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Prenatal antibiotics exposure and the risk of autism spectrum disorders: A population-based cohort study
Amani F Hamad1, Silvia Alessi-Severini1,2, Salaheddin M Mahmud1,3,4
1College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Insights
Prenatal antibiotic exposure was linked to a slight increase in autism spectrum disorder (ASD) risk. This association, while statistically significant, may not be clinically relevant due to potential confounding factors.
Area of Science:
- Perinatal health
- Neurodevelopmental disorders
- Microbiome research
Background:
- Prenatal antibiotic exposure may alter infant gut microbiota.
- This alteration is a potential factor in autism spectrum disorder (ASD) development.
Purpose of the Study:
- To investigate the association between prenatal antibiotic exposure and the risk of ASD.
- To analyze this relationship within a large Canadian population-based cohort.
Main Methods:
- Population-based cohort study of 214,834 children born in Manitoba, Canada.
- Exposure defined by antibiotic prescriptions during pregnancy.
- Autism spectrum disorder diagnosis as the outcome.
- Multivariable Cox proportional hazards regression analysis.
Main Results:
- 37.6% of children had prenatal antibiotic exposure.
- Prenatal antibiotic exposure was associated with a 10% increased risk of ASD (aHR 1.10 [95% CI 1.01, 1.19]).
- Increased risk was observed with exposure in the second (aHR 1.11) and third (aHR 1.17) trimesters.
Conclusions:
- Prenatal antibiotic exposure shows a small association with increased ASD risk.
- Potential residual confounding and confounding by indication suggest the observed risk increase may not be clinically significant.
- Further research is needed to clarify the clinical implications.
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.
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