Association between prenatal antibiotic exposure and autism spectrum disorder among term births: A population-based
Amanda S Nitschke1, Helena Abreu do Valle2, Bruce A Vallance3
1School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
Insights
Prenatal antibiotic exposure showed a small increased risk for autism spectrum disorder (ASD) in offspring. However, these findings should not alter clinical decisions on antibiotic use during pregnancy due to potential confounding.
Area of Science:
- Investigates the intersection of maternal health, microbiome research, and neurodevelopmental outcomes.
- Focuses on the impact of environmental factors during pregnancy on child health.
- Contributes to understanding the microbiome-gut-brain axis in early development.
Background:
- Prenatal antibiotic exposure can alter the maternal microbiome.
- Maternal microbiome changes may influence infant microbiome-gut-brain axis development.
- This pathway could potentially impact neurodevelopmental outcomes like autism spectrum disorder (ASD).
Purpose of the Study:
- To assess the association between prenatal antibiotic exposure and the risk of autism spectrum disorder (ASD) in term infants.
- To investigate specific exposure windows (trimesters, duration) and antibiotic classes.
- To control for potential genetic and environmental confounding factors.
Main Methods:
- Population-based retrospective cohort study in British Columbia, Canada (2000-2014).
- Exposure: antibiotic prescriptions filled during pregnancy.
- Outcome: ASD diagnosis. Analyzed using Cox proportional hazards models and conditional logistic regression in sibling pairs.
Main Results:
- Prenatal antibiotic exposure was associated with a 10% increased risk of ASD (HR 1.10).
- Increased risk observed particularly with first/second trimester exposure and longer durations (≥15 days).
- Association was attenuated in sibling analysis, suggesting residual confounding.
Conclusions:
- A small increase in ASD risk is associated with prenatal antibiotic exposure.
- The study highlights the need for careful consideration of antibiotic use during pregnancy.
- Results should not guide clinical decisions due to potential residual confounding.
Background:
Prenatal antibiotic exposure induces changes in the maternal microbiome, which could influence the development of the infant's microbiome-gut-brain axis.
Objectives:
We assessed whether prenatal antibiotic exposure is associated with an increased risk of autism spectrum disorder (ASD) in offspring born at term.
Methods:
This population-based retrospective cohort study included everyone who delivered a live singleton-term infant in British Columbia, Canada between April 2000 and December 2014. Exposure was defined as filling antibiotic prescriptions during pregnancy. The outcome was an ASD diagnosis from the British Columbia Autism Assessment Network, with a follow-up to December 2016. To examine the association among pregnant individuals treated for the same indication, we studied a sub-cohort diagnosed with urinary tract infections. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios (HR). The analysis was stratified by sex, trimester, cumulative duration of exposure, class of antibiotic, and mode of delivery. We ran a conditional logistic regression of discordant sibling pairs to control for unmeasured environmental and genetic confounding.
Results:
Of the 569,953 children included in the cohort, 8729 were diagnosed with ASD (1.5%) and 169,922 were exposed to prenatal antibiotics (29.8%). Prenatal antibiotic exposure was associated with an increased risk of ASD (HR 1.10, 95% confidence interval [CI] 1.05, 1.15), particularly for exposure during the first and second trimesters (HR 1.11, 95% CI 1.04, 1.18 and HR 1.09, 95% CI 1.03, 1.16, respectively), and exposure lasting ≥15 days (HR 1.13, 95% CI 1.04, 1.23). No sex differences were observed. The association was attenuated in the sibling analysis (adjusted odds ratio 1.04, 95% CI 0.92, 1.17).
Conclusions:
Prenatal antibiotic exposure was associated with a small increase in the risk of ASD in offspring. Given the possibility of residual confounding, these results should not influence clinical decisions regarding antibiotic use during pregnancy.
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