Antibiotic Exposure in the First Year of Life and the Risk of Attention-Deficit/hyperactivity Disorder

A Population-Based Cohort Study

Amani F. Hamad; Silvia Alessi-Severini; Salaheddin M. Mahmud; Marni Brownell; I fan Kuo

Disclosures

Am J Epidemiol. 2019;188(11):1923-1931. 

In This Article

Abstract and Introduction

Abstract

Early childhood antibiotic exposure induces changes in gut microbiota reportedly associated with the development of attention-deficit/hyperactivity disorder (ADHD). We conducted a population-based cohort study to examine the association between antibiotic use in the first year of life and ADHD risk. We included children born in Manitoba, Canada, between 1998 and 2017. Exposure was defined as having filled 1 or more antibiotic prescriptions during the first year of life. ADHD diagnosis was identified in hospital abstracts, physician visits, or drug dispensations. Risk of developing ADHD was estimated using Cox proportional hazards regression in a high-dimensional propensity score–matched cohort (n = 69,738) and a sibling cohort (n = 67,671). ADHD risk was not associated with antibiotic exposure in the matched-cohort (hazard ratio = 1.02, 95% confidence interval: 0.97, 1.08) or in the sibling cohort (hazard ratio = 0.96, 95% confidence interval: 0.89, 1.03). In secondary analyses of the matched cohort, ADHD risk increase was observed in those exposed to 4 or more antibiotic courses or a duration longer than 3 weeks. These associations were not observed in the sibling cohort. We concluded that antibiotic exposure in the first year of life does not pose an ADHD risk on a population level.

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder and is associated with significant burden worldwide.[1,2] More than half of children with ADHD continue to have the disorder in adulthood and live with many long-term adverse health and social outcomes.[3–6]

The worldwide ADHD prevalence in children has been estimated at 7.2%.[7] In the Canadian province of Manitoba, an annual age-standardized prevalence of 1.5% was reported for ADHD in 1999, and this rose to 2.8% in 2012.[8] Similar trends were reported in several other Canadian provinces.[8] Genetic factors have been demonstrated to play a role in ADHD etiology, with a heritability of 70%–80%.[9–14] Additionally, several environmental factors have shown possible association with ADHD risk, including low level of paternal education, low maternal age at delivery, prenatal smoking, prenatal illicit drug use, birth complications, low birth weight, preterm delivery, neonatal jaundice, childhood asthma, maternal depression, prenatal antidepressants, and acetaminophen exposure.[15–27]

Gut microbiota plays an important role in the communication between the gut and the brain, via the gut-brain axis.[28–30] Early-life changes in microbiota composition result in different brain developmental trajectories, potentially contributing to disorders such as ADHD.[29–31] Recent research has shown that subjects with ADHD have different microbiota composition compared with those without ADHD.[32] A small randomized study reported a lower risk of ADHD in infants who received a probiotic in the first 6 months of life, suggesting that microbiota does play a role in the development of ADHD.[33] It has been demonstrated that exposure to antibiotics in early life disrupts the equilibrium of gut microbiota and could potentially contribute to the development of ADHD.[30,31,34] In this study, we examined the association between antibiotic use in the first year of life and the risk of ADHD.

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