OSA is one of the most common health problems in the pediatric population, affecting 1% to 4% of all children in the United States [29]. The peak incidence of OSA in children is reported to range between 2 and 8 years due to the increased size of the lymphoid tissues within this age [34]. Nevertheless, the incidence and causes of OSA in young infants under 2 years of age are still understudied, as the diagnosis of OSA in this age group is very challenging due to the limitations of polysomnographic techniques [35]. The percentage of children with OSA and laryngomalacia varies in different studies, ranging from 79% to 14.3% [14,36] in relation to the children’s age.

Currently, there are several etiologic theories of laryngomalacia in the literature, but the precise etiopathogenetic features remain controversial [1]. Proposed etiologies include the anatomic theory, the cartilaginous theory, the neurologic theory, or a combination of these [3,10,37,38,39] (Table 1).

The “anatomic theory” is based on the evidence that one of the anatomic abnormalities seen in laryngomalacia is an unusually long and flaccid epiglottis, omega-shaped, which is displaced posteriorly against the posterior pharyngeal wall during inspiration. Another possible finding is the presence of short aryepiglottic folds that may retroflex a normally shaped epiglottis [3]. In other cases, bulky arytenoids may prolapse anteriorly during inspiration due to redundant mucosa overlying the arytenoids [40]. These changes may occur separately or in combination, and the most common is the association of a shortened aryepiglottic wall and a redundant arytenoid mucosa [16]. Malformations of the upper airway, of the central nervous system [41], and/or of the cardiac system may also be associated.

The “cartilaginous theory” refers to disorders in the cartilaginous framework of the larynx and trachea, causing a greater laxity in supraglottic structures [37]; a particular cartilage ‘immaturity’ with an increased malleability has been proposed by histological studies [1,42]. Gastroesophageal reflux (GER) is an important cofactor, probably causing cartilaginous modification and edema of the laryngeal mucosa, with a consequent obstruction of the laryngeal lumen [43].

Matthews et al. [43], with double probe pH monitoring, demonstrated that most children with laryngomalacia have a larynx exposed to acid on a regular basis. Garritano et al. [44] found GER in 88.2% of young patients undergoing supraglottoplasty for laryngomalacia and reported that gastroesophageal reflux and apnea may have a close relationship [38]. Arad-Cohen et al. [45] reported that apnea preceded reflux in 93.6% of episodes, and only 6.4% of apneic episodes were followed by reflux. Menon and colleagues [46] reported an increased frequency of apnea in infants with regurgitation, but this was not related to GER, while Kamal et al. [47] recently reported that neonates affected by GER developed OSA.

It is likely that laryngomalacia is often associated with GER [48]; however, the role of GER in the pathogenesis of laryngomalacia remains controversial. Even if several studies [1,42] have highlighted the presence of mild inflammation in the surgical specimens of children who undergo supraglottoplasty for laryngomalacia, eosinophilia, a proposed histological marker of GER [42], was only identified in a few cases (3 out 61). Evidence supporting the use of acid suppression therapy (AST) for laryngomalacia is limited because of the lack of randomized controlled trials [49].

The “neurological theory” [10] is supported by the fact that a child with laryngomalacia often has neurological comorbidities (with an incidence of 8–50%) correlated with hypotonia, prematurity, a history of Apparent Life-Threatening Event (ALTE). These children also have congenital syndromes (18.5%), with genetic anomalies present in 8–20% of cases, mainly represented by Down syndrome. Tanphaichitr and colleagues [50] have highlighted that children with laryngomalacia have a high incidence of central sleep apnea (CSA), demonstrating altered laryngeal tone and sensorimotor integrative function of the larynx, with subsequent lack of neuromotor coordination [39]. Weak laryngeal tone, apnea, and swallowing problems often coexist with laryngomalacia and could be related to an abnormal function of the pathway at the brainstem nuclei. The tendency for this condition to improve spontaneously within the first two years of life provides further support that growth and maturation may reduce the collapsibility of supraglottic tissues.

Obesity has been investigated as a potential link between laryngomalacia and obstructive apneas by Kennedy et al. [27], with a 578.1% increase in the frequency of laryngomalacia in patients with obesity compared to patients without obesity. Obese individuals have a greater potential for laryngeal collapse, particularly due to a high concentration of adipose tissue around the head and neck [51].

Children with laryngomalacia could present Synchronous Airway Lesions (SALs), with an incidence of 7.7–51.7% [52,53]. Bredun and colleagues [54] have described these lesions in 15.1% of children with laryngomalacia, and the associated malformation consisted of laryngotracheoesophageal cleft (61.1%), tracheomalacia and tracheobronchomalacia (16.7%), trachea-esophageal fistula (5.6%). Therefore, the endoscopic evaluation of laryngomalacia should always include the assessment of the lower airways in order to consider the eventual presence of SALs that could have a further clinical impact [55].

The diagnostic suspicion of laryngomalacia in infants (<2 years of age) arises from inspiratory stridor and can be easily confirmed by awake rhinopharyngolaryngoscopy. This diagnostic method allows us to appreciate static and dynamic anatomical supraglottic anomalies.

Several endoscopic classification systems have been proposed, firstly by McSwiney [56]. The most recent and simple, the Groningen classification of laryngomalacia [57], distinguished three different types of laryngomalacia: Type 1: the inward collapse of the arytenoid cartilages; Type 2: medial displacement of the aryepiglottic folds; and Type 3: posterocaudal displacement of the epiglottis against the posterior pharyngeal wall.

Rhinopharyngolaryngoscopy is also a critical procedure to rule out other potential anatomic airway lesions, such as laryngeal clefts or superior subglottic stenosis (5.6–16.7%) [25].

The diagnosis should be made as early as possible and eventually on the first day of life if stridor is present.

In older children, laryngomalacia should also be suspected in cases of obstructive sleep apnea symptoms, such as snoring, hyperactivity disorders, or attention-deficit.

In children even older, laryngomalacia should be suspected in case of recurrent OSA after adenotonsillectomy. Therefore, polysomnography (PSG) is essential to document OSA persistence or recurrence, and the International Pediatric Otorhinolaryngologic Group (IPOG) [58] has recently recommended PSG in the diagnostic work-up and decision-making in laryngomalacia, particularly when significant apnea is present.

DISE, which consists of the use of flexible fiberoptic rhinopharyngolaryngoscopy under sedation in the operating room with the patient spontaneously breathing, is useful in identifying potential surgical targets in refractory cases. Hypertrophy of the lingual tonsils and laryngomalacia are the most common findings in DISE studies [28].

Under sedation, it is also possible to complete the airway examination using a microlaryngotracheobronchoscopy, including the tracheal segment of the airway. This procedure can rule out the presence of tracheomalacia or subglottic stenosis, which is also possibly associated with laryngomalacia [59].

Sleep endoscopy is a novel diagnostic tool in the evaluation of children with obstructive sleep apnea that may lead to the observational diagnosis of sleep-dependent laryngomalacia in the absence of other symptoms or daily stridor [20].

Comparison between rhinopharyngoscopy and DISE is difficult as the airway dynamics differ between awake and asleep statuses and since each technique has specific inherent limitations [28]. Therefore, it may be reasonable to consider fiberoptic evaluation and DISE as complementary modalities when assessing supraglottic airway dynamics and severity of obstruction in infants with laryngomalacia, especially if surgical treatment is needed. Boudewyns et al. [60] showed that upper airway evaluation using DISE changed the treatment decision in 1/3 of their infants less than 2 years of age. This finding suggests that 1/3 of their patients could have been treated inadequately with standard adenotonsillectomy, and the multilevel obstruction could have been missed. Digoy and colleagues [26] described the procedure in children with laryngomalacia to evaluate the laryngeal contribution to sleep apnea. They performed the procedure under general anesthesia, induced with sevoflurane (8%) in 100% oxygen. The administration of sevoflurane was then reduced or stopped while the patient was spontaneously breathing, and at that moment, the surgeon performed either indirect laryngoscopy or direct laryngoscopy. Occasionally, small doses of intravenous propofol were administered to perform direct laryngoscopy. As the child then neared stage II anesthesia, dynamic breathing and pharyngolaryngeal muscle movements were examined. Therefore, they modified the practice in favor of flexible endoscopy, as this method can be done at a lighter level of anesthesia and may provide a more valid assessment of airway dynamics (see also Table 2).

At present, there is no unanimous consensus in the literature on DISE procedures in patients with laryngomalacia. Often, the assessment is performed under sedation in direct laryngoscopy, with the patient still breathing spontaneously; in other cases, a flexible instrument is used with different drugs for the sedation. Several methods have included propofol alone [61], propofol/narcotic combination [12], dexmedetomidine, ketamine/dexmedetomidine, and midazolam/narcotic [62,63,64]. Additionally, the type of laryngeal alteration detected is not always reported. No universal classification is used, and a comparison of results between different studies is difficult.

Some authors suggested the use of bronchoscopy to exclude the possible presence of associated subglottic malformations. Certainly, the use of this method is indicated when laryngeal endoscopic is negative, and this examination fails to fully explain the child’s symptoms [65].

Laryngomalacia most commonly affects infants and improves spontaneously by 2 years of age, as already described [69]. While in the majority of cases, laryngomalacia follows this safe pathway, rarely can it be severe enough to cause breathing and feeding disorders that can impact normal development and growth. In the most severe cases, laryngomalacia has been described as a cause of sudden infant death syndrome [70].

Approximately 5–20% of severe or refractory children require surgery [71]. To date, supraglottoplasty is the first-line treatment for this condition [5,25]. Surgical techniques to treat this pathology have evolved over time, ranging from tracheotomy to transoral procedures. Historically, tracheotomy was the only method of treating laryngomalacia [72]. The first surgical approach to epiglottis was performed by Iglauer in 1922, who removed the epiglottis using a nasal sling [73].

The use of supraglottoplasty for the treatment of severe laryngomalacia was first described by Holinger et al. in 1989 [72]. A year later, its use in the treatment of OSA in pediatric patients with laryngomalacia was described. Currently, this technique represents the gold standard for the management of this condition [74]. Supraglottoplasty can be bilateral or unilateral and can be performed with cold instruments, LASER CO₂, debridement, or radiofrequency [3,16,17,18,19,20,21,22,23,24,25,26]. This technique includes several procedures that are performed depending on the pathological site found (e.g., shortened aryepiglottic wall, omega-shaped epiglottis, redundant mucosa of the arytenoid regions) and it is anatomically divided into epiglottoplasty, aryepiglotticoplasty, and arytenoidoplasty [75]. Therefore, the main principle is to treat only the altered supraglottic structures and to tailor the treatment for each patient [18].

Laryngomalacia can also occur in children over the age of 2, often in association with residual OSA following adenotonsillectomy [12,76,77]. Clearly, the clinical, diagnostic, and especially therapeutic indications differ significantly between birth-onset and late-onset laryngomalacia. Patients with congenital laryngomalacia usually have a higher average AHI than patients with late laryngomalacia, but supraglottoplasty leads to excellent postoperative results in both groups (Figure 1). Treatment features within the included studies are presented in Table 3.

No new data were created or analyzed in this study. Data sharing is not applicable to this article, as this is a review paper.