Attention-deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder and frequently coexists with other neurodevelopmental conditions, including autism spectrum disorder, intellectual disability, and tic disorders (Thapar and Cooper, 2016). This disease is characterized by inattention, impulsivity, and hyperactivity, and its prevalence continues to rise, imposing substantial burdens on individuals, families, and society (Posner et al., 2020). ADHD has multiple etiological factors. Although genetic factors are crucial in ADHD etiology, mounting evidence indicates the significance of environmental factors (Thapar et al., 2013). Among these, prenatal risk factors are significant contributors. Despite extensive research, its risk factors remain inconclusive (Kian et al., 2022). Notably, studies examining prenatal antibiotic exposure remain limited and yield conflicting results regarding the risk of ADHD in offspring, partly due to the inherent uncontrollability of exposure conditions.
Antibiotics are the primary therapeutic agents for the prevention and treatment of infections. While most antibiotics demonstrate minimal adverse effects during administration, they alter gut microbiota composition, which may result in short- and long-term health consequences (Ramirez et al., 2020). Antibiotic use during pregnancy remains common, accounting for 80 % of prescription medications in Western countries. Beyond disrupting maternal microbiota (Kuperman and Koren, 2016), prenatal antibiotic exposure also modifies the composition of gut microbiota in infants (Grech et al., 2021).
Substantial evidence demonstrates a complex interplay between gut microbiota and the nervous system (He et al., 2024). Alterations in gut microbiota can affect behavior through gut-brain axis mechanisms, potentially contributing to neurodevelopmental disorders (Wang et al., 2023) including ADHD. Studies have identified distinct gut microbial compositions in ADHD patients compared with healthy controls (Liang-Jen et al., 2019; Jiang et al., 2018). Furthermore, gut microbiota from patients with ADHD affects brain function in mice (Tengeler et al., 2020), suggesting that microbial alterations may drive structural and functional brain changes. However, investigations into the relationship between prenatal antibiotic use and offspring neurodevelopmental disorders have yielded inconsistent results.
Given the increasing use of antibiotics, this meta-analysis aimed to synthesize available evidence to examine the link between maternal antibiotic use during pregnancy and the risk of childhood ADHD, providing evidence-based guidance for clinical practice.
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