Folic Acid as a Potential Adjunct in the Management of Primary Nocturnal Enuresis: A Clinical Trial Study

Abstract

Background: Primary nocturnal enuresis (PNE) is a common pediatric condition with a multifactorial etiology, involving both neurodevelopmental and nutritional factors. Recent evidence suggests that folic acid may contribute to neural maturation and bladder control. Objectives: The present study aimed to evaluate the therapeutic effect of folic acid supplementation on the frequency and severity of PNE in children. Methods: In a double-blind, randomized controlled trial, 68 children aged 5 - 18 years diagnosed with PNE were assigned to receive either folic acid supplementation or placebo over a sixty-day period. Baseline and post-treatment assessments included enuresis frequency and urinary control parameters. The number of dry nights was recorded at baseline, month 1, and month 2. Group-level means and standard deviations were compared using independent t-tests. Effect sizes (Cohen’s d) and percentage changes from baseline were calculated to assess the magnitude and clinical relevance of the intervention’s impact. Results: At baseline, there was no significant difference in the number of dry nights between groups (intervention: 19.2 ± 3.7; control: 18.9 ± 4.3; P = 0.63). By month 1, the intervention group showed greater improvement (24.5 ± 4.8 vs. 22.4 ± 5.1 dry nights; adjusted mean difference = 2.1, 95% CI: 0.9 - 3.3; P = 0.0004; Cohen’s d = 0.42). At month 2, this difference further increased (26.0 ± 4.6 vs. 23.2 ± 4.6; adjusted mean difference = 2.8, 95% CI: 1.7 - 3.9; P < 0.0001; Cohen’s d = 0.61). The intervention group achieved a 35.4% increase in dry nights from baseline, compared with 22.8% in the control group, indicating a moderate to large and clinically meaningful treatment effect. Conclusions: Folic acid supplementation may offer a safe and effective adjunctive treatment for PNE, potentially through its role in neurodevelopmental regulation. Further studies are warranted to confirm these findings and to explore the underlying mechanisms.