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

• Published in: Drug safety 2023-05, Vol.46 (5), p.467-478
• Main Authors: Njotto, Lembris L., Simin, Johanna, Fornes, Romina, Odsbu, Ingvild, Mussche, Isabelle, Callens, Steven, Engstrand, Lars, Bruyndonckx, Robin, Brusselaers, Nele
• Format: Article
• Language: English
• Subjects: Antibiotics; Attention deficit hyperactivity disorder; Autism; Births; Childhood; Children; Codes; Cohort analysis; Drug dosages; Drug Safety and Pharmacovigilance; Exposure; Hyperactivity; Influence; Medicine; Medicine & Public Health; Menstruation; Microbiota; Original; Original Research Article; Penicillin; Pharmacology/Toxicology; Population studies; Population-based studies; Pregnancy; Prescription drugs; Regression analysis; Risk
• ISSN: 0114-5916; 1179-1942
• DOI: 10.1007/s40264-023-01297-1

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. Plain Language Summary Antibiotics are commonly prescribed to pregnant women, infants, and toddlers. Antibiotic use during pregnancy may alter the maternal microbiota, which can influence the microbial colonisation of the gastrointestinal system of the foetus. It has been claimed that antibiotic use during pregnancy may have an effect on the gut-brain axis and, as a result, neurodevelopment. Neurodevelopmental disorder (NDD) is a category of illnesses characterised by functional impairments that manifest early in development. The most frequent NDDs are autism and attention-deficit/hyperactivity disorder (ADHD). In this large Swedish nation-wide study, we assessed whether antibiotic use during pregnancy and/or early in life affects the risk of developing autis