UNLABELLED: Evidence on the neuroendocrine effects of pediatric spa treatment remains limited. Salivary cortisol is a validated, non-invasive biomarker of hypothalamic-pituitary-adrenal (HPA) axis activity, which may serve as an indicator of physiological adaptation to structured environmental and behavioral interventions. To determine whether a standardized 28-day spa treatment is associated with changes in morning salivary cortisol in children aged 9-12 years with obesity or chronic respiratory diseases, and to compare cortisol trajectories in these diagnostic groups with those of healthy controls. This prospective observational study included 95 children undergoing spa treatment and 38 school-based healthy controls assessed 24 days apart. Morning saliva (07:45-08:30) was analyzed using a validated LC-MS/MS method. Cortisol was successfully measured in 34 of 36 children with obesity, 18 of 50 children with respiratory diseases not receiving corticosteroids, and 36 of 38 healthy controls. Somatic and functional assessments were performed across the clinical cohort. Children with obesity showed a significant decrease in morning salivary cortisol (3.32 → 2.36 nmol/L; mean change - 0.96 nmol/L; p = 0.004; d = - 0.54). Children with respiratory diseases showed a mild, non-significant increase (2.68 → 3.48 nmol/L; + 0.80 nmol/L; p = 0.057; d = 0.47). Healthy controls showed a small increase (3.52 → 4.02 nmol/L; + 0.50 nmol/L; p = 0.089; d = 0.25). Cortisol trajectories were broadly consistent with functional improvements within the spa cohort. Between-group differences should be interpreted in the context of natural variability and environmental factors influencing the school-based control population. CONCLUSIONS: Diagnosis-dependent changes in morning salivary cortisol were observed during a 28-day spa treatment program. The decrease in children with obesity and the mild increase in those with respiratory diseases may indicate differing patterns of physiological adaptation. These findings support the feasibility of incorporating salivary cortisol into future controlled pediatric trials aimed at evaluating neuroendocrine responses to spa therapy. WHAT IS KNOWN: • Salivary cortisol is a validated, non-invasive biomarker of hypothalamic-pituitary-adrenal (HPA) axis activity and is widely used in pediatric research on stress regulation. • Spa treatment (balneotherapy) combines environmental and behavioral components, yet biomarker-based studies have been conducted almost exclusively in adults. Evidence from pediatric spa populations is currently lacking. WHAT IS NEW: • This pilot study provides the first pediatric data on morning salivary cortisol measured before and after a structured 28-day spa treatment program. • These findings offer initial effect-size estimates and suggest that morning salivary cortisol may be feasible to incorporate as a non-invasive marker in future controlled pediatric studies assessing physiological adaptation during spa treatment.

Charles University Prague Faculty of Medicine in Plzen Jahodová 2889 42 Záběhlice 106 00 Praha 10 Hlavní město Prague Czech Republic

Institute for Postgraduate Medical Education Prague Czech Republic

Institute of Endocrinology Department of Steroids and Proteofactors Prague Czech Republic

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