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

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.

SUBMITTER: Yu MC

PROVIDER: S-EPMC8368245 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Yu Mei-Ching MC Wang Ta-Min TM Chiou Yee-Hsuan YH Yu Meng-Kung MK Lin Chiao-Fan CF Chiu Chih-Yung CY

Scientific reports 20210816 1

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 cont ...[more]

PMID: 34400733

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Project description:Childhood obesity increases the risk of obstructive sleep apnea syndrome, type 2 diabetes mellitus, cardiovascular abnormalities, and psychological and behavioral disorders. But it is unclear whether obesity is associated with childhood nocturnal enuresis (NE). This study aimed to assess the relationship between childhood obesity and NE in a nationally representative large sample in China. Subjects were enrolled from Urumqi, Chengdu, Xi'an, Hohhot, Wuhan, Canton, Shanghai, and Harbin cities in China in November and December 2005. The survey included 20,987 children aged 5-12 years and they and their caregivers completed questionnaires. Height and weight were measured by school teachers trained in healthcare. According to the WHO child growth standards, obesity was defined as a body mass index >95th percentile of peers with the same age and gender. NE was defined as bed wetting for more than twice a week for 3 consecutive months. Demographic variables were compared among different groups. The prevalence of obesity, asthma, attention-deficit/hyperactivity disorder (ADHD), depressive moods, and snoring were different between the NE and without-NE groups (P < 0.05). The raw odds ratio (OR) for NE and obesity was 1.36 (95%CI = 1.07-1.74; P = 0.013) and the adjusted OR was 1.42 (95%CI = 1.11-1.82; P = 0.005) in the multivariable analysis. When adjusting for co-occurring conditions, the results showed that asthma did not affect the risk of NE (OR = 1.42, 95%CI = 1.11-1.82; P = 0.005), but ADHD (OR = 1.41; 95%CI = 1.10-1.81; P = 0.006) and depressive moods (OR = 1.34; 95%CI = 1.07-1.76; P = 0.012) slightly weakens the association between NE in children and obesity, while snoring weakens the association between obesity and NE and the risk became non-significant (OR = 1.21; 95%CI = 0.94-1.56; P = 0.138). In conclusion, obese children were at a higher risk of incurring NE compared to non-obese children. This association was weaker in children who either snored, had ADHD, or had depressive mood.

Project description:Objective Primary nocturnal enuresis (PNE) is a common developmental condition in school-aged children. The objective is to better understand the pathophysiology of PNE by using insula-centered resting-state functional connectivity (rsFC). Methods We recruited 66 right-handed participants in our analysis, 33 with PNE and 33 healthy control (HC) children without enuresis matched for gender and age. Functional and structural MRI data were obtained from all the children. Seed-based rsFC was used to examine differences in insular functional connectivity between the PNE and HC groups. Correlation analyses were carried out to explore the relationship between abnormal insula-centered functional connectivity and clinical characteristics in the PNE group. Results Compared with HC children, the children with PNE demonstrated decreased left and right insular rsFC with the right medial superior frontal gyrus (SFG). In addition, the bilateral dorsal anterior insula (dAI) seeds also indicated the reduced rsFC with right medial SFG. Furthermore, the right posterior insula (PI) seed showed the weaker rsFC with the right medial SFG, while the left PI seed displayed the weaker rsFC with the right SFG. No statistically significant correlations were detected between aberrant insular rsFC and clinical variables (e.g., micturition desire awakening, bed-wetting frequency, and bladder volume) in results without global signal regression (GSR) in the PNE group. However, before and after setting age as a covariate, significant and positive correlations between bladder volume and the rsFC of the left dAI with right medial SFG and the rsFC of the right PI with right medial SFG were found in results with GSR in the PNE group. Conclusion To the best of our knowledge, this study explored the rsFC patterns of the insula in children with PNE for the first time. These results uncovered the abnormal rsFC of the insula with the medial prefrontal cortex without and with GSR in the PNE group, suggesting that dysconnectivity of the salience network (SN)-default mode network (DMN) may involve in the underlying pathophysiology of children with PNE. However, the inconsistent associations between bladder volume and dysconnectivity of the SN-DMN in results without and with GSR need further studies.

Dataset Information

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

Publications

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

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