Comparative Efficacy and Safety of Interventions for Nocturnal Enuresis: An Umbrella Review of Systematic Reviews and Meta-Analyses

Abstract

Context: Nocturnal enuresis (NE) is a prevalent pediatric condition associated with significant psychological and social burden. Despite the availability of various treatment modalities, direct comparisons of their efficacy and safety remain limited. Objectives: This umbrella review synthesizes evidence from published systematic reviews and meta-analyses to provide a comprehensive assessment of current interventions for NE. Data Sources: A systematic literature search was conducted in Scopus, PubMed, Embase, ISI Web of Science, and Google Scholar up to September 2024, following PRISMA guidelines and a registered PROSPERO protocol. Study Selection: Eligible studies were meta-analyses or systematic reviews reporting pooled effect estimates for NE treatments in children. Data Extraction: Data extraction included efficacy outcomes (odds ratios [OR], 95% confidence intervals [CI]), adverse event profiles, and study quality, assessed using AMSTAR-2 and GRADE frameworks. Results: Five meta-analyses encompassing 45 clinical trials and 4,134 participants met the inclusion criteria. Among placebo-controlled comparisons, electrical stimulation demonstrated the highest efficacy (OR = 22.01, 95% CI: 8.62 - 56.17, P < 0.001), with only mild skin irritation reported as an adverse event. In head-to-head active treatment comparisons, Tuina showed greater efficacy than herbal medicine (OR = 11.26, 95% CI: 5.38 - 23.57, P < 0.001) and other traditional Chinese medicine modalities (OR = 6.11, 95% CI: 3.87 - 9.65, P < 0.001), with no reported adverse events. Notably, the certainty of evidence for conventional interventions (electrical stimulation, desmopressin, alarm therapy) was moderate to high, while evidence for traditional Chinese medicine modalities was low to moderate due to risk of bias in underlying studies. Combination therapies (Tuina plus acupuncture or herbal medicine) outperformed monotherapies and were well tolerated. Laser acupuncture was superior to sham laser (OR = 6.80, 95% CI: 2.15 - 21.53, P = 0.001), but not to desmopressin. Alarm therapy showed comparable efficacy to desmopressin but was associated with a moderate risk of sleep disturbance and skin irritation. Across all interventions, safety profiles were generally favorable, with most classified as low risk for adverse events. Conclusions: Electrical stimulation demonstrated the highest efficacy with moderate-to-high certainty evidence. Tuina and related traditional Chinese medicine modalities showed efficacy in head-to-head comparisons but with lower overall certainty of evidence. Most interventions exhibited favorable safety profiles. However, the heterogeneity of comparators and limited direct head-to-head evidence highlight the need for further high-quality randomized trials and network meta-analyses. These findings can inform individualized, evidence-based management of NE in pediatric populations.