Pediatric Clinical Presentations of Obstructive Sleep Apnea Syndrome

The protection of children's health represents a priority focus in modern healthcare systems. Pediatric medical issues demonstrate unique characteristics, as multiple factors contribute to the early development of acute and chronic upper respiratory tract diseases, among which otorhinolaryngological pathology holds significant importance.

During childhood development, substantial anatomical and physiological changes occur in various organ systems and their functional structures. During periods of intensive morphological, physiological, and psychological transformation, children exhibit particular vulnerability to pathological influences, potentially disrupting the equilibrium between the organism and its environment.

A broad spectrum of childhood disorders has been associated with obstructive sleep apnea syndrome (OSAS). Recent studies reference approximately 80 sleep-related pathologies, including restless legs syndrome, snoring, insomnia, and sleep apnea (cessation of breathing during sleep) [1]. Considerable attention has been directed toward the quality of life impairment in patients with sleep-disordered breathing. As early as 1967, R. Jung and W. Kuhlo first distinguished sleep apnea as a distinct pathological entity from Pickwickian syndrome (characterized by recurrent nocturnal asphyxia episodes), identifying it as a cause of cerebral electrical instability with frequent nocturnal awakenings, hypercapnia, and severe hypoxia. Their research established that these pathophysiological changes fundamentally stem from obstructive sleep apnea, proposing tracheotomy as a potential corrective intervention [1].

OSAS represents a relatively prevalent pediatric condition whose clinical and social consequences often remain underestimated. The syndrome causes general malaise with chronic intoxication, daytime somnolence, headaches, appetite suppression, irritability, hyperactivity, rapid fatigue, and sleep disturbances. Characteristic pediatric symptoms also include frequent nocturnal urination, restless sleep, and behavioral changes [2]. Significant neurocognitive and cardiovascular complications correlate with growth impairments and mood disorders. The proposed mechanism involves recurrent upper airway collapse triggering a cascade of events leading to increased sympathetic nervous system tone and activation of the renin-angiotensin-aldosterone system. The pathophysiology prominently features repeated episodes of nocturnal hypoxemia and hypercapnia, ultimately resulting in vasoconstriction, endothelial dysfunction with myocardial remodeling, and hypertension development. This condition associates with pulmonary hypertension, metabolic syndrome, hyperactivity, inattention, memory impairment, learning difficulties, nocturnal enuresis, and increased healthcare utilization [3].

In infants, laryngomalacia, connective tissue dysplasia, and airway edema secondary to gastroesophageal reflux also constitute etiological factors for OSAS. During preschool years, adenotonsillar hypertrophy emerges as the predominant cause, confirmed through endoscopic and magnetic resonance imaging (MRI) findings. According to literature, adenotonsillectomy produces symptomatic improvement in 85% of such cases [4,5].

Recent neuroimaging studies utilizing brain tomography have demonstrated that more severe caregiver-reported sleep-disordered breathing symptoms in children correlate with reduced cortical gray matter thickness in frontal lobes, affecting executive functioning skills [6]. Consequently, upper airway obstruction during sleep represents a common source of pediatric morbidity, contributing to numerous clinical conditions including neurobehavioral problems and increased metabolic/cardiovascular system burden. The most robust evidence connects OSAS with hyperactivity, inattention, and social dysfunction—manifesting as diminished social competence, increased problematic behaviors, and reduced memory performance.

Epidemiological studies report inconsistent prevalence data for pediatric OSAS due to variable diagnostic criteria. Despite accumulating evidence of cognitive dysfunction in children who snore, extrapolating OSAS prevalence data across populations remains challenging.

Study Objective: To analyze literature data regarding clinical manifestations, laboratory/instrumental diagnostic methods, and prevalence of OSAS in children. We conducted a systematic review of PubMed, EMBASE, and Web of Science publications (January 1970-March 2024) addressing epidemiological, pathogenetic, and clinical-laboratory aspects of OSAS across pediatric and adult populations.

Causes of Obstructive Sleep Apnea in Children

It is reported that snoring occurs in 3–15% of the pediatric population, particularly in children aged 3 to 6 years (13–35%) [7, 8]. The prevalence of obstructive sleep apnea syndrome (OSAS) is estimated to be 1–5% among children, with the highest incidence occurring between 2 and 6 years of age (peaking at 2.5 years in boys and 4 years in girls), without significant gender differences.

In Russia, the prevalence of OSAS in children remains understudied [7, 8].

A spectrum of sleep-related breathing disorders exists, including obstructive hypoventilation, hyperventilation, central sleep apnea, and other breathing disturbances in children. Obstructive sleep apnea syndrome (OSAS) is the most severe manifestation of obstructive hypoventilation.

The key clinical features of OSAS in children include:

• Snoring
• Decreased blood oxygen levels
• Cessation of pulmonary ventilation despite ongoing respiratory effort due to periodic collapse of the upper airways at the pharyngeal level
• Severe sleep fragmentation
• Excessive daytime sleepiness

In children, obstructive breathing disorders can be classified into three distinct phenotypes (according to foreign literature):

1. Upper airway resistance syndrome (UARS)
2. Primary snoring (rhonchopathy)
3. Obstructive sleep apnea/hypopnea syndrome (OSAHS) – the most severe form of obstructive sleep disorders [9].

In preschool-aged children, hypertrophy of the tonsils (lymphoepithelial pharyngeal ring) is the primary cause of airway narrowing during sleep [1, 8]. However, the degree of tonsillar hypertrophy does not directly correlate with the number of apnea episodes. While children with enlarged tonsils do not necessarily snore more frequently, they experience longer apnea episodes and greater decreases in blood oxyhemoglobin levels.

The etiology of adenotonsillar hypertrophy is strongly influenced by lymphotropic viruses and bacteria capable of intracellular persistence and latent infection (e.g., herpesviruses, chlamydia, mycoplasma, streptococcus), which contribute to chronic infection and prolonged antigenic stimulation of lymphoid tissue [6]. This leads to pathological immune, toxic, and neuroreflex mechanisms, including:

• Activation of pro-inflammatory cytokines (IL-6, IL-8, TNF-α)
• Increased endogenous nitric oxide production in peripheral blood [7, 10].

Chronic adenotonsillar hypertrophy, tonsillitis, and adenoiditis alter both systemic and local immune parameters, though research on immune changes in adenotonsillar pathology remains limited and contradictory [11].

Obesity as a Major Risk Factor

Obesity is a significant risk factor for OSAS in children, becoming the dominant factor in adolescents [12]. Obesity can lead to insulin resistance, hepatic steatosis, and increased production of pro-inflammatory mediators (leptin, IL-6, TNF-α) [12–14]. Among asthmatic children, those with obesity have a fourfold higher risk of developing OSAS, especially with poor pharmacological control [12–14].

Metabolic Effects of Melatonin

Melatonin plays a crucial role in metabolism (lipolytic and hypoglycemic effects), with well-documented links to obesity and insulin resistance. Studies confirm that melatonin deficiency is associated with all components of metabolic syndrome:

• Essential for insulin synthesis, secretion, and activation
• Regulates GLUT4 glucose transporter expression
• Activates G-protein-coupled receptors, ensuring normal insulin receptor function [15, 16].

Additionally, melatonin is a potent mitochondrial protector, and its deficiency is linked to reduced energy synthesis and slower metabolism, contributing to obesity [15]. Therefore, normalizing sleep is critical in treating metabolic disorders such as obesity, insulin resistance, type 2 diabetes, and metabolic syndrome [12–14].

Other Contributing Factors

Other important factors in pediatric OSAS include:

• Allergic rhinitis and nasopharyngeal pathology
• Congenital craniofacial anomalies (e.g., Crouzon, Down, Hunter, Pierre Robin, Goldenhar syndromes, oculo-mandibulo-facial syndrome)
• Nasal cavity obstructions, laryngeal tumors, laryngomalacia, tracheobronchomalacia
• Cystic fibrosis, bilateral vocal cord paralysis
• Neurological disorders (e.g., cerebral palsy, myopathies) [1, 14, 19–22].

A history of allergic rhinitis, nasal septal deformities, turbinate hypertrophy, chronic rhinosinusitis exacerbations (moderate to severe) can worsen OSAS symptoms, necessitating treatment adjustments, including antibiotic therapy [23].

Clinical Manifestations of Sleep Apnea in Children

One of the hallmark symptoms of obstructive sleep apnea syndrome (OSAS) in children is snoring, particularly when sleeping in the supine position, which exacerbates upper airway obstruction.

Key Clinical Features of OSAS in Children

• Mouth breathing
• Snorting and noisy breathing during sleep
• Witnessed breathing pauses (most noticeable in the supine position)
• Increased motor activity during sleep (restlessness, frequent position changes)
• Restless legs syndrome
• Nocturnal enuresis (bedwetting)
• Excessive daytime sleepiness
• Morning headaches
• Attention deficits, hyperactivity, and learning difficulties

The prevalence of snoring varies slightly across age groups, being more common in preschool-aged children than in older children [9, 22]. The presence of multiple symptoms should raise clinical suspicion of sleep-disordered breathing and prompt further evaluation for OSAS.

Challenges in Diagnosis

Young children cannot self-report snoring, and since snoring is more frequent in preschoolers than in older children [9, 22], parental observation of nighttime symptoms and daytime behavior is crucial.

Clinically, snoring should not be dismissed as benign, as it correlates with:

• Daytime symptoms: Chronic fatigue, depression, anxiety, and behavioral disturbances.
• Nighttime symptoms: Night sweats, bruxism (teeth grinding), sleepwalking, sleep talking, nightmares, restless sleep, and enuresis.

The severity of snoring depends on the size and anatomical positioning of hypertrophied lymphoid tissue [1].

Snoring vs. OSAS: A Diagnostic Dilemma

While most children with OSAS snore, not all children who snore have OSAS. Differentiating between primary snoring (benign) and OSAS remains a well-recognized challenge in pediatric sleep medicine.

Key diagnostic difficulties include:

• Lack of standardized snoring criteria
• Symptom variability (most apneic events occur during REM sleep in the later part of the night, making them harder for parents to observe) [8, 9, 24]

Long-Term Complications

Untreated pediatric OSAS can lead to adult-like complications, including:

• Chronic intermittent hypoxia → impaired growth and systemic metabolic dysfunction
• Obesity (which worsens snoring and apnea severity)
• Cardiovascular sequelae:
  • Pulmonary hypertension
  • Right ventricular hypertrophy (cor pulmonale)
  • Elevated biomarkers of endothelial damage (C-reactive protein, brain natriuretic peptide, adhesion molecules, myeloid-related protein 8/14, fatty acid-binding protein) [3, 26]
• Neurocognitive and developmental delays

Given the multisystemic impact of OSAS, early recognition and intervention are critical to prevent long-term cardiopulmonary, metabolic, and neurodevelopmental consequences. A high index of suspicion, combined with parental reports and objective sleep studies, is essential for accurate diagnosis and management.

Diagnosis of Obstructive Sleep Apnea Syndrome in Children

The diagnosis of pediatric obstructive sleep apnea syndrome (OSAS) involves:

1. A thorough clinical history with emphasis on physical examination findings, particularly in ENT evaluation
2. Documentation of nocturnal and daytime symptoms along with comorbidities through specialized parental questionnaires
3. Mandatory nocturnal oximetry and ambulatory polysomnography

For patients with residual OSAS post-surgery, drug-induced sleep endoscopy (DISE) should be considered to identify anatomical sites of potential airway collapse [27].

When adenotonsillectomy is contraindicated, or when residual OSAS persists post-operatively, or in cases with comorbidities, additional evaluation and a modified management plan are often required. This may include:

• Positive airway pressure (PAP) ventilation
• Weight management
• Dental procedures
• Secondary airway surgery
• Pharmacological therapy

Treatment selection should be individualized based on:

• The child's comorbidities
• Patient/family preferences
• Disease severity
• Should be planned in consultation with pediatric otolaryngology or sleep medicine specialists

Clinical data, patient histories, and parental questionnaires remain important for diagnosis and may serve as supplementary diagnostic tools for assessing OSAS probability, though they carry significant uncertainties themselves [8,9,28].

The gold standard for OSAS diagnosis and severity stratification is polysomnography (PSG). Inpatient and autonomous PSG includes evaluation of:

• Sleep phase architecture
• Thoracic and abdominal respiratory movements
• Muscle tone
• Body position
• Electrocardiogram
• Blood oxygen saturation [29]

However, PSG remains a labor-intensive and expensive testing method, often requiring nursing supervision and video monitoring. Moreover, the availability of pediatric sleep laboratories is limited even in countries with advanced healthcare systems, leading to the search for less complex and more convenient testing methods [8,30].

A more accessible and convenient alternative to PSG is cardiorespiratory monitoring (CRM). This method records:

• Respiratory effort
• Airflow
• Blood oxygen saturation
• Electrocardiogram

Limitations of CRM:

• Does not assess sleep criteria
• May underestimate sleep apnea severity due to inability to measure wake periods

These limitations mean CRM is primarily recommended for identifying children at high risk of OSAS [31,32]. The advantages of CRM include its simplicity and the ability to conduct the study at home.

Even with significant upper airway obstruction during sleep, examination findings while awake may appear completely normal. Static imaging methods (lateral radiography, MRI) are unsuitable for reliably identifying dynamic upper airway obstruction during sleep. Pulse oximetry may serve as a good alternative for assessing obstruction severity and establishing an OSAS diagnosis [9,33].

Nocturnal computerized pulse oximetry has been proposed as an abbreviated and inexpensive testing method for OSAS diagnosis. This method offers several advantages:

• Simple to perform and interpret
• Low cost
• Doesn't require close supervision
• Can be performed at home under normal sleep conditions
• Based on detecting abrupt SpO2 drops (desaturations) that accompany obstructive apneas and hypopneas during both REM and non-REM sleep [1,34].

Several systematic reviews have analyzed original articles to:

1. Establish reference values for nocturnal oximetry parameters in healthy children
2. Identify abnormal oximetry patterns predictive of OSAS in habitual snorers
3. Determine oximetry deviations that may predict treatment response and potential OSAS complications [32]

Findings suggesting OSAS:

• Nocturnal SpO2 drops <90%
• 2 clusters of desaturation events (≥4%)
• Oxygen desaturation index (ODI4) >2.2 events/hour (uncommon in children without OSAS)
• ≥3 desaturation clusters plus ≥3 SpO2 drops below 90% during nocturnal oximetry suggests moderate-to-severe OSAS
• ODI4 >2 events/hour combined with OSAS symptoms shows high positive predictive value for apnea-hypopnea index >1 event/hour [35,36]

Children without desaturation event clusters have low risk of serious respiratory complications after adenotonsillectomy. Thus, nocturnal pulse oximetry becomes a valuable tool to guide treatment decisions when polysomnography is unavailable. While a positive result can confirm OSAS diagnosis, a negative result doesn't exclude pathology. For this reason, pulse oximetry alone is insufficient for OSAS diagnosis [37,38].