Risk factors and interventions for pediatric allergic diseases: an umbrella review

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Background: The global burden of pediatric allergic diseases continues to rise. However, clinical and public health decisions remain guided by an extensive yet fragmented evidence base characterized by substantial uncertainty, hindering the development of effective preventive and therapeutic strategies. Objective: To address this evidence gap, we conducted a comprehensive umbrella review to establish a hierarchically structured evidence map of all reported risk factors and interventions for pediatric allergic diseases. Methods: We systematically searched PubMed for systematic reviews and meta-analyses (published up to February 23, 2025) on risk factors or interventions for core pediatric allergic conditions. Methodological quality was assessed using AMSTAR 2. Statistically significant associations ( p <0.05) were graded into four evidence levels—strong, highly suggestive, suggestive, or weak—based on predefined criteria including statistical significance, sample size, heterogeneity (I 2 ), small-study effects (Egger’s test), excess significance bias, and robustness in 10% credibility ceiling analysis. Results: This review synthesizes evidence from 60 meta-analyses, encompassing 176 unique associations. Despite the extensive factors discussed in the literature, rigorous grading identified only three risk factors supported by strong evidence: neonatal jaundice, pesticide exposure, and postnatal maternal depression. Six additional associations (involving five factors)—acid suppressants, birthweight, cesarean section, montelukast, and Chinese herbal bath—were graded as highly suggestive. The vast majority of investigated factors, including many nutritional supplements and environmental modifications, were supported by only weak or non-suggestive evidence. Conclusion: This umbrella review reveals a pronounced disparity between the volume of published literature and the strength of available evidence in pediatric allergy. The findings argue for a strategic shift in research focus: from underpowered associative studies toward 1) mechanistic investigation of the identified strong risk factors, and 2) definitive trials for highly suggestive interventions.

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