Prenatal antibiotics exposure and the risk of autism spectrum disorders: A population-based cohort study

Abstract

Background Prenatal antibiotic exposure induces changes in infants’ gut microbiota composition and is suggested as a possible contributor in the development of autism spectrum disorders (ASD). In this study, we examined the association between prenatal antibiotic exposure and the risk of ASD. Methods This was a population-based cohort study utilizing the Manitoba Population Research Data Repository. The cohort included 214 834 children born in Manitoba, Canada between April 1, 1998 and March 31, 2016. Exposure was defined as having filled one or more antibiotic prescription during pregnancy. The outcome was autism spectrum disorder diagnosis. Multivariable Cox proportional hazards regression was used to estimate the risk of developing ASD in the overall cohort and in a sibling cohort. Results Of all subjects, 80 750 (37.6%) were exposed to antibiotics prenatally. During follow-up, 2965 children received an ASD diagnosis. Compared to children who were not exposed to antibiotics prenatally, those who were exposed had a higher risk of ASD: (adjusted HR 1.10 [95% CI 1.01, 1.19]). The association was observed in those exposed to antibiotics in the second or third trimester (HR 1.11 [95% CI 1.01, 1.23] and 1.17 [95% CI 1.06, 1.30], respectively). In the siblings’ cohort, ASD risk estimate remained unchanged (adjusted HR 1.08 [95% CI 0.90, 1.30], although it was not statistically significant. Conclusions Prenatal antibiotic exposure is associated with a small increase in the risk of ASD. Given the potential of residual confounding beyond what it was controlled through our study design and because of possible confounding by indication, such a small risk increase in the population is not expected to be clinically significant.

The Association between Autism Spectrum Disorder and Pre- and Postnatal Antibiotic Exposure in Childhood—A Systematic Review with Meta-Analysis

“…Our results indicated that pre- and postnatal antibiotic use increased the ASD risk. This is consistent with previous reports that pre- and postnatal antibiotic use causes ASD in children [10,13,17,18,19]. In our study, both pre- and postnatal antibiotic use increased the ASD risk (Figure 2); however, only prenatal, but not postnatal, antibiotic use was significantly elevated in children with ASD compared to controls (Figure 3).…”

“…Therefore, infant mercury poisoning caused by seafood consumption by the mother, pediatric vaccination, and prenatal use of antibiotics has been suggested to cause ASD [9]. Moreover, studies have reported that pre- [10,11,12] and postnatal exposure to antibiotics and acetaminophen increases the ASD risk [13,14,15,16].…”

“…Studies have suggested that when the altered microbiome is passed onto the fetus, it increases the risk of colitis and ASD by impeding neurological development [13,17,18,19]. Further, antibiotic exposure has been reported to be weakly associated with the risk for ASD [10]; however, this association cannot be clearly established given the difficulty of measuring fetal antibiotic exposure. Studies have also reported that postnatal antibiotic exposure is associated with ASD; specifically, postnatal use of acetaminophen and antibiotics, as well as ear infection, were reported to increase the risk for ASD [16].…”

The Promising Role of Probiotics in Managing the Altered Gut in Autism Spectrum Disorders

“…Multiple factors could contribute in dysbiosis in ASD, including the restricted diets that they follow, in response to allergies and gastrointestinal discomfort [39]. As the gut microbiota expands greatly after birth, several investigators explored the possibility of the role of early exposure to antibiotics, either prenatally or at early life, in causing this dysbiosis [100,101]. Indeed, oral antibiotics disrupt the gut microbiota by indirectly promoting the growth of pathogenic microbiota resulting in GIS [100].…”

Impaired Hypothalamic Microglial Activation in Offspring of Antibiotic-Treated Pregnant/Lactating Rats Is Attenuated by Prebiotic Oligofructose Co-Administration

“…Prenatal antibiotic use is also associated with increased risk of childhood asthma [15] and obesity [16]. Although other conditions have been associated with early life antibiotic exposure, some of the data is conflicting such as with autism spectrum disorder (ASD) [17], while other emerging evidence suggests that neonatal antibiotic use increases the risk of developing functional gastrointestinal disorders including infantile colic and regurgitation [18]. Given that antibiotic use during pregnancy and/or intrapartum will continue to be clinically indicated, it is crucial to identify ways in which the risks of this early life antibiotic exposure, particularly on the developing brain and behavior, can be mitigated.…”