Sleep in infants, children, and adolescents is a dynamic and important process. The development of sleep parallels physical, behavioral, and neurologic development, and there are key reciprocal relationships between these aspects of development. As our understanding of sleep in children continues to evolve, it has become evident that the development of new diagnostic and therapeutic approaches must be paralleled by increased awareness of sleep problems among medical practitioners. Thus, the aim of this article is to provide an overview of sleep in children, including important aspects of sleep-related physiology, key relationships between sleep and growth and development, and the most prevalent sleep disorders that pediatricians are likely to encounter.
Key Features of Sleep in Childhood
The most dramatic evolution in sleep takes place within the first 12 months of life, but as a physiologic process sleep continues to evolve over a lifetime. As early as 18 weeks postconception, neurogenesis has been detected in the primary control center of the circadian timing system, the suprachiasmatic nucleus.1 In the neonatal period, sleep is divided into quiet sleep, active sleep, and indeterminate sleep. Prior to 32 weeks of gestation, sleep is undifferentiated into such stages. At full term, behavioral observations are required to differentiate quiet sleep and active sleep states due to subtle differences in electroencephalogram (EEG) patterns in neonates.2 The transition from neonatal to infantile sleep, in which rapid eye movement (REM) and non-REM (NREM) sleep are differentiated, generally occurs by 2 months of postgestational age and is marked by the appearance of sleep spindles on electroencephalography. By age 5 to 6 months, EEG waveforms called K-complexes are present, and sleep can reliably be classified into stages N1 and N2 (light sleep), N3 (slow wave or deep sleep), and REM as seen in older children and adults.3 Infants have frequent, short sleep cycles with a high percent of REM sleep. As the child develops, sleep cycles lengthen, percent of REM and N3 sleep decreases, and total sleep hours decrease (Figure 1),4 with increased fragmentation and decreased REM seen later in adult life.
Evolution of sleep over time. Reprinted with permission from Roffwarg et al.4
Sleep duration requirements vary widely in infancy, with ranges that gradually decrease and narrow with age (Table 1). The diurnal circadian rhythm begins to develop early in infancy, and undergoes a “phase delay” during adolescence, causing a predilection toward later sleep and wake times.5 The dyssynchrony between sleep phase and societal demands, such as school, commonly result in insufficient sleep in adolescents and is a major cause of daytime sleepiness, reduced academic performance, problems with mood, and even increased risk-taking behaviors in teens.6,7 Furthermore, there is substantial evidence that delaying school start times by 30 to 60 minutes for middle and high school students leads to increased sleep duration, improved attendance, less daytime sleepiness, better grades, and fewer motor vehicle accidents.8 In a policy statement published in 2014, the American Academy of Pediatrics recommended that “middle and high schools should aim for a starting time of no earlier than 8:30 AM.”9
Recommended Sleep Times for Infants and Children
Sleep, Growth, and Development
The relationship between the hypothalamic-pituitary-adrenal (HPA) axis and sleep is complex but central to development. Different elements of the HPA axis are active in different patterns during wakefulness and sleep at different stages of development. For example, N3 sleep suppresses cortisol release but is closely tied to secretion of growth hormone.11 As the amount of N3 sleep per night declines with age, so too does secretion of nocturnal growth hormone12 (Figure 2). As would be expected, factors that reduce or disrupt N3 sleep, such as obstructive sleep apnea (OSA), similarly disrupt growth hormone secretion and may in severe cases lead to growth restriction,13 but treatment of disruptive factors can restore normal HPA function.14 Sleep is also integrally related to puberty. Gonadotropin-releasing hormone (GnRH) is secreted at relatively high levels and in a pulsatile fashion in the neonatal period, followed by marked suppression and quiescence after 6 to 12 months of age.15 At the onset of puberty, there is a sleep-entrained reactivation of GnRH and downstream hormone secretion, with the resulting sex steroids emitted at peak amplitude during REM sleep.16
Slow-wave sleep and growth hormone over the lifetime. Reprinted with permission from Van Cauter et al.12
Poor sleep, whether in the form of inadequate hours or disrupted sleep, as with OSA and restless leg syndrome (RLS), has also been associated with neurocognitive and behavioral deficits, including symptoms of inattention and hyperactivity mirroring attention-deficit/hyperactivity disorder, lower IQ scores, and worse behaviors.17,18
Disorders of Sleep
Sleep-related breathing concerns are among the most common reasons for referral to sleep clinics. Typically, these referrals are prompted by snoring or witnessed apneas. Adenotonsillar hypertrophy in the setting of daytime symptoms of sleepiness, inattentiveness, and behavioral or academic problems may also prompt a referral.
Obstructive sleep apnea. In OSA, snoring is the most common symptom, and children are less likely to exhibit dramatic pauses in breathing than adults. Sleep apnea is defined based on a composite index of number of apneas (cessation of airflow) and hypopneas (decreases in airflow that affect sleep continuity and/or oxygen saturation) per hour. This is called the apnea-hypopnea index (AHI). In children, the occurrence of one or more obstructive respiratory events per hour during polysomnography (obstructive AHI of ≥1) is diagnostic of OSA. Snoring may occur in the absence of sleep apnea (primary snoring), but a thorough evaluation including polysomnography should be considered prior to making this diagnosis. Of note, there is growing evidence that even primary snoring may have neurodevelopmental consequences.
Adenotonsillar hypertrophy. Adenotonsillar hypertrophy is the most common physical finding in children with OSA,19 and it is a common therapeutic target. Thus, children with snoring and adenotonsillar hypertrophy, especially with daytime symptoms such as inattention, hyperactivity, or sleepiness, warrant a sleep study or referral to a sleep specialist (Table 2). In some instances of definite adenotonsillar hypertrophy, adenotonsillectomy may be undertaken without evaluation by asleep specialist, although there is substantial variability in this practice. Continuous positive airway pressure is also used in children for the treatment of OSA, typically in older children or in those refractory to adenotonsillectomy.
Signs and Symptoms of Obstructive Sleep Apnea
Central sleep apnea. Central sleep apnea (CSA) occurs when there is a pause in breathing without evidence of associated respiratory effort. A small amount of central apnea can be physiologic, especially in infants as their respiratory centers develop. However, excessive CSA can be a sign of brainstem dysfunction, as can be seen with Chiari malformation or brainstem tumor.
Catathrenia. Catathrenia, or expiratory moaning in sleep, is considered a normal variant and may be mistaken for sleep-disordered breathing. Polysomnography may be required to make this distinction.
Insomnia is among the most common sleep complaints in children, with prevalence estimates ranging as high as 20% to 30%.20 Insomnia includes difficulty with sleep initiation, maintenance, or early waking that occurs despite adequate age-appropriate opportunity for sleep, resulting in daytime impairment for the child or family.21 Most commonly, insomnia in young children results from inadequate sleep training, or insufficient limit-setting in regard to the bedtime routine. This “behavioral” insomnia is generally divided into the sleep-onset association subtype and the limit-setting subtype. Children with sleep-onset association insomnia develop a dependence on certain circumstances to initiate or return to sleep, or have difficulty with self-soothing. Sleep latency may be normal in this case, but repetitive awakenings are common. The “limit-setting” type insomnia involves bedtime refusal or stalling, typically resulting in prolonged sleep onset but otherwise relatively normal sleep maintenance.
Treating behavioral insomnia of childhood centers on optimizing sleep hygiene, establishing consistent bedtime routines, and promoting age-appropriate self-soothing. Factors such as nursing to sleep, parental presence at sleep onset, and co-sleeping may contribute to insomnia.22 Soporific agents are rarely required. In many cases, behavioral insomnia of childhood can be successfully managed in general pediatric practice, although refractory cases and those complicated by other sleep disorders warrant referral to a sleep specialist.
Parasomnias are undesirable behaviors that occur during sleep, often associated with sleep-wake transitions. Certain parasomnias are exceedingly common, with nearly 30% of children experiencing at least one episode of sleepwalking (somnambulism), and at least half experiencing sleep talking (somniloquy).23 Sleep talking is common enough that it has been reclassified in the International Classification of Sleep Disorders, third edition24 as a normal variant. Parasomnias can be divided into those occurring out of NREM and during REM sleep.
NREM-related parasomnias. The NREM-related parasomnias, including sleep walking, confusional arousals, and sleep terrors, occur most often with partial arousals from stage N3 sleep, are most common in the first half of the night, and are not recalled by the person on awakening. They all tend to resolve with age, and supportive care is indicated. Sleep walking involves leaving the bed during the partial arousal, so a safe environment should be created to avoid injury and one should screen for sources of increased arousals such as sleep-disordered breathing.25 Confusional arousals are essentially partial arousals marked by disorientation without leaving the bed, and sleep terrors are partial arousals with autonomic arousal and behavioral upset. If sleep terrors occur predictably, scheduled partial awakenings 30 minutes prior may be helpful.25 In evaluating for parasomnias, the occurrence of repetitive or stereotyped movements or vocalizations during sleep should prompt an evaluation for nocturnal epilepsy (see following text).
REM-related parasomnias. The REM-related phenomena, including nightmares, sleep paralysis, and REM behavior disorder, arise from REM sleep and are typically seen in the second half of the night, when REM periods are longer and more frequent. Nightmares, in contrast to night terrors, have this later timing, are typically followed by an arousal as opposed to return to sleep, and are more likely to be remembered by the child.24 In sudden-onset and/or disturbing nightmares, an inquisition into possible sources of trauma may be beneficial.
Sleep paralysis occurs on awakening and involves temporary paralysis of skeletal muscles (sparing ocular and respiratory function), which tends to be distressing to the person. This may occur independently (often associated with sleep deprivation) or as a feature of narcolepsy.26 In the absence of other symptoms of narcolepsy, ensuring adequate sleep and reassurance are appropriate.
REM behavior disorder involves the acting out of dreams due to loss of REM-related atonia, typically in the second half of the night. It is extremely rare in children, and when it does occur it is typically associated with neurologic disorders.
Sleep-Related Movement Disorders
RLS is characterized by an urge to move the legs, which is worst at night or with inactivity, is partially relieved by movement, and occurs predominantly at night. This is often accompanied by odd or unpleasant sensations in the legs. Children should be encouraged to describe the sensation in their own words, and sensations such as “creepy crawly,” “shark bites,” and “just weird” are not uncommon.27 Sleep disruption, including both difficulty initiating and maintaining sleep, is common. RLS may also be responsible for at least a portion of cases of growing pains, and a majority of pediatric cases have been associated with low serum ferritin levels.28 Iron supplementation for ferritin levels below 50 to 75 mcg/L can improve RLS symptoms (guidelines vary). Identification of causative or exacerbating factors, such as insufficient sleep, caffeine, antihistamines, antidepressants, and neuroleptics, is also critical. Although an overnight sleep study may provide supporting evidence for RLS, it is a clinical diagnosis and a sleep study is not required. In severe cases or those not improved by iron supplementation, referral to a sleep specialist for pharmacotherapy may be indicated.
Many children with epilepsy exhibit a diurnal pattern to their seizures. Drowsiness and transitional sleep are peak times for seizures in many children, whereas seizures arising out of REM sleep are rare. Furthermore, certain epileptic syndromes feature almost exclusively nocturnal seizures. Thus, nocturnal epileptic seizures represent an important consideration in the differential diagnosis of unusual nighttime behaviors, although they are far less common than parasomnias and other more benign phenomena.28
Seizures can be difficult to distinguish from parasomnias, but a careful history can often clarify the differential diagnosis. In all uncertain cases, referral to a neurologist or sleep specialist is indicated. The most common nocturnal epilepsy syndrome is benign epilepsy with centrotemporal spikes (BECTS), formerly known as benign Rolandic epilepsy. Seizures typically occur soon after falling asleep or early in the morning just before awakening. The semiology of BECTS is typically hemifacial numbness, tingling or twitching, tongue numbness or weakness, drooling, difficulty speaking, and occasionally symptoms involving a unilateral arm or leg. Although this condition is typically self-limited, the treatment practices regarding BECTS vary, and there is evidence to suggest that treatment may improve neurocognitive outcomes if seizures are well-controlled.28
Nocturnal frontal lobe epilepsy is rare but important to diagnose correctly, as these seizures are difficult to distinguish from other nocturnal behaviors. Overnight EEG monitoring is often required, and focal lesions are sometimes the underlying etiology. These seizures often present as hypermotor behaviors that are stereotyped in nature. Such behaviors can be quite complex and often include expressions of fear and disorientation. The stereotyped nature of these seizures may be helpful in distinguishing them from other parasomnias, but in many cases, long-term EEG monitoring is required to establish the diagnosis.28
Lastly, infantile spasms represent an important condition about which the general pediatrician should be aware. Infants with this condition typically present in the first few months of life with quick “jack-knife” flexor contractions or Moro-like extension postures that usually involve the upper extremities, chest, and sometimes neck and lower extremities. The spasms frequently occur in clusters during sleep-wake transitions and are sometimes followed by crying. It is of critical importance that infantile spasms are recognized early, as they are commonly associated with developmental regression, and because early intervention may improve developmental outcomes.29
Persistent daytime sleepiness is always pathologic in children. Most often, this is the result of insufficient sleep, especially in teenagers. Factors that disrupt sleep, such as OSA, tend to cause daytime inattentiveness, hyperactivity, and difficulty focusing before resulting in sleepiness in elementary school-aged children, whereas sleepiness tends to result more readily in adolescents. The exception is with central nervous system hypersomnias such as narcolepsy, Kleine-Levin syndrome, and idiopathic hypersomnia. Of these, narcolepsy is by far the most common,30 and is often underdiagnosed given the broad phenotype.
Narcolepsy. Narcolepsy is a disorder of REM sleep regulation, classically characterized by irrepressible daytime sleepiness causing sleep attacks and abnormalities of sleep architecture, and may be associated with cataplexy (associated with hypocretin deficiency in narcolepsy type 1), sleep paralysis, and sleep-related hallucinations.24 Depression, anxiety, obesity, and autonomic changes can also be associated. Peak incidence follows a bimodal distribution between adolescence and early adulthood, with roughly half of adults with narcolepsy experiencing symptom onset in childhood.30,31 In children without cataplexy (narcolepsy type 2), daytime sleepiness may be the only overt symptom.
Kleine-Levin syndrome. Kleine-Levin Syndrome is an extremely rare condition of recurrent periods of excessive sleepiness lasting days to weeks, with return to normal alertness in between. During the hypersomnolence episodes, patients often display cognitive dysfunction, altered perception, eating disorder (either hyperphagia or anorexia), or disinhibited behavior (with hypersexuality seen far less often in children than in adults).32
Idiopathic hypersomnia. Idiopathic hypersomnia, as the name implies, is a diagnosis of exclusion in which the patient meets criteria for daily excessive sleepiness based on sleep laboratory testing, but does not meet criteria for another disorder. If there is any concern for hypersomnolence that is not easily explained by behavioral insufficient sleep, the patient warrants referral to a sleep specialist.