Urine metabolic phenotyping in children with nocturnal enuresis and comorbid neurobehavioral disorders

Mei-Ching Yu,Chiao-Fan Lin,Yee-Hsuan Chiou,Meng-Kung Yu,Ta-Min Wang,Chih-Yung Chiu

doi:10.1038/s41598-021-96104-1

Abstract

Nocturnal enuresis (NE) is a common problem among 10% school-aged children. The etiologies underlying childhood NE is complex and not fully understood nowadays. Nevertheless, increasing evidence suggests a potential link between neurobehavioral disorders and enuresis in children. In this study, we aimed to explore novel metabolomic insights into the pathophysiology of NE and also, its association with pediatric psychiatric problems. Urine collected from 41 bedwetting children and 27 healthy control children was analyzed by using 1H-nuclear magnetic resonance spectroscopy from August 2017 to December 2018. At regular follow-up, there were 14 children with refractory NE having a diagnosis of attention deficient hyperactivity disorder (ADHD) or anxiety. Eventually, we identified eight significantly differential urinary metabolites and particularly increased urinary excretion of betaine, creatine and guanidinoacetate linked to glycine, serine and threonine metabolism were associated with a comorbidity of neurobehavioral disorders in refractory bedwetting children. Notably, based on physiological functions of betaine acting as a renal osmolyte and methyl group donor, we speculated its potential role in modulation of renal and/or central circadian clock systems, becoming a useful urinary metabolic marker in diagnosis of treatment-resistant NE in children affected by these two disorders.

Highlights

Nocturnal enuresis (NE) is a common problem among 10% school-aged children
Based on the association with daytime voiding dysfunction, it can be further categorized into mono-symptomatic nocturnal enuresis (MNE) and non-monosymptomatic nocturnal enuresis (NMNE), respectively[2]
Males and females with childhood NE were at equal risk for a comorbidity of attention deficient hyperactivity disorder (ADHD) or anxiety

Summary

Introduction

Nocturnal enuresis (NE) is a common problem among 10% school-aged children. The etiologies underlying childhood NE is complex and not fully understood nowadays. Numerous clinical studies and population-based studies have uncovered the strong association between enuresis and attention deficit hyperactivity disorder (ADHD)[10,11,12,13,14,15]. In this modern world, ADHD is the most common neurodevelopmental disorder affecting 7.2–15.5% of school-aged children and adolescents, in b oys[16]. Psychiatric problems and NE are still a “chicken-and-egg” situation, this bidirectional relationship between the two disorders is potentially explained by deficits in arousal and/or developmental delays in central nervous s ystem[17,18]

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