Mechanisms and Predisposing Factors For Sleep-Related Breathing Disorders in Children - UpToDate

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Mechanisms and predisposing factors for sleep-related

breathing disorders in children
Authors: Gerald M Rosen, MD, Keith L Cavanaugh, MD, FAAP, FCCP, Brianne Barnett Roby, MD
Section Editor: Ronald D Chervin, MD, MS
Deputy Editor: Alison G Hoppin, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2020. | This topic last updated: Mar 19, 2020.
INTRODUCTION
Children are the gold standard for sleep quality. Children normally have a brief latency to sleep onset
and then breathe quietly and comfortably during sleep. Sleep efficiency (time asleep/time in bed) is
high (greater than 90 percent). There are few behavioral arousals during the night, and the child
awakens in the morning refreshed and ready to learn and play. During the day, children are normally
very alert and do not display signs of sleepiness (which can include hyperactivity and poor impulse
control). For younger children, a certain frequency of napping is normal and expected. Sleep-related
breathing disorders in children occur along a spectrum of severity, ranging from primary snoring on
the mild end of the spectrum to obstructive sleep apnea (OSA) on the serious end of the spectrum.
This topic review will discuss the normal physiology of sleep in children and the factors that disturb
respiration during sleep and contribute to the development of a sleep-related breathing disorder,
including OSA. The evaluation of the child with snoring or suspected OSA and the management of
the child with OSA are discussed separately. (See "Evaluation of suspected obstructive sleep apnea
in children" and "Management of obstructive sleep apnea in children" and "Adenotonsillectomy for
obstructive sleep apnea in children".)
SLEEP STAGES
Starting at birth, a child's sleep can be divided into rapid eye movement (REM) and non-REM
(NREM) sleep and scored polygraphically using the American Academy of Sleep Medicine (AASM)
Manual for the Scoring of Sleep and Associated Events [1]. (See "Stages and architecture of normal
sleep" and "Sleep physiology in children", section on 'Sleep states'.)
REM sleep is a physiologically activated sleep state characterized by:
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● Generalized muscle atonia

● Increased cerebral blood flow
● Desynchronized electroencephalography (EEG)
● Variability of heart rate, respiratory rate, and blood pressure
● Increased upper airway resistance
During REM sleep, bursts of phasic events have both central and peripheral nervous system
manifestations (for example, in the form of ponto-geniculo-occipital waves and muscle twitches
despite the atonia, respectively). Most dreaming occurs during REM sleep.
By comparison, NREM sleep is a more quiescent state characterized by:
● Reduced, but not absent, muscle tone

● Decreased cerebral blood flow
● Synchronized EEG
● Regular heart rate, respiratory rate, and blood pressure
● Increased upper airway resistance [2,3]
After age two months, NREM sleep is subdivided into stages N1, N2, and N3 by EEG criteria, which
roughly parallel increasing depth of sleep [1]. NREM sleep, REM sleep, and brief periods of
wakefulness alternate in a regular and predictable pattern throughout the sleep period, defining the
ultradian rhythm. (See "Stages and architecture of normal sleep".)
The NREM-REM cycle length increases from 60 minutes at infancy to 90 minutes in adolescents and
adults. NREM sleep stage N3 is also labeled as "slow-wave sleep." Slow-wave sleep predominates
in the early part of the sleep period, whereas REM sleep predominates in the latter part of the sleep
period. A normal night's sleep for a child is comprised of 5 to 10 NREM-REM sleep cycles woven
together seamlessly, so that the transitions from one cycle to the next are behaviorally inapparent.
CHANGES IN RESPIRATORY PHYSIOLOGY DURING SLEEP
During sleep in a normal child there is a modest increase in upper airway resistance and a small
decrease in nocturnal ventilation. Overnight polysomnography (PSG) studies in normal children have
quantified these changes, establishing norms for nocturnal ventilation in children (table 1) [4-6].
These normative studies have demonstrated that there is a small decrease in oxygen saturation (0 to
7 percent) and a rise in end-tidal PCO2 (0 to 13 mmHg). Brief central apneas (pauses) are common
in children, especially in association with movements, but obstructive apneas are never normal in
children.
The decrease in ventilation is caused by both an increase in upper airway resistance and a decrease
in central respiratory drive, as detailed below [2-4]:

Increased upper airway resistance — Although the nose is the site of greatest resistance in the
upper airway, the pharynx is the site of the greatest increase in airway resistance during sleep [7].
This increase in resistance is due to the decreased size of the pharynx associated with relaxation of
the pharyngeal dilators.
The pharynx provides a conduit for air, solids, and liquids, and is intimately involved in breathing,
digestion, and speaking (image 1). In its role as an organ of respiration, the pharynx must remain
patent. In its role as an organ of digestion, the pharynx moves to occlude and protect the
nasopharynx and larynx, while directing solids and liquids into the esophagus during swallowing and
out of the mouth during vomiting. In its role as an organ of speech, the pharynx provides a steady,
highly regulated flow of air that is variably directed into the nose and mouth.
To fulfill these diverse functions, the pharynx is constructed as a rigid tube with a mobile, collapsible
segment in the middle. The collapsible section of the pharynx is controlled by at least 20 sets of
paired muscles, which can alter its size, shape, and dynamics, and behaves like a Starling resistor
(figure 1). The collapsibility of the pharynx is a necessity for it to fulfill its roles in digestion, phonation,
and to protect the airway from aspiration, but it is a liability in its role as an organ of respiration and is
central to the understanding to the pathophysiology of sleep-related breathing disorders.
The pharyngeal dilators are a group of muscles that provide the postural tone to the pharynx during
wakefulness and maintain pharyngeal patency in the face of the subatmospheric intraluminal
pressure generated during inspiration. The pharyngeal dilators that have been studied during sleep in
adults are [8,9]:
● Genioglossus [10-14]
● Posterior cricoarytenoids [15]
● Tensor veli palatini [16]
● The nasal inspiratory muscle (the alae nasi), which affects the airway patency by causing the
nasal ala to flare and open during inspiration [17]
● Superior constrictor muscle, which also supports the tonsils and prevents them from collapsing
when tonically contracted
● Levator veli palatine, which gives tone to the soft palate along with the tensor veli palatini
During wakefulness and sleep, the pharyngeal dilators help to maintain pharyngeal patency by tonic
contraction (which is present throughout the respiratory cycle) and/or phasic contractions (which are
synchronized with the contraction of the respiratory pump muscles, thereby helping to stiffen the
upper airway prior to and during inspiration). During sleep in individuals without a sleep-related
breathing disorder, there is a decrease in activity of the pharyngeal dilators that results in a decrease
in pharyngeal size and a concomitant increase in upper airway resistance [8-10,15-19].
As a group, the pharyngeal dilators can be considered accessory muscles of respiration. Their
activity during sleep is modulated by the respiratory control center of the medulla, which receives
input from the pharyngeal mechanoreceptors. The mechanoreceptors are the afferent limb of a

complex pharyngeal reflex that maintains pharyngeal patency during inspiration [20]. These reflexes
have been demonstrated in both children and adults and they augment activation of the pharyngeal
dilators in response to negative intraluminal pressure and hypercapnia [21-23]. Topical anesthesia of
the pharynx and glottis in adults [24] and children [25] during wakefulness results in a substantial
decrease in upper airway size and increase in upper airway resistance, suggesting that the
pharyngeal mechanoreceptors play an important role in maintenance of pharyngeal patency during
wakefulness. These reflexes likely play an even more important role during sleep in adults and
children with sleep-disordered breathing.
In contrast with adults, normal children snore infrequently and rarely have obstructive apneas during
sleep. This is consistent with the better preservation of upper airway patency in response to
subatmospheric pressure. Adults with obstructive sleep apnea syndrome (OSAS) tend to have
repetitive obstructive apneas, while children with OSAS frequently manifest a pattern of persistent,
partial upper airway obstruction, rather than discrete apneas [4]. Thus, the pattern of upper airway
muscle recruitment in children with OSAS [26] may be different from that in adults; children may have
greater upper airway muscle activation, thereby preventing total airway occlusion [27].
Decreased central respiratory drive — If the increased upper airway resistance is reversed by
nasal continuous positive airway pressure (CPAP) or is minimized by having patients breathe a low
density gas, there is still a small decrease in ventilation, suggesting an independent decrease in
central respiratory drive during sleep [18]. This decrease has been attributed to the loss of a
"wakefulness respiratory drive," the nature of which is not completely understood. (See "Control of
ventilation".)
Other factors — Other important changes in respiratory physiology during sleep include:
● A decrease in load compensation

● An increase in the contribution of the intercostal muscles to inspiratory effort during non-rapid
eye movement (NREM) sleep
● A decrease in lung volumes during rapid eye movement (REM) sleep
● A decrease in synchronization of the pharyngeal dilators with diaphragmatic contractions during
REM sleep
BALANCE OF FORCES MODEL OF UPPER AIRWAY OBSTRUCTION
The pharyngeal narrowing that occurs during sleep can be understood to result from a balance
between forces that tend to collapse the airway and the pharyngeal dilators that attempt to maintain
pharyngeal patency (figure 2) [28].
This balance is affected by:
● The skeletal and soft tissue anatomy of the upper airway

● The neuromuscular tone of the pharyngeal dilators

● Suction pressure generated by the inspiratory pump muscles
During wakefulness, obstructive apneas are rare even in individuals with markedly enlarged tonsils,
obesity, craniofacial anomalies, and abnormal neuromuscular tone because the pharyngeal dilators
are able to compensate for whatever factors are present that might lead to upper airway collapse.
During sleep, the neuromuscular tone of the pharyngeal dilators, and possibly their coordination with
the inspiratory pump muscles, is diminished so that they are less able to compensate. Pharyngeal
dilator muscle activity decreases during NREM sleep in children and decreases further during REM
sleep [13]. These changes in tone of the pharyngeal dilators result in one of three possible outcomes
(figure 2):
● Normal sleep – During sleep in normal children and adults, there is a small decrease in the size
of the pharyngeal airway, resulting in a small but clinically insignificant increase in upper airway
resistance.
● Obstructive apneas and hypopneas – Obstructive sleep apnea (OSA) in most adults and
many children is characterized by repeated transient collapse of the pharyngeal airway. These
events are known as obstructive apneas if the airway closes completely or hypopneas if it closes
partially.
● Obstructive hypoventilation – In obstructive hypoventilation (OHV) there is continuous partial

collapse of the pharyngeal airway, resulting in increased upper airway resistance and continuous
hypoventilation, associated with hypercapnia and hypoxemia but without cyclic discrete
obstructive events. This finding is common in young children but less common in adults [29]. The
International Classification of Sleep Disorders (ICSD) classifies obstructive hypoventilation as a
form of pediatric OSA; obstructive hypoventilation is defined as at least 25 percent of total sleep
time with hypercapnia (PaCO2>50 mmHg) associated with either snoring, flattening of the
inspiratory nasal pressure waveform, or paradoxical thoracoabdominal motion [30].
OBSTRUCTIVE SLEEP APNEA AND OBSTRUCTIVE HYPOVENTILATION
Sleep in children with sleep-related breathing disorders is different from sleep in normal children. For
children with sleep-related breathing disorders, the increase in upper airway resistance during sleep
is exaggerated and can lead to markedly increased work of breathing with snoring, obstructive sleep
apnea (OSA), and/or obstructive hypoventilation (OHV), resulting in sleep disruption, hypoxia, and
hypercarbia.
Sleep-related breathing disorders in children ranges on a spectrum from snoring to obstructive

hypoventilation to complete obstructive apnea. The precise point along this spectrum that is defined
as abnormal is subject to some controversy. There is a growing body of literature describing the
physiologic consequences of sleep-related breathing disorders in a child, which include impaired
growth, systemic or pulmonary hypertension, and myocardial remodeling. In addition, there appear to
be associations between OSA and neurocognitive and behavioral problems, including attention
deficit disorder and poor school performance [31]. (See "Evaluation of suspected obstructive sleep
apnea in children", section on 'Screening'.)
OSA and OHV are present only in the sleeping state. Typically, normal children have no obstructive
apneas or hypopneas during sleep. In adults, up to five apneas or hypopneas per hour may be
normal (ie, an apnea/hypopnea index of less than five per hour). (See "Evaluation of suspected
obstructive sleep apnea in children", section on 'Respiratory events'.)
Airway collapse — OSA or OHV is caused by complete or partial collapse of one or multiple
segment(s) of the extrathoracic airway during sleep. This is the result of the cumulative effect of two
factors, the relative contribution of which varies among individuals (see 'Increased upper airway
resistance' above):
● An anatomically small upper airway

● Decreased neuromuscular tone of the pharyngeal dilators during sleep
The upper airway of children with OSA/OHV tends to be smaller than that of normal controls. This
has been demonstrated by magnetic resonance imaging (MRI) [32-34], pharyngometry (image 2 and
figure 3A-B) [35], and drug-induced sleep endoscopy (DISE). Dynamic MRI studies of the upper
airway during tidal breathing under light sedation have demonstrated that the cross-sectional area of
the upper airways of children with OSA are significantly smaller at all levels, from the epiglottis
inferiorly to the nasopharynx superiorly, compared with normal controls; these differences are also
seen dynamically when the inspiration of a normal control is compared with that of a child with OSA
(image 3) [34]. Note that the airway of the normal control is:
● Larger at all pharyngeal levels

● The lateral dimension is consistently larger than the AP dimension
● There is very little change in the size and shape of the airway between inspiration and expiration
In contrast, in children with OSA the airway is:
● Smaller at all levels

● The AP dimension is consistently larger than the lateral dimension
● There is a substantial change in the size of the airway between inspiration and expiration, which
is most apparent in the nasopharynx
Although children with OSA/OHV often have anatomically smaller upper airways compared with the
general population, they do not usually exhibit any upper airway obstruction during wakefulness,
because of neuromuscular compensation mediated by the pharyngeal dilators, particularly the
genioglossus during wakefulness. However, upper airway obstruction occurs if this compensatory
activation is eliminated, as occurs during sleep or during anesthesia with muscular paralysis [28].
Patterns of OSA/OHV in children — Sleep-related breathing disorders in children are most often
characterized by prolonged obstructive hypoventilation during sleep, rather than by discrete
obstructive apneas [13,36] (see 'Balance of forces model of upper airway obstruction' above). Sleep
architecture often is preserved; there may be little sleep fragmentation and sleep stage distribution
may appear normal. The polysomnogram often displays phasic augmentation of chin and intercostal
electromyographic (EMG) activity during non-rapid eye movement (NREM) sleep. Paradoxical chest
and abdominal movements suggest an obstructive breathing pattern in older children. They are seen
during rapid eye movement (REM) sleep in normal children up until 31 months of age. By
adolescence, paradoxical chest wall movement is not seen in normal subjects [29].
The hypoventilation typically worsens during REM sleep because lung volumes are lower, intercostal
muscles do not substantially contribute to inspiratory effort, and the pharyngeal dilators are less
effective as compared with NREM sleep. This often leads to an overnight oximetry tracing in which:
● REM periods are often associated with hypoventilation and significant oxygen desaturations
● NREM stage N3 (slow-wave sleep) is relatively protected without desaturations
● NREM stage N2 shows modest desaturations
These clinical findings can be understood in terms of how a child compensates for increased
resistive loads. At sleep onset, there is decreased tone of the pharyngeal dilators, leading to a
decrease in size of the airway. This in turn causes an increase in upper airway resistance, resulting
in a decrease in intraluminal pressures in the pharynx. The decreased airflow, increased negative
pressure, and increased CO2 stimulate the pharyngeal mechanoreceptors to augment pharyngeal
dilator contractions [13]. In a child without sleep-related breathing disorders, this response maintains
airway patency.
In children with sleep-related breathing disorders, this response does not completely relieve the
upper airway obstruction. In the mildest form of sleep-disordered breathing, a modest decrease in the
size of the pharyngeal airway leads to turbulent airflow causing vibration of the soft palate and
snoring. As the upper airway obstruction worsens, hypoventilation ensues, with a rise in PCO2 and/or
a decrease in arterial oxygen saturation. This further stimulates the pharyngeal dilators and the
respiratory pump muscles. In many children with OSA, this response usually is sufficient to maintain
a partially open pharyngeal airway for long periods of sleep without experiencing discrete obstructive
apneic events. By contrast, adults with OSA are more likely to have acute obstructive apneic events,
leading to arousal, perhaps because the pharyngeal dilators are less effective and/or the pharynx is
more collapsible as compared with children.
Arousal — Arousal is the ultimate defense against obstructive apnea since it leads to a change from
the sleeping to the waking state, which in turn results in the opening of the pharyngeal airway and
relief of the obstruction. Children use this strategy much less often than adults. Several studies have
demonstrated that the majority of obstructive apneas in children during both REM and NREM sleep
are terminated without a cortical EEG arousal [36,37]. However, many of these events are associated
with a subcortical arousal as manifest by a movement and a change in the pulse transit time [38].
The significance of these subcortical arousals is not known.

PREDISPOSING FACTORS
Sleep-disordered breathing in children has been associated with a variety of factors, including
craniofacial anatomy, adenotonsillar hypertrophy, obesity, upper airway inflammatory processes,
environmental exposures, asthma, prematurity, and genetic variation. Each of these factors likely
contributes to sleep-disordered breathing because of effects on the anatomy of the upper airway,
intrinsic compliance of its walls, and/or its neuromuscular control.
Anatomic factors anywhere along the upper airway can decrease airway size or stability, and may
therefore contribute to the development of obstructive sleep apnea (OSA)/obstructive hypoventilation
(OHV) (table 2).
Enlarged tonsils and adenoids — The most common and often the only obvious factor limiting
airway size and leading to OSA/OHV in children is enlarged tonsils (palatine and lingual) and
adenoids. The smallest cross-sectional area of the pharyngeal airway in children is the retropalatal
area, where the tonsils and adenoids overlap (figure 3A) [32,37]. However, adenotonsillar size alone
cannot explain the presence of OSA/OHV, since the majority of children with grossly enlarged tonsils
and adenoids do not have OSA/OHV and the tonsils of children with OSA/OHV are not larger than
those of children without OSA/OHV [39]. Most studies of children with sleep-disordered breathing
have shown only a modest positive correlation between adenotonsillar size and severity of OSA
[40,41], and some have shown no correlation [42]. There is an important interaction between obesity
and adenotonsillar hypertrophy, which are the two most common predisposing factors for OSA/OHV.
In nonobese, otherwise healthy children, the success rate of adenotonsillectomy for OSA is
approximately 80 percent [43]. These and other factors relevant to decisions about whether to
perform adenotonsillectomy are discussed in a separate topic review. (See "Adenotonsillectomy for
obstructive sleep apnea in children".)
Most children with OSA/OHV and adenotonsillar hypertrophy and no other contributing factors are
cured after a tonsillectomy and adenoidectomy, as indicated by a postoperative apnea index <1.
Overall, tonsillectomy is effective for control of OSA/OHV in 60 to 80 percent of children with
significant tonsillar hypertrophy [44]. In those children not cured of their OSA/OHV by
adenotonsillectomy, it is presumed that a substantial part of the OSA/OHV was caused by subtle
craniofacial or neuromuscular factors or pharyngeal instability, not simply enlarged tonsils and
adenoids [45]. This is most apparent in children with obesity, in whom a minority have complete
resolution of OSA/OHV after adenotonsillectomy, although most experience improvement in
symptoms. In other children, the OSA/OHV initially improves after adenotonsillectomy but later recurs
due to adenoidal tissue regrowth or other factors such as lingual tonsillar hypertrophy, and may
resolve after a second surgery. Failure to resolve OSA/OHV following adenotonsillectomy in some
patients highlights the complex nature of the airway; such patients may need further assessment to
determine level of obstruction, as it may be multifactorial [46]. (See "Adenotonsillectomy for
obstructive sleep apnea in children", section on 'Success rates'.)

Obesity — Obesity is a common factor contributing to the OSA in adults, probably because it
decreases the size and/or increases the collapsibility of the pharyngeal airway. Although obesity is
not as common a cause of OSA/OHV in children as it is in adults, the prevalence of OSA/OHV in
obese children is higher than in nonobese children, and this is particularly true for adolescents [47-
51]. Because the prevalence and severity of obesity in children is increasing, obesity is likely to
become an increasingly important cause of pediatric sleep-related breathing disorders in the future.
In a population-based study, the risk of sleep-disordered breathing was increased four- to fivefold in
children with obesity, which was defined in this case by a body mass index (BMI) >28 [52]. The risk
of OSA increased by 12 percent for every 1 kg/m2 increase in BMI above the mean.
Obesity contributes to airway narrowing in several ways, including fatty infiltration of areas
surrounding the airway, tongue, or fat pads lateral to the airway. In many cases, obesity and
adenotonsillar hypertrophy combine to cause OSA in an individual patient, and children with obesity
are more likely than lean patients to have residual OSA after adenotonsillectomy; up to 75 percent of
obese patients who undergo adenotonsillectomy for OSA have residual OSA postoperatively [53].
Essentially no improvement is seen with adenotonsillectomy alone in patients with severe obesity
(body mass index [BMI] Z-score >3) [54]. (See "Adenotonsillectomy for obstructive sleep apnea in
children", section on 'Risk factors for persistent disease'.)
Inflammation — Both obesity and OSA are inflammatory conditions with additive effects on
comorbidities that are mediated by inflammatory processes [31]. These comorbidities include
atherogenesis/cardiovascular disease and associated lipid abnormalities, insulin resistance, and fatty
liver disease [55-58]. These comorbidities seem to be mediated at least in part by increased
production of leptin, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), which are
independently induced by obesity and OSA [31]. Among children with asthma, those who are obese
have a fourfold increase in their risk of OSA [52]. Moreover, children with poorly-controlled asthma
are much more likely to have OSA than those with well-controlled asthma. Treatment of upper airway
inflammation with montelukast and nasal corticosteroids improves OSA [59]. All of these lines of
evidence suggest a causal relationship between upper airway inflammation and sleep-disordered
breathing, although the precise mechanism has not been identified. (See "Management of
obstructive sleep apnea in children", section on 'Adjunct therapies'.)
Environmental factors — Cigarette smoke exposure has been identified as a risk factor for children
in the development of sleep-disordered breathing, after controlling for other relevant factors [42]. The
mechanism for the association is not fully understood but may be related to irritation or inflammation
of the mucosa in the upper airway. Exposure to secondhand smoke remains an important problem. In
the United States in 2011 to 2012, 40 percent of 3- to 11-year-old children overall, and 70 percent of
black children, were regularly exposed to secondhand smoke [60]. Similarly, exposure to air
pollutants have been associated with sleep-disordered breathing [61,62]. (See "Secondhand smoke
exposure: Effects in children".)

Mucopolysaccharidoses — Children with any of the mucopolysaccharidoses and mucolipidoses

who have significant infiltration and accumulation of macromolecules in the tissues of their upper
airway are more likely to have OSA/OHV [63]. These children are also more likely to have respiratory
complications in the perioperative period and to have persistent OSA after adenotonsillectomy. (See
"Mucopolysaccharidoses: Clinical features and diagnosis" and "Adenotonsillectomy for obstructive
sleep apnea in children", section on 'Risk factors for persistent disease'.)
Craniofacial anomalies — In children with craniofacial anomalies, the characteristics most

commonly associated with OSA/OHV are:
● Midfacial hypoplasia
● Retro/micrognathia
● An acutely angled skull base
● Narrow maxillary arch
● Nasoseptal obstruction
● Macroglossia
● Other soft tissue abnormalities
These anomalies lead to a decrease in the size of the nasopharynx, oropharynx, or hypopharynx,
and can predispose the pharynx to collapse during sleep [64]. In some syndromes associated with
sleep-related breathing disorders, the obstruction can be attributed to specific anatomical sites (table
3). Management of these patients may include diagnostic procedures to determine the anatomic
site(s) of obstruction, and adjunctive surgical procedures to relieve the obstruction. Drug-induced
sleep endoscopy (DISE) is a diagnostic tool to identify the site or sites of upper airway collapse that
leads to OSA; the technique utilizes an anesthetic induction to simulate the upper airway relaxation
that occurs during natural sleep. The site of obstruction determined on DISE can then be
appropriately addressed surgically [65,66]. (See "Adenotonsillectomy for obstructive sleep apnea in
children", section on 'Management of patients with residual OSA after adenotonsillectomy'.)
The role of subtle craniofacial factors in the absence of obvious anomalies is less clear. In one study,
the mandibular dimensions of children with a sleep-related breathing disorder but without obvious
craniofacial abnormalities were no different than in children without a sleep-related breathing disorder
[67]. However, a narrow maxillary arch has been associated with OSA in children, and orthodontic
correction with rapid maxillary expansion has resulted in resolution of the sleep-related breathing
disorder [68]. (See "Management of obstructive sleep apnea in children", section on 'Orthodontics'.)
Neuromuscular factors — Neuromuscular factors affect the size, shape, compliance, and
coordination of the pharyngeal airway, which can have an important effect on the development of
sleep-related breathing disorders. Neuromuscular control of the upper airway is mediated by local
mechanoreceptor reflexes and by central drive, coordinated through the respiratory control center in
the medulla.
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The most common clinical neuromuscular problems contributing to OSA/OHV are alterations in
muscle tone (either hypotonia or hypertonia). However, the precise mechanism by which changes in
tone affect the pharyngeal airway has not yet been elucidated. Chronic changes in muscle tone may
have prominent effects on growth and development of the facial skeleton, and thereby affect upper
airway patency.
Impairment of the coordination and synchronization of the respiratory pump muscles with the
pharyngeal dilator muscles may also be a cause of OSA/OHV in children. This occurs during hiccups
[69] and when children with congenital alveolar hypoventilation are provided with diaphragmatic
pacers during sleep [70]. In both cases, the inspiratory pump functions independently of the
pharyngeal dilators, resulting in upper airway obstruction. This illustrates the importance of
synchronization of the pharyngeal dilators with the muscles of inspiration.
Dysfunction of the central nervous system may cause central sleep apnea (CSA) when the
respiratory control center of the medulla is affected or OSA/OHV if the central nervous system
dysfunction leads to neuromuscular dysfunction. As examples, either CSA or OSA may result from
compression of the brainstem as seen in children with Chiari malformation [71,72] or dysfunction of
the brainstem as seen in children with bulbar palsy or brainstem tumors [73]. The airway obstruction
may be caused by peripheral neuromuscular dysfunction or vocal cord paralysis. (See "Congenital
central hypoventilation syndrome and other causes of sleep-related hypoventilation in children",
section on 'Other causes of central sleep apnea'.)
Combined anatomic and neuromuscular factors — Anatomic and neuromuscular factors often
combine to cause a sleep-related breathing disorder, but the relative contribution of each can be hard
to predict. Both factors are often seen together in children with craniofacial syndromes, making them
at especially high risk for the development of a sleep-related breathing disorder.
The most common example is found in children with trisomy 21 (Down syndrome), which is
characterized by midfacial hypoplasia, a high-arched palate, macroglossia, cranial base anomalies,
and hypotonia. In one report, 81 percent of children with trisomy 21 had OSA or OHV; this study
used a daytime nap study, which may have underestimated the true incidence of OSA/OHV [74] (see
"Down syndrome: Clinical features and diagnosis"). For this reason, the American Academy of
Pediatrics (AAP) has recommended that all children with trisomy 21 have a polysomnogram before
four years of age, to evaluate for sleep-disordered breathing [75].
Drugs — In human and/or animal studies, alcohol, chloral hydrate, benzodiazepines, and general
anesthetics have all been shown to selectively decrease the activity of the pharyngeal dilators to a
greater extent than they affect the diaphragm. This imbalance could lead to an increased tendency of
the upper airway to collapse during inspiration. Case reports describe individuals who suffered acute
and sometimes fatal worsening of their OSA after treatment with these agents.
Narcotic analgesics are powerful respiratory depressants, leading to a marked decrease in hypoxic
and hypercarbic ventilatory drive and increased arousal threshold, making it harder for children to

arouse after an obstructive apnea. Together, these factors can be a dangerous combination in a child
with a sleep-related breathing disorder.
Genetics — The role of genetics in the development of OSA/OHV in children is intriguing but not well
understood. Familial aggregation of OSA has been noted in studies of adults and children, in both
obese and nonobese populations. In African American children, sleep-disordered breathing is 3.5
times more likely than in Caucasian children, after controlling for other factors such as obesity and
asthma [42,52]. The mechanism for this association is not understood. Obesity, craniofacial
morphology, and ventilatory control all are highly heritable traits and are important in the
pathophysiology of sleep-related breathing disorders. However, the genetic determinants of sleep-
related breathing disorders have not yet been delineated in either adults or children. This is an area
of active research, and it is likely the genetic factors for OSA will be much better characterized in the
next few years.
SUMMARY
● An obstructive sleep-related breathing disorder (or sleep-disordered breathing) is characterized

by discrete apneas, hypopneas, and respiratory effort-related arousals or by more continuous
reductions in gas exchange (hypoventilation). These conditions are caused by upper airway
obstruction that occurs exclusively during sleep. Sleep-related breathing disorders in children
occur along a spectrum of severity. (See 'Introduction' above.)
● Sleep is categorized into rapid eye movement (REM) and non-REM sleep (NREM). REM sleep
is associated with low muscle tone and in most pediatric patients, increased vulnerability to
obstructive sleep apnea (OSA). (See 'Sleep stages' above.)
● For children with a sleep-related breathing disorder, the increase in upper airway resistance
during sleep is exaggerated. This can lead to markedly increased work of breathing, snoring,
OSA, and/or obstructive hypoventilation (OHV). Immediate consequences can include sleep
disruption, hypoxia, and hypercarbia. (See 'Balance of forces model of upper airway obstruction'
above and 'Obstructive sleep apnea and obstructive hypoventilation' above.)
● The various factors that can limit the size of the upper airway are cumulative. In many children
with sleep-related breathing disorders, multiple factors contribute to the problem and must be
addressed for successful treatment. (See 'Predisposing factors' above.)
● The most common factor that restricts airway size and contributes to OSA/OHV in children is
enlarged tonsils (palatine and lingual) and adenoids. However, the majority of children with
grossly enlarged tonsils and adenoids do not have OSA/OHV, making it clear that adenotonsillar
size alone cannot explain the presence of a sleep-related breathing disorder in children. (See
'Enlarged tonsils and adenoids' above.)

● Obesity provides an increasingly common contribution to OSA/OHV in adults and children,

probably because obesity decreases the size and/or increases the collapsibility of the
pharyngeal airway. In many cases, both obesity and adenotonsillar hypertrophy together
contribute to OSA in an individual patient. (See 'Obesity' above.)
● Other factors contributing to OSA/OHV in some individuals include mucopolysaccharidoses,

craniofacial anomalies, neuromuscular factors, drugs that relax pharyngeal dilators or decrease
respiratory drive, inflammatory processes, environmental exposures, or genetic factors. (See
'Predisposing factors' above and 'Genetics' above.)
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Topic 6347 Version 23.0

GRAPHICS
Polysomnographic values in healthy children*
Children
Recommended classified as
Mean ± SD Range
normal values abnormal
n (percent)
Apnea index (n/h) 0.1 ± 0.5 0 to 3.1 ≤ 1¶ 1 (2)
Maximum PETCO2 (mmHg) 46 ± 4 38 to 53 ≤ 53 ¶ 0 (0)
Minimum PETCO2 (mmHg) 38 ± 3 28 to 44 NA NA
Change in PETCO2 (mmHg) 7±3 2 to 11 ≤ 13 0

Δ
Duration of hypoventilation 6.9 ± 19.1 0 to 90.5 ≤ 60 3 (6)
(percent TST)
Maximum SaO2 (percent) 100 ± 1 98 to 100 NA NA
Minimum SaO2 (percent) 96 ± 2 89 to 98 ≥ 92 Δ 2 (4)
Desaturation >4 percent/h 0.3 ± 0.7 0 to 4.4 ≤ 1.4 Δ 1 (2)

TST (n)
Change in SaO2 (percent) 4±2 0 to 11 ≤ 8¶ 2 (4)
Apnea index: number of obstructive apneas of any length per hour of sleep; TST: total sleeping time.
* The number of children classified as abnormal represents the number of children who would be judged to have an
abnormality based on the recommended values. Apnea index is defined as the number N of obstructive apneas of any length
per hour of sleep.
¶ Recommended normal values based on mean ± 2 SD when parameters follow a normal distribution.
Δ For data that are not normally distributed, the recommended normal values are based on inclusion of 97 percent of
subjects tested for one-tailed distribution.
Reproduced with permission from: Marcus EL, Omlin K, Basinski D, et al. Normal polysomnographic values for children and
adolescents. Am Rev Respir Dis 1992; 146:1236.
Graphic 62237 Version 3.0

MRI imaging to measure the airway and related

structures
Magnetic resonance imaging (MRI) of a healthy subject. A) Anatomical outlines

of an axial T1 image at the level of the maximal tonsillar area. Transverse red
arrow represents the intermandibular distance. B) Anatomical outlines of a
midsagittal T1 image. Oblique red arrow represents the mental spine-clivus
oblique distance.
Reproduced with permission from Arens R, McDonough JM, Costarino A, et al.

Magnetic resonance imaging of the upper airway structure of children with obstructive
sleep apnea syndrome. Am J Respir Crit Care Med 2001; 164:6998. Official Journal of
the American Thoracic Society. Copyright © 2001 American Thoracic Society.

Starling resistor model of the upper airway
The tendency of the upper airway to collapse is determined by its critical closing
pressure, designated as P crit . When P crit is below tracheal pressure (P DS ),
airway is open without airflow limitation. When P crit is greater than tracheal
pressure (P DS ) but less than nasal pressure (P US ), there is partial airway
collapse with maximal inspiratory airflow limitation. When P crit is above nasal
pressure (P US ), there is complete obstructive apnea.
R US : upstream resistance; P US : upstream pressure; R DS : downstream resistance;

PDS: downstream pressure.
Adapted from: Marcus EL, McCalley SA, Carrol JL, et al, J Appl Physiol 1994; 77:918.

Partial airway collapse
Model of counterbalancing forces that influence airway patency
Adapted with permission from Thach, B. Neuromuscular control of the upper airway. In:
Beckerman, R, Brouillette, R, Hunt, C (Eds), Respiratory Control Disorders in Infants and
Children, Baltimore, Williams & Wilkins, 1990, p. 47.

MRI of the airway in a child with obstructive sleep apna
T1-weighted midsagittal and axial magnetic resonance imaging (MRI) of a

control subject (C) and a subject with obstructive sleep apnea (OSA). Note that
the subject with OSA has a narrow nasopharyngeal (top right) and
oropharyngeal (lower right) airway.
C: control; OSAS: obstructive sleep apnea.
Reproduced with permission from Arens, R, McDonough, JM, Costarino, A, et al.

Magnetic resonance imaging of the upper airway structure of children with obstructive
sleep apnea syndrome. Am J Respir Crit Care Med 2001; 164:698. Official Journal of
the American Thoracic Society. Copyright ©2001 American Thoracic Society.

Upper airway size analysis in obstructive sleep apnea
Segmental analysis-percent airway centerline length versus (A) mean airway

cross-sectional area, (B) minimal cross-sectional area, and (C) volume. Data
points represent mean values ±SD along 10 percent segments. Dotted lines
represent estimated measurements between data points. Solid blue circles =
subjects with obstructive sleep apnea; open red circles = control subjects.
Regions of the adenoid and tonsils adjacent to the airway are shown by
horizontal bars. Note the overlap regions for tonsils and adenoid.
OSA: obstructive sleep apnea

* p <0.05
** p <0.005
*** p <0.0005
Reproduced with permission from Arens R, McDonough JM, Corbin AM, et al. Upper
airway size analysis of children with obstructive sleep apnea syndrome. Am J Respir
Crit Care Med 2003; 167:65. Official Journal of the American Thoracic Society.
Copyright © 2003 American Thoracic Society.

Airway shape analysis in obstructive sleep apnea
Shape analysis: Average anterior-posterior (A-P) and lateral (LAT) dimension at several oropharyngeal
levels. Lines link segmental volume levels. Subjects with obstructive sleep apnea (OSA) are shown in red;
control subjects in blue. Open triangles: inspiratory A-P and lateral dimension in OSA; closed triangles:
expiratory A-P and lateral dimension in OSA; open squares: inspiratory A-P and lateral dimension in
control subjects; closed squares: expiratory A-P and lateral dimension in control subjects. Ellipses
illustrate relative differences in A-P and lateral dimensions in OSA and control subjects. Ellipses are shown
for minimum during inspiration (filled ellipses) and maximum during expiration (open ellipses).
Reproduced with permission from: Arens R, Sin S, McDonough J, et al. Changes in upper airway size during tidal
breathing in children with obstructive sleep apnea syndrome. Am J Respir Crit Care Med 2005; 171:1298. Official
Journal of the American Thoracic Society. Copyright © 2005 American Thoracic Society.

Upper airway size during tidal breathing
Dynamic changes in cross-sectional area at midtonsillar level (level 2) during tidal breathing
of control subjects (top panels); and in subjects with obstructive sleep apnea (bottom
panels), with 5-vol increments of inspiration (Ins) and 5-vol increments of expiration (Exp).
Note the differences in anteroposterior (A-P) and lateral airway dimension.
%: percent; Ins: inspiration; Exp: expiration.
Reproduced with permission from: Arens R, Sin S, McDonough J, et al. Changes in upper airway
size during tidal breathing in children with obstructive sleep apnea syndrome. Am J Respir Crit
Care Med 2005; 171:1298. Official Journal of the American Thoracic Society. Copyright © 2005
American Thoracic Society.

Anatomic factors contributing to upper airway obstruction in children
Nose
Deviated septum
Rhinitis (allergic or non-allergic)
Choanal atresia
Nasal polyps
Oropharynx
Tonsillar hypertrophy*
Macroglossia
Retro/micrognathia
Infiltration by mucopolysaccarides (Hunter/Hurler syndromes)
Obesity
Oropharyngeal burns
Acute skull base angle
Pharyngeal flap
High arched palate
Nasopharynx
Midfacial hypoplasia
Adenoidal hypertrophy*
Hypopharynx
Laryngotracheomalacia
Vocal cord paralysis
Vascular ring
Subglottic stenosis
Hemangioma
Neurofibroma
* Most common factors.

Syndromes that have obstructive sleep apnea as a finding and the factors that
contribute to the obstruction
Maxillary
Choanal
Hypoplasia Cranial Hypotonia
Micro- Atresia Macro- Other
Syndrome (Small Base of
gnathia or glossia Anomalies
Nasal Anomalies Pharynx
Stenosis
Capsule)
Achondroplasia + + +
Apert + + +
Beckwith- + + CNS anomalies

Wiedemann
Camptomelic + Tracheal,
and dysplasia bronchial
cartilage
anomalies;
Cerebro- +
costo-
mandibular
Charge + + CNS anomalies

association
Crouzon + + + Tracheal ring

anomalies
De Lange + + CNS anomalies
Diastrophic + +
dysplasia
Femoral +
dysgenesis
Fetal alcohol + + CNS anomalies
Fetal + CNS anomalies

hydantoin
Freeman- + Multiple
Sheldon contractures
Fronto- + + Cranial
metaphyseal overgrowth;
dysplasia scoliosis
Hallermann- + +
Streiff
Hemifacial + + Pharyngeal
microsomia asymmetry
Holo- + + + + CNS anomalies

prosencephaly
sequence
Larsen's + Connective
tissue dysplasia
Marshall- + + + + + CNS anomalies

Smith
Nager + + + +
Otopalato- + +
digital
Pfeiffer + + + Tracheal ring

anomalies
Prader-Willi + CNS anomalies

Pykno- + + +
dysostosis
Robin +
sequence
(isolated)
Rubinstein- + + + + CNS anomalies

Taybi
Shprintzen + + Laryngeal web;

retrognathia
Shprintzen- + + + +
Goldberg
Spondylo- +
epiphyseal
dysplasia
Stickler + + + Short
genioglossus;
soft tracheal
cartilage
Storage +
disorders
(lysosomal,
etc)
Steinert + + Myotonia
Townes + +
Treacher + + + +
Collins
Turner + Short neck
Chromosome disorders
Down + + + + CNS anomalies
syndrome
(Trisomy 21)
Trisomy 18 + + + CNS anomalies

Trisomy 13 + + + CNS anomalies;
holoprosencephaly
Trisomy 4p + + CNS anomalies;
short neck
6q-deletion + CNS anomalies;
laryngeal
dysfunction
Reproduced with permission from: Sher AE. Obstructive sleep apnea syndrome: a complex disorder of the upper airway.
Otolaryngol Clin North Am 1990; 23:593. Copyright ©1990 Elsevier.

Contributor Disclosures
Gerald M Rosen, MD Nothing to disclose Keith L Cavanaugh, MD, FAAP, FCCP Nothing to
disclose Brianne Barnett Roby, MD Nothing to disclose Ronald D Chervin, MD, MS Patent Holder:
University of Michigan [Sleep disorders (Patents and copyrighted material for assessment and treatment of
patients with sleep disorders)]. Other Financial Interests: American Academy of Sleep Medicine [Sleep
disorders (Standards, conferences, services to support physicians and patients)]; International Pediatric Sleep
Association [Sleep disorders (Standards, conferences, services to support physicians and patients)]. Alison G
Hoppin, MD Nothing to disclose
Contributor disclosures are reviewed for conﬂicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform
to UpToDate standards of evidence.
Conﬂict of interest policy

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Mechanisms and predisposing factors for sleep-related

REM sleep is a physiologically activated sleep state characterized by:

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● Generalized muscle atonia

By comparison, NREM sleep is a more quiescent state characterized by:

● Reduced, but not absent, muscle tone

CHANGES IN RESPIRATORY PHYSIOLOGY DURING SLEEP

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● A decrease in load compensation

BALANCE OF FORCES MODEL OF UPPER AIRWAY OBSTRUCTION

This balance is affected by:

● The skeletal and soft tissue anatomy of the upper airway

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● Suction pressure generated by the inspiratory pump muscles

● Obstructive hypoventilation – In obstructive hypoventilation (OHV) there is continuous partial

OBSTRUCTIVE SLEEP APNEA AND OBSTRUCTIVE HYPOVENTILATION

Sleep-related breathing disorders in children ranges on a spectrum from snoring to obstructive

● An anatomically small upper airway

● Larger at all pharyngeal levels

In contrast, in children with OSA the airway is:

● Smaller at all levels

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Mucopolysaccharidoses — Children with any of the mucopolysaccharidoses and mucolipidoses

Craniofacial anomalies — In children with craniofacial anomalies, the characteristics most

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● An obstructive sleep-related breathing disorder (or sleep-disordered breathing) is characterized

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● Obesity provides an increasingly common contribution to OSA/OHV in adults and children,

● Other factors contributing to OSA/OHV in some individuals include mucopolysaccharidoses,

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6. Montgomery-Downs HE, O'Brien LM, Gulliver TE, Gozal D. Polysomnographic characteristics

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37. Arens R, Marcus CL. Pathophysiology of upper airway obstruction: a developmental

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Otorhinolaryngol 1987; 13:149.

45. Tal A, Bar A, Leiberman A, Tarasiuk A. Sleep characteristics following adenotonsillectomy in

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55. Kheirandish-Gozal L, Sans Capdevila O, Kheirandish E, Gozal D. Elevated serum

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Topic 6347 Version 23.0

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Polysomnographic values in healthy children*

Apnea index (n/h) 0.1 ± 0.5 0 to 3.1 ≤ 1¶ 1 (2)

Maximum PETCO2 (mmHg) 46 ± 4 38 to 53 ≤ 53 ¶ 0 (0)

Minimum PETCO2 (mmHg) 38 ± 3 28 to 44 NA NA

Change in PETCO2 (mmHg) 7±3 2 to 11 ≤ 13 0

Maximum SaO2 (percent) 100 ± 1 98 to 100 NA NA

Minimum SaO2 (percent) 96 ± 2 89 to 98 ≥ 92 Δ 2 (4)

Desaturation >4 percent/h 0.3 ± 0.7 0 to 4.4 ≤ 1.4 Δ 1 (2)

Change in SaO2 (percent) 4±2 0 to 11 ≤ 8¶ 2 (4)

Graphic 62237 Version 3.0

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MRI imaging to measure the airway and related

Magnetic resonance imaging (MRI) of a healthy subject. A) Anatomical outlines

Reproduced with permission from Arens R, McDonough JM, Costarino A, et al.

Graphic 78760 Version 3.0