Jong Yeob Kim1, Min Je Choi1, Sungji Ha2, Jimin Hwang3, Ai Koyanagi4,5, Elena Dragioti6, Joaquim Radua7,8,9, Lee Smith10, Louis Jacob4,11, Gonzalo Salazar de Pablo12,13,14, Seung Won Lee15, Dong Keon Yon16, Trevor Thompson17, Samuele Cortese18,19,20,21, Gianluca Lollo22, Chih-Sung Liang23,24, Che-Sheng Chu25,26,27,28, Paolo Fusar-Poli12,29,30,31, Keun-Ah Cheon2, Jae Il Shin32, Marco Solmi12,18,33,34,35. 1. Yonsei University College of Medicine, Seoul, South Korea. 2. Department of Child and Adolescent Psychiatry, Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea. 3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. 4. Research and Development Unit, Parc Sanitari Sant Joan de Déu/CIBERSAM, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain. 5. ICREA, Barcelona, Spain. 6. Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden. 7. Mental Health Research Networking Center (CIBERSAM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 8. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. 9. Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden. 10. Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK. 11. Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France. 12. Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. 13. Child and Adolescent Mental Health Services, South London & Maudsley NHS Trust, London, UK. 14. Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. 15. Department of Data Science, Sejong University College of Software Convergence, Seoul, South Korea. 16. Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea. 17. Centre for Chronic Illness and Ageing, University of Greenwich, London, UK. 18. Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life sciences & Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK. 19. Solent NHS Trust, Southampton, UK. 20. Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK. 21. Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, New York, USA. 22. Department of Gastroenterology, Ospedale Regionale di Bellinzona e Valli (Ente Ospedaliero Cantonale: EOC), Bellinzona, Switzerland. 23. Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan. 24. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. 25. Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. 26. Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. 27. Society of Psychophysiology, Non-invasive Neuromodulation Consortium for Mental Disorders, Taipei, Taiwan. 28. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 29. OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK. 30. Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. 31. National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK. 32. Department of Pediatrics, Yonsei University College of Medicine, Seoul, South Korea. 33. Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada. 34. Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada. 35. Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, Ontario, Canada.
Abstract
Children with autism spectrum disorder (ASD) are frequently diagnosed with co-occurring medical conditions including inflammatory bowel disease (IBD). To investigate the association, we conducted a systematic review registered in PROSPERO (ID:CRD42021236263) with a random-effects meta-analysis. We searched PubMed, Embase, and PsycInfo (last search on January 25, 2021), and manually searched relevant publications. We included observational studies measuring the association between ASD and IBD. The primary outcome was the association (odds ratio, OR) between ASD and later development of IBD. Sensitivity analyses were conducted by quality, confounding adjustment, and study design. We performed meta-regression analyses and assessed heterogeneity, publication bias, and quality of studies with the Newcastle-Ottawa Scale. Overall, we included six studies consisting of eight datasets, including over 11 million participants. We found that ASD was significantly associated with subsequent incident IBD (any IBD, OR = 1.66, 95% confidence interval[CI] = 1.25-2.21, p < 0.001; ulcerative colitis, OR = 1.91, 95%CI = 1.41-2.6, p < 0.001; Crohn's disease, OR = 1.47, 95%CI = 1.15-1.88, p = 0.002). ASD and IBD were also associated regardless of temporal sequence of diagnosis (any IBD, OR = 1.57, 95%CI = 1.28-1.93, p < 0.001; ulcerative colitis, OR = 1.7, 95%CI = 1.36-2.12, p < 0.001; Crohn's disease, OR = 1.37, 95%CI = 1.12-1.69, p = 0.003). Sensitivity analyses confirmed the findings of the main analysis. Meta-regression did not identify any significant moderators. Publication bias was not detected. Quality was high in four datasets and medium in four. In conclusion, our findings highlight the need to screen for IBD in individuals with ASD, and future research should identify who, among those with ASD, has the highest risk of IBD, and elucidate the shared biological mechanisms between ASD and IBD. LAY SUMMARY: This systematic review and meta-analysis of eight observational datasets found that individuals with autism spectrum disorder (ASD) are more likely to develop any inflammatory bowel disease, ulcerative colitis, or Crohn's disease. Our findings highlight the need to screen for inflammatory bowel disease in patients with ASD and elucidate the shared biological mechanisms between the two disorders.
Children with autism spectrum disorder (ASD) are frequently diagnosed with co-occurring medical conditions including inflammatory bowel disease (IBD). To investigate the association, we conducted a systematic review registered in PROSPERO (ID:CRD42021236263) with a random-effects meta-analysis. We searched PubMed, Embase, and PsycInfo (last search on January 25, 2021), and manually searched relevant publications. We included observational studies measuring the association between ASD and IBD. The primary outcome was the association (odds ratio, OR) between ASD and later development of IBD. Sensitivity analyses were conducted by quality, confounding adjustment, and study design. We performed meta-regression analyses and assessed heterogeneity, publication bias, and quality of studies with the Newcastle-Ottawa Scale. Overall, we included six studies consisting of eight datasets, including over 11 million participants. We found that ASD was significantly associated with subsequent incident IBD (any IBD, OR = 1.66, 95% confidence interval[CI] = 1.25-2.21, p < 0.001; ulcerative colitis, OR = 1.91, 95%CI = 1.41-2.6, p < 0.001; Crohn's disease, OR = 1.47, 95%CI = 1.15-1.88, p = 0.002). ASD and IBD were also associated regardless of temporal sequence of diagnosis (any IBD, OR = 1.57, 95%CI = 1.28-1.93, p < 0.001; ulcerative colitis, OR = 1.7, 95%CI = 1.36-2.12, p < 0.001; Crohn's disease, OR = 1.37, 95%CI = 1.12-1.69, p = 0.003). Sensitivity analyses confirmed the findings of the main analysis. Meta-regression did not identify any significant moderators. Publication bias was not detected. Quality was high in four datasets and medium in four. In conclusion, our findings highlight the need to screen for IBD in individuals with ASD, and future research should identify who, among those with ASD, has the highest risk of IBD, and elucidate the shared biological mechanisms between ASD and IBD. LAY SUMMARY: This systematic review and meta-analysis of eight observational datasets found that individuals with autism spectrum disorder (ASD) are more likely to develop any inflammatory bowel disease, ulcerative colitis, or Crohn's disease. Our findings highlight the need to screen for inflammatory bowel disease in patients with ASD and elucidate the shared biological mechanisms between the two disorders.