Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: a Swedish Population-Based Cohort Study

Lembris L. Njotto, Johanna Simin, Romina Fornes, Ingvild Odsbu, Isabelle Mussche, Steven Callens, Lars Engstrand, Robin Bruyndonckx and Nele Brusselaers ()
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Lembris L. Njotto: Hasselt University
Johanna Simin: Centre for Translational Microbiome Research (CTMR), Karolinska Institutet
Romina Fornes: Centre for Translational Microbiome Research (CTMR), Karolinska Institutet
Ingvild Odsbu: The Norwegian Institute of Public Health
Isabelle Mussche: Centre for Ambulatory Revalidation (CAR) Ascendre
Steven Callens: Ghent University Hospital
Lars Engstrand: Centre for Translational Microbiome Research (CTMR), Karolinska Institutet
Robin Bruyndonckx: Hasselt University
Nele Brusselaers: Centre for Translational Microbiome Research (CTMR), Karolinska Institutet

Drug Safety, 2023, vol. 46, issue 5, No 5, 467-478

Abstract: Abstract Introduction Antibiotics represent the most common type of medication used during pregnancy and infancy. Antibiotics have been proposed as a possible factor in changes in microbiota composition, which may play a role in the aetiology of autism and attention deficit/hyperactivity disorder (ADHD). Our aim was to investigate the association between maternal and early-life antibiotic use and autism and ADHD in childhood. Methods This Swedish nation-wide population-based cohort study included all first live singleton births (N = 483,459) between January 2006 and December 2016. The association of dispensed antibiotics with autism and ADHD in children aged ≤ 11 years was estimated by applying multivariable logistic regression and generalised estimating equations models. Results Of the mothers, 25.9% (n = 125,106) were dispensed ≥1 antibiotic during the exposure period (from 3 months pre-conception to delivery), and 41.6% (n = 201,040) of the children received ≥ 1 antibiotic in early life (aged ≤ 2 years). Penicillin was the most prescribed antibiotic class (17.9% of mothers, 38.2% of children). Maternal antibiotic use was associated with an increased risk of autism [odds ratio (OR) = 1.16, 95% confidence interval (CI) 1.09–1.23] and ADHD (OR = 1.29, 95% CI 1.21–1.36) in childhood. Early-life exposure to antibiotics showed an even stronger association [autism (OR = 1.46, 95% CI 1.38–1.55); ADHD (OR = 1.90, 95% CI 1.80–2.00)]. Both maternal and childhood-exposure sub-analyses suggested a dose-response relationship. Conclusion Maternal and early-life antibiotic use was associated with an increased risk of autism and ADHD in childhood. However, differences were noted by exposure period and antibiotic classes.

Date: 2023
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DOI: 10.1007/s40264-023-01297-1

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