Article Text

Download PDFPDF

Original research
Clinical characteristics, associated comorbidities and hospital outcomes of neonates with sleep disordered breathing: a retrospective cohort study
  1. Bhavesh Mehta1,2,
  2. Karen Waters3,
  3. Dominic Fitzgerald4,
  4. Nadia Badawi5,6
  1. 1Department of Neonatology, The Children’s Hospital at Westmead, Sydney, New South Wales, Australia
  2. 2University of Sydney, Sydney, New South Wales, Australia
  3. 3Sleep Medicine, Children's Hospital at Westmead, Westmead, New South Wales, Australia
  4. 4Respiratory and Sleep Medicine, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
  5. 5Discipline of Child & Adolescent Health, Faculty of Medicine & Health, The University of Sydney, Cerebral Palsy Alliance Research Institute, Camperdown, Sydney, New South Wales, Australia
  6. 6Grace Centre for Newborn Care, Children's Hospital at Westmead, Sydney, New South Wales, Australia
  1. Correspondence to Dr Bhavesh Mehta; bhavesh.mehta{at}health.nsw.gov.au

Abstract

Objective Awareness of the need for early identification and treatment of sleep disordered breathing (SDB) in neonates is increasing but is challenging. Unrecognised SDB can have negative neurodevelopmental consequences. Our study aims to describe the clinical profile, risk factors, diagnostic modalities and interventions that can be used to manage neonates with SDB to facilitate early recognition and improved management.

Methods A single-centre retrospective study of neonates referred for assessment of suspected SDB to a tertiary newborn intensive care unit in New South Wales Australia over a 2-year period. Electronic records were reviewed. Outcome measures included demographic data, clinical characteristics, comorbidities, reason for referral, polysomnography (PSG) data, interventions targeted to treat SDB and hospital outcome. Descriptive analysis was performed and reported.

Results Eighty neonates were included. Increased work of breathing, or apnoea with oxygen desaturation being the most common reasons (46% and 31%, respectively) for referral. Most neonates had significant comorbidities requiring involvement of multiple specialists (mean 3.3) in management. The majority had moderate to severe SDB based on PSG parameters of very high mean apnoea-hypopnoea index (62.5/hour) with a mean obstructive apnoea index (38.7/hour). Ten per cent of patients required airway surgery. The majority of neonates (70%) were discharged home on non-invasive ventilation.

Conclusion SDB is a serious problem in high-risk neonates and it is associated with significant multisystem comorbidities necessitating a multidisciplinary team approach to optimise management. This study shows that PSG is useful in neonates to diagnose and guide management of SDB.

  • Sleep
  • Neonatology
  • Infant

Data availability statement

Data are available upon reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

WHAT IS ALREADY KNOWN ON THIS TOPIC

  • The profile of neonates with sleep disordered breathing (SDB) has not been adequately described leading to possible delay in recognising this problem. Diagnosis and management of SDB in neonates is challenging due to lack of universally agreed thresholds/criteria.

WHAT THIS STUDY ADDS

  • SDB can be a serious problem in neonates, which is usually associated with multisystem comorbidities, especially craniofacial and airway structural abnormalities. It requires coordinated efforts of a multidisciplinary team to ensure comprehensive management of neonates with SDB.

  • Timely evaluation and therapeutic intervention can lead to resolution of SDB in this population. Polysomnography as a diagnostic modality is helpful even at this young age.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • This study highlights the importance of SDB surveillance in high-risk neonatal population. Effort is required to develop clinical guideline and consensus-based recommendation to standardise the management of SDB in neonates.

Introduction

Sleep disordered breathing (SDB) is a group of conditions characterised by abnormal respiratory patterns during sleep with variable severity. In neonates, it includes periodic breathing, apnoea of prematurity, central sleep apnoea (CSA) and obstructive sleep apnoea (OSA) as opposed to terms used in older children including primary snoring, upper airway resistance syndrome and obstructive hypoventilation.1 Central apnoea is commonly seen in healthy newborns, is usually benign, and its frequency decreases with age.2 3 OSA is the most severe form of SDB with an estimated prevalence of 1%–4% among paediatric population.4 5 SDB has not been thoroughly investigated in young infants and its prevalence remains unknown in neonatal population.

Neonates are anatomically and physiologically prone to have SDB, especially those with certain comorbidities and craniofacial anomalies.6 If undiagnosed and untreated, OSA can lead to significant growth and neurobehavioural consequences in children.7–9 This warrants the need for early identification and timely intervention at a time of rapid brain development, especially as evidence suggests that treatment may improve quality of life and neurocognitive function.10

There has been growing recognition of SDB as a concern in neonates and data are slowly emerging about its profile.6 11 12 However, managing SDB in neonates is challenging due to the complex pathophysiology, lack of normative data and lack of agreement on diagnostic and treatment thresholds. There remain significant variations in knowledge and practices among neonatologists and sleep physicians when treating neonates with suspected SDB.13 14 A recent survey of paediatric sleep and pulmonology experts from eight different countries showed there was no agreement on the diagnostic threshold for the obstructive apnoea hypopnea index (OAHI) to diagnose OSA in young infants.14 Our primary aim was to highlight the identifiable risk factors associated with the presence and severity of SDB in neonates. Furthermore, we wanted to describe indications for obtaining a sleep study, use of various diagnostic tools and therapeutic interventions used to manage SDB in neonates as well as their hospital outcome. Collectively, this information will serve to increase awareness and help clinicians manage SDB in neonates.

Methods

This was a retrospective cohort study conducted at a tertiary level surgical newborn intensive care unit in New South Wales, Australia. We identified all neonates <1 month of postmenstrual age (PMA) who were referred to our institution over the 2-year period from July 2016 to June 2018 for investigation and management of suspected SDB. Patients were identified from the sleep department database and further clinical information was obtained from review of the electronic medical record. The diagnosis of SDB was based on a combination of clinical features (increased work of breathing, noisy breathing, desaturation), oxycapnography study and/or polysomnography (PSG). We collected data about relevant investigations, multidisciplinary teams involved and interventions undertaken to treat SDB to the time of hospital discharge.

PSGs were performed using all standard channels by a certified sleep technician using clinical polysomnography software (Compumedics, Victoria, Australia). All PSGs were performed at term between 37 and 44 weeks PMA. All PSGs included were the first performed studies. All PSGs were reviewed and reported by a paediatric sleep physician using the scoring guidelines of American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events.15–17 Based on previous studies, severity of SDB was classified using the total apnoea-hypopnoea index (AHI): an AHI of <5 was considered normal, AHI of 5 to 9.9 mild, AHI of 10 to 14.9 moderate and AHI of 15.0 or higher was considered severe SDB.6 12 PSG data related to CSA were also collected and reported.

Oxycapnography study was performed using the Radiometer TCM4. It included time matched recording of child’s oxygen saturation (SpO2), transcutaneous carbon dioxide (TcCO2) level and heart rate during sleep. The recorded data were downloaded in a software (Visi-download by Stowood build 080219) and analysed. The mean TcCO2 and SpO2 level and percentage of SpO2 readings <90% were recorded. Combinations of abnormalities in respiratory parameters along with clinical symptoms were taken as a indicators of SDB.

Data were analysed using R core team 2023 (www.R-project.org). Data are presented as a number or percentage, mean with SD and median with IQR.

Patient and public involvement

Patients or members of the public were not involved in the design or conduct of the study.

Results

Eighty neonates were included with most (70%) born at term. The majority of newborns were referred due to an abnormal/noisy breathing pattern or unexplained apnoea and oxygen desaturations (table 1).

Table 1

Demographics and reason for referral for sleep consult

A wide variety of comorbidities were found in 61 (76.3%) newborns (table 2). Craniofacial malformations and airway anomalies were the most common (30/80) comorbidities including Pierre Robin sequence (17), cleft palate (2) and airway anomalies (11) (vocal cord palsy (5), laryngomalacia (3), tracheomalacia (2) and one case of pyriform aperture stenosis). A high proportion (21/80) of neonates were diagnosed with genetic syndromes including neuromuscular disorders, skeletal dysplasias and chromosomal anomalies. Other comorbidities included chronic lung disease (6) and structural disorders affecting the neurological system (eg Dandy Walker syndrome) (3) and heart (1).

Table 2

Clinical profile and comorbidities of neonates referred for assessment of SDB

Table 3 describes investigations undertaken for diagnosis and management. A multidisciplinary approach was used (mean 3.3 teams/patient). PSG studies were performed in 67 (84%) patients. The mean (±SD) PMA at the time of PSG study was 41 (±2.4) weeks. The mean AHI of the study population who underwent PSG was very high (62.5±39). Based on AHI criteria, the majority (53/67) of patients had severe SDB. OSA was the predominant SDB seen in our cohort with a very high mean obstructive apnoea index (OAI) of 38.7 (±34). Mean central apnoea index (CAI) was 9(±10.8) and mean duration of CA was 5.5(±2) s. Chromosomal analysis was performed in most patients (61.3%). Half the study patients (40/80) had some form of brain imaging and in 21% (17/80) it was abnormal. MRI abnormalities included diffusion restriction and white matter changes, hydrocephalus, abnormalities of cerebellum and brainstem and myelination abnormalities. About half (47.5%) of the study population had an airway assessment completed by the otolaryngology team.

Table 3

Investigations done to diagnose and manage SDB

Table 4 describes the interventions and outcome measures. Most (73/80) neonates were diagnosed with SDB. Interventions included non-invasive respiratory support, home oxygen, home apnoea monitoring and surgery. A substantial proportion (40%) of study patients underwent some form of surgery, however surgical interventions targeted to improve SDB were performed in only 10% of patients. Airway surgical interventions included mandibular distraction osteogenesis (MDO), supraglottoplasty, lip–tongue adhesion and repair of laryngeal cleft. Only one patient underwent a tracheostomy. Almost a third of study patients were started on a proton pump inhibitor. Only one patient died in hospital who had a lethal form of skeletal dysplasia. Most (70%) were discharged home on continuous positive airway pressure (CPAP).

Table 4

Interventions and hospital outcome of neonates referred for assessment of SDB

Discussion

The unique characteristic of our study is that it focuses entirely on neonates (aged <1 month). In this retrospective study, we found that SDB can be a serious issue in high-risk neonatal population, occurring in almost 91% (73/80) of the study population. The majority had moderate to severe SDB. OSA was the most predominant SDB seen in our study cohort. This study demonstrates how medically complex these neonates are given the presence of spectrum of risk factors and comorbidities (table 2). However, with involvement of multidisciplinary specialist teams, these neonates were able to be managed appropriately.

The most common presenting symptoms were increased respiratory work of breathing and unexplained apnoea or desaturation highlighting that neonates do not present with the typical symptoms of OSA in older infants and children with snoring and restless sleep. Some infants were referred after a Brief Resolved Unexplained Episode (BRUE). Literature suggests that an apparent life-threatening event (ALTE) or BRUE may be the first clinical sign of SDB and these infants should be further evaluated .18 19 Guilleminault et al observed that ALTE/BRUE were more prevalent in children with micrognathia, retrognathia and anatomic anomalies that increase the risk of SDB.20 About 9% of the neonates in our study were evaluated due to family history of sudden infant death syndrome (SIDS). In a large cohort study from Denmark,21 a fourfold higher risk of SIDS was observed among siblings of children who died of SIDS. Other studies also support investigating siblings.22 Almost a third of our study cohort was born preterm, which is in line with the literature suggesting that premature infants may be at higher risk for SDB secondary to anatomical and physiologic variances.23 24

While tonsil and adenoid hypertrophy are the main cause of OSA in older children, literature suggests anomalies of upper airway anatomy, and craniofacial malformations are the main underlying factors in neonates,6 11 12 which is in keeping with the comorbidities seen in our study. Several genetic syndromes were found to be associated with SDB in our study, similar to what is described in the literature.6 11 12 These syndromes most likely either lead to increased upper airway obstruction (large tongue, small midface and/or small jaw) or cause hypotonia predisposing neonates to hypoventilation and SDB. Our data emphasise the need to be proactive in neonates with these conditions to the possible diagnosis of SDB. Overall, very high incidence of SDB in our high-risk cohort is supported by the literature showing that children with craniofacial anomalies had an estimated prevalence of SDB in up to 67% patients.25

This study underlines the need for multidisciplinary specialist teams in the management of SDB in neonates. In our study, multiple specialists were involved in the care of each patient with sleep physicians, otolaryngologists and geneticists the most frequently involved. Kaditis et al underlined the importance of multidisciplinary approach for management of SDB in children aged 1–23 months.26

PSG was done in majority (84%) of our study cohort, which is the gold standard to diagnose SDB. Diagnosing SDB based on neonatal PSG remains challenging as normative data are not well established and cut-off levels for various parameters in PSG to categorise pathologically significant SDB in neonates are still being defined.14 A recent study from Daftary et al3 showed that healthy newborns have much higher mean AHI (14.9±9.1), OAI (2.3±2.5) and CAI (5.4±6.2) compared with older children. Our study cohort had significantly elevated AHI and OAI, confirming the severity of SDB in our cohort. AHI is calculated by adding central and obstructive apnoea and hypopnoea. The high mean AHI (62.5) of our study cohort was mainly contributed by the OAI, which was significantly higher (38.7±34) than the expected range described in the literature.2 3 27 Although mean CAI of our study cohort was slightly higher than Daftary et al’s study,3 it was within the expected range for healthy neonates as per the review by Ng and Chan.2 It is well known that SDB can be a mixture of obstructive or central apnoea, especially in high-risk neonates with certain comorbidities. However, based on the PSG results, it is clear that the most predominant type of SDB in our study cohort was OSA and in majority it was moderate–severe as reflected by very high mean OAI. We decided to choose OAI as a marker of severity of OSA because its scoring criteria is clearly defined by AASM while scoring hypopnoea is difficult and categorising central versus obstructive hypopnoea is even more difficult. Therefore, OAHI can be difficult to replicate with possibility of significant interobserver variability. Despite the lack of universally accepted guideline for diagnosis and severity criteria for SDB in neonates,12 our data support the usefulness of PSG in medically complex neonates at an early age not only to diagnose SDB but also to guide management.

Thirteen (16%) neonates had compelling clinical signs/symptoms of OSA like increased work of breathing, high CO2 levels and oxygen desaturation. Therefore, treatment was initiated, and diagnosis was based on obvious clinical features and oxycapnography study. The international classification of sleep disorders also supports clinical diagnosis of OSA in paediatric age based on one or more symptoms.28 Previous studies in children have shown that oxycapnography alone is a reasonable screening tool in a diverse patient cohort with neuromuscular, congenital cardiac and genetic problems.29 30 However, its sensitivity depends on the severity of SDB; a normal oximetry does not rule out SDB and therefore does not replace PSG. Another limitation is its inability to differentiate between obstructive and central apnoea. A high prevalence of movement artefacts can make data interpretation challenging. A recent study showed good correlation between the desaturation index obtained from an overnight oximetry study to the OAHI obtained from PSG in young infants (<6 months) at risk of SDB.31 In our study, oxycapnography was only used in very severe cases who had obvious clinical symptoms and physician decided to initiate treatment over waiting for PSG date. We believe that oxycapnography can play an important role in screening for moderate to severe SDB in high-risk infants and help in treatment monitoring once diagnosis is established by PSG.

The clinical intervention was triggered for all but seven neonates (73/80, 91%) in our study based on very high mean AHI, OAI and obvious clinical features of SDB. Clinical factors, such as comorbidities, current symptoms and physical examination findings played equally important role in determining SDB diagnosis and management decisions.

Adeno-tonsillectomy is the first-line treatment in children with OSA, however establishing the specific cause of SDB is critical to selecting the optimal therapy in newborns. Ten per cent neonates in our study underwent surgery to relieve OSA. CPAP was prescribed to neonates with no indication of surgical treatment. All neonates underwent a pressure titration study during PSG to determine the optimal CPAP setting. Efficacy of CPAP was judged by improvement in clinical signs and normalisation of respiratory parameters, which was confirmed by follow-up oxycapnography and blood gases. Majority of our study cohort (70%) were successfully stablished, maintained and discharged on home CPAP therapy. CPAP is reported to be an effective treatment for upper airway obstruction in Pierre Robin sequence and can be used as a first-line treatment in selected patients.32 33 In a study of sleep apnoea in infants by Robinson et al,34 CPAP showed the highest decrease in AHI for all nonsurgical interventions used. Retrospective studies support the use of CPAP to treat SBD in infants with genetic and muscular problems.35 36 Midface hypoplasia has been described with the prolonged use of CPAP, but long-term outcome and potential reversibility of this finding are unknown.37 Long-term compliance and a high dropout rate is a major issue with CPAP use.38

Neonates with severe OSA, who did not respond to medical management by CPAP, were evaluated for surgical interventions, including lip–tongue adhesion, MDO and tracheostomy. MDO has been reported to relieve OSA in micrognathic infants and improve feeding and growth. Most of the studies have reported both short-term and long-term near-normalisation of OSA after MDO.39 40 In our study, only one patient underwent tracheostomy. Literature supports doing tracheostomy only as a last resort when other interventions fail.26

Other therapies included anti gastro-oesophageal reflux disease (GORD) treatment was used in 30% of our study population. Literature shows that GORD is commonly seen in infants with SDB, however, it remains unclear whether a causal relationship exists between the two.41

Limitations

Our study had several limitations including being a single-centre retrospective study. Being the major referral centre of the state, our cohort represents a highly biased population who were at high risk of SDB. This is a likely explanation for the very high rate of polysomnographic abnormalities among our study cohort. It is possible that infants with severe disease were selectively referred compared with those with milder SDB. Another limitation was that in number of cases diagnosis was based on oxycapnography study and clinical features. The major reason for this choice of diagnostic test in some cases were obvious signs of SDB and inability to undertake a full sleep study due to the medical fragility of the child while they were in a neonatal intensive care unit. We acknowledge that while oxycapnography has a high diagnostic positive predictive value, a reliable negative predictive value is lacking. The criteria for SDB severity based on AHI cutoffs vary in the literature for newborns and it is possible that we might have under or overestimated the burden of SDB. Another limitation was lack of repeat PSG data prior to discharge to confirm resolution of SDB postintervention. In our cohort, treatment was monitored by serial follow-up oxycapnography, blood gas parameters and clinical improvement of signs and symptoms. Our usual protocol is to do a follow-up PSG in 3–4 months postdischarge.

Conclusion

Our data demonstrate that SDB is common in high-risk neonates and are often associated with significant multisystem comorbidity where craniofacial abnormalities and airway malformations (38%) and genetic syndromes were common (26%). It must be identified and treated promptly to avoid negative consequences. However, diagnosis and management of SDB in the neonatal period are complex. This study identifies the critical need to establish normative data for the neonatal population. The establishment of reference values and treatment thresholds for the neonates will help clinicians in making decision based on polysomnographic findings and it will help in standardising the practices. This study also highlights an urgent need for outcome-based research. Longitudinal studies are needed to establish the relationship between SDB in infancy and long-term outcomes.

Data availability statement

Data are available upon reasonable request.

Ethics statements

Patient consent for publication

Ethics approval

Sydney Children’s Hospitals Network Human Research Ethics Committee approved the project. Approval ID is LNR/15/SCHN/470. Participants gave informed consent to participate in the study before taking part.

References

Footnotes

  • Contributors BM: participated in the design of the study, ethics application, collection of data, performed data analysis and drafted the initial manuscript. KW, DF and NB: participated in the conceptualisation and design of the study, reviewed and revised the manuscript and approved the final manuscript as submitted. BM acts as a guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer-reviewed.