The effectiveness of hyperbaric oxygen therapy in children and adolescents and with autism spectrum disorders: A systematic review and meta-analysis

Background: Hyperbaric oxygen therapy (HBOT) is considered a potential treatment for autism spectrum disorders, aiming to improve the underlying pathophysiological mechanisms. It has been studied in several clinical trials, but the effectiveness is still controversial. Purpose: This systematic review aimed to systematically evaluate the effectiveness of hyperbaric oxygen therapy in the treatment of autism in children and adolescents. Methods: We systematically searched seven databases (PubMed, Embase, Cochrane Libraries, Web of Science, CNKI, Wanfang, and SinoMed) up to March 20, 2024, as well as references lists. The included studies evaluated the effect of HBOT on improving the core symptoms of autism and other specific symptoms (e.g., communication, sociability, cognitive awareness, behavior), including RCTs and quasiexperimental studies. The Cochrane Collaboration's Risk of Bias Assessment Tool for Randomized Trials (RoB2.0) and the JBI Risk of Bias Tool for Quasi- Experimental Studies were used as quality assessment tools. A random effects model was used to conduct a meta- analysis of the core and specific symptoms of autism. Sensitivity analyses and meta-regression were performed to identify sources of heterogeneity and assess result robustness. A Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence certainty analysis was performed for outcomes. This systematic review is registered with PROSPERO (CRD42024527220). Results: A total of 17 studies with 890 patients were ultimately included in the metaanalysis. The meta-analysis revealed moderately large, significant effects of hyperbaric oxygen therapy, reducing core symptoms of autism [SMD =-0.66, 95 % CI (-1.04,-0.28), P = 0.0006], and improving three aspects of daily performances (communication [SMD =- 0.88, 95 % CI (-1.71,-0.04), P = 0.04], cognitive awareness [SMD =-0.93, 95 % CI (-1.51,-0.35), P = 0.002], and behavior [SMD =-0.80, 95 % CI (- 1.46,-0.13), P = 0.02] in children and adolescents with autism. This systematic review and meta-analysis have limitations such as poor quality and high heterogeneity of the included study. Conclusion: These findings underscore the potential benefits of hyperbaric oxygen therapy in managing autism- related symptoms and improving daily functioning in affected children and adolescents. Future rigorously designed, high-quality studies are required to confirm the efficacy of hyperbaric oxygen therapy and establish standard treatment protocols.