Prenatal and early childhood antibiotic exposure and the risk of neurodevelopmental disorders

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dc.contributor.authorHamad, Amani
dc.contributor.examiningcommitteeMahmud, Salaheddin M. (Community Health Sciences) Brownell, Marni (Community Health Sciences) Guttmann, Astrid (University of Toronto)en_US
dc.contributor.supervisorKuo, I Fan (Pharmacy) Alessi-Severini, Silvia (Pharmacy)en_US
dc.date.accessioned2019-11-18T15:17:15Z
dc.date.available2019-11-18T15:17:15Z
dc.date.issued2019-11en_US
dc.date.submitted2019-11-15T18:25:06Zen
dc.degree.disciplinePharmacyen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractBackground: Early life changes in microbiota composition as a result of antibiotic exposure potentially impair brain development and increase the risk of neurodevelopmental disorders. In this project, I examined the association of antibiotic exposure during the first year of life and prenatal antibiotic exposure with the risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Methods: A population-based cohort study was conducted which included children born in Manitoba, Canada between the fiscal years 1998 and 2016/2017 and utilized administrative databases in Manitoba. Exposure was defined as having filled one or more antibiotic prescriptions during the first year of life or pregnancy. The outcome was ASD or ADHD diagnosis identified in hospital abstracts, physician visits, drug dispensations or educational special needs funding data. Cox proportional hazards regression models were used to estimate the risk of ASD or ADHD in the entire population and a sibling cohort. The risk of ADHD was additionally estimated in a high dimensional propensity score (HDPS)-matched cohort. Results: In a cohort of 214 834 children, antibiotic use in the first year of life was associated with a small reduction in ASD risk (Hazard ratio [HR] 0.91, 95% CI 0.84-0.99) but this was not observed in the sibling cohort (HR 1.03, 95% CI 0.86-1.23). Prenatal antibiotic exposure was associated with a small increase in ASD risk in the overall cohort (HR 1.10, 95% CI 1.01-1.19) and in the sibling cohort (HR 1.08, 95% CI 0.90-1.30). In a cohort of 187 605 children, antibiotic exposure in the first year of life was not associated with ADHD risk in the HDPS-matched cohort (HR 1.02, 95% CI 0.97-1.08) and in the sibling cohort (HR 0.96, 95% CI 0.89-1.03). Prenatal antibiotic exposure was associated with increased ADHD risk in the HDPS-matched cohort (HR 1.22, 95% CI 1.17-1.27) but the risk was attenuated in the sibling cohort (HR 1.06, 95% CI 0.99 - 1.13). Conclusions: No association was observed between antibiotic exposure in the first year of life and ASD or ADHD risk. In addition, no clinically-significant association was observed between prenatal antibiotic exposure and ASD or ADHD risk.en_US
dc.description.noteFebruary 2020en_US
dc.identifier.citationHamad AF, Alessi-Severini S, Mahmud S, Brownell M and Kuo I. Early Childhood Antibiotics Use and Autism Spectrum Disorders: A Population-Based Cohort Study. Int J Epidemiol 2018; 47 (5):1497-1506en_US
dc.identifier.citationHamad AF, Alessi-Severini S, Mahmud S, Brownell M and Kuo I. Prenatal Antibiotics Exposure and the Risk of Autism Spectrum Disorders: A Population-Based Cohort Study. PLOS ONE 2019; 14: e0221921en_US
dc.identifier.citationHamad AF, Alessi-Severini S, Mahmud S, Brownell M and Kuo I. Antibiotic Exposure in the First Year of Life and the Risk of Attention-Deficit/Hyperactivity Disorder: a Population-Based Cohort Study. Am J Epidemiol 2019; 188: 1923–1931en_US
dc.identifier.citationHamad AF, Alessi-Severini S, Mahmud S, Brownell M and Kuo I. Prenatal Antibiotic Exposure and the Risk of Attention Deficit/Hyperactivity Disorder: A Population-Based Cohort Study. CMAJ (submitted) 2019en_US
dc.identifier.urihttp://hdl.handle.net/1993/34375
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectNeurodevelopmental disordersen_US
dc.subjectAntibioticsen_US
dc.subjectMicrobiotaen_US
dc.subjectASDen_US
dc.subjectADHDen_US
dc.titlePrenatal and early childhood antibiotic exposure and the risk of neurodevelopmental disordersen_US
dc.typedoctoral thesisen_US
local.subject.manitobayesen_US
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