Evidence strength of exposure-outcome associations in pediatric allergic diseases: an umbrella review of meta-analyses.

Abstract

Pediatric allergic diseases are influenced by a wide range of environmental, perinatal, and developmental exposures; however, the strength and credibility of reported associations remain unclear. We conducted an umbrella review to systematically evaluate and grade the strength of evidence for exposure-outcome associations in pediatric allergic diseases. We systematically searched for systematic reviews and meta-analyses investigating exposures associated with pediatric allergic diseases. A total of 176 exposure-outcome associations were extracted and re-evaluated using standardized evidence grading criteria, incorporating statistical significance, heterogeneity, sample size, and potential bias. Associations were classified into strong, highly suggestive, suggestive, and weak or non-suggestive evidence. Sixty systematic reviews and meta-analyses comprising 176 exposure-outcome associations were included. Only three associations were supported by strong evidence: neonatal jaundice, pesticide exposure, and postnatal maternal depression. Six associations were classified as highly suggestive (three from binary outcomes and three from continuous outcomes after applying a pragmatic sample size criterion), and eight as suggestive, while the remaining 159 associations were rated as weak or non-suggestive evidence. Overall, most associations showed limited robustness, with substantial heterogeneity and evidence of potential bias across studies. Only a small proportion of reported exposure-outcome associations in pediatric allergic diseases are supported by strong evidence. Early-life and environmental exposures, including perinatal factors and pesticide exposure, may represent important risk domains; however, most associations lack sufficient evidence to support causal inference. These findings highlight the need for higher-quality evidence and more rigorous evaluation of environmental risk factors in pediatric allergy research. This umbrella review systematically evaluates the strength of evidence for associations between multiple exposures and pediatric allergic diseases. Only a small proportion of associations are supported by strong or highly suggestive evidence, while most associations show weak or non-suggestive evidence. These findings highlight substantial uncertainty in the current literature and emphasize the need for more robust evidence before drawing causal or clinical conclusions.