Elevated Nocturnal CO₂ and Autonomic Dysfunction in Children With Down Syndrome

Sleep-disordered breathing (SDB) frequently complicates Down syndrome (DS). Beyond upper airway obstruction, emerging evidence suggests an autonomic nervous system (ANS) dysfunction affecting CO₂ regulation. The aim of this study was to investigate nocturnal gas exchanges in children with DS and compare them to what has been observed in typically developing (TD) children, describe clinical signs of SDB and ANS dysfunction, executive functioning and motor skills and explore potential associations between PtcCO₂ levels and neuropsychological outcomes.

In this prospective study, children with DS aged 4-16 years without previously identified obstructive sleep apnoea were recruited between October 2019 and March 2022. Clinical assessment, autonomic symptom, executive function questionnaires and home overnight transcutaneous oxycapnography were performed; children with symptoms and/or elevated PtcCO₂ underwent polysomnography.

Forty-eight children with DS (median age: 8.0 [7.0-12.0] years) were included, of whom 30 had interpretable overnight SpO₂ and PtcCO₂ recordings. Median mean nocturnal PtcCO₂ was 44 [40-46] mmHg, significantly higher than in TD children (p = 0.01), including in the subgroup with no or mild OSA (45 [41.5-46] mmHg). The most frequent clinical signs of SDB were restless sleep (62%), concentration difficulties (54%) and snoring (48%), whereas ophthalmic (51%) and digestive (46%) symptoms of autonomic dysfunction were common. No association was found between nocturnal PtcCO₂ and executive functioning or motor skills.

Children with DS exhibit higher nocturnal PtcCO₂ levels than TD children, along with clinical features suggestive of dysautonomia, supporting the hypothesis of a global ANS dysfunction affecting chemosensitivity.