Pre- and postnatal antibiotic exposure and risk of developing attention deficit hyperactivity disorder-A systematic review and meta-analysis combining evidence from human and animal studies

Abstract

This study investigated the effects of early antibiotic exposure on ADHD risk by (1) integrating meta-analytical evidence from human observational studies examining the association between prenatal or early postnatal antibiotic exposure on the risk of developing ADHD; and (2) reviewing evidence from experimental animal studies on the effects of early antibiotic exposure on behavior. Sixteen human studies and five rodent studies were reviewed. A quantitative meta-analysis with 10 human studies indicated an increased risk for ADHD after prenatal antibiotic exposure (summary effect estimate Hazard Ratio (HR) 1.23, 95% CI 1.09-1.38; N = 2,398,475 subjects) but not after postnatal exposure within the first two years of life (summary effect estimate HR 1.12, 95% CI 0.95-1.32; N = 1,863,867 subjects). The rodent literature suggested that peri-natal antibiotic exposure has effects on social behavior, anxiety and aggression, alongside changes in gut microbial composition. Human and rodent findings thus suggest prenatal antibiotic exposure as a possible risk factor for ADHD, and suggest that an early disruption of the gut microbiome by antibiotics may interfere with neurodevelopment.

Keywords: Antibiotics; Attention-deficit/hyperactivity disorder; Gut-brain axis; Microbiome; Neurodevelopment.