Voiding Dysfunction/Enuresis
High Risk of Sleep Disordered Breathing in the Enuresis Population Alexandra Bascom, Todd Penney, Mike Metcalfe, Aaron Knox, Manisha Witmans, Trina Uweira and Peter Douglas Metcalfe* From the Faculty of Medicine (AB, TP, MM, AK) Division of Pulmonary Medicine, Department of Pediatrics (MW) and Divisions of Otolaryngology (TU), Urology (PDM) and Pediatric Surgery (TU, PDM), Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
Abbreviations and Acronyms DVISS ⫽ Dysfunctional Voiding and Incontinence Symptom Score LUTS ⫽ lower urinary tract symptoms MNE ⫽ monosymptomatic enuresis NMNE ⫽ nonMNE OSA ⫽ obstructive sleep apnea OSA-18 ⫽ OSA QOL survey PSQ-22 ⫽ Modified Pediatric Sleep Questionnaire QOL ⫽ quality of life REM ⫽ rapid eye movement SDB ⫽ sleep disordered breathing Study received institutional ethics approval. * Correspondence: University of Alberta, Stollery Children’s Hospital, 2C3.79 WMC, 8440-112 St., Edmonton, Alberta T6G 2B7, Canada. (e-mail:
[email protected]).
Purpose: Enuresis is 1 of the most common complaints facing pediatric urologists and it has significant implications with respect to quality of life. Although the pathophysiology is incompletely understood, there is growing evidence that sleep disordered breathing in children, including obstructive sleep apnea, has a fundamental role. There are also potentially fundamental differences between monosymptomatic enuresis, which may be a sleep disorder, and nonmonosymptomatic enuresis, which may relate to a primary bladder storage problem. We prospectively evaluated the incidence of obstructive sleep apnea in patients with enuresis and analyzed differences between patients with monosymptomatic and nonmonosymptomatic enuresis. Materials and Methods: A total of 69 children with enuresis were given 3 validated questionnaires to complete, including the Dysfunctional Voiding and Incontinence Symptom Score, the Obstructive Sleep Apnea Quality of Life survey and the Modified Pediatric Sleep Questionnaire. The Dysfunctional Voiding and Incontinence Symptom Score quantifies patient dysfunctional voiding habits. The Obstructive Sleep Apnea Quality of Life survey evaluates patient quality of life in regard to obstructive sleep apnea and its effects. Modified Pediatric Sleep Questionnaire results describe the severity of patient sleep disturbances. Results: The mean Obstructive Sleep Apnea Quality of Life Survey score was 43 and 54% of patients had positive Modified Pediatric Sleep Questionnaire results, indicating that obstructive sleep apnea was prevalent in our population. Those with enuresis and daytime incontinence were significantly more likely to have sleep disordered breathing than those with monosymptomatic enuresis (p ⬍0.05). Conclusions: Our study confirms the link between sleep disordered breathing and enuresis. All pediatric health care providers should be aware of this risk. The risk may be magnified in patients with concomitant daytime incontinence. Key Words: urinary bladder, urinary incontinence, enuresis, sleep apnea syndromes, questionnaires
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ENURESIS is 1 of the most common pediatric urological complaints, affecting up to 15% of 5-year-old and 5% of 10-year-old children.1 Despite its prevalence we are without a definitive treat-
ment or clear etiology.2 Although it is not a medical health risk, the psychological and emotional impact is substantial. Current treatment modalities include behavioral therapy such
0022-5347/11/1864-1710/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 186, 1710-1714, October 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.04.017
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HIGH RISK OF SLEEP DISORDERED BREATHING IN ENURESIS POPULATION
as optimizing bladder and bowel habits, alarm therapy and pharmacological remedies.2,3 The pathogenesis of enuresis is currently unknown but several theories exist.4 Functional bladder capacity is implicated, especially in children with enuresis and daytime incontinence.5 However, in patients with MNE there may be abnormal nocturnal urine production,6 bladder relaxation and arousal.7 Altered diurnal antidiuretic hormone secretion, central nervous system disturbances and psychological components are also implicated.2 Contemporary retrospective data suggest that OSA may be related to enuresis. Obstructive SDB occurs in approximately 3% of children and it is primarily caused by adenotonsillar hypertrophy.8,9 Several retrospective reviews in the pediatric population described improvement in enuresis when patients were treated for OSA. Çinar et al achieved 63% complete resolution and 4% partial resolution of enuresis after surgical treatment for upper airway obstruction.10 Basha et al noted similar results after adenoidectomy or tonsillectomy with total resolution of enuresis in 61.4% of patients.11 Brooks and Topol reported that children with a respiratory disturbance index (the number of apneas plus hypopneas per hour of sleep) of greater than 1 were at higher risk for enuresis than those with a respiratory disturbance index of less than 1.12 However, these findings are not universal. A recent prospective trial showed no improvement in enuresis after tonsillectomy.13 The pathophysiology of this relationship is not completely understood. However, increases in intrathoracic pressure during an apneic episode may result in right atrial stretch, and the release of atrial and brain natriuretic peptides, which increase sodium and water excretion. Ultimately this may result in antidiuretic hormone inhibition.14 However, several studies have also shown a link between abnormal sleep patterns on electroencephalogram and enuresis.15,16 Yeung et al noted an abnormal cortical arousal pattern during sleep studies.7 Several previous groups that examined relationships between OSA and enuresis did not assess the incidence of OSA in the enuretic population or distinguish between MNE and NMNE. We prospectively investigated the OSA prevalence in children who presented to a pediatric urology clinic with nocturnal enuresis. Our hypothesis was that OSA and SDB have a prominent role in patients with MNE and a lesser role in those with enuresis and intermittent daytime incontinence.
MATERIALS AND METHODS After receiving institutional ethics approval consecutive patients who presented with enuresis to the pediatric
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urology clinic at Stollery Children’s Hospital were asked to participate in this study. Patients were excluded from analysis if they had neurological disorders that caused a significant developmental delay, neuropathic bladder, recurrent urinary tract infections or a significant congenital bladder anomaly. Patients with craniofacial abnormalities that correlate with OSA, eg Down syndrome, were also excluded. Patients were given 3 validated questionnaires upon presentation, including DVISS,17 OSA-18 and PSQ-22. Questionnaire results were coded and the treating physician was blinded to results. The presence of intermittent daytime incontinence was determined by the history taken by the treating pediatric urologist, in which any degree of daytime incontinence was considered positive. Patients were then categorized as having enuresis with daytime incontinence.
Dysfunctional Voiding and Incontinence Symptom Score We used DVISS to quantify daytime LUTS. This questionnaire, which was validated to determine the presence of daytime bowel and bladder symptoms,18 consists of 10 questions, each with a score of 0 to 3. We used a total score of 7 or greater, which is associated with significant daytime symptoms, to determine the presence of enuresis with LUTS. The determination of daytime incontinence was considered independent of the DVISS score, which was blinded. Due to the multiple variables assessed by DVISS, it is possible to have a positive DVISS score while being continent during the day.
OSA Quality of Life Survey OSA-18 evaluates patient QOL secondary to OSA symptoms, eg snoring, frequent upper respiratory tract infections, mood swings, poor concentration, etc.19 Each question has a score range of 1 to 7. The total score was calculated for each patient and we assigned a range in respect to effect on QOL, including small—less than 60, moderate— 60 to 80 and severe— greater than 80.
Modified Pediatric Sleep Questionnaire The PSQ-22 score evaluates sleep quality and symptoms related to sleep quality.20 PSQ-22 consists of 12 sections of questions. If more than a third of the questions in the first 10 sections are answered yes, a positive test result is recorded, indicating that the patient has sleep problems. We recorded and correlated additional demographics, including body mass index, family history and previous attempted therapies. Scores on the described surveys were recorded and analyzed using the t and chi-square tests.
RESULTS We studied 69 patients who presented to a pediatric urology clinic with complaints of enuresis during 12 months. Of these children 39 were male and 30 were female. Average age at presentation was 9 years (range 5 to 17). A total of 15 patients (22%) reported a family history positive for NE and 1 (1.5%) reported a family history positive for OSA. Four pa-
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tients (6%) previously underwent adenotonsillectomy for OSA or other SDB symptoms and 13 (19%) were classified as obese, defined as a weight of greater than the 97th percentile. Dysfunctional Voiding and Incontinence Symptom Score A total of 56 patients (81%) presented with a positive DVISS score, indicating enuresis with LUTS. Another 24 patients (35%) had enuresis with daytime incontinence. OSA Quality of Life Survey The overall mean OSA-18 score in all patients was 43 (range 18 to 116), indicating mild impairment to QOL with respect to sleep apnea symptoms. QOL was categorized as mildly impaired in 80% of patients, moderately impaired in 15% and severely impaired in 5%. The mean OSA-18 score in those presenting with a positive DVISS score was 43 of a possible 126. This was not statistically significantly different compared to the mean score of 38 in patients without LUTS. However, the mean OSA-18 score in patients with daytime incontinence was 52, significantly higher than the average score of 38 in those with MNE (p ⬍0.01, fig. 1). Modified Pediatric Sleep Questionnaire A total of 37 patients (54%) had a positive score on PSQ-22, indicating a substantial risk of sleep related breathing disorder. Of those who scored positive on DVISS 33 (58%) had a positive PSQ-22 score, significantly more than the 40% with negative DVISS results (p ⬍0.05). Similarly 21 of 44 patients (48%) with MNE scored positively on the PSQ-22 vs 16 of 23 (70%) with concordant daytime incontinence (p ⬍0.05, fig. 2).
Figure 1. Mean OSA-18 score per group was 42, indicating at least mild OSA prevalence. Significant differences were seen in OSA related QOL in 52 patients who were incontinent day and night vs 38 with only nocturnal enuresis, and in obese vs nonobese patients. Star indicates p ⬍0.05.
Figure 2. Of patients 54% had positive PSQ-22 results, indicating high SDB likelihood. Significantly more patients had positive PSQ score if they also had daytime incontinence or positive DVISS. Star indicates p ⬍0.05.
Of the 13 obese patients 10 (77%) had a mean OSA-18 score of 52 and positive PSQ-22 score. Of the 54 children who were not obese 27 (50%) had a mean OSA-18 score of 40 and a positive PSQ-22. There was no significant difference in the PSQ-22 score in children classified as obese. However, the mean OSA-18 score was significantly higher in patients classified as obese than in those with weight within the normal range (p ⬍0.05).
DISCUSSION Our data indicate that a significant proportion of patients with enuresis have a high likelihood of SDB. Thus, there may be benefits to screening these children for OSA. This risk is further magnified in patients with abnormal daytime voiding. Further study is required to determine how best to screen these patients. DVISS is a statistically validated functional voiding symptom score that can provide an accurate, objective measure of voiding symptoms. Since there is no readily available gold standard diagnostic test for SDB, OSA-18 and PSQ-22 are used together to determine the likelihood of SDB. OSA-18 assesses SDB related QOL in the pediatric population. PSQ-22 focuses on SDB from snoring to daytime sleepiness to behavioral problems. A high OSA-18 score and a positive PSQ-22 help physicians recognize when a child is at risk for SDB and should be evaluated further. However, some parameters of these questionnaires include questions on emotional lability, difficulty concentrating, hyperactivity and other behavior problems. Since PSQ-22 and the OSA-18 are more positive in patients with NMNE than in those with MNE, to our knowledge it remains to be deter-
HIGH RISK OF SLEEP DISORDERED BREATHING IN ENURESIS POPULATION
mined whether the effect of being wet during the day impacts patient QOL sufficiently to skew the data or whether sleep dysfunction is severe enough to affect daytime voiding function. Some cases of childhood OSA resolve with normal development while others must be treated to avoid significant hypercapnia, hypoxemia, behavioral problems, hyperactivity, poor school performance, failure to thrive and enuresis.11 Stone et al found that patients with enuresis had a significantly higher total PSQ-22 score.16 Yeung et al noted that children with enuresis are deep sleepers with impaired arousability.7 They experience less deep nonREM and REM sleep, and lighter nonREM sleep, leading to poor quality sleep and a poorly rested child. Thus, NMNE and OSA may impact daytime function in similar fashion by making it difficult for the child to sleep properly. We compared patients with abnormal daytime voiding to patients with MNE since we expected the latter group to be at higher risk for SDB. Conventional thinking in children with daytime and nighttime incontinence is that the primary problem is an
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overactive bladder with a small capacity, which is different from MNE. However, our data suggest that the opposite is true since patients with enuresis and daytime incontinence were more likely to have SDB than those with MNE. PSQ-22 and OSA-18 results were significantly higher in patients with daytime and nighttime incontinence. The significance is difficult to assess and needs further investigation and validation but our results may provide novel insights into daytime LUTS. Perhaps decreased concentration and attention secondary to primary sleep abnormalities is responsible for some LUTS.
CONCLUSIONS These data have significant implications since they should alert pediatric practitioners to the potential association between enuresis and SDB. Investigations of sleep disturbances and more specifically SDB may be warranted in patients who present with enuresis. Future study will determine the best means of screening and how enuresis treatment affects sleep quality.
REFERENCES 1. Firoozi F, Batniji R, Aslan AR et al: Resolution of diurnal incontinence and nocturnal enuresis after adenotonsillectomy in children. J Urol 2006; 175: 1885.
8. Chang SJ and Chae KY: Obstructive sleep apnea syndrome in children: epidemiology, pathophysiology, diagnosis and sequelae. Korean J Pediatr 2010; 53: 863.
2. Robson WL: Clinical practice. Evaluation and management of enuresis. N Engl J Med 2009; 360: 1429.
9. Burg CJ and Friedman NR: Diagnosis and treatment of sleep apnea in adolescents. Adolesc Med State Art Rev 2010; 21: 457.
3. Brown ML, Pope AW and Brown EJ: Treatment of primary nocturnal enuresis in children: a review. Child Care Health Dev 2011; 37: 153.
10. Çinar U, Vural C, Çakir B et al: Nocturnal enuresis and upper airway obstruction. Int J Pediatr Otorhinolaryngol 2001; 59: 115.
4. Nevéus T: Diagnosis and management of nocturnal enuresis. Curr Opin Pediatr 2009; 21: 199. 5. Dehoorne JL, Walle CV, Vansintjan P et al: Characteristics of a tertiary center enuresis population, with special emphasis on the relation among nocturnal diuresis, functional bladder capacity and desmopressin response. J Urol 2007; 177: 1130. 6. Mevorach RA, Bogaert GA and Kogan BA: Urine concentration and enuresis in healthy preschool children. Arch Pediatr Adolesc Med 1995; 149: 259. 7. Yeung CK, Diao M and Sreedhar B: Cortical arousal in children with severe enuresis. N Engl J Med 2008; 358: 2414.
11. Basha S, Bialowas C, Ende K et al: Effectiveness of adenotonsillectomy in the resolution of nocturnal enuresis secondary to obstructive sleep apnea. Laryngoscope 2005; 115: 1101. 12. Brooks LJ and Topol HI: Enuresis in children with sleep apnea. J Pediatr 2003; 142: 515. 13. Kalorin CM, Mouzakes J, Gavin JP et al: Tonsillectomy does not improve bedwetting: results of a prospective controlled trial. J Urol 184: 2527. 14. Capdevila OS, Crabtree V, Kheirandish-Gozal L et al: Increased morning brain natriuretic peptide levels in children with nocturnal enuresis and sleep-disordered breathing: a community-based study. Pediatrics 2008; 121: e1208.
15. Dhondt K, Raes A, Hoebeke P et al: Abnormal sleep architecture and refractory nocturnal enuresis. J Urol 2009; 182: 1961. 16. Stone J, Malone PS, Atwill D et al: Symptoms of sleep-disordered breathing in children with nocturnal enuresis. J Pediatr Urol 2008; 4: 197. 17. Farhat W, Bagli DJ, Capolicchio G et al: The dysfunctional voiding scoring system: quantitative standardization of dysfunctional voiding symptoms in children. J Urol 2000; 164: 1011. 18. Farhat W, McLorie GA, O’Reilly S et al: Reliability of the pediatric dysfunctional voiding symptom score in monitoring response to behavioral modification. Can J Urol 2001; 8: 1401. 19. Silva VC and Leite AJ: Quality of life in children with sleep-disordered breathing: evaluation by OSA-18. Braz J Otorhinolaryngol 2006; 72: 747. 20. Chervin RD, Hedger K, Dillon JE et al: Pediatric sleep questionnaire (PSQ): validity and reliability of scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems. Sleep Med 2000; 1: 21.
EDITORIAL COMMENT Nocturnal enuresis is a heterogeneous condition that occurs only during sleep. However, it is associated with somatic and psychological symptoms
that occur during the day.1 These authors administered 3 parental questionnaires that, although validated, still reflect subjective parental views
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and attributions. Thus, results do not reflect objective findings or diagnoses. A few interesting findings are reported. QOL was decreased on a disease specific (not generic) questionnaire in children with NMNE and obesity. The study group consisted mainly of children with NMNE, of whom a third had additional daytime incontinence. QOL as well as health related QOL is a multidimensional umbrella construct encompassing several domains, including behavior. Behavioral problems and disorders are increased in children with daytime incontinence and NMNE, and in turn they are associated with QOL.1,2 On generic questionnaires health related QOL did not differ among children with MNE, NMNE or daytime incontinence.3 Also, health related QOL in children with urinary incontinence did not differ from that in pediatric patients with asthma, arthritis, atopic dermatitis, cystic fibrosis or epilepsy.3 QOL was decreased in children with daytime incontinence compared to controls.2 However, results depend on the informant since parental (proxy) and child based questionnaires can differ. QOL was not decreased
when children were asked, but only by parental reporting. Thus, it seems that parents may overestimate QOL in their children. Parents also reported a high rate of sleep rated breathing symptoms, not disorders. Again, children with NMNE, daytime incontinence and obesity were at highest risk. In future studies objective polysomnography, sleep laboratory based studies are needed in carefully selected patient groups. Based on the findings of this study it would be most interesting to focus on children with NMNE with or without daytime incontinence as well as on those with obesity, which carries multiple long-term medical risks. They have been a neglected group in studies of nocturnal enuresis. Also, a focus on behavioral problems and disorders instead of on the umbrella construct of QOL would have more practical relevance.1 Alexander von Gontard Department of Child and Adolescent Psychiatry Saarland University Hospital Homburg, Germany
REFERENCES 1. von Gontard A, Baeyens D, Van Hoecke E et al: Psychological and psychiatric issues in urinary and fecal incontinence. J Urol 2011; 185: 1432.
2. Bachmann C, Lehr D, Janhsen E et al: Health related quality of life of a tertiary referral center population with urinary incontinence using the DCGM-10 questionnaire. J Urol 2009; 182: 2000.
3. Natale N, Kuhn S, Siemer S et al: Quality of life and self-esteem in children with urinary incontinence— urge incontinence and voiding postponement. J Urol 2009; 182: 692.