Background The prevalence of obstructive sleep apnea (OSA) in children with Down syndrome is as high as 80% with limited treatment options. While adenotonsillectomy is the first line treatment, less than 33% of children with Down syndrome have resolution of OSA after adenotonsillectomy alone, and subsequent positive airway pressure (PAP) support is often poorly tolerated. Upper airway stimulation, which stimulates the hypoglossal nerve to protrude the tongue and open the airway during sleep, has shown efficacy for adults with OSA, but had not been evaluated in pediatric populations. Our objective was to describe the efficacy of upper airway stimulation for adolescent patients with Down syndrome and severe OSA.

Methods We conducted a Phase 1, single-arm, multi-center trial of the safety and efficacy of hypoglossal stimulation in adolescent patients with Down syndrome and persistent severe OSA. Patients with Down syndrome were included if they were between 10-21 years old, had persistent severe OSA (AHI >10 after adenotonsillectomy and inability to tolerate CPAP), and had a drug-induced sleep endoscopy that did not show circumferential palatal collapse. Polysomnographic and quality of life outcomes were assessed at 1, 2, 6, and 12 months postoperatively. The prespecified primary outcomes were safety and the change in apnea-hypopnea index (AHI) from baseline to 12 months postoperatively.

Results Among the 42 patients, 28 patients (66.7%) were male with a mean (SD) age of 15.1 (3.0). The mean decrease in AHI was 12.9 events/h (95% CI, –17.0 to –8.7 events/h). The 12-month response rate was 65.9%, and 73.2% of patients had a 12-month AHI <10 events/h. The most common complication was temporary oral discomfort, which occurred in 5 patients (11.9%). The reoperation rate was 4.8%. The mean improvement for the OSA-18 total score was 34.8 (95% CI, –42.1 to –27.5) and for the Epworth Sleepiness Scale score was 5.1 (95% CI, –7.4 to –2.8). The mean (SD) duration of nightly therapy was 9.0 (1.8) hours, with 40 patients (95.2%) using the device >4 hours nightly.

Conclusion Upper airway stimulation was safely performed for adolescents who had Down syndrome and persistent severe OSA after adenotonsillectomy with PAP intolerance. Patients had significant improvements in polysomnographic and quality of life outcomes 1 year after surgery. These results describe a novel therapy option for treatment resistant OSA in children with Down syndrome, which led to FDA approval for this indication.