J Pediatr Intensive Care 11(1):32–40 Zhao X et al (2022) Sleep cycle in children with severe acute bronchopneumonia during mechanical ventilation at different depths of sedation. BMC Pediatr 22(1):589 Drouot X et al (2012) A new classification for sleep analysis in critically ill patients. Sleep Med 13(1):7–14 Watson PL et al (2013) Atypical sleep in ventilated patients: empirical electroencephalography findings and the path toward revised ICU sleep scoring criteria. Crit Care Med 41(8):1958–1967 Watson PL et al (2013) Atypical sleep in ventilated patients: empirical electroencephalography findings and the path toward revised ICU sleep scoring criteria. Crit Care Med 41(8):1958–1967 van Twist E et al (2023) An EEG-based sleep index and supervised machine learning as a suitable tool for automated sleep classification in children. J Clin Sleep Med van Twist E et al (2024) An electroencephalography-based sleep index and supervised machine learning as a suitable tool for automated sleep classification in children. J Clin Sleep Med 20(3):389–397 van Twist E et al Clinical validation of two machione learning models for automated sleep classification in critically ill children von Elm E et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370(9596):1453–1457 Veldscholte K et al (2022) Continuous Versus Intermittent Nutrition in Pediatric Intensive Care Patients: Protocol for a Randomized Controlled Trial. JMIR Res Protoc 11(6):e36229 Dereymaeker A et al (2017) Review of sleep-EEG in preterm and term neonates. Early Hum Dev 113:87–103 Berry RB, Quan SF, Abreu AR et al for the American Academy of Sleep Medicine, The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Version 2.6. 2020, American Academy of Sleep Medicine: Darien, IL Daftary AS et al (2019) Polysomnography Reference Values in Healthy Newborns. J Clin Sleep Med 15(03):437–443 Duenas-Meza E et al (2015) Overnight Polysomnographic Characteristics and Oxygen Saturation of Healthy Infants, 1 to 18 Months of Age, Born and Residing At High Altitude (2,640 Meters). Chest 148(1):120–127 Scholle S et al (2011) Normative values of polysomnographic parameters in childhood and adolescence: quantitative sleep parameters. Sleep Med 12(6):542–549 Kato I et al (2000) Frequency of obstructive and mixed sleep apneas in 1,023 infants. Sleep 23(4):487–492 Veselis RA et al (1993) The effects of midazolam on the EEG during sedation of critically ill patients. Anaesthesia 48(6):463–470 Matejcek M et al (2008) Effect of Morphine on the Electroencephalogram and Other Physiological and Behavioral Parameters. Neuropsychobiology 19(4):202–211 Wang D et al (2015) Comparing the effect of hypercapnia and hypoxia on the electroencephalogram during wakefulness. Clin Neurophysiol 126(1):103–109 Young GB (2000) The EEG in Coma. J Clin Neurophysiol 17(5):473–485 Horsten S et al (2018) Systematic review of the effects of intensive-care-unit noise on sleep of healthy subjects and the critically ill. Br J Anaesth 120(3):443–452 Stremler R et al (2021) Objective sleep characteristics and factors associated with sleep duration and waking during pediatric hospitalization. JAMA Netw Open 4(4):e213924–e213924 Chen HL et al (2022) Rapid Eye Movement Sleep during Early Life: A Comprehensive Narrative Review. Int J Environ Res Public Health, 19(20) Medic G, Wille M, Hemels ME (2017) Short- and long-term health consequences of sleep disruption. Nat Sci Sleep 9:151–161 Liu J et al (2024) Childhood sleep: physical, cognitive, and behavioral consequences and implications. World J Pediatr 20(2):122–132 Morrison AL (2004) Implications of sleep deprivation for children in the pediatric intensive care unit. Pediatr Crit Care Med 5(3):291–292 Besedovsky L, Lange T, Haack M (2019) The Sleep-Immune Crosstalk in Health and Disease. Physiol Rev 99(3):1325–1380 Reinke L et al (2014) Intensive care unit depth of sleep: proof of concept of a simple electroencephalography index in the non-sedated. Crit Care 18(2):R66 Sentner T et al (2022) The Sleep Well Baby project: an automated real-time sleep-wake state prediction algorithm in preterm infants. Sleep Wang X et al (2023) Feasibility of automated early postnatal sleep staging in extremely and very preterm neonates using dual-channel EEG. Clin Neurophysiol 146:55–64 Additional Declarations No competing interests reported. Supplementary Files SupplementsSleepdisturbance.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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What is New","content":"\u003cul\u003e\n \u003cli\u003eSleep in the PICU is frequently disrupted, but detailed PSG data in critically ill children are limited, often exclude young infants and patients with CNS injury, and lack EEG assessment.\u003c/li\u003e\n \u003cli\u003eThis study compares sleep parameters of critically ill and non-critically ill hospitalized children to reference ranges of healthy controls.\u003c/li\u003e\n \u003cli\u003eCritically ill children show reduced REM and N3 sleep, sleep fragmentation, loss of day-night variation and EEG abnormalities.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eSleep may play a pivotal role in recovery from illness, considering its essential roles in tissue repair, immune function, cognitive function, pain management and hormonal regulation.[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] However, critically ill children admitted to the pediatric intensive care unit (PICU) are at risk of disrupted and even abnormal sleep due to pathological, environmental and pharmacological factors.[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] While these children may frequently exhibit the behavioural state of sleep on account of continuous sedation, this apparent sleep may restorative qualities.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Unfortunately, detailed understanding of what sleep during critical illness and sedation in a hospital environment entails in children is currently lacking.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eOnly five studies have described sleep in the PICU using gold standard overnight polysomnography (PSG) testing, reporting sleep fragmentation, reduced rapid-eye-movement (REM) sleep and a loss of circadian rhythm.[\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] However, these studies typically excluded infants under three months of age and children with central nervous system (CNS) injuries, who comprise a substantial portion of PICU admissions. Such exclusions may be motivated by the difficulty of sleep scoring in the presence of atypical electroencephalogram (EEG) patterns, although none of the studies reported on this.[\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] Previously published automated sleep scoring algorithms using EEG also performed poorly in critically ill children as compared to non-critically ill children, suggesting fundamental differences in sleep and EEG patterns.[\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] Relative contributions of critical illness, sedation and the hospital environment to these differences are yet to be disentangled.\u003c/p\u003e\u003cp\u003eThe present study describes sleep (disruptions) in critically ill children, including young infants and patients with CNS injury, and in non-critically ill hospitalized children, by comparing parameters of sleep quality and quantity with age-specific reference ranges. Underlying EEG patterns are assessed for atypical features to determine sleep scoring feasibility. The findings provide insight into how critical illness and the hospital environment may contribute to sleep disruptions.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003e Observational cohort study conducted at Erasmus MC Sophia Children\u0026rsquo;s Hospital, Rotterdam, The Netherlands in accordance with the 1975 Helsinki Declaration and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] Two populations were studied: critically ill children and non-critically ill children with suspected sleep disordered breathing (SDB), hereafter referred to as PICU and SDB group, respectively. Sleep measurements in the PICU group were obtained during two clinical studies: the Critical Clock study (Netherlands Trial Register (NTR): NL8533) investigating circadian rhythm; and the ContInNuPIC study (NTR NL7877) investigating intermittent feeding with overnight fasting. Both studies were approved by the appropriate review committees (NL72302.000.19, \u0026ldquo;ContInNuPIC\u0026rdquo;, 2020; NL72597.078.20, \u0026ldquo;Critical Clock\u0026rdquo;, 2020). Written informed consent was obtained from patients and/or parents or legal guardians. Separate consent was obtained for PSG. In the SDB group, sleep measurements were obtained from a retrospective database, with consent waived by the Erasmus MC Medical Ethics Committee (MEC-2021-0121, \u0026ldquo;Sleep studies\u0026rdquo;, 2021).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy population\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003ePICU group\u003c/h2\u003e\u003cp\u003eIn the PICU group, eligible patients were critically ill children (aged term to 18 years) admitted to the PICU with expected stay\u0026thinsp;\u0026ge;\u0026thinsp;48 hours. Exclusion criteria for ContInNuPIC mainly concerned contra-indications for prolonged fasting.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Exclusion criteria for Critical Clock were the diagnosis of a syndrome associated with severe mental retardation (trisomy 21 was not an exclusion criterion), hydrocortisone use in the three days prior to admission, melatonin use within 24 hours prior to admission, weight\u0026thinsp;\u0026lt;\u0026thinsp;2.0 kg and patients expected not to receive an arterial line. The criteria were intended to exclude pre-existent circadian rhythm disruptions and to minimize the burden of blood sampling. Both studies also excluded patients transferred from another PICU, patients participating in trials with conflicting study procedures and previously included patients. In addition to sleep measurements, medical records were screened for the following: age, gender, private room or ward, diagnosis upon admission, Pediatric Index of Mortality 3 (PIM3) score, Pediatric Logistic Organ Dysfunction 2 (PELOD-2) score from the day of PSG, CNS injury, sedative and norepinephrine dosage during the PSG (cumulative dose from noon to noon), ventilator support and duration of PICU stay. Duration of mechanical ventilation and PICU stay were counted from the day of PSG and censored on study day 31 as this was the follow-up limit. Duration of PICU stay was only counted when patients required critical care, i.e. not when they were awaiting transfer. Death was treated as a competing risk factor and also censored on day 31.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSDB group\u003c/h3\u003e\n\u003cp\u003eIn the SDB group, sleep measurements were obtained from non-critically ill children who underwent PSG for diagnostic purposes between May 2017 and June 2021. Age categories were established: 0\u0026ndash;2 months, 2\u0026ndash;6 months, 6\u0026ndash;12 months, 1\u0026ndash;2 years, 3\u0026ndash;4 years, 5\u0026ndash;8 years, 9\u0026ndash;12 years and 13\u0026ndash;18 years.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] Fifteen recordings of distinct patients were randomly collected per age category (120 in total). If patients had undergone multiple PSGs, the last one was used. In addition, medical records were screened for age, gender, PSG indication and possible diagnosis of epilepsy or neurocognitive impairment.\u003c/p\u003e\n\u003ch3\u003eSleep measurement\u003c/h3\u003e\n\u003cp\u003eAll PSGs were recorded at 250 or 256 Hz (Brain RT, OSG, Rumst, Belgium or Morpheus, Micromed S.p.A., Treviso, Italy) and scored conform the American Academy of Sleep Medicine (AASM) criteria.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] In the PICU group, patients underwent sleep measurement with 24-hour PSG using optional EEG derivations.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Sleep scoring was performed by a European Sleep Research Society certified and experienced sleep technologist (KB) and reviewed by a clinical neurophysiologist (DS). Both were blinded to subject characteristics other than age and gender. In the SDB group, sleep measurements were conducted with recommended EEG derivations in a high or medium care unit.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Scoring was performed by sleep technicians under supervision of a clinical neurophysiologist. All sleep was scored into REM and non-REM (NREM) stages 1\u0026ndash;3 (N1-3). The transitional sleep stage for young infants (age\u0026thinsp;\u0026lt;\u0026thinsp;2 months) is not used in our center. Epochs meeting criteria for transitional sleep were instead scored as NREM sleep. If abnormalities affected EEG features used for sleep scoring, scoring was based on remaining features. Not scoring or scoring epochs as unclassified NREM sleep (N) was minimized. Scored sleep measurements were extracted for analysis from RT Software Suite v4.05.00.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eSleep characteristics\u003c/h2\u003e\u003cp\u003eParameters of sleep quality and quantity were derived from scored PSGs. Total sleep time (TST) was calculated for the entire recording in the SDB group and for both the entire recording and for nighttime in the PICU group. Other parameters were calculated for nighttime only for maximal comparability to reference ranges. Nighttime was defined as 21:00 to 07:00 for the PICU group, and as mean PSG start time until mean PSG end time for the SDB group. Sleep parameters included the proportion of sleep stages for REM, NREM, N1, N2 and N3 relative to nighttime TST; sleep proportion (nighttime TST as a proportion of TST in entire recording, corrected for daytime and nighttime measurement duration); sleep period (continuous sleep between two wake epochs); sleep period duration (time from first to last sleep epoch), awakening index (number of awakenings per hour of TST of entire recording) and sleep efficiency (nighttime TST as a proportion of sleep period duration).\u003c/p\u003e\u003cp\u003eReference ranges of sleep parameters were obtained from studies with PSG-based sleep measurement, as detailed in \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSupplemental Methods A.\u003c/span\u003e[\u003cspan additionalcitationids=\"CR25 CR26\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eDescriptive statistics were reported as count (percentage) and mean (standard deviation (SD)) or median (first quartile, third quartile (Q1-Q3)). The primary outcome was the deviation from normal sleep during critical illness, assessed by comparing the PICU group to reference ranges.[\u003cspan additionalcitationids=\"CR25 CR26\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] The secondary outcome was deviation from normal sleep in the SDB population, assessed by comparison of mean (SD) sleep parameters per age group to the reference ranges. Sleep parameter values were considered abnormal when exceeding the mean with 2 SD, the 5th to 95th percentile or the range, whichever was reported. Nighttime sleep proportion\u0026thinsp;\u0026ge;\u0026thinsp;50% of total sleep signified no day-night variation. Analyses were conducted in python (version 3.11) and R (version 4.3.0), with packages listed in \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSupplemental Methods B\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eStudy population\u003c/h2\u003e\u003cp\u003eBetween May 2020 and July 2022, 140 and 25 PICU patients were included in the ContInNuPIC and Critical Clock study respectively. Sleep measurements were feasible in 34 patients and ultimately 25 measurements conducted in distinct patients were included (\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSupplemental Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e)\u003c/span\u003e. Characteristics of the PICU and SDB group are reported in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In the PICU group, age varied between 3 days and 17 years, with median 3.6 (1.0, 20.4) months. Six patients (24.0%) had CNS injury and five (20.0%) encephalopathy. Most PICU patients received sedative medication, primarily midazolam (16, 64.0%) and various opioids (18, 72.0%). In the SDB group, characteristics varied across age categories (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In total, 35 children (29.2%) had neurocognitive impairment and eight (6.7%) had a history of epilepsy. PSG was mainly indicated for suspected airway obstruction (62, 51.7%). Fifteen children (12.5%) were already asleep when PSG recordings started. Twelve (10.0%) children had obstructive sleep apnea (OSA) during PSG, of which five severe, three moderate and four mild.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatient characteristics of the PICU and SDB group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003ePICU group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSDB group\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSample size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e120\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale gender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e13 (52.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e59 (49.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (months)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e3.6 (1.0, 20.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36.7 (6.1–107.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndication of PICU admission/PSG recording\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac/cardiothoracic surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e8 (32.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e1 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory/pulmonary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e7 (28.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11 (9.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfectious\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e4 (16.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeurological/neuromuscular\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e3 (12.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetabolic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e1 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOncological\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e1 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAirway obstruction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e62 (51.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCentral sleep apnea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (12.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay of sleep measurement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e3 (2, 7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType of room (multi-patient ward)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e17 (68.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (5.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eContInNuPIC: intervention (nighttime fasting)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e7 (28.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eContInNuPIC: control (day and night feeding)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e14 (56.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCritical Clock\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e4 (16.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePIM3 score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e-3.57 (-4.45, -1.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePIM3 mortality risk\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e0.03 (0.01, 0.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePELOD-2 score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e7 (6, 9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMechanical ventilation during measurement\u003c/p\u003e\u003cp\u003e(including non-invasive BiPAP)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e20 (80.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSedative use\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEsketamine (mg/kg/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.05 (4.03, 9.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFentanyl (µg/kg/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(3.85, 4.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMidazolam (µg/kg/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.53 (2.33, 4.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMorphine (µg/kg/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e229 (137, 242)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePropofol (mg/kg/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2,97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRemifentanil (µg/kg/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e167 (108, 223)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNorepinephrine\u003csup\u003e3\u003c/sup\u003e (mg/kg/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.80 (2.01, 223)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLength of PICU stay (days)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e12.5 (5, 26.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as n (%) or median (Q, Q3) where applicable (N/A indicates not applicable). BiPAP = Bilevel Positive Airway Pressure; CNS = central nervous system; PELOD = Paediatric Logistic Organ Dysfunction; PICU = pediatric intensive care unit; PIM3 = Paediatric Index of Mortality 3.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic characteristics of the control group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAge category\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eNeurocognitive impairment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eHistory of epilepsy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c7\" namest=\"c4\"\u003e\u003cp\u003ePSG indication\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eOSA\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAirway obstruction\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNeuromuscular disease\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePulmonary disease\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCentral sleep apnea\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0–2 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (66.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2–6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (53.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (20.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6–12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (20.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1–3 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (80.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (20.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3 (20.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3–5 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (20.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (20.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (80.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5–9 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (60.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9–13 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (20.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13–18 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (20.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eTotal\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (29.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e62 (51.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 (9.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e15 (12.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003eData are presented as n (%). Note that there are 15 children per age category and 120 children in total. PSG = polysomnography; OSA = obstructive sleep apnea.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eSleep characteristics in critically ill children\u003c/h2\u003e\u003cp\u003eResults of primary analysis showed deviations from normal sleep during critical illness (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSupplemental Table S2\u003c/span\u003e). Nighttime TST appeared normal, with only four (16.0%) children sleeping less, but day-night variation was absent as median nighttime sleep was only 50.9% (49.5, 55.5) of 24-hour TST. This led to high TST over 24 hours. REM sleep was considerable reduced in nearly all (24, 96.0%) patients and occasionally (6, 24.0%) absent, while NREM sleep was increased (20, 80.0%). In nine patients where NREM stages were discernable we observed more N1 (5 of 9, 55.6%) and N2 (4 of 9, 44.4%) but less N3 sleep (6 of 9, 66.7%). Reduced N3 sleep was prominent in patient with CNS injury (3 of 6, 50.0%), alongside reduced REM (6 of 6, 100.0%) and increased NREM or N1 and N2 sleep (4 of 6, 66.7%). In young infants up to one month, similar patterns in REM and NREM sleep were observed, with normal (4 of 6, 66.7%) to high (2 of 6, 33.3%) sleep efficiency. In patients older than one month, sleep efficiency was mainly reduced (10 of 19, 53.0%).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSelection of sleep parameters of critically ill children compared to literature reference ranges\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParticipant/Age\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNighttime TST min (%24h TST)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eREM\u003c/p\u003e\u003cp\u003e%TST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNREM\u003c/p\u003e\u003cp\u003e%TST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN1\u003c/p\u003e\u003cp\u003e%TST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN2\u003c/p\u003e\u003cp\u003e%TST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eN3\u003c/p\u003e\u003cp\u003e%TST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSE\u003c/p\u003e\u003cp\u003e% SPT\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1. 0–1 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e378 (49.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e63.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2. 0–1 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e413.5 (49.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e82.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e69.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3. 0–1 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e545.5 (49.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e62.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e91.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4. 0–1 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e534 (50.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e99.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e89.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5. 0–1 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e435 (57.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e72.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6. 0–1 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e393 (51.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e69.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e65.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7. 1–2 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e405 (54.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e71.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8. 1–2 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e357.5 (65.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e63.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e60.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9. 1–2 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e437 (48.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e72.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10. 2–6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e260.5 (50.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e81.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e43.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11. 2–6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e543.5 (50.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e91.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e91.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12. 2–6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e433 (55.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e89.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e85.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13. 2–6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e385.5 (49.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e91.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e64.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e14. 2–6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e223.5 (44.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e79.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e38.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e15. 2–6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e517 (55.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e33.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e86.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e16. 2–6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83 (29.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e14.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e17. 6–12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e366.5 (55.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e47.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e62.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e18. 1–3 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e578.5 (51.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e52.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e28.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e96.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e19. 1–3 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e459.5 (56.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e53.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e19.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e77.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e20. 5–9 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e390 (50.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e26.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e57.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e67.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e21. 9–13 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e342.5 (59.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e42.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e54.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e57.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e22. 13–18 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e552 (50.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e73.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e21.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e92.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e23. 13–18 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e261 (44.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e54.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e30.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e43.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24. 13–18 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e323 (56.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e50.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e53.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e25. 13–18 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e575 (51.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e95.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003eSelection of nighttime sleep characteristics (columns) of individual patients (rows, in order of increasing age) and the corresponding values which are either in range (black), below range (blue) or above range (red) with regard to reference ranges of healthy controls. Grey values represent values for which no valid reference range was found. Up two months of age, we assumed differentiation of different NREM stages is not yet present in healthy children. The complete table is available in the supplements. NREM = non-rapid-eye-movement sleep (N); REM = rapid-eye-movement sleep; SE = Sleep efficiency; SPT = sleep period time; TST = total sleep time\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eSleep scoring in critically ill children\u003c/h2\u003e\u003cp\u003eAmong PICU patients, 19 (76.0%) had abnormalities in the underlying EEG. Nine (36.0%) patients exhibited excessive slow wave activity during wake. In these patients, epochs with a marked increase in slow waves were scored N3, while remaining epochs were scored based on the presence of other features. Eight patients (32.0%) lacked specific EEG features expected for their age. Sleep spindles, expected after nine weeks, were absent in six out of seventeen patients in this age category; and K-complexes, expected after six months, were absent in two out of nine patients in this age category.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] In four (16.0%) patients, EEG abnormalities precluded distinction of NREM sleep stages, although these should have been discernible at their age. Two of these patients, both with severe CNS injuries, displayed atypical EEG patterns with abundant theta and delta activity without sleep spindles or K-complexes. All hypnograms are available in \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSupplemental Figure S2\u003c/span\u003e, the last hypnogram showing an older patient (patient Y) in whom NREM stages could not be distinguished.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eSleep characteristics in non-critically ill children\u003c/h2\u003e\u003cp\u003eResults of secondary analysis, deviations from normal sleep in non-critically ill hospitalized children, are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSupplemental Table S3\u003c/span\u003e. Children in the SDB group showed reduced proportions of REM sleep up to six months of age, lower sleep efficiency and higher awakening index above the age of nine years and shorter mean sleep period duration in all age groups for which reference values were available.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSelection of mean sleep parameters in the control group compared to literature reference ranges\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTST\u003c/p\u003e\u003cp\u003emin\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eREM\u003c/p\u003e\u003cp\u003e%TST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNREM\u003c/p\u003e\u003cp\u003e%TST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN1\u003c/p\u003e\u003cp\u003e%TST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN2\u003c/p\u003e\u003cp\u003e%TST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eN3\u003c/p\u003e\u003cp\u003e%TST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSE\u003c/p\u003e\u003cp\u003e% SPT\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0–2 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e498.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e59.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e0.5\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003e5.6\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e71.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2–6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e524.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e20.1\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e5.4\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003e14.0\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003e28.5\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e81.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6–12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e535.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e11.5\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003e27.5\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003e32.2\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e85.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1–3 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e493.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e28.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e33.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e83.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3–5 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e540.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e41.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e89.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5–9 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e507.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e35.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e33.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e86.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9–13 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e408.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e32.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e36.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e77.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13–18 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e412.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e38.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e30.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e82.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003eSelection of sleep characteristics (in columns) per age category (in rows, in order of increasing age) and the corresponding values which are either in range (black), below range (blue) or above range (red) with regard to reference ranges of healthy controls. Grey values represent values for which no valid reference range was found. Values were considered abnormal when they exceeded either mean with 2 standard deviations, the 5th to 95th percentile range or the range, whichever was reported in the respective article. AI = awakening index; NREM = non-rapid-eye-movement sleep (N); REM = rapid-eye-movement sleep; SE = Sleep efficiency; SPD = average sleep period duration; SPT = sleep period time; TST = total sleep time\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis observational study describes sleep (disruptions) in critically ill and non-critically ill hospitalized children aged 0 to 18 years. Through inclusion of young infants and children with CNS injury, and by reporting on the underlying EEG, this study addresses critical gaps in pediatric sleep research. Critical illness was associated with disrupted sleep, specifically reduced duration, high fragmentation and reduced REM and N3 sleep. Underlying EEGs showed frequent abnormalities, with abundant slow waves, absence of prominent sleep features and non-discernible NREM sleep. In non-critically ill children with suspected SDB, sleep was mainly disrupted by high fragmentation and occasionally reduced REM sleep.\u003c/p\u003e\u003cp\u003eThe findings obtained here align with previous sleep studies in critically ill PICU patients, reporting higher 24-hour TST, loss of day-night variation and reduced REM sleep.[\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e–\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Our study adds that young infants in the PICU tend to experience higher sleep efficiency and fewer awakenings, whilst CNS injured patients experienced less REM and N3 sleep, as compared to healthy reference ranges. Sleep efficiency is rarely reported in the PICU as it requires clearly defined sleep onset and wake periods. Yet, it was included here as a measure of sleep continuity. To account for disrupted circadian rhythm, we calculated sleep efficiency from the first to last sleep epoch during nighttime. Despite its limitations in critically ill populations, our findings of low sleep efficiency and high awakening index, particularly in children over one year, align with adult literature and one pediatric study.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eIn contrast, findings on NREM sleep and in particular N3 sleep in critically ill children deviate from previous studies. While generally N3 sleep was reduced when NREM stages were discernable, there was considerable interpatient variability (e.g. one patient spent almost 80.0% of TST in N3 sleep). Dervan et al. reported normal mean proportions of N3 sleep with similar interpatient variability as observed here, while Zhao et al. reported means of 61.1% and 83.1%.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] These discrepancies may reflect the challenge in distinguishing pathological slow wave activity from physiological N3 sleep, potentially leading to mislabeling.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Therefore, the present study uniquely reported on underlying EEGs. Slow waves were in abundance among critically ill children, requiring an adaptation of sleep scoring, and may reflect sedation or analgesics, hypercapnia and/or encephalopathy.[\u003cspan additionalcitationids=\"CR29 CR30\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e–\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] Importantly, sedatives may reduce environmental sensitivity, lowering the awakening index and prolonging mean sleep periods, even for increased illness severity.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe observed abnormalities in underlying brain activity and overall difficulty experienced during sleep scoring in critically ill children raises concern whether the observed sleep was truly restorative sleep. The abnormal EEG patterns observed in two older patients with CNS injuries resembled non-typical sleep stages At1 and At2 described by Watson et al., which are associated with encephalopathy.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] While their classification offers guidance for handling the most abnormal EEG patterns, it remains difficult to distinguish restorative sleep from sedation induced or pathological states. Perhaps more importantly, findings of the present study raise the question whether critically ill patients retain the capacity for healthy (restorative) sleep, and whether the hospital environment harbors modifiable targets to improve this.\u003c/p\u003e\u003cp\u003eThe hospital environment and iatrogenic factors likely contribute to sleep disruptions.[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] In non-critically ill children exposed to a high or medium care unit, we observed reduced REM sleep up to six months of age. Normally, REM sleep typically reduces from around 50.0% in the neonatal period to a stable 20.0% at two years of age.[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] In non-critically ill children aged one year and older, mean sleep period durations were reduced and in the ages nine to eighteen years sleep efficiency was reduced due to high fragmentation. While these disruptions may be due to underlying sleep disorders, such as SDB/OSA, the influence of the hospital setting and/or PSG cannot be dismissed. Disrupted sleep can exacerbate the stress response, impair cognition and weaken the immune system, potentially prolonging admission and increasing complication risk.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR36 CR37\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e–\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] Increased illness severity may also enhance the homeostatic process driving sleep, creating a vicious cycle in which critical illness and sleep disruption reinforce one another. It seems imminent that strategies to optimize sleep in the PICU may contribute to individual recovery trajectories and, potentially, outcomes.\u003c/p\u003e\u003cp\u003eThe present study has several strengths. Firstly, our study is the first to include patients of all ages and a wide variety of (critical) illnesses. Including a non-critically ill group provided insight into relative contributions of illness and the hospital environment to sleep disruption. Finally, the use of 24-hour PSG enabled evaluation of day-night variation, reflecting circadian rhythm. However, several limitations must be acknowledged. First, sleep is a dynamic process that changes as children grow and mature, which we aimed to describe as comprehensively as possible. The study was designed to be longitudinal, but logistical constraints resulted in single sleep measurements per patient, obtained on day 1, 3, 7 or 14 of the study. The SDB group is not a healthy population, but was nonetheless selected for methodological and ethical reasons. As fifteen children in the SDB group were already asleep when PSG started, their sleep efficiency and sleep period duration may not be accurate, therefore we averaged across age categories. Furthermore, the small sample size and heterogeneity of the cohort did not permit statistical analysis. Lastly, reference ranges were limited by differential measurement conditions and reporting standards.\u003c/p\u003e\u003cp\u003eThe present study provides valuable insight into how critical illness and the hospital environment disrupt sleep in children, which may bear implications for the standard of pediatric (critical) care. Much work remains to clarify the exact role of sleep in short- and long-term recovery from critical illness. An important step in future research is the development of patient-friendly, automated sleep measurement tools.[\u003cspan additionalcitationids=\"CR40\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e–\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] Such tools would facilitate larger, longitudinal sleep studies in the PICU, enable bedside monitoring and support personalized interventions. However, these tools require understanding and consensus on how to interpret atypical EEG patterns in critically ill children. Finally, establishing comprehensive pediatric reference values is essential, by including all sleep characteristics and preferably obtaining them over 24 hours to assess sleep disruptions.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis observational study describes sleep in critically ill and non-critically ill hospitalized children, as compared to healthy reference ranges. Critically ill children in the PICU, including young infants and CNS injured patients, exhibited EEG abnormalities, loss of REM and N3 sleep, high fragmentation and absent day-night variation. Non-critically ill children mainly showed high fragmentation and reduced sleep efficiency. Findings suggest underlying illness and sedative medications disrupt sleep, with the hospital environment likely contributing. Further research is needed to clarify how sleep affects both short- and long-term recovery from critical illness.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAASM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAmerican Academy of Sleep Medicine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAwakening index\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCentral nervous system\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEEG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eElectroencephalography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInterquartile range (Q1, Q3)\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMEC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMedical Ethics Committee\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNREM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNon-rapid-eye-movement\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOSA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eObstructive sleep apnea\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePELOD-2\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePediatric Logistic Organ Dysfunction 2\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePICU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePediatric intensive care unit\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePIM3\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePediatric Index of Mortality 3\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePSG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePolysomnography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eREM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eRapid-eye-movement\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSDB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSleep disordered breathing\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSleep efficiency\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eStandard deviation\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSPD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSleep period duration\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSPT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSleep period time\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSTROBE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eStrengthening the Reporting of Observational Studies in Epidemiology\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTST\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTotal sleep time\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthorship statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Sophia Research Foundation under grant number S19-33 and the Department of Neonatal and Pediatric Intensive Care, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have nothing to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. The ContInNuPIC trial was approved by the Dutch national review board, the Central Committee on Research Involving Human Subjects (NL72302.000.19). The Critical Clock study and the use of diagnostic and follow-up polysomnograms were approved by the Erasmus MC Medical Ethics Review Committee (NL72597.078.20, MEC-2020-0333 and MEC-2021-0121, respectively).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient consent statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll ContInNuPIC and Critical Clock trial participants and/or their parents or legal guardians provided written informed consent to participate in this study and to publish individual data. Given the potential discomfort of the application and removal of the electrodes, separate consent was asked for the PSG on the day of measurement. Consent for the use of diagnostic and follow-up polysomnograms was waived due to the retrospective nature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIndividual patient data reported in this article can be shared in the context of a collaboration, after de-identification, to researchers who provide a methodologically sound proposal and after approval by the internal scientific committee. Proposals should be addressed to the corresponding author. Data requestors must sign a data transfer agreement to gain access.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eStremler R et al (2021) Objective Sleep Characteristics and Factors Associated With Sleep Duration and Waking During Pediatric Hospitalization. JAMA Netw Open 4(4):e213924\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDavis KF, Parker KP, Montgomery GL (2004) Sleep in infants and young children: Part one: normal sleep. J Pediatr Health Care 18(2):65\u0026ndash;71\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatel AK, Shumway RV (2023) KR et al., Physiology, Sleep Stages. StatPearls, Treasure Island (FL)\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKudchadkar SR, Aljohani OA, Punjabi NM (2014) Sleep of critically ill children in the pediatric intensive care unit: a systematic review. Sleep Med Rev 18(2):103\u0026ndash;110\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCooper AB et al (2000) Sleep in critically ill patients requiring mechanical ventilation. Chest 117(3):809\u0026ndash;818\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmbrogio C et al (2008) Assessment of sleep in ventilator-supported critically III patients. Sleep 31(11):1559\u0026ndash;1568\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCarno MA, Connolly HV (2005) Sleep and sedation in the pediatric intensive care unit. Crit Care Nurs Clin North Am 17(3):239\u0026ndash;244\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKakar E et al (2022) Sleep assessment in critically ill adults: A systematic review and meta-analysis. J Crit Care 71:154102\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCarno MA et al (2004) Sleep monitoring in children during neuromuscular blockade in the pediatric intensive care unit: a pilot study. Pediatr Crit Care Med 5(3):224\u0026ndash;229\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGottschlich MM et al (1997) Lack of Effect of Sleep on Energy Expenditure and Physiologic Measures in Critically Ill Burn Patients. J Am Diet Assoc 97(2):131\u0026ndash;139\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAl-Samsam RH, Cullen P (2005) Sleep and adverse environmental factors in sedated mechanically ventilated pediatric intensive care patients. Pediatr Crit Care Med 6(5):562\u0026ndash;567\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDervan LA, Wrede JE, Watson RS (2022) Sleep Architecture in Mechanically Ventilated Pediatric ICU Patients Receiving Goal-Directed, Dexmedetomidine- and Opioid-based Sedation. J Pediatr Intensive Care 11(1):32\u0026ndash;40\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhao X et al (2022) Sleep cycle in children with severe acute bronchopneumonia during mechanical ventilation at different depths of sedation. BMC Pediatr 22(1):589\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDrouot X et al (2012) A new classification for sleep analysis in critically ill patients. Sleep Med 13(1):7\u0026ndash;14\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWatson PL et al (2013) Atypical sleep in ventilated patients: empirical electroencephalography findings and the path toward revised ICU sleep scoring criteria. Crit Care Med 41(8):1958\u0026ndash;1967\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWatson PL et al (2013) Atypical sleep in ventilated patients: empirical electroencephalography findings and the path toward revised ICU sleep scoring criteria. Crit Care Med 41(8):1958\u0026ndash;1967\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Twist E et al (2023) An EEG-based sleep index and supervised machine learning as a suitable tool for automated sleep classification in children. J Clin Sleep Med\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Twist E et al (2024) An electroencephalography-based sleep index and supervised machine learning as a suitable tool for automated sleep classification in children. J Clin Sleep Med 20(3):389\u0026ndash;397\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Twist E et al Clinical validation of two machione learning models for automated sleep classification in critically ill children\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evon Elm E et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370(9596):1453\u0026ndash;1457\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVeldscholte K et al (2022) Continuous Versus Intermittent Nutrition in Pediatric Intensive Care Patients: Protocol for a Randomized Controlled Trial. JMIR Res Protoc 11(6):e36229\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDereymaeker A et al (2017) Review of sleep-EEG in preterm and term neonates. Early Hum Dev 113:87\u0026ndash;103\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBerry RB, Quan SF, Abreu AR et al for the American Academy of Sleep Medicine, The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Version 2.6. 2020, American Academy of Sleep Medicine: Darien, IL\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDaftary AS et al (2019) Polysomnography Reference Values in Healthy Newborns. J Clin Sleep Med 15(03):437\u0026ndash;443\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDuenas-Meza E et al (2015) Overnight Polysomnographic Characteristics and Oxygen Saturation of Healthy Infants, 1 to 18 Months of Age, Born and Residing At High Altitude (2,640 Meters). Chest 148(1):120\u0026ndash;127\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eScholle S et al (2011) Normative values of polysomnographic parameters in childhood and adolescence: quantitative sleep parameters. Sleep Med 12(6):542\u0026ndash;549\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKato I et al (2000) Frequency of obstructive and mixed sleep apneas in 1,023 infants. Sleep 23(4):487\u0026ndash;492\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVeselis RA et al (1993) The effects of midazolam on the EEG during sedation of critically ill patients. Anaesthesia 48(6):463\u0026ndash;470\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMatejcek M et al (2008) Effect of Morphine on the Electroencephalogram and Other Physiological and Behavioral Parameters. Neuropsychobiology 19(4):202\u0026ndash;211\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang D et al (2015) Comparing the effect of hypercapnia and hypoxia on the electroencephalogram during wakefulness. Clin Neurophysiol 126(1):103\u0026ndash;109\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYoung GB (2000) The EEG in Coma. J Clin Neurophysiol 17(5):473\u0026ndash;485\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHorsten S et al (2018) Systematic review of the effects of intensive-care-unit noise on sleep of healthy subjects and the critically ill. Br J Anaesth 120(3):443\u0026ndash;452\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStremler R et al (2021) Objective sleep characteristics and factors associated with sleep duration and waking during pediatric hospitalization. JAMA Netw Open 4(4):e213924\u0026ndash;e213924\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen HL et al (2022) Rapid Eye Movement Sleep during Early Life: A Comprehensive Narrative Review. Int J Environ Res Public Health, 19(20)\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMedic G, Wille M, Hemels ME (2017) Short- and long-term health consequences of sleep disruption. Nat Sci Sleep 9:151\u0026ndash;161\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu J et al (2024) Childhood sleep: physical, cognitive, and behavioral consequences and implications. World J Pediatr 20(2):122\u0026ndash;132\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMorrison AL (2004) Implications of sleep deprivation for children in the pediatric intensive care unit. Pediatr Crit Care Med 5(3):291\u0026ndash;292\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBesedovsky L, Lange T, Haack M (2019) The Sleep-Immune Crosstalk in Health and Disease. Physiol Rev 99(3):1325\u0026ndash;1380\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eReinke L et al (2014) Intensive care unit depth of sleep: proof of concept of a simple electroencephalography index in the non-sedated. Crit Care 18(2):R66\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSentner T et al (2022) The Sleep Well Baby project: an automated real-time sleep-wake state prediction algorithm in preterm infants. Sleep\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang X et al (2023) Feasibility of automated early postnatal sleep staging in extremely and very preterm neonates using dual-channel EEG. Clin Neurophysiol 146:55\u0026ndash;64\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"pediatric intensive care unit, critically ill children, sleep, polysomnography, electroencephalogram","lastPublishedDoi":"10.21203/rs.3.rs-8174098/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8174098/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: To describe sleep (disruptions) in critically ill and non-critically ill hospitalized children, by comparing sleep parameters to reference ranges of healthy children.\u003cbr\u003e\n \u003cstrong\u003eMethods:\u003c/strong\u003e Observational cohort study in a tertiary, university children’s hospital. Twenty-five critically ill children with expected PICU stay ≥ 48 hours who underwent 24-hour polysomnography (PSG) and 120 non-critically ill children who underwent diagnostic PSG between May 2017 and June 2021 for suspected sleep disordered breathing (SDB) were included. In both groups, nighttime sleep parameters were determined and compared to age-specific reference ranges obtained from literature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAmong critically ill children, comparison to reference ranges showed reduced rapid-eye-movement (REM) sleep (24, 96%) and, in those with discernable non-REM stages, reduced non-REM 3 sleep (4 of 6, 67%). Median nighttime sleep accounted for 50.9% (interquartile range (IQR) 49.5–55.5) of total 24-hour sleep. Moreover, EEG abnormalities were prominent (19, 76%), including abundant slow-wave activity (9, 36%), lacking sleep spindles (6, 24%) and/or K-complexes (2, 8%) and abnormal background EEG with persistent theta and delta activity (2, 8%). In non-critically ill children with suspected SDB, comparison to reference ranges showed reductions in REM sleep (age ≤ 6 months), reduced mean sleep period duration (age ≥ 1 year), and low sleep efficiency and high awakening index in older children.\u003cbr\u003e\n \u003cstrong\u003eConclusions: \u003c/strong\u003eCritically ill children exhibit disrupted sleep architecture, loss of day-night variation and atypical EEG. Non-critically ill children mainly exhibit fragmented and reduced sleep. These findings foster better understanding of how critical illness and the hospital environment affect sleep in children.\u003c/p\u003e","manuscriptTitle":"Disrupted sleep patterns and atypical electroencephalograms in children admitted to the pediatric intensive care unit: an observational cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-28 17:45:29","doi":"10.21203/rs.3.rs-8174098/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dca3c1e2-91cd-4c85-890c-d61e9f1ded97","owner":[],"postedDate":"November 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-19T09:24:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-28 17:45:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8174098","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8174098","identity":"rs-8174098","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}