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

PLoS One. 2019 Aug 29;14(8):e0221921. doi: 10.1371/journal.pone.0221921. eCollection 2019.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / adverse effects*
  • Autism Spectrum Disorder / epidemiology*
  • Autism Spectrum Disorder / etiology*
  • Female
  • Humans
  • Male
  • Maternal Exposure / adverse effects*
  • Middle Aged
  • Population Surveillance
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Sensitivity and Specificity
  • Siblings
  • Young Adult


  • Anti-Bacterial Agents

Grant support

AFH was supported by the University of Manitoba Evelyn Shapiro Award for Health Services Research. The sponsor had no role in study design, data collection, analysis or interpretation of the data, or writing of the manuscript or in the decision to submit the paper for publication.