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Table 1.  Patient Characteristics and Baseline Polysomnogram Findings
Patient Characteristics and Baseline Polysomnogram Findings
Table 2.  Patterns of Obstruction Observed During Drug-Induced Sleep Endoscopy
Patterns of Obstruction Observed During Drug-Induced Sleep Endoscopy
Table 3.  Polysomnogram Results Before and After Implantation
Polysomnogram Results Before and After Implantation
Table 4.  Baseline and Follow-up Domain Scores for the Obstructive Sleep Apnea–18 (OSA-18) Survey (n = 5)
Baseline and Follow-up Domain Scores for the Obstructive Sleep Apnea–18 (OSA-18) Survey (n = 5)
1.
Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome, American Academy of Pediatrics.  Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome.  Pediatrics. 2002;109(4):704-712.PubMedGoogle ScholarCrossref
2.
Marcus  CL, Brooks  LJ, Draper  KA,  et al; American Academy of Pediatrics.  Diagnosis and management of childhood obstructive sleep apnea syndrome.  Pediatrics. 2012;130(3):576-584.PubMedGoogle ScholarCrossref
3.
Breslin  J, Spanò  G, Bootzin  R, Anand  P, Nadel  L, Edgin  J.  Obstructive sleep apnea syndrome and cognition in Down syndrome.  Dev Med Child Neurol. 2014;56(7):657-664.PubMedGoogle ScholarCrossref
4.
Sedaghat  AR, Flax-Goldenberg  RB, Gayler  BW, Capone  GT, Ishman  SL.  A case-control comparison of lingual tonsillar size in children with and without Down syndrome.  Laryngoscope. 2012;122(5):1165-1169.PubMedGoogle ScholarCrossref
5.
Levanon  A, Tarasiuk  A, Tal  A.  Sleep characteristics in children with Down syndrome.  J Pediatr. 1999;134(6):755-760.PubMedGoogle ScholarCrossref
6.
Lynch  MK, Elliott  LC, Avis  KT, Schwebel  DC, Goodin  BR.  Quality of life in youth with obstructive sleep apnea syndrome (OSAS) treated with continuous positive airway pressure (CPAP) therapy.  Behav Sleep Med. 2017;30:1-8.PubMedGoogle ScholarCrossref
7.
Hawkins  SM, Jensen  EL, Simon  SL, Friedman  NR.  Correlates of pediatric CPAP adherence.  J Clin Sleep Med. 2016;12(6):879-884.PubMedGoogle ScholarCrossref
8.
Marcus  CL, Rosen  G, Ward  SL,  et al.  Adherence to and effectiveness of positive airway pressure therapy in children with obstructive sleep apnea.  Pediatrics. 2006;117(3):e442-e451.PubMedGoogle ScholarCrossref
9.
D’Souza  JN, Levi  JR, Park  D, Shah  UK.  Complications following pediatric tracheotomy.  JAMA Otolaryngol Head Neck Surg. 2016;142(5):484-488.PubMedGoogle ScholarCrossref
10.
Hartnick  CJ, Bissell  C, Parsons  SK.  The impact of pediatric tracheotomy on parental caregiver burden and health status.  Arch Otolaryngol Head Neck Surg. 2003;129(10):1065-1069.PubMedGoogle ScholarCrossref
11.
Schwartz  AR, Bennett  ML, Smith  PL,  et al.  Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea.  Arch Otolaryngol Head Neck Surg. 2001;127(10):1216-1223.PubMedGoogle ScholarCrossref
12.
Van de Heyning  PH, Badr  MS, Baskin  JZ,  et al.  Implanted upper airway stimulation device for obstructive sleep apnea.  Laryngoscope. 2012;122(7):1626-1633.PubMedGoogle ScholarCrossref
13.
Strollo  PJ  Jr, Soose  RJ, Maurer  JT,  et al; STAR Trial Group.  Upper-airway stimulation for obstructive sleep apnea.  N Engl J Med. 2014;370(2):139-149.PubMedGoogle ScholarCrossref
14.
Woodson  BT, Soose  RJ, Gillespie  MB,  et al; STAR Trial Investigators.  Three-year outcomes of cranial nerve stimulation for obstructive sleep apnea: the STAR Trial.  Otolaryngol Head Neck Surg. 2016;154(1):181-188.PubMedGoogle ScholarCrossref
15.
Hohenhorst  W, Ravesloot  MJL, Kezirian  EJ, de Vries  N,.  Drug-induced sleep endoscopy in adults with sleep-disordered breathing: technique and the VOTE classification system.  Oper Tech Otolaryngol. 2012;23:11-18.Google ScholarCrossref
16.
Maurer  JT, Van de Hening  PH, Lin  HS, Baskin  J, Anders  C,  et al.  Operative technique of upper airway stimulation: an implantable treatment of obstructive sleep apnea.  Oper Tech Otolaryngol. 2012;23:227-233.Google ScholarCrossref
17.
American Academy of Sleep Medicine manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Version 2.0. https://aasm.org/asm-scoring-manual-version2-0-3-is-now-available. Accessed October 2, 2017.
18.
Franco  RA  Jr, Rosenfeld  RM, Rao  M.  Quality of life for children with obstructive sleep apnea.  Otolaryngol Head Neck Surg. 2000;123(1, pt 1):9-16.PubMedGoogle ScholarCrossref
19.
Sohn  H, Rosenfeld  RM.  Evaluation of sleep-disordered breathing in children.  Otolaryngol Head Neck Surg. 2003;128(3):344-352.PubMedGoogle ScholarCrossref
20.
Diercks  GR, Keamy  D, Kinane  TB,  et al.  Hypoglossal nerve stimulator implantation in an adolescent with Down syndrome and sleep apnea.  Pediatrics. 2016;137(5):e201533663.PubMedGoogle ScholarCrossref
21.
Thottam  PJ, Choi  S, Simons  JP, Kitsko  DJ.  Effect of adenotonsillectomy on central and obstructive sleep apnea in children with Down syndrome.  Otolaryngol Head Neck Surg. 2015;153(4):644-648.PubMedGoogle ScholarCrossref
22.
Baldassari  CM, Kepchar  J, Bryant  L, Beydoun  H, Choi  S.  Changes in central apnea index following pediatric adenotonsillectomy.  Otolaryngol Head Neck Surg. 2012;146(3):487-490.PubMedGoogle ScholarCrossref
23.
McEvoy  RD, Antic  NA, Heeley  E,  et al; SAVE Investigators and Coordinators.  CPAP for prevention of cardiovascular events in obstructive sleep apnea.  N Engl J Med. 2016;375(10):919-931.PubMedGoogle ScholarCrossref
Original Investigation
January 2018

Hypoglossal Nerve Stimulation in Adolescents With Down Syndrome and Obstructive Sleep Apnea

Author Affiliations
  • 1Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston
  • 2Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts
  • 3University Hospitals, Cleveland Medical Center, Cleveland, Ohio
  • 4Rainbow Babies and Children’s Hospital, Case Western University, Cleveland, Ohio
  • 5Pediatric Sleep Associates, Massachusetts General Hospital for Children, Boston
  • 6Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
  • 7Down Syndrome Program, Division of Medical Genetics, Department of Pediatrics, Massachusetts General Hospital, Boston
  • 8Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania
JAMA Otolaryngol Head Neck Surg. 2018;144(1):37-42. doi:10.1001/jamaoto.2017.1871
Key Points

Question  Can the hypoglossal nerve stimulator be safely implanted in children with Down syndrome, and is it effective in alleviating nocturnal airway obstruction?

Findings  In this case series of the first 6 children to receive the hypoglossal nerve stimulator implant, stimulation was well tolerated and resulted in a reduction in apnea hypopnea index, as well as improvement in quality of life.

Meaning  The hypoglossal nerve stimulator is a potential therapeutic option for adolescents with Down syndrome and severe obstructive sleep apnea.

Abstract

Importance  Obstructive sleep apnea (OSA) affects up to 60% of children with Down syndrome (DS) and may persist in half of patients after adenotonsillectomy. Children with DS who have persistent OSA often do not tolerate treatment with positive pressure airway support devices or tracheotomy for their residual moderate to severe OSA. The hypoglossal nerve stimulator is an implantable device that delivers an electrical impulse to anterior branches of the hypoglossal nerve in response to respiratory variation, resulting in tongue base protrusion that alleviates upper airway obstruction in adults.

Objective  To determine whether hypoglossal nerve stimulation is safe and effective in children with DS.

Design, Setting, and Participants  Case series of the first 6 adolescents with DS to undergo hypoglossal nerve stimulator implantation. Participants were 6 children and adolescents (12-18 years) with DS and severe OSA (apnea hypopnea index [AHI] > 10 events/h) despite prior adenotonsillectomy.

Intervention  Inspire hypoglossal nerve stimulator placement.

Main Outcomes and Measures  Patients were monitored for adverse events. Adherence to therapy was measured by hours of use recorded by the device. Efficacy was evaluated by comparing AHI and OSA-18, a validated quality-of-life instrument, scores at baseline and follow-up.

Results  In 6 patients (4 male, 2 female; aged 12-18 years), hypoglossal nerve stimulator therapy was well tolerated (mean use, 5.6-10.0 h/night) and effective, resulting in significant improvement in OSA. At 6- to 12-month follow-up, patients demonstrated a 56% to 85% reduction in AHI, with an overall AHI of less than 5 events/h in 4 children and less than 10 events/h in 2 children. Children also demonstrated a clinically significant improvement (mean [SD] overall change score, 1.5 [0.6]; range, 0.9-2.3) on the OSA-18, a validated quality-of-life instrument.

Conclusions and Relevance  Hypoglossal nerve stimulation was well tolerated and effective in the study population, representing a potential therapeutic option for patients with DS and refractory OSA after adenotonsillectomy who are unable to tolerate positive pressure airway devices.

Trial Registration  clinicaltrials.gov Identifier: NCT2344108

Introduction

Obstructive sleep apnea (OSA) affects up to 5.7% of the general pediatrics population and up to 80% of patients with Down syndrome (DS). In children, OSA is associated with adverse behavior and quality of life (QOL), as well as cardiopulmonary complications.1-3 In children with adenotonsillar hypertrophy, adenotonsillectomy (T&A) is the initial treatment of choice. However, more than 60% of children with DS will demonstrate persistent airway obstruction after T&A due to reduced muscle tone, macroglossia, maxillary hypoplasia, and lingual tonsil hypertrophy.4,5

Positive pressure airway support treatments, supplemental oxygen delivery, oromaxillofacial surgery, and, in severe cases, tracheotomy are often required to treat residual airway obstruction; however, these treatments are problematic. Although they are effective when used properly, many children do not adhere to noninvasive airway support therapy, with some series demonstrating high dropout rates and nonadherence rates ranging from 40% to 50%.6-8 Tracheotomy bypasses upper airway obstruction completely; however, it is associated with a host of short-term and long-term complications in up to 19% of patients, including risks of accidental decannulation, wound breakdown, formation of suprastomal granulation tissue and collapse, and, rarely, life-threatening hemorrhage from tracheoinominate fistula formation and death.9 Additionally, for caregivers, pediatric tracheotomy is associated with substantial caregiver burden and reduced mental health.10

The hypoglossal nerve stimulator (Inspire Medical Systems) is an implantable device that, using a sensing electrode placed between the intercostal muscles and stimulation lead placed around anterior branches of the hypoglossal nerve, delivers electrical impulses to tongue protrusor muscles at the time of inspiration, alleviating upper airway obstruction.11 In neurotypical adults with moderate OSA and an apnea hypopnea index (AHI) of less than 50 events/h, body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) less than 32, and without circumferential airway collapse at the level of the velopharynx, hypoglossal nerve stimulation has been shown to be an effective treatment for OSA.12,13 In adults, prospective studies demonstrate that therapy remains well tolerated and effective up to 36 months after implantation.14

Given the prevalence of persistent OSA after T&A in patients with DS, as well as anatomic considerations in this population, we developed a pilot study to primarily evaluate the safety of hypoglossal nerve stimulation in children with DS and residual OSA after T&A. Safety data, including perioperative complications, and tolerance of hypoglossal nerve stimulation were collected. As a secondary outcome, adherence to therapy and efficacy data were also collected. Here we present 6-month and 1-year follow-up data of the first 6 pediatric patients to ever receive the hypoglossal nerve stimulator implant.

Methods

This study was approved by the institutional review board at Massachusetts Eye and Ear Infirmary, Harvard Medical School, as well as by the US Food and Drug Administration, which issued an investigational device exemption. Verbal assent was obtained from all patients, and written consent was obtained from study participants or their legal guardians prior to study participation and nerve stimulator implantation. As part of this pilot study, we were approved to enroll 6 adolescents and young adults, 10 to 21 years of age, with DS and refractory OSA after T&A who were unable to tolerate continuous positive airway pressure (CPAP) or dependent on a tracheotomy at night. Patients were identified as candidates for implantation by the DS clinic at our institution and underwent initial evaluation by the surgical team. Patients with any medical conditions necessitating future magnetic resonance imaging were excluded because the current generation of the device is incompatible with magnetic resonance imaging. Parents also had to attest to their child’s ability to cooperate with examinations and communicate discomfort. To participate, patients had to be medically stable with a BMI of less than 32. Patients without a polysomnogram (PSG) within 6 months underwent PSG to identify baseline characteristics and verify inclusion criteria, including AHI between 10 and 50 events/h and a central apnea contribution of less than 25%. Patients meeting PSG criteria then underwent drug-induced sleep endoscopy (DISE) under sedation with propofol and/or dexmedetomidine, at the discretion of supervising anesthesiologists, to evaluate upper airway anatomy at the level of the velopharynx, oropharynx, tongue base, and hypopharynx. Examination findings were evaluated using the VOTE (velopharynx, oropharynx including the palatine tonsils, tongue, and epiglottis) classification scheme, which has been described previously.15 Circumferential collapse at the level of the velopharynx would exclude a patient from study participation. Objective inclusion criteria, including BMI, PSG findings, and anatomic findings, were based on the inclusion criteria used in prior studies of the hypoglossal nerve stimulator in adult patients.13

Study participants meeting inclusion criteria then underwent hypoglossal nerve stimulator implantation using standard techniques, which have been described previously.16 Briefly, the hypoglossal nerve stimulator is implanted through 3 incisions. The hypoglossal nerve is exposed through a submental incision and its anterior branches are dissected with the aid of electromyographic potential monitoring to identify branches to include within the cuff of a stimulating electrode. An impulse generator is placed in the right chest superficial to the pectoralis through an incision below the clavicle, much like a cardiac pacemaker. Finally, a third incision in the right thorax is made to place a pleural sensing lead between the internal and external intercostal muscles. All patients underwent postoperative posterior-anterior and lateral chest radiography to rule out pneumothorax and to document device position. All participants received perioperative antibiotics and were hospitalized overnight for monitoring.

One month after implantation, the nerve stimulators were activated in the clinic then turned off. The evening of the clinic appointment, patients underwent titration of their devices during an overnight PSG, then were discharged to use therapy nightly to become acclimated to the device. Follow-up PSGs and further device titrations were then performed at 2, 6, and 12 months after implantation to allow additional device optimization. Throughout the study period, participants were monitored for any adverse events. Weekly use questionnaires were completed and corroborated with total hours of use and mean use per week calculations automatically registered by the device itself at the time of device checks before each PSG. Mean nightly use was calculated by dividing the mean use per week recorded by the device by 7. All PSGs were scored using American Academy of Sleep Medicine (AASM) pediatric standards.17 All sleep studies and device titrations performed after implantation were conducted at our institution and interpreted, using the AASM criteria, by 1 of 2 board-certified sleep medicine specialists (D.K., T.B.K.).

In addition to safety and efficacy data, QOL data were obtained as a secondary outcome measure. The OSA-18 survey, which is a valid and reliable discriminative QOL instrument in children with sleep-disordered breathing,18 was used to assess QOL at baseline and at 2, 6, and 12 months after implantation. At most recent follow-up, a change score was calculated by subtracting the mean survey score from the mean score at baseline. One patient, patient 3, was excluded from follow-up analysis because only 1 of 18 questions was filled out at follow-up. Data from other surveys with 7-point response scales suggest that change scores of less than 0.5 represent trivial change, 0.5 to 0.9 indicate a small change, 1.0 to 1.4 demonstrate a moderate change, and 1.5 or greater indicate a large change.19

Results

Preliminary results of the first 6 patients to receive hypoglossal nerve stimulator implantation as part of this pilot study are presented here. Five-month follow-up results of the first implant recipient have been reported previously.20

Six patients, 4 male and 2 female, with residual OSA after T&A, age 12 to 18 years, were enrolled. All 6 patients were either unable to tolerate a CPAP trial (n = 2) or their CPAP therapy failed as a result of intolerance of associated equipment or sinonasal symptoms related to therapy (n = 4). One patient had a long-standing tracheotomy. Patient characteristics, including baseline PSG measurements, are included in Table 1. Three patients underwent DISE on the same date as implantation due to travel from a distance and/or parent request that the patient only be sedated and undergo anesthesia once given the added risks of anesthesia in the DS population; these deviations from protocol were approved by the institutional review board. Patterns of obstruction on DISE are presented in Table 2; none of the patients demonstrated circumferential collapse at the level of the velopharynx, and therefore all were candidates for implantation.

All patients underwent hypoglossal nerve stimulator implantation without intraoperative complications. All patients received 24 hours of perioperative antibiotics. All patients were hospitalized overnight for observation, and pain was well controlled using acetaminophen; use of narcotics after initial recovery in the postanesthesia care unit was minimized. All patients were discharged on postoperative day 1.

Two patients experienced adverse events in the perioperative period necessitating readmission. Patient 2 was rehospitalized the morning of postoperative day 2 with irritation, and possibly mild cellulitis, of his upper chest incision; this improved with antibiotic administration and he was discharged on postoperative day 4 to complete a course of oral antibiotics. He remained afebrile. Patient 3 was readmitted on postoperative day 3 due to poor pain control and discomfort, as well as purulent nasal discharge in the setting of known sinusitis; he was admitted for narcotic administration under direct monitoring and antibiotics, did not have adverse respiratory events, and was discharged home the following morning with narcotic medication to be used as needed and to complete a course of oral antibiotics.

All patients underwent activation 1 month after implantation. All patients tolerated stimulation and initial titration without discomfort and were discharged to use the device nightly and become acclimated to stimulation. The goal of initial activation and titration was not to optimize therapy, however, due to concerns that the children would not necessarily tolerate therapeutic levels of stimulation initially. Patient 4 demonstrated emergence of severe central apnea consistent with postobstructive hypoventilation syndrome, which has been described previously in children with severe OSA after T&A or with the initiation of CPAP therapy.21,22 She was admitted for 24-hour observation and continued therapy with the use of nocturnal supplemental oxygen. She was discharged home the following day with nocturnal oxygen and continuous oxygen saturation monitoring until respiratory center recalibration, and she continued to use therapy nightly. Her central apnea had resolved by her next sleep study, which was performed 3 months later, and she was weaned off supplemental oxygen.

All 6 patients demonstrated improvement in their airway obstruction with stimulation during their first PSG immediately following device activation, although further titration was needed in subsequent PSGs to optimize therapy (Table 3). At 6-month (n = 1) and 1-year follow-up (n = 5), all patients demonstrated persistent improvement in their AHI in response to therapy, with a 56% to 85% reduction in AHI compared with their preoperative baseline. At follow-up, whereas OSA persisted in all patients, it was no longer severe (AHI > 10 events/h); 4 patients demonstrated mild OSA (AHI ≤ 5 events/h), and 2 demonstrated moderate OSA (5 < AHI ≤ 10 events/h). At the time of most recent follow-up, all patients were using therapy nightly, with a mean duration of 5.6 to 10.0 h/night (Table 3).

Patient 1 was decannulated 4 months after implantation. Patients 2 and 3, who had previously been poorly tolerant of CPAP, were able to discontinue CPAP use. Prior to implantation, 3 patients (patients 1, 2, and 6) had no rapid eye movement sleep during baseline PSG recording, likely secondary to repeated arousals in the setting of severe upper airway obstruction with frequent respiratory events. However, each of these patients demonstrated emergence of rapid eye movement sleep with device use (20%, 21%, and 22% of total sleep time, for patients 1, 2, and 6, respectively), representing a more normal sleep pattern.

For the 5 patients with completed OSA-18 questionnaires at follow-up, all patients demonstrated improvement in their QOL. There was a large improvement (change score ≥1.5) in sleep disturbance, caregiver concerns, and the mean OSA-18 score, and a moderate improvement (1.0 ≤ change score ≤ 1.4) in daytime problems associated with OSA (Table 4).

Discussion

Here we present preliminary results of, to our knowledge, the first 6 pediatric hypoglossal nerve stimulator recipients ever implanted. In carefully selected children and adolescents with DS, surgical implantation and use were well tolerated. After appropriate device titration, the nerve stimulator was effective in relieving upper airway obstruction with a greater than 50% reduction in AHI in all patients. In patients reliant on tracheotomy and CPAP, nerve stimulator therapy was so successful that these therapies could be discontinued after initial titration sessions. Patients not only exhibited an improvement in their AHI but also showed clinically significant improvement in their QOL based on validated QOL instruments.

Based on parent report and corroboration from device interrogation at follow-up visits, patients were using the stimulator for a mean duration of 5.6 to 10.0 h/night (group mean, 8.8 h/night). Adherence to therapy was significantly higher than mean adherence to CPAP therapy in adult patients, which has been reported previously to be as low as 3.3 h/night.23 Despite the effectiveness of CPAP when used properly, lack of adherence to therapy may be a contributing factor in recent studies demonstrating no reduction of cardiovascular event risk with CPAP therapy in adult patients with moderate to severe sleep apnea and cardiovascular disease.23 Further study is needed to determine whether hypoglossal stimulation therapy reduces cardiovascular risk in both pediatric and adult patients with OSA. However, we demonstrate that adherence to therapy, which may be an important factor in the prevention of long-term sequelae, was not problematic in our patient population.

Limitations

In our patients who have completed the 1-year pilot study, voltage settings were relatively stable; however, further long-term study is needed to determine whether effectiveness, particularly through other measures of gas exchange, and stimulation parameters remain stable over a longer period in this patient population. Studies of stimulation in adult patients have shown a persistent response over 36 months.13,14 Hypoglossal nerve stimulation represents a potential therapeutic option for children with DS and refractory OSA after T&A who are unable to tolerate noninvasive interventions. For this pilot study, we chose older children and adolescents for implantation due to concern about the size of the impulse generator device, as well as the potential for growth during puberty to displace the device’s stimulation and sensing leads. In addition, the battery of the impulse generator will need to be replaced approximately every 10 years due to limitations in battery capacity, which raises additional safety concerns. The ideal age for implantation in the pediatric population has not been established. Additionally, it remains unclear whether hypoglossal nerve stimulation may represent a treatment option for pediatric patients without DS who demonstrate persistent OSA after T&A. The risks and benefits of implantation, as well as long-term follow-up, will need to be considered as more data are collected on initial pediatric implant recipients.

The patients and families included in this pilot study represent a unique group. Patients were high functioning, able to communicate well with investigators and their families. Patient families were also motivated to proceed with surgery and to help facilitate adherence to therapy. This could limit applicability of our results to other adolescents and young adults with DS who may be less communicative and cooperative, and whose families may not be as involved in their care.

Conclusions

Adolescents and young adults with DS are at increased risk for refractory severe OSA. We demonstrate that therapy was well tolerated and effective, both in improving QOL and in reducing AHI, in our patient population. Hypoglossal nerve stimulator implantation represents a potential therapeutic option, but further research is needed to optimize patient selection and better assess long-term efficacy.

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Article Information

Corresponding Author: Christopher J. Hartnick, MD, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 (christopher_hartnick@meei.harvard.edu).

Accepted for Publication: July 25, 2017.

Published Online: November 2, 2017. doi:10.1001/jamaoto.2017.1871

Author Contributions: Dr Diercks had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Diercks, Keamy, Kinane, Skotko, De Guzman, Soose, Hartnick.

Acquisition, analysis, or interpretation of data: Diercks, Wentland, Keamy, Kinane, Grealish, Dobrowski.

Drafting of the manuscript: Diercks, Kinane.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Diercks, Wentland, Grealish.

Administrative, technical, or material support: Wentland, Keamy, Kinane, Skotko, De Guzman, Grealish, Soose.

Supervision: Wentland, Keamy, Kinane, Soose, Hartnick.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kinane reports he was a paid consultant for Sarepta Therapeutics for US Food and Drug Administration submission of drug for Duchenne muscular dystrophy. Dr Skotko reports grants from Transition Therapeutics and F. Hoffmann-La Roche, Inc; consults on the topic of Down syndrome (DS) through Gerson Lehrman Group; has an R40 grant to study obstructive sleep apnea in patients with DS from the Health Resources and Services Administration’s Maternal & Child Health Bureau; receives remuneration from DS nonprofit organizations for speaking engagements and associated travel expenses; receives annual royalties from Woodbine House, Inc, for a family-oriented book about DS; and has served as an expert witness for legal cases in which DS is discussed. Dr Skotko also serves in a nonpaid capacity on the Honorary Board of Directors for the Massachusetts Down Syndrome Congress, the Board of Directors for the Band of Angels Foundation, and the Professional Advisory Committee for the National Center for Prenatal and Postnatal Down Syndrome Resources. Dr Skotko has a sister with DS. Dr Soose reports grants and personal fees from Inspire Medical Systems, outside the submitted work. No other disclosures are reported.

Funding/Support:Inspire Medical Systems provided technical support and provided the nerve stimulators used in this study free of charge. Massachusetts Eye and Ear Infirmary staff and facilities waived professional, facility, and operating room fees for this study.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Luke Lozier, Quan Ni, PhD, and Michael Coleman, BA, RST, RPSGT, Inspire Medical Systems, provided technical support and guidance during the planning and execution of this project. Alison Schwartz, MD, contributed to project design. They did not receive additional compensation beyond their salaries.

Additional Information: US Food and Drug Administration approval: This study was approved under investigational device exemption G140209.

References
1.
Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome, American Academy of Pediatrics.  Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome.  Pediatrics. 2002;109(4):704-712.PubMedGoogle ScholarCrossref
2.
Marcus  CL, Brooks  LJ, Draper  KA,  et al; American Academy of Pediatrics.  Diagnosis and management of childhood obstructive sleep apnea syndrome.  Pediatrics. 2012;130(3):576-584.PubMedGoogle ScholarCrossref
3.
Breslin  J, Spanò  G, Bootzin  R, Anand  P, Nadel  L, Edgin  J.  Obstructive sleep apnea syndrome and cognition in Down syndrome.  Dev Med Child Neurol. 2014;56(7):657-664.PubMedGoogle ScholarCrossref
4.
Sedaghat  AR, Flax-Goldenberg  RB, Gayler  BW, Capone  GT, Ishman  SL.  A case-control comparison of lingual tonsillar size in children with and without Down syndrome.  Laryngoscope. 2012;122(5):1165-1169.PubMedGoogle ScholarCrossref
5.
Levanon  A, Tarasiuk  A, Tal  A.  Sleep characteristics in children with Down syndrome.  J Pediatr. 1999;134(6):755-760.PubMedGoogle ScholarCrossref
6.
Lynch  MK, Elliott  LC, Avis  KT, Schwebel  DC, Goodin  BR.  Quality of life in youth with obstructive sleep apnea syndrome (OSAS) treated with continuous positive airway pressure (CPAP) therapy.  Behav Sleep Med. 2017;30:1-8.PubMedGoogle ScholarCrossref
7.
Hawkins  SM, Jensen  EL, Simon  SL, Friedman  NR.  Correlates of pediatric CPAP adherence.  J Clin Sleep Med. 2016;12(6):879-884.PubMedGoogle ScholarCrossref
8.
Marcus  CL, Rosen  G, Ward  SL,  et al.  Adherence to and effectiveness of positive airway pressure therapy in children with obstructive sleep apnea.  Pediatrics. 2006;117(3):e442-e451.PubMedGoogle ScholarCrossref
9.
D’Souza  JN, Levi  JR, Park  D, Shah  UK.  Complications following pediatric tracheotomy.  JAMA Otolaryngol Head Neck Surg. 2016;142(5):484-488.PubMedGoogle ScholarCrossref
10.
Hartnick  CJ, Bissell  C, Parsons  SK.  The impact of pediatric tracheotomy on parental caregiver burden and health status.  Arch Otolaryngol Head Neck Surg. 2003;129(10):1065-1069.PubMedGoogle ScholarCrossref
11.
Schwartz  AR, Bennett  ML, Smith  PL,  et al.  Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea.  Arch Otolaryngol Head Neck Surg. 2001;127(10):1216-1223.PubMedGoogle ScholarCrossref
12.
Van de Heyning  PH, Badr  MS, Baskin  JZ,  et al.  Implanted upper airway stimulation device for obstructive sleep apnea.  Laryngoscope. 2012;122(7):1626-1633.PubMedGoogle ScholarCrossref
13.
Strollo  PJ  Jr, Soose  RJ, Maurer  JT,  et al; STAR Trial Group.  Upper-airway stimulation for obstructive sleep apnea.  N Engl J Med. 2014;370(2):139-149.PubMedGoogle ScholarCrossref
14.
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