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

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. Lembris L. Njotto and Johanna Simin shared first authorship. Robin Bruyndonckx and Nele Brusselaers shared the last authorship.

Risk factors and clinical characteristics of autism spectrum disorder with regression in China

“…Notably, specific antibiotic classes like penicillin and non-penicillin beta-lactam antibacterials used by mothers showed an elevated risk of ASD. These findings provide additional evidence connecting antibiotic use, alterations in the gut microbiome, and the development of ASD (Njotto et al, 2023). Furthermore, there is an association between fever, gastrointestinal symptoms, and ASD.…”

Association between exposure to antibiotics during pregnancy or early infancy and risk of autism spectrum disorder, intellectual disorder, language disorder, and epilepsy in children: population based cohort study

“… 12 A later cohort study based on the Swedish population found an increased risk of autism spectrum disorder after use of antibiotics both during pregnancy and during infancy, with an odds ratio of 1.16 (95% confidence interval 1.09 to 1.23) and 1.46 (1.38 to 1.55), respectively. 13 However, the authors noted that confounding by indication or genetics could not be ruled out. Likewise, a recent meta-analysis showed that an increased risk of autism (pooled odds ratio 1.13, 1.07 to 1.21) associated with antibiotic use in early life was no longer apparent when only the sibling matched studies were pooled (1.04, 0.97 to 1.11).…”

“… 11 Few epidemiological studies have investigated an association between prenatal or infant antibiotic use and neurodevelopmental disorders such as autism spectrum disorder and epilepsy. 12 13 14 15 However, the evidence remains limited and inconclusive, possibly owing to insufficient control for confounding in some studies. Because infection, in both severe and less severe forms, has been linked with neurodevelopmental consequences, confounding by indication is of particular concern in investigating the role of antibiotics in neurodevelopmental disorders.…”

The Autism Spectrum Disorder and Its Possible Origins in Pregnancy

“…They observed that the offspring, especially the males, showed an altered pattern of ultrasonic communication, reduced social motivation and social interaction, as well as anxiety-like behavior [ 136 ]. In this context, a population-based study in Sweden examined the association between antibiotic use during pregnancy and ASD diagnosis and found that maternal antibiotic use was associated with a higher risk of childhood ASD [(OR) = 1.16, (95% CI) 1.09–1.23] [ 137 ]. It is suggested that changes in the maternal microbiota caused by antibiotic use may play a role in the development of this disorder [ 136 , 137 ].…”

“…In this context, a population-based study in Sweden examined the association between antibiotic use during pregnancy and ASD diagnosis and found that maternal antibiotic use was associated with a higher risk of childhood ASD [(OR) = 1.16, (95% CI) 1.09–1.23] [ 137 ]. It is suggested that changes in the maternal microbiota caused by antibiotic use may play a role in the development of this disorder [ 136 , 137 ].…”