Intervention Protocol

You have free access to this content

Hyperbaric oxygen therapy for autism spectrum disorder (ASD) in children and adults

  1. Tao Xiong,
  2. Hongju Chen,
  3. Rong Luo,
  4. Dezhi Mu*

Editorial Group: Cochrane Developmental, Psychosocial and Learning Problems Group

Published Online: 17 JAN 2014

DOI: 10.1002/14651858.CD010922

How to Cite

Xiong T, Chen H, Luo R, Mu D. Hyperbaric oxygen therapy for autism spectrum disorder (ASD) in children and adults (Protocol). Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD010922. DOI: 10.1002/14651858.CD010922.

Author Information

  1. West China Second University Hospital, Sichuan University, Department of Pediatrics, Chengdu, Sichuan, China

*Dezhi Mu, Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 17, Section Three, Ren Min Nan Lu Avenue, Chengdu, Sichuan, 610041, China.

Publication History

  1. Publication Status: New
  2. Published Online: 17 JAN 2014



Additional references

Abdallah 2012
Aman 1987
  • Aman MG, Richmond G, Stewart AW, Bell JC, Kissel RC. The aberrant behavior checklist: factor structure and the effect of subject variables in American and New Zealand facilities. American Journal of Mental Deficiency 1987;91(6):570-8.
Anitha 2012
  • Anitha A, Nakamura K, Thanseem I, Yamada K, Iwayama Y, Toyota T, et al. Brain region-specific altered expression and association of mitochondria-related genes in autism. Molecular Autism 2012;3(1):12.
Bai 2008
  • Bai J, Luan Z, Zhou CL, Qu SQ, Jiang Y, Wang ZY. Effect of hyperbaric oxygenation on the differentiation of implanted human neural stem cells into neurons in vivo. Zhongguo Dang Dai Er Ke Za Zhi 2008;10(2):195-8.
Bent 2012
  • Bent S, Bertoglio K, Ashwood P, Nemeth E, Hendren RL. Brief report. Hyperbaric oxygen therapy (HBOT) in children with autism spectrum disorder: a clinical trial. Journal of Autism and Developmental Disorders 2012;42(6):1127-32.
Brkic 2012
  • Brkic P, Stojiljkovic M, Jovanovic T, Dacic S, Lavrnja I, Savic D, et al. Hyperbaric oxygenation improves locomotor ability by enhancing neuroplastic responses after cortical ablation in rats. Brain Injury 2012;26(10):1273-84.
Calvert 2007
Cebula 2012
  • Cebula KR. Applied behavior analysis programs for autism: sibling psychosocial adjustment during and following intervention use. Journal of Autism and Developmental Disorders 2012;42(5):847-62.
Chen 2009a
  • Chen Y, Nadi NS, Chavko M, Auker CR, McCarron RM. Microarray analysis of gene expression in rat cortical neurons exposed to hyperbaric air and oxygen. Neurochemical Research 2009;34(6):1047-56.
Chen 2009b
  • Chen S, Xiao N, Zhang X. Effect of combined therapy with ephedrine and hyperbaric oxygen on neonatal hypoxic-ischemic brain injury. Neuroscience Letters 2009;465(2):171-6.
Ching 2012
Chungpaibulpatana 2008
  • Chungpaibulpatana J, Sumpatanarax T, Thadakul N, Chantharatreerat C, Konkaew M, Aroonlimsawas M. Hyperbaric oxygen therapy in Thai autistic children. Journal of the Medical Association of Thailand 2008;91(8):1232-8.
Connors 2006
Currenti 2010
Dawson 2012
  • Dawson G, Jones EJ, Merkle K, Venema K, Lowy R, Faja S, et al. Early behavioral intervention is associated with normalized brain activity in young children with autism. Journal of the American Academy of Child and Adolescent Psychiatry 2012;51(11):1150-9.
Devlin 2012
Dufour-Rainfray 2011
  • Dufour-Rainfray D, Vourc'h P, Tourlet S, Guilloteau D, Chalon S, Andres CR. Fetal exposure to teratogens: evidence of genes involved in autism. Neuroscience & Biobehavioral Reviews 2011;35(5):1254-65.
Edwards 1997
  • Edwards S, Fletcher P, Garman M, Hughes A, Letts C, SinkaI I. The Reynell Developmental Language Scales III. Windsor: NFER-Nelson, 1997.
Efrati 2013
  • Efrati S, Fishlev G, Bechor Y, Volkov O, Bergan J, Kliakhandler K, et al. Hyperbaric oxygen induces late neuroplasticity in post stroke patients - randomized, prospective trial. PLoS One 2013;8(1):e53716.
Egger 1997
  • Egger M, Davey-Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphic test. BMJ 1997;315(7109):629-34.
El-Ansary 2012
Eldevik 2009
  • Eldevik S, Hastings RP, Hughes JC, Jahr E, Eikeseth S, Cross S. Meta-analysis of early intensive behavioral intervention for children with autism. Journal of Clinical Child and Adolescent Psychology 2009;38(3):439-50.
Freeman 1986
  • Freeman BJ, Ritvo ER, Yokota A, Ritvo A. A scale for rating symptoms of patients with the syndrome of autism in real life settings. Journal of the American Academy of Child and Adolescent Psychiatry 1986;25(1):130-6.
Freiberger 2006
  • Freiberger JJ, Suliman HB, Sheng H, McAdoo J, Piantadosi CA, Warner DS. A comparison of hyperbaric oxygen versus hypoxic cerebral preconditioning in neonatal rats. Brain Research 2006;1075(1):213-22.
Gal 2012
  • Gal G,  Abiri L,  Reichenberg A,  Gabis L,  Gross R. Time trends in reported autism spectrum disorders in Israel, 1986-2005. Journal of Autism and Developmental Disorders 2012;42(3):428-31.
Ghanizadeh 2012
  • Ghanizadeh A. Hyperbaric oxygen therapy for treatment of children with autism: a systematic review of randomized trials. Medical Gas Research 2012;2:13.
Gill 2004
Granpeesheh 2010
  • Granpeesheh D, Tarbox J, Dixon DR, Wilke AE, Allen MS, Bradstreet JJ. Randomized trial of hyperbaric oxygen therapy for children with autism. Research in Autism Spectrum Disorders 2010;4(2):268-75.
Griffiths 1996
  • Griffiths R, Huntley M. The Griffiths Mental Development Scales: From Birth to 2 Years. Henley-on-Thames, UK: Test Agency Ltd, 1996.
Haley 1992
  • Haley SM, Coster WJ, Ludlow LH, Haltiwanger JT, Andrellos PJ. Pediatric Evaluation of Disability Inventory (PEDI). San Antonio: Pearson, 1992.
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011.
Howlin 2009
  • Howlin P, Magiati I, Charman T. Systematic review of early intensive behavioral interventions for children with autism. American Journal on Intellectual Developmental Disabilities 2009;114(1):23-41.
Hughes 2008
Hughes 2009
Ichim 2007
Ito 2005
  • Ito H, Mori K, Hashimoto T, Miyazaki M, Hori A, Kagami S, et al. Findings of brain 99mTc-ECD SPECT in high-functioning autism—3-dimensional stereotactic ROI template analysis of brain SPECT. The Journal of Medical Investigation 2005;52(1-2):49-56.
Jesner 2007
Kane 2012
  • Kane MJ, Angoa-Perez M, Briggs DI, Sykes CE, Francescutti DM, Rosenberg DR, et al. Mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors: possible relevance to autism. PLoS One 2012;7(11):e48975.
Kasari 2012
Kasari 2012a
  • Kasari C, Gulsrud A, Freeman S, Paparella T, Hellemann G. Longitudinal follow-up of children with autism receiving targeted interventions on joint attention and play. Journal of the American Academy of Child and Adolescent Psychiatry 2012;51(5):487-95.
Leckman 1989
  • Leckman JF, Riddle MA, Hardin MT, Ort SI, Swartz KL, Stevenson J, et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. Journal of the American Academy of Child and Adolescent Psychiatry 1989;28(4):566-73. [PUBMED: 2768151]
Leiter 1980
  • Leiter RG. Leiter International Performance Scale Instruction Manual. Revised. Wood Dale: Stoelting, 1980.
Li 2009
  • Li JS, Zhang W, Kang ZM, Ding SJ, Liu WW, Zhang JH, et al. Hyperbaric oxygen preconditioning reduces ischemia-reperfusion injury by inhibition of apoptosis via mitochondrial pathway in rat brain. Neuroscience 2009;159(4):1309-15.
Li 2009a
Lin 2012a
  • Lin KC, Niu KC, Tsai KJ, Kuo JR, Wang LC, Chio CC, et al. Attenuating inflammation but stimulating both angiogenesis and neurogenesis using hyperbaric oxygen in rats with traumatic brain injury. The Journal of Trauma and Acute Care Surgery 2012;72(3):650-9.
Lin 2012b
  • Lin H, Chang CP, Lin HJ, Lin MT, Tsai CC. Attenuating brain edema, hippocampal oxidative stress, and cognitive dysfunction in rats using hyperbaric oxygen preconditioning during simulated high-altitude exposure. The Journal of Trauma and Acute Care Surgery 2012;72(5):1220-7.
Lord 1994
  • Lord C, Rutter M, Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders 1994;24(5):659-85.
Lord 1997
  • Lord C, Rutter M, DiLavore PC. Autism Diagnostic Observation Scale - Generic. Chicago, IL: University of Chicago Press 1997.
Lou 2006
  • Lou M, Chen Y, Ding M, Eschenfelder CC, Deuschl G. Involvement of the mitochondrial ATP-sensitive potassium channel in the neuroprotective effect of hyperbaric oxygenation after cerebral ischemia. Brain Research Bulletin 2006;69(2):109-16.
Lovaas 1987
  • Lovaas OI. Behavioral treatment and normal educational and intellectual functioning in young autistic children. Journal of Consulting and Clinical Psychology 1987;55(1):3-9.
Lowe 1976
  • Lowe M, Costello AJ. Manual for the Symbolic Play Test. Windsor: National Foundation for Educational Research, 1976.
Maezawa 2011
Maglione 2012
  • Maglione MA, Gans D, Das L, Timbie J, Kasari C. Nonmedical interventions for children with ASD: recommended guidelines and further research needs. Pediatrics 2012;130 Suppl 2:S169-78.
Malek 2013
  • Malek M, Duszczyk M, Zyszkowski M, Ziembowicz A, Salinska E. Hyperbaric oxygen and hyperbaric air treatment result in comparable neuronal death reduction and improved behavioral outcome after transient forebrain ischemia in the gerbil. Experimental Brain Research 2013;224(1):1-14.
Matson 2011
  • Matson JL, Sipes M, Fodstad JC, Fitzgerald ME. Issues in the management of challenging behaviours of adults with autism spectrum disorder. CNS Drugs 2011;25(7):597-606.
McPheeters 2011
  • McPheeters ML,  Warren Z,  Sathe N,  Bruzek JL,  Krishnaswami S,  Jerome RN,  et al. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics 2011;127(5):e1312-21.
Miljkovic-Lolic 2003
  • Miljkovic-Lolic M, Silbergleit R, Fiskum G, Rosenthal RE. Neuroprotective effects of hyperbaric oxygen treatment in experimental focal cerebral ischemia are associated with reduced brain leukocyte myeloperoxidase activity. Brain Research 2003;971(1):90-4.
Mrsić-Pelcić 2004
  • Mrsić-Pelcić J, Pelcić G, Vitezić D, Antoncić I, Filipović T, Simonić A, et al. Hyperbaric oxygen treatment: the influence on the hippocampal superoxide dismutase and Na+,K+-ATPase activities in global cerebral ischemia-exposed rats. Neurochemistry International 2004;44(8):585-94.
Msall 1994
  • Msall ME, DiGaudio K, Rogers BT, LaForest S, Catanzaro NL, Campbell J, et al. The Functional Independence Measure for Children (WeeFIM). Conceptual basis and pilot use in children with developmental disabilities. Clinical pediatrics 1994;33(7):421-30.
Mu 2013
  • Mu J, Ostrowski RP, Soejima Y, Rolland WB, Krafft PR, Tang J, et al. Delayed hyperbaric oxygen therapy induces cell proliferation through stabilization of cAMP responsive element binding protein in the rat model of MCAo-induced ischemic brain injury. Neurobiology of Disease 2013;51:133-43.
Muhle 2004
Muller-Bolla 2006
  • Muller-Bolla M, Collet JP, Ducruet T, Robinson A. Side effects of hyperbaric oxygen therapy in children with cerebral palsy. Undersea and Hyperbaric Medicine 2006;33(4):237-44.
Nye 2005
O'Hearn 2008
Pardo 2007
Phillips 2005
Reichow 2012
Review Manager 2013
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2013.
Rimland 1999
  • Rimland B, Edelson SM. Autism Treatment Evaluation Checklist (ATEC), 1999.
Rossignol 2007
Rossignol 2009a
  • Rossignol DA,  Rossignol LW,  Smith S,  Schneider C,  Logerquist S,  Usman A,  et al. Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial. BMC Pediatrics 2009;9:21.
Rossignol 2009b
  • Rossignol DA. Novel and emerging treatments for autism spectrum disorders: a systematic review. Annals of Clinical Psychiatry 2009;21(4):213-36.
Rossignol 2012a
  • Rossignol DA,  Bradstreet JJ,  Van Dyke K,  Schneider C,  Freedenfeld SH,  O'Hara N,  et al. Hyperbaric oxygen treatment in autism spectrum disorders. Medical Gas Research 2012;2(1):16.
Rossignol 2012b
Sallows 2005
Siniscalco 2012
  • Siniscalco D, Sapone A, Giordano C, Cirillo A, De Novellis V, De Magistris L, et al. The expression of caspases is enhanced in peripheral blood mononuclear cells of autism spectrum disorder patients. Journal of Autism and Developmental Disorders 2012;42(7):1403-10.
Sumen-Secgin 2005
  • Sumen-Secgin G, Cimsit M, Ozek M, Eroglu L. Antidepressant-like effect of hyperbaric oxygen treatment in forced-swimming test in rats. Methods and Findings in Experimental and Clinical Pharmacology 2005;27(7):471-4.
Thom 2006
  • Thom SR, Bhopale VM, Fisher D. Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. Toxicology and Applied Pharmacology 2006;213(2):152-9.
Thom 2011
Thorndike 1986
  • Thorndike R, Hagen E, Sattler J. The Stanford-Binet Intelligence Scale. 4th Edition. Itasca: The Riverside Publishing Company, 1986.
Vargas 2005
Vismara 2012
  • Vismara LA, Young GS, Rogers SJ. Telehealth for expanding the reach of early autism training to parents. Autism Research and Treatment 2012;2012:1-12. [DOI: 10.1155/2012/121878]
Wang 2007a
  • Wang XL, Yang YJ, Wang QH, Xie M, Yu XH, Liu CT, et al. Changes of Wnt-3 protein during the proliferation of endogenous neural stem cells in neonatal rats with hypoxic-ischemic brain damage after hyperbaric oxygen therapy. Chinese Journal of Contemporary Pediatrics 2007;9(3):241-6.
Wang 2007b
  • Wang XL, Yang YJ, Wang QH, Yu XH, Xie M, Liu CT, et al. Effect of hyperbaric oxygen therapy administered at different time on white matter damage following hypoxic-ischemic brain damage in neonatal rats. Chinese Journal of Contemporary Pediatrics 2007;9(4):308-12.
Wang 2009
  • Wang XL, Yang YJ, Xie M, Yu XH, Wang QH. Hyperbaric oxygen promotes the migration and differentiation of endogenous neural stem cells in neonatal rats with hypoxic ischemic brain damage. Chinese Journal of Contemporary Pediatrics 2009;11(9):749-52.
Warren 2011
  • Warren Z, McPheeters ML, Sathe N, Foss-Feig JH, Glasser A, Veenstra-Vanderweele J. A systematic review of early intensive intervention for autism spectrum disorders. Pediatrics 2011;127(5):e1303-11.
WHO 1993
  • World Health Organisation. The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. Geneva: WHO, 1993.
Williams 2010
Williams 2012
Wilson 2006
  • Wilson HD, Wilson JR, Fuchs PN. Hyperbaric oxygen treatment decreases inflammation and mechanical hypersensitivity in an animal model of inflammatory pain. Brain Research 2006;1098(1):126-8.
Yamashita 2009
  • Yamashita S, Hirata T, Mizukami Y, Cui YJ, Fukuda S, Ishida K, et al. Repeated preconditioning with hyperbaric oxygen induces neuroprotection against forebrain ischemia via suppression of p38 mitogen activated protein kinase. Brain Research 2009;1301:171-9.
Yang 2007
  • Yang MS, Gill M. A review of gene linkage, association and expression studies in autism and an assessment of convergent evidence. International Journal of Developmental Neuroscience 2007;25(2):69-85.
Yin 2013
  • Yin X, Meng F, Wang Y, Wei W, Li A, Chai Y, et al. Effect of hyperbaric oxygen on neurological recovery of neonatal rats following hypoxic-ischemic brain damage and its underlying mechanism. International Journal of Clinical and Experimental Pathology 2013;6(1):66-75.