Antibiotic exposure and adverse long-term health outcomes in children: A systematic review and meta-analysis

Background: Antibiotics are amongst the most commonly used drugs in children. In addition to inducing antibiotic resistance, antibiotic exposure has been associated with adverse long-term health outcomes.Methods: A systematic search using PRISMA guidelines to identify original studies reporting associations between antibiotic exposure and adverse long-term health outcomes in children. Overall pooled estimates of the odds ratios (ORs) were obtained using random-effects models.Results: We identified 160 observational studies investigating 21 outcomes in 22,103,129 children. Antibi-otic exposure was associated with an increased risk of atopic dermatitis (OR 1.40, 95% confidence interval (CI) 1.30-1.52, p < 0.01), allergic symptoms (OR 1.93, 95%CI 1.66-2.26, p < 0.01), food allergies (OR 1.35, 95%CI 1.20-1.52, p < 0.01), allergic rhinoconjunctivitis (OR 1.66, 95%CI 1.51-1.83, p < 0.01), wheezing (OR 1.81, 95%CI 1.65-1.97, p < 0.01), asthma (OR 1.96, 95%CI 1.76-2.17, p < 0.01), increased weight gain or overweight (OR 1.18, 95%CI 1.11-1.26, p < 0.01), obesity (OR 1.21, 95%CI 1.05-1.40, p < 0.01), juvenile idiopathic arthritis (OR 1.74, 95%CI 1.21-2.52, p < 0.01), psoriasis (OR 1.75, 95%CI 1.44-2.11, p < 0.01), autism spectrum disorders (OR 1.19, 95%CI 1.04-1.36, p = 0.01) and neurodevelopment disorders (OR 1.29, 95%CI 1.09-1.53, p < 0.01). Dose-response effects and stronger effects with broad-spectrum antibiotic were often reported. Antibiotic exposure was not associated with an altered risk of allergic sensitisation, infantile colic, abdominal pain, inflammatory bowel disease, celiac disease, type 1 diabetes, fluorosis, and attention deficit hyperactivity disorder. Conclusion: Although a causal association cannot be determined from these studies, the results support the meticulous application of sound antibiotic stewardship to avoid potential adverse long-term health outcomes.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )