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

Date Published: August 29, 2019

Publisher: Public Library of Science

Author(s): Amani F. Hamad, Silvia Alessi-Severini, Salaheddin M. Mahmud, Marni Brownell, I fan Kuo, Cheryl S. Rosenfeld.


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.

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.

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.

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.

Partial Text

Autism spectrum disorders (ASD) are characterized by impairment in social communication and interaction with repetitive patterns of behavior [1]. The burden of ASD is significant with 62 million cases worldwide [2]. Genetics are primary contributors to the development of ASD; however, the increasing prevalence of ASD suggests a role of environmental factors [3–7].

Findings from this large population-based cohort study showed a 10% increase in the risk of ASD in children exposed to antibiotics prenatally compared to those who were not exposed. This association was dependent on region and was only observed in those residing in rural regions. The increased risk was shown in those exposed to penicillins and other beta lactams and in those exposed to antibiotics in the second or third trimester. The highest risk was observed in those exposed to antibiotics for longer than two weeks or who received 3 or more antibiotic courses. The lack of association in the two negative controls provides confidence that the findings are reliable.

Our results suggest that prenatal antibiotic exposure is associated with a small, albeit clinically non-significant increase in the risk of ASD which may have been influenced by unmeasured confounding.