Snoring is a very frequent complaint affecting 10% to 12% of all children 1 and is the primary symptom of obstructive sleep apnea (OSA). OSA is the occurrence of repeated events of partial or complete upper airway obstruction during sleep, leading to disruption of normal ventilation, and to hypoxemia and sleep fragmentation. The pathophysiology of pediatric OSA is multifactorial, but adenotonsillar hypertrophy with or without concurrent obesity constitutes the major pathophysiologic mechanism underlying OSA in children. 2 Pediatric OSA has been extensively associated with an increased risk for behavioral and mood disturbances, as well as with cognitive defi cits. Furthermore, cardiovascular and metabolic morbidities, such as pulmonary hypertension, systemic hypertension, endothelial dysfunction, insulin resistance, and serum lipid alterations, are also frequently observed. 3 However, identifi cation of those children who have developed any such OSAassociated morbidities is diffi cult, and is usually complicated by the need for laborious and onerous test batteries that are not routinely available in most clinical settings. Therefore, such assessments are usually not pursued.Background: Pediatric obstructive sleep apnea (OSA) is associated with cognitive dysfunction, suggesting altered neurotransmitter function. We explored overnight changes in neurotransmitters in the urine of children with and without OSA. Methods: Urine samples were collected from children with OSA and from control subjects before and after sleep studies. A neurocognitive battery assessing general cognitive ability (GCA) was administered to a subset of children with OSA. Samples were subjected to multiple enzyme-linked immunosorbent assays for 12 neurotransmitters, and adjusted for creatinine concentrations. Results: The study comprised 50 children with OSA and 20 control subjects. Of the children with OSA, 20 had normal GCA score (mean Ϯ SD) (101.2 Ϯ 14.5) and 16 had a reduced GCA score (87.3 Ϯ 13.9; P , .001). Overnight increases in epinephrine, norepinephrine, and g -aminobutyric acid (GABA) levels emerged in children with OSA; taurine levels decreased. Using combinatorial approaches and cutoff values for overnight changes of these four neurotransmitters enabled prediction of OSA (area under the curve [AUC]: 0.923; P , .0001). Furthermore, GABA and taurine alterations, as well as overnight reductions in phenylethylamine, were more prominent in children with OSA and low GCA than in children with OSA and normal GCA ( P , .001), and they reliably discriminated GCA status (AUC: 0.977; P , .0001). Conclusions: Pediatric OSA is associated with overnight increases in urinary concentrations of catecholamines indicative of heightened sympathetic outfl ow. Increases in GABA levels and decreases in taurine levels could underlie mechanisms of neuronal excitotoxicity and dysfunction. Combinatorial approaches using defi ned cutoffs in overnight changes in concentrations of selected neurotransmitters in urine may not only predict OSA but also the presence ...