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/ )

Automated summary

This study systematically searched and analyzed observational studies, and found associations between antibiotic exposure and adverse long-term health outcomes in children. These outcomes include atopic dermatitis, allergic symptoms, food allergies, allergic rhinoconjunctivitis, wheezing, asthma, increased weight gain or overweight, obesity, juvenile idiopathic arthritis, psoriasis, autism spectrum disorders, and neurodevelopment disorders. The results suggest the need for careful antibiotic stewardship to avoid potential negative health outcomes.