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Otitis media, antibiotics, and risk of autism spectrum disorder
Theresa Wimberley1,2,3, Esben Agerbo1,2,3, Carsten B Pedersen1,2,3
1iPSYCH-The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus and Copenhagen, Aarhus University, Denmark.
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. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We investigated whether otitis media ear infections and antibiotic treatment were associated with autism spectrum disorder. Autism was more common in children who had had an otitis media infection or who had been treated with antibiotics. Given the observational nature of our data, our study cannot be used to conclude that otitis media or use of antibiotics cause autism, as our findings may be subject to unobserved confounding.
Insights
Otitis media infections and antibiotic use were linked to a higher autism risk in children. However, having both conditions did not further increase autism risk, suggesting no synergistic effect.
Area of Science:
- Pediatric Health
- Neurodevelopmental Disorders
- Microbiome Research
Background:
- Otitis media infections and antibiotic treatments are common in childhood.
- Alterations in gut microbiota composition due to antibiotics are hypothesized to influence immune system regulation.
- Previous research suggests a potential link between otitis media, antibiotic use, and autism spectrum disorder (ASD).
Purpose of the Study:
- To investigate the association between otitis media, antibiotic prescriptions, and the risk of developing autism spectrum disorder.
- To examine the interplay between these factors in a large pediatric population.
Main Methods:
- A population-based cohort study in Denmark, following 780,547 children from birth (1997-2008) to 2012.
- Utilized national health registries to identify cases of otitis media and antibiotic prescriptions.
- Calculated adjusted hazard ratios and absolute risks of autism.
Main Results:
- The absolute risk of autism before age 10 was elevated in children with a history of otitis media (1.2% females, 3.3% males) and antibiotic prescriptions (0.6% females, 2.7% males) compared to controls (0.4% females, 1.9% males).
- Increased hazard ratios for autism were associated with otitis media (1.83) and antibiotic usage (1.29).
- A history of both otitis media and antibiotic treatment did not show a significantly increased risk compared to having one or the other.
Conclusions:
- Otitis media and antibiotic treatment are independently associated with an increased risk of autism spectrum disorder.
- Little evidence supports a synergistic effect between otitis media infections and antibiotic treatment regarding autism risk.
- The observational nature of the study precludes causal inference, with potential for unobserved confounding.
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