Theresa Wimberley1,2,3, Esben Agerbo1,2,3, Carsten B Pedersen1,2,3, Søren Dalsgaard1,2,4, Henriette Thisted Horsdal1,2,3, Preben B Mortensen1,2,3, Wesley K Thompson1,5,6, Ole Köhler-Forsberg7,8, Robert H Yolken9. 1. iPSYCH-The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus and Copenhagen, Aarhus University, Denmark. 2. NCRR-The National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus BSS, Aarhus University, Aarhus, Denmark. 3. CIRRAU-Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark. 4. Department for Child and Adolescent Psychiatry, Hospital of Telemark, Kragerø, Norway. 5. Mental Health Center Sct. Hans, Institute of Biological Psychiatry, Denmark. 6. University of California, San Diego, La Jolla, California. 7. Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark. 8. Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. 9. Stanley Division of Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
Otitis media infections and antibiotic treatment have been linked to the risk of developing autism spectrum disorder. Broad-spectrum antibiotics may alter the composition of the gut flora microbiota, which is hypothesized to be involved in the regulation of the immune system. This study examines the interplay among otitis media, antibiotics, and the subsequent risk of developing autism. Based on the entire Danish population, 780,547 children were followed from birth (January 1, 1997 to December 31, 2008) until December 31, 2012. We calculated adjusted hazard ratios and absolute risks of autism with 95% confidence intervals (CIs) related to previous otitis media diagnoses and antibiotic prescriptions redeemed at Danish pharmacies. The absolute risk of autism before age 10 was increased among children with otitis media (1.2% for females and 3.3% for males) and in children who had redeemed an antibiotic prescription (0.6% and 2.7% for females and males) compared to children without a history of otitis media and antibiotics usage (0.4% for females and 1.9% for males). Similarly, we found an increased hazard ratio of autism associated with otitis media (1.83 95% CI 1.71-1.95) and antibiotics usage (1.29 95% CI 1.17-1.43). A history of both otitis media and antibiotic treatment did not further increase the risk of autism. Although the risk of autism was associated with otitis media and treatment with antibiotics, we found little evidence of a synergistic effect between otitis media infections and treatment with antibiotics. Autism Res 2018, 11: 1432-1440.
Otitis media infections and antibiotic treatment have been linked to the risk of developing autism spectrum disorder. Broad-spectrum antibiotics may alter the composition of the gut flora microbiota, which is hypothesized to be involved in the regulation of the immune system. This study examines the interplay among otitis media, antibiotics, and the subsequent risk of developing autism. Based on the entire Danish population, 780,547 children were followed from birth (January 1, 1997 to December 31, 2008) until December 31, 2012. We calculated adjusted hazard ratios and absolute risks of autism with 95% confidence intervals (CIs) related to previous otitis media diagnoses and antibiotic prescriptions redeemed at Danish pharmacies. The absolute risk of autism before age 10 was increased among children with otitis media (1.2% for females and 3.3% for males) and in children who had redeemed an antibiotic prescription (0.6% and 2.7% for females and males) compared to children without a history of otitis media and antibiotics usage (0.4% for females and 1.9% for males). Similarly, we found an increased hazard ratio of autism associated with otitis media (1.83 95% CI 1.71-1.95) and antibiotics usage (1.29 95% CI 1.17-1.43). A history of both otitis media and antibiotic treatment did not further increase the risk of autism. Although the risk of autism was associated with otitis media and treatment with antibiotics, we found little evidence of a synergistic effect between otitis media infections and treatment with antibiotics. Autism Res 2018, 11: 1432-1440.
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