Prim Care Clin Office Pract 32 (2005) 549562

Pediatric Sleep Disorders

Philip K. Capp, MDa, Phillip L. Pearl, MDa,*, Daniel Lewin, PhDb
Department of Neurology, Childrens National Medical Center, 111 Michigan Avenue NW, George Washington University School of Medicine and Health Sciences, Washington, DC 20010-2970, USA b Department of Psychology, Childrens National Medical Center, 111 Michigan Avenue NW, George Washington University School of Medicine and Health Sciences, Washington, DC 20010-2970, USA
a

Disturbed sleep in a child is an issue of understandable concern for parents and a common reason for visits to a primary care clinician. Despite the prevalence of sleep disorders in children, there is a great disparity in physician training in sleep medicine and skill in diagnosing and treating sleep disorders [1]. The sleep disorders that commonly present from infancy through adolescence range in severity from transient diculties settling at night to life-threatening conditions that are essential targets for prevention and early intervention by clinicians. This article begins with a review of sleep architecture in children and progresses chronologically through sleep disorders in infancy, childhood, and adolescence. Pediatric sleep architecture Sleep architecture is dened as the organization and relatively reliable cycling of sleep stages within the nighttime sleep period. A brief review of sleep architecture is useful for the ensuing discussion of commonly encountered sleep disturbances in children. Of particular interest to clinicians are the normal changes in sleep architecture that begin in the fetal stage and continue to evolve through adolescence and into adulthood. Wakefulness is characterized by the presence of alpha waves (813 Hz frequency) over the posterior brain regions on electroencephalogram (EEG). The disappearance of alpha activity and the emergence of a low-voltage mixed-frequency EEG heralds the onset of stage 1 nonrapid eye movement

* Corresponding author. E-mail address: ppearl@cnmc.org (P.L. Pearl). 0095-4543/05/$ - see front matter 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2005.02.005 primarycare.theclinics.com

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sleep (NREM) sleep. With the emergence of K complexes and sleep spindles, stage 2 sleep is the most abundant sleep stage after 3 months of age. Stages 3 and 4 NREM sleep, or delta sleep, are marked by the gradual prominence of delta waves (12 Hz). A background composed of 20% to 50% delta waves corresponds to stage 3, and one of 50% or more delta waves corresponds to stage 4 sleep. Stages 1 through 4 sleep comprise what is collectively referred to as stage NREM sleep. After an average duration of 90 to 120 minutes for a complete cycle of NREM sleep, the EEG shifts to a low-voltage pattern coupled with loss of muscle tone and the advent of rapid eye movements, corresponding to the stage of rapid eye movement (REM) sleep, or so-called dreaming sleep [2]. The ontogeny of sleep development reveals major changes during the fetal, neonatal, and infantile periods. As early as 10 weeks, spontaneous fetal movements are evident. Cyclic patterns of movement are detectable by 20 weeks. Infants initiate sleep through an active sleep state that is observed by 32 weeks and is notable through REMs, body movements, irregular breathing, and EEG continuity. This state is the forerunner of stage REM. At the conclusion of active sleep in the infant, there is a period known as quiet sleep that is a prelude to stage NREM. Quiet sleep has an EEG pattern of periodic midvoltage mixed-frequency activity alternating with quiescent periods of attenuated voltages, associated with a lack of body movement. The trace alternant EEG pattern corresponding to quiet sleep becomes apparent by 32 weeks gestation [3]. By 3 months of age, the normally developing infant will enter sleep through NREM stages 1 through 4, rather than active sleep. From 3 to 6 months of age and through adulthood, the four NREM stages are fully delineated. There is a reliable cycling of NREM and REM sleep with a predominance of stages 3 and 4 during the rst half of the night and stage REM during the second half of the night. K complexes and spindles, the EEG hallmarks of stage 2 sleep, arise by 9 weeks of age.

Box 1. Average daily sleep requirements 1 Week: 16.5 hours 6 Months: 14.5 hours 12 Months: 13.8 hours 2 Years: 13 hours 3 Years: 12 hours 5 Years: 11 hours 9 Years: 10 hours Adolescent: 9 hours Adult: 8 hours

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The time spent in REM sleep and total sleep varies markedly with age. By 12 months, REM sleep accounts for 20% to 25% of total sleep time, a proportion that remains through adulthood. The total sleep requirement progressively decelerates throughout infancy and childhood, until reaching an average 9.5-hour requirement during adolescence, 8 hours in adulthood, and then lesser amounts with aging, as shown in Box 1. There is an EEG trend of decreasing amplitudes during NREM stages 3 and 4 over time. These trends may parallel important changes in brain development and learning. By 6 months of age, daytime sleep usually becomes consolidated into a morning and afternoon nap. By 18 to 24 months of age, there is generally one long afternoon nap. By 5 or 6 years of age, many children have given up their afternoon nap. The extent to which the elimination of the afternoon nap is the result of entry into kindergarten is not known. The establishment of the 24-hour circadian rhythm begins at 3 to 6 months of age. Before 3 months of age, the sleep pattern is composed of short 3- to 4-hour periods of wakefulness alternating with 3- to 4-hour periods of sleep. These rhythms are probably more reliably linked to feeding schedules than to cues of light and dark. Entrainment to the lightdark cycle, feeding schedules, and social outings occurs between 3 and 6 months of age. In the second 6 months of life, nocturnal awakenings return for unknown reasons and are exacerbated by nocturnal feeding and overattention. By 1 year of age, most infants will sleep through the night without an awakening. During the rst decade, the highest propensity to fall asleep occurs between 7:30 PM and 9:00 PM with a wake time between 6:00 AM and 7:30 AM. In adolescence, there is a delay in the sleep phase to a later period, between 11:00 PM and 1:00 AM. An understanding of the organization of sleep stages and the timing and duration of the sleep drive from infancy through adolescence is necessary in the diagnosis and treatment of sleep disorders. A hypnogram showing the typical changes in sleep stages over the course of a night is shown in Fig. 1.

Wake REM nREM 1 nREM 2 nREM 3 nREM 4

2200 2300 2400 0100 0200 0300 0400 0500 0600 0700 0800

Fig. 1. Hypnogram showing typical sleep architecture of an overnight recording in an 8-yearold child.

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Pediatric sleep disorders Pediatric sleep disorders have been dened and grouped according to the type of disruption of sleep architecture. The dyssomnias refer to a group of disorders aecting normal sleep or wakefulness. The parasomnias are abnormal behavioral or physiologic events that occur in association with sleep stages or the transition between sleeping and waking. Sleep disturbances associated with specic medical and psychiatric conditions merit a separate class [4]. Pediatric sleep disturbances range from common, self-limited, benign entities to singular and uncommon diseases of varying severity [5]. Sleep disorders of infancy Sudden infant death syndrome Sudden infant death syndrome (SIDS) is the most critical sleep disorder of infancy and has been the focus of major public education campaigns. The incidence of SIDS has decreased from 1.2 cases per 100,000 live births before 1992 to less than 0.8 cases per 100,000 live births from 1992 to 1995 [6,7]. SIDS aects infants between 4 weeks and 12 months of age with a peak incidence at 2 to 3 months of age. October and March tend to be the peak months for SIDS. Other risk factors exist, including prematurity, complicated pregnancy or delivery, maternal drug addiction, maternal smoking, maternal chronic disease, neonatal intensive care admission, multiple pregnancies, young age of mother, family history of SIDS, developmental defects, and respiratory syncytial virus infection [8]. The etiology of SIDS remains elusive, but certain theories have evolved, including ECG abnormalities (especially prolonged QT interval [9]), upper airway abnormalities, laryngospasm, seizures, respiratory infections, and increased apnea in infants following apparent life-threatening events [10]. The Back-to-Sleep Campaign, launched in 1994, aims to educate parents to not put infants to sleep in the prone position to avoid accidental suocation; by far the easiest target for public health campaigns. Central hypoventilation syndrome As compelling to identify as SIDS, although rarer, are congenital syndromes that result in sleep disturbance, such as central hypoventilation syndrome (the mythical Ondine Curse), leading to a disruption in the autonomic control of breathing while asleep. In 1978, the co-occurrence of Hirschsprungs disease and central hypoventilation was named Haddad syndrome and was later expanded to include neuroblastoma, a triad currently known as the neurocristopathy syndrome [11,12]. This anomaly of neural crest cell development may not be associated with any symptoms while awake, but rather the loss of carbon dioxide sensitivity and the associated central drive to ventilate while asleep. Symptoms of respiratory

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failure are prominent within hours after birth, necessitating ventilatory and metabolic support. The behavioral insomnias of childhood The most common sleep disorders encountered from infancy through the school-age years involve the child who has trouble making the wake-to-sleep transition independent of their parents. Parental calming behaviors (eg, rocking, holding, patting, nursing, bottle feeding, pacier use, car rides) may inadvertently lead to a sleep-onset association disorder. An infant may not learn to self-soothe and instead, learns to fall asleep only in the presence of certain environmental cues. As infants learn to sleep without the external comfort of a bottle or a parent, parents also learn to gradually wean the child from the expectation of intervention. As parents withdraw themselves during the wake-to-sleep transition, the infant becomes less dependent on the presence of the parent for the induction of sleep. These behavioral modication approaches are acceptable for infants aged 5 months or older. Infants may learn to expect feedings during the night and will wake to this cue, a self-perpetuating cycle exacerbated by associated bedwettings and possibly circadian rhythm eects. If this learned hunger is allowed to persist, a diurnal pattern may ensue, with increased body temperature, gut motility, and insulin secretion, that perpetuates sleep disruptions. Spacing feedings at longer intervals and tapering feeding amounts by an ounce every 1 to 2 days are eective therapeutic interventions. Poor limit-setting on the part of the parent can give rise to the limit-setting sleep disorder that often emerges after 18 months of age and manifests as diculty falling asleep along with stalling behaviors. A parents unwillingness to set consistent guidelines for sleep, such as timed door closings and safety gates for older children, combined with oppositional behavior from the child, leads to a decreased amount of total sleep (for parent and child). Social stressors in the infants environment caused by fear and anxiety in abusive, neglectful, or dysfunctional families will impair sleep, as will neurologic impairments and medical factors including middle ear disease, gastroesophageal reux, milk allergy, and certain medications. Sleep disorders of childhood Parasomnias The parasomnias of childhood are divided into those occurring in NREM sleep and REM sleep [4]. The NREM parasomnias consist of partial arousals, disorientation, and motor disturbances. The occurrence of NREM parasomnias in or during the transition from deep/delta (stage 4) sleep leads to amnesia for the event and behaviors attributable to deep sleep and more arousable states. The episodes are characterized by a high waking threshold and motor events, including sleepwalking/somnambulism and

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sleep terrors/pavor nocturnes. These commonly occur during the rst two thirds of the night, when deep/delta NREM sleep predominates. As children get older, the time spent in deep/delta sleep decreases, as do the NREM parasomnias. Parasomnias may run in families and occur with some frequency in children up to the age of 3. The most common causes are irregular sleepwake schedules and sleep deprivation. Drugs such as doxepin, lithium, and the neuroleptics that have the potential to increase the amount of delta/deep sleep may trigger events. Along similar lines, anxiety, frightening experiences, sleep/wake cycle disturbances, and medical illness may also lead to an increased occurrence. Benzodiazepines (specically clonazepam) and, less frequently, tricyclic antidepressants are eective when the events are persistent and when there is a high risk of injury. Preemptive safety measures, such as parental supervision, use of gates, and removal of other hazards (eg, locking windows and doors, securing furniture that could topple), are important to prevent injuries [13]. Parasomnias of REM sleep cluster in the later third of the night and include nightmares, sleep paralysis, and REM sleep behavior disorder. In contrast to the NREM events, there is signicant daytime sleepiness following these occurrences, and less association with a genetic predisposition. Nightmares are often vividly remembered. Sleep paralysis is associated with narcolepsy. REM sleep behavior disorder, rare in children and adolescents, mainly occurs in older people and is associated with loss of normal atonia during stage REM. Nocturnal epileptic seizures may occur in NREM and REM sleep and may be dicult for the clinician to separate, as they share characteristics of motor and autonomic activation. Videopolysomnography may be necessary to distinguish seizures from parasomnias [14]. The parasomnias include the group of rhythmic movement disorders, including body rocking and head banging/jactatio capitis nocturna. These activities, although generally benign, can result in injury to the child and precautions should be taken to maintain a safe environment and emphasize behavioral modication [15]. Behavioral interventions are generally most eective in treating these disorders. In adults, the connection between sleep disturbances, such as the parasomnias and psychopathology, has been demonstrated, but this association in children remains under investigation [1618]. Nocturnal enuresis, or nocturnal bedwetting, is observed in children after the age at which normal control of bladder function is attained. With increasing age comes a decrease in the incidence of enuresis, with the disorder found more commonly in men at all ages. Genetic factors have been identied, but the hereditary factors are only one of the physiologic and psychologic factors surrounding this condition. Clinicians divide enuresis into primary and secondary categories. Primary enuresis is dened as a persistent history of bedwetting without a period of continence, and secondary enuresis is bedwetting that occurs after 6 months of continence. Of these two types, primary enuresis is the most common, and

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secondary enuresis is an indication of an underlying physiologic or psychologic disorder. Congenital abnormalities, infection, or irritation of the urinary tract should be considered in secondary enuresis. Comorbid medical conditions, such as diabetes or sleep apnea, may contribute to nocturnal enuresis [19]. Finally, psychologic trauma may be causal but is often a diagnosis of exclusion if a rm history is not available. Behavioral modications are the mainstay of treatment, are varied in their approach, and require persistence. They include nighttime uid restriction; behavior modication with charts, rewards, and sometimes negative reinforcers; bell-and-pad systems; bladder exercises (eg, pelvic contractions, stream interruption); predetermined awakenings; and relaxation/mental imagery training. Medications are reserved for failure of behavioral treatments and include imipramine, oxybutynin, or desmopressin. If psychologic etiologies are identied, psychotherapy may be benecial. Psychiatric disorders Psychiatric disturbances have been associated with sleep disorders, and therefore attention-decit hyperactivity disorder (ADHD), the most prevalent psychiatric disorder in children, should be considered if a suggestive history exists [20]. Sleep disturbance is not a diagnostic criterion for ADHD in the current DSM-IV guideline, but is often comorbid. Recently described connections between ADHD and periodic leg movements in children may lead to future insights and treatment options [2123]. Other mood and anxiety disorders can also disrupt sleep and should be part of the psychiatric screening history. Primary medical disorders Gastroesophageal reux and asthma are frequent disrupters of sleep in the childhood years, as is sleep apnea. Epilepsy is intricately connected with sleep. Landau-Klener syndrome (LKS) illustrates an example of sleeptriggered epilepsy, characterized by electrographic status epilepticus during slow-wave sleep and acquired auditory agnosia. EEG ndings are conspicuously absent during the day. Although rare, LKS may occasionally be mistaken for autism. Other epileptic entities that may be unmasked or exacerbated by drowsiness or sleep include juvenile myoclonic epilepsy (Janz syndrome), benign rolandic epilepsy in children, and West syndrome (infantile spasms) in infants. Sleep apnea Obstructive sleep apnea syndrome (OSAS) is increasingly recognized as a common condition in children and may be on the rise as a result of increasing rates of obesity and a decrease in the frequency of adenoidtonsillectomy. OSAS is an insidious respiratory disturbance of sleep characterized by a partial (hypopnea) or complete cessation of airow caused by upper airway obstruction and intact respiratory eort (Fig. 2).

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Fig. 2. Polysomnograph page showing an episode of obstructive apnea and hypopnea. Note only partial loss of airow during hypopnea. EOG, electro-oculogram; EMG, electromyogram.

Risk factors for OSAS have been well-described in adults, and many of the same risk factors are applicable to children, such as obesity, craniofacial abnormalities, and reactive airways disease [24]. Factors contributing to hypotonia, particularly of the oropharyngeal dilator muscles that maintain airway patency during inspiration, are more serious and include cerebral palsy, tracheomalacia, neuromuscular weakness, cervical cord problems, and hydrocephalus. Developmental delay, pulmonary hypertension, cor pulmonale, cognitive disability, and cardiac arrhythmias are potential complications of OSAS. Other symptoms of upper airway obstruction may include snoring, paradoxical breathing, apnea, tachypnea, mouth breathing, cyanosis, diaphoresis, enuresis, multiple arousals, morning headaches, vomiting, unusual sleep positioning, excessive daytime tiredness, developmental delay, hyperactivity, irritability, school problems, feeding diculties, gastroesophageal reux, and recurrent aspiration. Impaired daytime functioning is often observed, but excessive daytime sleepiness has not been found to be a strong indicator of childhood OSAS, in a marked departure from adult indicators [25]. Overnight polysomnography (PSG) is required for the diagnosis of sleep apnea. Even a seasoned pediatric sleep specialist cannot reliably

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dierentiate primary snoring (ie, loud snoring in the absence of OSAS) from OSAS. Adenoid and tonsil hypertrophy are the most common and reversible causes of OSAS in children. More serious underling pathology or refractory cases may require a more involved treatment plan, including continuous positive airway pressure (CPAP) and possibly tracheostomy or uvulopalatopharyngoplasty. With careful follow-up and monitoring to allow for changing respiratory pressure requirements that occur with development, CPAP has been shown to be a safe and eective treatment when indicated for OSA in infants, children, and adolescents [26]. Sleep disorders of adolescence Adolescent sleep-need is greater than that of adults. Because of the prevalence of external pressures (eg, school, job-related, a high motivation to engage in social behaviors, use of electronic media), adolescents average less than 7.5 hours of sleep. The estimated sleep-need during adolescence, however, is greater than 9 hours per night. Less sleep in adolescence has been correlated with poor grades in school and higher mortality in motor vehicle accidents, catapulting this issue from purely medical interest to great public health concern [27]. Restless legs syndrome and periodic limb movement disorder Recently, there has been documentation of an increase in the prevalence of restless legs syndome (RLS) and periodic limb movement disorder (PLMD) among children and adolescents, with a particularly high prevalence among children diagnosed with ADHD [22]. RLS is dened as unpleasant sensory disturbances that tend to occur before bedtime. Although children under age 10 may not be able to conrm that they experience uncomfortable sensations in their legs or arms, older children report a wide variety of sensations that may include tingling, growing pains, and motor restlessness. Movement almost always results in relief of the sensations. RLS is diagnosed through interviews, whereas PLMD is diagnosed in the sleep laboratory. The disorders co-occur in about 80% of cases and can cause insomnia and disrupted nighttime sleep. Low serum ferritin has been associated with RLS and PLMD. Treatment with iron supplementation (ferrous gluconate or ferrous sulfate) and dopamine agonists [24] has been eective. Sleep phase delay The complex interplay of biologic and environmental factors that aect adolescent sleep patterns lead to circadian shifts with subsequent sleep phase delay. Adolescents have a biological propensity to go to bed later and wake

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up later, but are forced to wake up earlier during the week because of early high school start times. During the week many adolescents accumulate a sleep debt that leads to sleeping in on weekends. This progressive pattern of sleeping later causes further delays in the circadian rhythm, leading to excessive daytime sleepiness as reliably measured by multiple sleep latency testing (MSLT) [28]. Later sleep times and pubertal inuences delay numerous biological phenomena, including the normal secretion of melatonin, further deranging the sleep cycle [29]. Therapy for sleep phase delay is purely behavioral. Known as chronotherapy, the adolescents bedtime is advanced by strict 15-minute intervals (Phase Advance Chronotherapy), or progressively delayed by 3 to 4 hours per night until a normal bedtime is reached (Phase Delay Chronotherapy). Although more dicult to implement, Phase Delay Chronotherapy has been more eective, although it demands a time commitment of about 1 week [30]. Other interventions, such as timed light exposure and melatonin, are likely to be eective in advancing an adolescents sleep cycle. Narcolepsy Usually diagnosed in adolescence or young adulthood, narcolepsy is dened as the clinical tetrad of irresistible daytime somnolence, cataplexy (ie, the sudden loss of muscle tone usually associated with an intensely emotional event), sleep paralysis, and hypnagogic or hypnopompic hallucinations. These phenomena represent intrusions of REM sleep characteristics during periods of wakefulness. Narcolepsy is diagnosed in the absence of another contributory general medical condition, including depression or concomitant substance abuse [5]. Aecting from two to ve out of 100,000 people, narcolepsy approaches an incidence similar to that of parkinsonian syndrome and multiple sclerosis [31]. Studies have shown that in the absence of cataplexy, which is the most orid sign of the disease, the diagnosis and treatment of narcolepsy can be delayed, and it is often misdiagnosed as a psychiatric disorder [32]. Cataplexy can occasionally be confused with intentional unresponsiveness or conversion disorder. A clinical diagnosis can be made in the absence of the classic tetrad of symptoms and generally consists of the sleep history and the documentation of two sleep-onset REM naps during daytime MSLT, following overnight PSG to rule out other sleep pathology. The identication of a deciency of a newly discovered neurotransmitter, hypocretin, in animal models of narcolepsy and, later, aected patients has led to a fundamental new understanding of this intriguing sleep disorder [3336]. Research has established that a cerebrospinal uid assay for hypocretin can be diagnostically useful, especially in cases involving cataplexy and an indeterminate MSLT [37]. The hypocretin/orexin neurotransmitter system projects into the locus ceruleus, a prominent

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regulator of NREM versus REM sleep. Other neurotransmitter systems have been identied as important in narcolepsy, including the striatal dopaminergic pathway [38]. Further research into these neurotransmitter systems is promising for future therapy. Nonpharmacologic therapy includes family and individual education, frequent naps, and attention to sleep hygiene. Pharmacologic intervention with psychostimulants can provide benet [39]. Modanil, a compound pharmacologically dierent from psychostimulants, has been shown to be safe and eective for the treatment of excessive daytime sleepiness in children who have narcolepsy [40,41]. Klein-Levin syndrome Klein-Levin syndrome is a rare clinical syndrome that aects adolescents and presents with excessive daytime sleepiness [42]. The triad of hypersomnia, compulsive hyperphagia, and indiscriminate hypersexuality has a periodicity that lasts about 4 weeks, repeating over symptom-free intervals of weeks to months before spontaneously remitting. Irritability, depression, confusion, and visual and auditory hallucinations are often present, as is a history of antecedent viral syndrome or head injury. Anorexia and insomnia may replace hyperphagia and hypersomnia, representing an atypical form of the disorder that may confound the diagnosis. There appears to be a 3:1 male predominance. General medical conditions A variety of medical and neurologic conditions, such as depression, substance abuse, adverse eects of medication, indolent infection, encephalitis, third ventricle tumors, and hydrocephalus, may manifest as excessive daytime sleepiness. Postconcussive syndromes may manifest hypersomnia extending as long as 3 years after the incident [43]. Public health issues The eects of adolescent sleep deprivation have become a public health issue, with ramications for trac safety and even school start times. Data compiled by the National Highway Trac and Safety Administration shows that adolescents are at greatest risk of dying in car crashes, partly as a result of drowsy driving. With the drowsing eect of early school start times compounded by the demands of homework, part-time jobs, extracurricular activities, and late-night socializing or computer use, motor vehicle accidents may aect the most energetic and dedicated teenagers [44]. The eects of sleep deprivation are exacerbated by alcohol, further complicating the issue for adolescents irting with substance abuse and the responsibilities of driving.

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The national debate on later school start times is currently trying to reconcile the recognized 9-hour sleep demands of adolescents with the schedules of public transportation, school, and extracurricular activities. The National Sleep Foundation has published a booklet of recommendations for parents and teens that can be used in clinical practice [45]. Summary Pediatric sleep disorders represent a heterogeneous collection of disturbances that require varied intervention strategies. The diagnosis of some sleep disorders (eg, OSAS, narcolepsy, PLMD) require PSG, whereas others can be diagnosed during an oce visit with a thorough medical, psychiatric, and sleep history. Sleep disorders place children at risk for school failure, accidents, and social problems, and can place a signicant burden on families and the parentchild relationship.

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