Abstract
Many potential environmental risk factors, protective factors, and biomarkers of AR have been published, but so far, the strength and consistency of their evidence are unclear. We conducted a comprehensive review of environmental risk, protective factors, and biomarkers for AR to establish the evidence hierarchy. We systematically searched Embase, PubMed, Cochrane Library, and Web of Science electronic database from inception to December 31, 2022. We calculated summary effect estimate (odds ratio (OR), relative risk (RR), hazard ratio (HR), and standardized mean difference (SMD)), 95% confidence interval, random effects p value, I(2) statistic, 95% prediction interval, small study effects, and excess significance biases, and stratification of the level of evidence. Methodological quality was assessed by AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). We retrieved 4478 articles, of which 43 met the inclusion criteria. The 43 eligible articles identified 31 potential environmental risk factors (10,806,206 total population, two study not reported), 11 potential environmental protective factors (823,883 total population), and 34 potential biomarkers (158,716 total population) for meta-analyses. The credibility of evidence was convincing (class I) for tic disorders (OR = 2.89, 95% CI 2.11-3.95); and highly suggestive (class II) for early-life antibiotic use (OR = 3.73, 95% CI 3.06-4.55), exposure to indoor dampness (OR = 1.49, 95% CI 1.27-1.75), acetaminophen exposure (OR = 1.54, 95% CI 1.41-1.69), childhood acid suppressant use (OR = 1.40, 95% CI 1.23-1.59), exposure to indoor mold (OR = 1.66, 95% CI 1.26-2.18), coronavirus disease 2019 (OR = 0.11, 95% CI 0.06-0.22), and prolonged breastfeeding (OR = 0.72, 95% CI 0.65-0.79). This study is registered in PROSPERO (CRD42022384320).