Combining high-dose vitamin D supplementation (VDS) with enuresis alarm (EA) therapy results in significant reductions in wet-night frequency and improves treatment response, satisfaction, and quality of life (QoL) relative to EA alone in children with primary monosymptomatic nocturnal enuresis (PMNE) and serum 25-hydroxyvitamin D (25[OH]D) levels below 30 ng/mL, a study has shown.
“High-dose VDS combined with EA was effective and well tolerated for treating PMNE in children with vitamin D insufficiency, supporting its potential as a promising therapeutic approach,” the authors said.
A total of 304 children were assessed for eligibility, of whom 262 met the criteria and were randomized to the VDS + ES (n=130) or the EA alone group (n=132). [J Urol 2026;216:182-193]
The VDS + EA group demonstrated higher response rates (RR, 1.22, 95 percent confidence interval [CI], 1.01‒1.49; p=0.04), complete response rates (RR, 1.54, 95 percent CI, 1.10‒2.15; p=0.01), a greater reduction in weekly wet nights (median difference, 1, 95 percent CI, 0‒2; p=0.003), and greater improvements in QoL and treatment satisfaction than the EA group.
No significant between-group difference was seen in the risk of treatment-emergent adverse events.
“These findings support the potential role of serum 25(OH)D assessment in children with PMNE,” the authors said. “In patients with vitamin D insufficiency, adding high-dose VDS to EA may improve treatment response and patient-reported outcomes without increasing adverse events, representing a practical adjunctive treatment option.”
Psychological health
PMNE is associated with several psychological health problems, including mood disturbances and attention-deficit/hyperactivity disorder (ADHD). [Compr Psychiatry 2021;104:152208]
Studies have shown that vitamin D has beneficial effects on mood regulation and that children with ADHD are more likely to develop vitamin D deficiency. [Depress Anxiety 2020;37:549-564; Adv Nutr 2018;9:9-20]
“Thus, VDS may improve PMNE through behavioral modulation,” the authors said. “However, establishing a causal relationship is challenging, as retrospective questionnaires cannot determine whether emotional and behavioural problems preceded the development of NE.” [J Am Acad Child Adolesc Psychiatry 2017;56:250-257]
Furthermore, PMNE and ADHD do not often occur simultaneously. Rather, PMNE could show a predisposition to subsequent ADHD, and it remains a challenge to diagnose ADHD in preschool-aged children, according to the authors. [J Am Acad Child Adolesc Psychiatry 2017;56:250-257]
“In our study, psychological health was assessed, and post hoc analyses were stratified by risk status,” they said. “Children at risk for psychological health problems demonstrated a higher response rate to VDS compared with those not at risk, although the difference was not statistically significant.”
Study details
The current study was a two-arm randomized clinical trial conducted at a tertiary centre in China between December 2024 and May 2025. Children with PMNE and serum 25(OH)D <30 ng/mL were randomized to receive either 8 weeks of VDS (vitamin D3 soft capsules, 2,400 ID/d) plus EA or EA lone.
Treatment response was the primary outcome, while the change in weekly frequency of wet nights, QoL scores, and treatment satisfaction were secondary. The authors also assessed safety by recording treatment-emergent adverse events.
The study was limited by its design, which may introduce bias, and the exclusion of children with neurodevelopmental disorders, which may limit generalizability. It also has a relatively short-follow-up period, and its subgroups analyses were exploratory.