Children with laryngomalacia requiring supraglottoplasty: an association with future development of sleep disordered breathing

Introduction

Laryngomalacia is the most common cause of stridor in infants accounting for up to 75% of cases (1). It is characterised by the collapse of redundant supraglottic structures during inspiration that may be secondary to immature laryngeal cartilage or abnormal sensorimotor integration (2,3). Most symptoms resolve spontaneously by 24 months of age. Approximately 20% of patients experience feeding difficulties, aspiration, failure to thrive, cyanotic spells, respiratory distress, and obstructive sleep apnoea (4,5). It is this cohort of patients that progresses to surgical intervention, by way of supraglottoplasty.

Supraglottoplasty involves division of the aryepiglottic folds and removal of redundant mucosa to reduce the prolapse of supraglottic structures into the airway. Improvement of stridor and work of breathing are seen in nearly all neurologically uncompromised patients who undergo supraglottoplasty as seen by improvement in stridor/work of breathing, weight gain, swallowing mechanics and apnoea/hypopnea index (AHI) (6).

Sleep disordered breathing (SDB) is a spectrum of disorders ranging from simple snoring to obstructive sleep apnea (OSA). SDB carries an estimated prevalence of 1–5% in the paediatric population and presents most commonly between the ages of 2–8 years (5,7). Children with SDB have been shown to have poorer neurocognitive and behavioural outcomes, memory performance, attention and school performance (8,9).

Laryngomalacia and OSA are distinct disease processes but are often simultaneously present with a reported incidence of OSA in patients with laryngomalacia of 79% (5). To the best of the investigator’s knowledge, no publications exist reporting the subsequent diagnosis of paediatric SDB in otherwise well patients following supraglottoplasty for the treatment of infantile laryngomalacia.

We aim to present the outcomes of this case series, to establish a potential association between patients with laryngomalacia requiring supraglottoplasty and subsequent development of SDB in childhood. This will aid in the future evaluation of this hypothesis with a multi-institutional trial.

Further investigation of the incidence of SDB in laryngomalacia will allow for earlier recognition and intervention, thus providing better standards of care to allow these children to harness their potential.

Methods

A retrospective review of children who underwent supraglottoplasty in the first 18 months of life from 2014 to 2021, at Queensland Children’s Hospital was performed. The clinical database was searched using Systematized Nomenclature of Medicine (SNOMED) and International Classification of Diseases, Tenth Revision (ICD-10) codes for supraglottoplasty and aryepiglottoplasty. The study is reported in accordance with the STROBE reporting guidelines (available at https://www.theajo.com/article/view/10.21037/ajo-23-63/rc).

Patients were included if they had a primary diagnosis of laryngomalacia in the absence of comorbidities that could contribute to SDB. This included history of craniofacial anomalies, Down syndrome and cardiac anomalies. Patients were excluded if other upper airway surgery under the same general anaesthetic for supraglottoplasty was performed or if they were lost to follow-up before the age of 2 years. Patients were excluded if SDB was recognised at the time of surgery.

The electronic medical record for each patient was reviewed and the following data collected: age, gender, indigenous status, gestational age at birth (segregated into term: ≥37 weeks gestation, late pre-term: 34–36 weeks, moderate pre-term: 32–33 weeks, early pre-term: <32 weeks), history of reflux, food allergy or intolerance, age when supraglottoplasty was performed, indication for supraglottoplasty, whether polysomnogram (PSG) was performed prior to and post intervention, results of PSG (simple snoring, mild sleep apnea: AHI 1–4, moderate sleep apnea: AHI 5–9, or severe sleep apnea: AHI ≥10, presence of central sleep apnea), requirement of supplemental oxygen prior to and post intervention, resolution of symptoms post intervention, length of follow-up in months, incidence of SDB on follow-up established either via clinical presentation by an otolaryngologist or via PSG and whether further surgical intervention was required to manage new onset of SDB. SDB was defined as a history of nightly snoring, with or without parentally observed apneas. OSA was diagnosed based on PSG results showing an AHI greater than 1. Data was de-identified, collected and stored in a secure online database (REDCap 10.0.19).

Statistical analysis

Means and standard deviations (SDs) were used to summarize continuous variables. Counts and percentages were used to summarize categorical variables. The significance of the associations between categorical outcome variables and the explanatory groups (or equivalently, the differences in outcome proportions between groups) were compared using either Fisher’s exact test or the Chi-squared test. The Chi-squared test was used whenever the expected number of outcomes in each subgroup (for example. males with SDB, males without SDB, females with SDB, females without SDB) was greater than 5. Fisher’s exact test was used in cases where this assumption was not met.

For each test, the null hypothesis was deemed when there was no association between the outcome (dependent) variable and the explanatory (independent) variable (or equivalently, the outcome proportions are the same for all groups). Findings were considered statistically significant at P<0.05.

Ethical statement

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by Children’s Health Queensland HHS HREC (LNR 2021 QCHQ 73903). Because of the retrospective nature of the research, the requirement for informed consent was waived.

Results

Initial search of the data base identifying patients who had undergone supraglottoplasty within the first 18 months of life revealed 147 patients. Of these, 82 were considered to have comorbidities or congenital disease associated with SDB. A further 13 patients of the remaining 65 had undergone either tonsillectomy, adenoidectomy or both at the time of supraglottoplasty and were therefore deemed ineligible for consideration. Three additional patients were removed due to an existing pre-operative diagnosis of SDB. Of the remaining 49 patients, 18 were lost to follow-up resulting in 31 patients who had undergone supraglottoplasty without significant comorbidities (see Figure 1).

Figure 1 Flow diagram outlining patient selection process. SDB, sleep disordered breathing.

A total of 31 patients were available for assessment. This was segregated into 58% (18/31) male and 42% (13/31) female. A total of 10% (3/31) patients identified as either Aboriginal or Torres Strait Islander (see Table 1).

A total of 4 patients were born prematurely; 3 were late pre-term (34–36 weeks) and 1 was moderate pre-term 32–34 weeks). There was no statistically significant association with the incidence of prematurity and onset of SDB post supraglottoplasty (P value >0.9).

Several indications were determined for supraglottoplasty. Stridor was documented in 30 patients 97% (30/31). A total of 84% (26/31) patients had an additional documented indications for surgery. This included feeding difficulties which was seen in 58% (18/31), failure to thrive in 35% (11/31), severe dyspnoea in 6% (2/31), 10% (3/31) experienced apnoeic spells, and 6% (2/31) experienced cyanotic spells. For the remaining 5 cases, no additional information on the indication for surgery was provided. The mean age at which supraglottoplasty was performed was 4 months (SD: ±4 months).

Pre-operatively, a total of 39% (12/31) of patients revealed a history of gastroesophageal reflux disease (GORD). With respect to food allergy or intolerance, 3% (1/31) of patients confirmed symptoms on history. Supplemental oxygen was required in 13% (4/31) of patients.

All patients showed symptom improvement following surgical intervention. On subsequent follow-up, 39% (12/31) developed new onset SDB. There was no difference between sex and the development of post-operative SDB symptoms (males 9/18, 50% vs. females 3/13, 23%, P value =0.2, Table 2).

The mean age of post-operative SDB diagnosis was 23 months (SD: ±14 months). Post-operative PSG was performed on two of these patients; one demonstrated mixed sleep apnea with an AHI of 4 with additional central apneas, while the other showed no obstructive or central apneas, with an AHI of less than 1.

Of these 12 patients with new onset SDB after their supraglottoplasty, 3 required further surgical intervention (25%). Two patients underwent adenotonsillectomy and the third underwent adenoidectomy with a repeat supraglottoplasty.

There was no significant association between any of the indications for supraglottoplasty and the subsequent development of SDB (see Table 3). Furthermore, no correlation was seen with an increasing number of indications for supraglottoplasty and the incidence of SDB (P value =0.3).

Discussion

SDB in children is associated with decreased intelligence, memory performance, attention, and school performance (6). On the severe end of the SDB spectrum, there is evidence to suggest that patients with chronic untreated OSA can develop hypertension, cardiovascular disease, metabolic disorders and obesity (10).

The main objective of this review was to generate a hypothesis that patients who have previously undergone supraglottoplasty are at risk of developing future SDB. The incidence of SDB in the general paediatric population is 1–5% (5,7). In this review, incidence of SDB was 39%. This greater incidence was subject to numerous biases including a small sample size, non-standardised follow-up protocols and limited patients with PSGs upon representation. The exclusion of patients with SDB as an initial symptom of laryngomalacia in this review does not eliminate the possibility that some infants included retrospectively might have had some degree of SDB at the outset. Consequently, what appears to be new-onset SDB could, in fact, represent residual or recurrent disease. This may explain the cases of early SDB identified within this series. This possibility is supported by the inherent limitations of retrospective studies, which may not capture all aspects of initial presentations accurately.

The causes of SDB can be secondary to structural and systemic factors. Structural factors include upper airway resistance secondary to nasal obstruction, adenoid, tonsil and tongue hypertrophy, laryngomalacia, craniofacial defects or uncommonly space occupying lesions within the upper airway. Systemic factors include reduced tone of the upper airway with or without a background of a known syndrome such as downs or cerebral palsy, obesity and family history of SDB.

Whilst many theories postulating the aetiology of laryngomalacia exist, the most widely supported is the impaired laryngeal neuromuscular tone and resultant prolapse of supra-glottic tissue causing airway obstruction (11). This loss of tone is modulated by changes in either peripheral or central vagal nerve function (3). In support of this, histological tissue of superior laryngeal nerve branches within supra-arytenoid mucosa of patients with severe laryngomalacia have shown significantly greater nerve diameter and surface area when compared to age-matched autopsy supra-arytenoid tissue (3). Thus, patients with laryngomalacia have reduced underlying tone due to a developing neurological system.

Although most patients experiencing laryngomalacia are conservatively managed, up to 20% of patients will require surgical intervention. This is largely in the way of supraglottoplasty to divide aryepiglottic folds and remove excess mucosa overlying the arytenoids (12). Success in managing symptoms of stridor and feeding difficulty occurs in 94% of cases (11). However, the underlying factor of hypotonia remains. Thus, the potential underlying link of hypotonia affecting laryngomalacia in infancy, may also contribute to SDB developed later in childhood as structural factors such as adenotonsillar hypertrophy become more prominent.

There was a greater incidence of SDB in males within the current cohort (although not statistically significant). Similarly, a higher incidence of laryngomalacia has been found in Caucasian male paediatric patients (3). In contrast, the incidence of SDB in pre-pubertal children is comparable between males and females which is thought to coincide with the peak age of adenotonsillar hypertrophy between the ages of 2 and 8 years (13,14). In this series, the increased incidence in males may be a reflection of the combination of patients with known laryngomalacia and patients being followed up to an average of 2 years, thereby not allowing for adenotonsillar hypertrophy to play a significant role in obstruction.

However, there is incongruence in the current series with respect to the mean age of SDB diagnosis. The mean age of SDB diagnosis was established at 23 months, which precedes the typical hypertrophy of adenotonsillar tissue. Furthermore, only 25% of patients diagnosed with SDB progressed to require surgical intervention. This may highlight that other factors such as hypotonia, may be contributing to symptoms of SDB. It is also plausible that families who have dealt with laryngomalacia are more attuned to the recurrence of noisy breathing in their child and are likely to seek medical attention earlier compared to families without such experiences. Future research focusing on identifying these risk factors and associations would be advantageous.

As only 10% of patients identified as Aboriginal or Torres Strait Islander, any inference regarding differences in trends related to the link between laryngomalacia and the risk of subsequent SDB development are difficult to ascertain in this series. Whilst data on the incidence of Laryngomalacia in the paediatric indigenous population is limited, the incidence of SDB is well documented and seen in up to 50 percent (14,15). Expanding our understanding of this relationship between laryngomalacia and SDB may be of benefit in future research to enhance future close the gap initiatives.

The severity of laryngomalacia increases with the presence of secondary airway lesions, hypoxia, medical co-morbidities such as neurological or cardiac disorders, congenital anomalies and swallow dysfunction (3). Patients in this study were excluded from assessment if there was known concomitant comorbidities were present. It could be expected that the presence of more than one clinical signs or symptoms, in addition to stridor, which lead to the requirement of supraglottoplasty (namely failure to thrive, feeding difficulties, cyanotic spells, pre-operative hypoxia) would correlate with an increased incidence of SDB. However, this was difficult to interpret with the limited number of patients.

Conclusions

This case series aimed to highlight the possible association with patients undergoing supraglottoplasty, and the subsequent development of SDB. By understanding the correlation between incidence of patients with laryngomalacia and the future development of SDB, the practitioner can improve awareness and educate families on the signs and symptoms of SDB. The surgeon or primary practitioner may choose to continue to follow up beyond the routine 2 years in patients who have previously required surgical intervention for laryngomalacia to address signs and symptoms of SDB and prevent long term sequalae. Prospective research is required to further investigate this link.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://www.theajo.com/article/view/10.21037/10.21037/ajo-23-63/rc

Data Sharing Statement: Available at https://www.theajo.com/article/view/10.21037/ajo-23-63/dss

Peer Review File: Available at https://www.theajo.com/article/view/10.21037/ajo-23-63/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://www.theajo.com/article/view/10.21037/ajo-23-63/coif). H.B. serves as the Editor-in-Chief of the Australian Journal of Otolaryngology from April 2024 to December 2029. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by Children’s Health Queensland HHS HREC (LNR 2021 QCHQ 73903). Because of the retrospective nature of the research, the requirement for informed consent was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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