Otitis media, antibiotics, and risk of autism spectrum disorder

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.

Neonate gut colonization: The rise of a social brain

“…An earlier population‐based cohort study revealed that antibiotic use during pregnancy is associated with a 50%‐100% increase in ASD risk, while according to a recent large prospective cohort study, otitis media and the administration of broad‐spectrum antibiotics during early childhood increase ASD risk. However, in this latter investigation, there was no significant synergistic effect of otitis media and antibiotic use, suggesting that antibiotics did not modify the association between infection and ASD . Contrary to these findings, another large cohort study failed to reveal any significant association between antibiotic use during infancy and ASD risk .…”

Early Life Exposure to Antibiotics and Autism Spectrum Disorders: A Systematic Review

“…Four of those studies were cohort studies, and seven of them were case–control studies. Among the included cohort studies, three Danish studies (Atladottir et al 2012; Wimberley et al 2018; Axelsson et al 2019) were performed in overlapping populations. Five studies examined prenatal antibiotic exposure, five assessed early childhood antibiotic exposure and 1 study examined both types of exposure (Wimberley et al 2018).…”

“…Among the included cohort studies, three Danish studies (Atladottir et al 2012; Wimberley et al 2018; Axelsson et al 2019) were performed in overlapping populations. Five studies examined prenatal antibiotic exposure, five assessed early childhood antibiotic exposure and 1 study examined both types of exposure (Wimberley et al 2018). In the majority of included studies, use of any antibiotic, for any indication and duration and at any dose within the defined time period, was analyzed.…”

“…Prenatal antibiotic exposure as a risk factor for autism was examined in two large Danish cohort studies performed in overlapping populations. The studies involved, respectively: 96,736 children, including 976 with ASD (Atladottir et al 2012) and 780,547 children, including 9352 with autism (Wimberley et al 2018). Population of the first study was most likely contained within the population of the second, therefore, we didn’t perform a meta-analysis.…”

An approach to gut microbiota profile in children with autism spectrum disorder

“…However, the aetiology of the nutritional and GI problems of ASD remains unknown (McElhanon et al, 2014;Ferguson et al, 2016;Martínez-González and Andreo-Martínez, 2019) and everything seems to indicate that it is a combination of associated factors (Buie, 2015). Other authors suggest that abnormal GM in ASD may be caused by the overuse of antibiotics (Sandler et al, 2000;Krajmalnik-Brown et al, 2015;Wimberley et al, 2018) or a pathophysiological cascade of interactions between environmental factors and key genes. In addition, the neurological alterations associated with atypical growth of the head in children with ASD during the uterine period, which occurs more frequently in late gestations, can also be a possible trigger of ASD (Bonnet-Brilhault et al, 2018).…”