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Nitschke, Amanda

University of British Columbia

Background: Antibiotics are among the most used medications during pregnancy, and while their short-term benefits are clear, their potential long-term effects are underexplored. Antibiotic exposure induces changes in the maternal microbiome, which could in turn influence the development of the infant’s microbiome with implications for neurodevelopment. This thesis examined the associations of 1) intrapartum antibiotic exposure and 2) prenatal antibiotic exposure with autism spectrum disorder (ASD) in offspring. Methods: Using multiple linked population-level datasets, we examined everyone who delivered a live singleton term infant in British Columbia, Canada between April 1st 2000 and December 31st 2014. To examine the associations among pregnant individuals treated for the same indication, we studied sub-cohorts of those diagnosed 1) as group B streptococcus-positive, and 2) with urinary tract infections. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios. Sensitivity analyses were conducted to examine the impact of different classes of antibiotics, and to assess for dose-response and temporal relationships. Additionally, potential effect modification was examined based on sex and mode of delivery. To account for unmeasured confounding, we ran a conditional logistic regression of discordant sibling pairs. Results: We found no association between intrapartum antibiotic administration and ASD in offspring. In contrast, we observed a small statistically significant increase in risk of ASD associated with prenatal antibiotic exposure. In particular, highest risk was observed if exposure took place during the second trimester, to penicillins or other beta lactams, and for 15 days or longer. Among the cohort restricted to pregnant individuals diagnosed with UTIs, findings showed a positive association between prenatal antibiotics and ASD with an increased effect size; yet, this association was no longer statistically significant, possibly due to a reduced sample size. The relationship between prenatal antibiotic exposure and ASD was no longer significant in the conditional logistic regression. Conclusions: Overall, our findings suggest that the risk of ASD should not factor into clinical decisions on whether to administer antibiotics both prenatally and during labour and delivery. Results may suggest a hypothesized role of impaired fetal metabolic programming by the maternal microbiome and metabolome in ASD development.

Text

2022-10-19

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/82897

Population and Public Health

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/