ADHD and autism spectrum disorder in children with nocturnal enuresis: association and impact on treatment duration — a nationwide register-based cohort study

Attention-deficit/hyperactive-disorder (ADHD) and autism spectrum disorder (ASD) may contribute to treatment failure or a prolonged disease course in children with nocturnal enuresis (NE). We investigated the association between NE and subsequent diagnoses of ADHD or ASD. In addition, we examined whether these conditions influence NE treatment duration. We conducted a nationwide register-based cohort study including all Danish residents < 18 years diagnosed with NE from January 1, 1996, to December 31, 2023. Children with NE were age- and sex-matched 1:3 to controls without NE. The primary outcome was a composite of ADHD or ASD diagnosis after NE onset. Cox proportional hazards models adjusted for age, sex, comorbidities, and concomitant medicine were used. Among children with NE, the influence of ADHD or ASD diagnosis on NE treatment duration was evaluated as a secondary outcome. The cohort comprised 124,558 children with NE and 373,674 controls. During follow-up, 11.3% of children with NE were diagnosed with ADHD or ASD compared with 5.6% of controls. NE was associated with an increased hazard of ADHD or ASD (adjusted HR 1.87, 95% CI 1.83–1.91), with similar estimates for ADHD and ASD individually. Children diagnosed with ADHD or ASD during their NE course had significantly longer treatment duration than neurotypical children (median treatment duration 5.2 years vs. 0.8 years), and those diagnosed with ADHD early in their NE course had a shorter treatment duration than those diagnosed later. Children with NE have an increased risk of underlying ADHD or ASD. Children with co-occurring ADHD or ASD experienced a more prolonged course of NE treatment. These findings suggest that underlying ADHD or ASD should be considered in children with treatment-refractory NE.