- Email: [email protected]
Nocturnal Enuresis in Children: Prevalence, Correlates, and Relationship with Obstructive Sleep Apnea
Nocturnal Enuresis in Children: Prevalence, Correlates, and Relationship with Obstructive Sleep Apnea Miao Shang Su, MD,* Albert M. Li, MRCP, MD,* Hung K. So, PhD, Chun T. Au, MPhil, Crover Ho, RPSGT, and Yun K. Wing, MRCP, FRCPsych, FHKAM (Psych) Objectives To examine the prevalence and correlates of nocturnal enuresis (NE) in primary school children, and to compare the prevalence of NE in children with and those without obstructive sleep apnea (OSA).
Study design Parents of children aged 6-11 years completed a questionnaire eliciting information on sleeprelated symptoms, demography, and family and past medical history. Children screened due to high risk for OSA, along with a randomly chosen low-risk group, underwent overnight polysomnography (PSG). Results A total of 6147 children (3032 girls) were studied. The overall prevalence of NE ($1 wet night/month) was 4.6% (6.7% of boys and 2.5% of girls). Boys had a significantly greater prevalence across all age groups. In 597 children (215 girls) who underwent PSG, the prevalence of NE was not greater in children with OSA, but was increased with increasing severity of OSA in girls only. Boys with NE had longer deep sleep duration. Sex and sleep-related symptoms were associated with NE. Conclusions This community-based study demonstrated a sex-associated prevalence of NE in relation to increasing OSA severity. (J Pediatr 2011;159:238-42).
N
octurnal enuresis (NE) is a common problem that can cause much distress to affected families.1 In general, NE is not considered a significant clinical problem when the number of wet nights is fewer than 1 per month.2 Using 1 or >1 episode per month as a cutoff, the reported prevalence rate for NE varies from 3.8-13.0%.3-10 This variance is related in part to age. NE occurs when a child is unable to suppress nocturnal bladder contractions. Evidence suggests a possible association with sleep-disordered breathing.11 Several studies have reported a close relationship between obstructive sleep apnea (OSA) and NE.12-15 Children with OSA have increased negative intrathoracic pressure as a result of increased inspiratory effort during sleep. The continual swing in intrathoracic pressure causes cardiac distention that can lead to release of atrial natriuretic peptide, triggering enuresis.16 However, a recent study did not support a positive relationship between OSA and NE.17 It is important to note that previous studies were limited by their patient selection and lack of matched control subjects for comparison.12-17 In the present study, we aimed to identify the prevalence, sleep study characteristics, and risk factors associated with NE in children, and to compare the prevalence of NE in children with and those without OSA.
Methods First Phase: Sleep Questionnaire This study was part of an epidemiologic study examining the prevalence of OSA in Hong Kong Chinese children.18,19 The study protocol was approved by the pertinent Institutional Ethics Review Committee. Parents of children aged 6-11 years in 13 randomly selected primary schools were invited to participate. They attended an education forum where details of the study were explained. A validated parent-completed OSA screening questionnaire (the Hong Kong Children Sleep Questionnaire [HK-CSQ])20 and a personally addressed letter asking for consent were then distributed with the help of school teachers. Parents who failed to return the HK-CSQ questionnaire within 1 week were sent another copy along with a self-addressed envelope to facilitate its return. The HK-CSQ sought information regarding sleep habits and problems of the participants in the past 12 months. The information obtained included nocturnal From the Department of Respiratory Medicine, Wenzhou OSA symptoms (ie, snoring, witnessed apnea, labored breathing, and mouth Medical College Affiliated Second Hospital–Yuying BMI HK-CSQ NE OAHI OSA PSG REM
Body mass index Hong Kong Children Sleep Questionnaire Nocturnal enuresis Obstructive apnea hypopnea index Obstructive sleep apnea Polysomnography Rapid eye movement
Children’s Hospital, Zhejiang, People’s Republic of China (M.S.); and Department of Pediatrics, Prince of Wales Hospital (A.L., H.S., C.A.) and Department of Psychiatry, Shatin Hospital (C.H., Y.W.), The Chinese University of Hong Kong, Shatin, Hong Kong *Contributed equally to this work. Supported by funding from the Research Grants Council of the Hong Kong Special Administrative Region (CUHK4161/02M). The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2011.01.036
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Vol. 159, No. 2 August 2011 breathing), symptoms of parasomnias (ie, presence and frequency of NE, night terrors, nightmares, somnambulism, sleep talking, and bruxism), and daytime symptoms (ie, morning headache, recurrent upper airway infections, daytime sleepiness in different situations, and hyperactivity). Parents provided answers on a 5-point frequency scale (0, ‘‘never’’; 1, ‘‘rarely,’’ 0-1 night per month; 2, ‘‘sometimes,’’ 1-2 nights per month; 3, ‘‘often,’’ 1-2 nights per week; and 4, ‘‘frequently,’’ 3 nights or more per week), along with a ‘‘don’t know’’ option. In addition, the following information was elicited: history of respiratory diseases, including allergic rhinitis, nasosinusitis, asthma, tonsillitis, and pharyngitis or laryngitis; parental education; and physical measurements. Data from 3 survey questions covering snoring, nocturnal mouth breathing, and night sweats were used to classify survey participants as being at high risk or at low risk for potential OSA. It was found that a composite HKCSQ score from the 3 questions (total score, 0-12) of $7 had a sensitivity of 75.4% and specificity of 80.5% in predicting for the presence of OSA.20 All children belonging to the high risk for OSA group and a randomly chosen sample of subjects at low risk for OSA were invited to undergo an overnight polysomnography (PSG) study. Second Phase: Polysomnography A single attended overnight PSG study was performed in a dedicated sleep laboratory with a CNS 1000P polygraph (CNS, Chanhassen, Minnesota).21 All computerized sleep data were manually edited by experienced PSG technologists and clinicians in accordance with standardized criteria.22 Hypopnea was defined as a $50% reduction in the amplitude of the airflow signal. It was counted only if longer than 2 baseline breaths and associated with oxygen desaturation of at least 4% and/or arousals. The obstructive apnea hypopnea index (OAHI) was defined as the total number of obstructive apneic and hypopneic episodes per hour of sleep. The arousal index was defined the total number of arousals per hour of sleep. Definitions of NE and OSA Children aged 6 years and older who were reported to have 1 or more wet nights per month over the past 12 months were defined as having NE. Those who were reported as never having wet nights over the past 12 months served as controls. The children who underwent PSG were separated into OSA cases and non-OSA controls, using an OAHI $1 as the cutoff. Statistical Analysis Descriptive data are presented as percentages for discrete variables and as means (SD) or medians (IQR) for continuous variables. The c2 test and Mann-Whitney U test were used to compare variables between children with and without NE. Exploratory factor analysis was used to identify the underlying patterns among the various sleep-related symptoms. Correlation coefficients were analyzed by principal component analysis and subsequent rotation according to the standard varimax criterion. In this type of analysis, the
correlation between parameters was attributed to their common dependence on independent entities, called ‘‘factors.’’ The coefficients that link parameters to factors are called ‘‘factor loadings;’’ the number of factors was chosen to be as small as possible but large enough to account for most of the variation within the data. It was decided a priori that the number of factors in the varimax rotation would be based on the number of eigenvalues >1.0 in the principal component analysis. Logistic regression analysis was used to determine the association between NE and risk factors that were found to be significant on univariate analysis. For the first logistic regression model, a total of 5403 children were included. NE was the dependent variable, and age, male sex, body mass index (BMI) z score, and sleep-related symptoms were the independent variables. The second logistic model included only subjects who had undergone overnight PSG. A P value < .05 was considered significant. All analyses were performed using SPSS version 15.0 (SPSS Inc, Chicago, Illinois).
Results A total of 6147 completed questionnaires for 3032 girls and 3115 boys aged 6 to 11 years were analyzed (Table I). The overall prevalence of NE was 285/6147 (4.6%), with boys 3 times more likely than girls to be affected (209/3115 [6.7%] vs 76/3032 [2.5%]). The prevalence of NE declined gradually with increasing age, from 9.0% at age 6 years to 1.9% at age 11 years. In each age group, the prevalence of NE was significantly greater in boys than in girls. Based on the completed questionnaires, 568 children (9.2%; 396 boys and 172 girls) were identified to be at high risk for OSA, of whom 397 (70%; 279 boys and 118 girls) agreed to take part in the second phase of our study. Two hundred children (103 boys and 97 girls) identified to be at low risk for OSA also were invited to undergo overnight Table I. Characteristics of the study subjects without NE and with NE Age, years, mean SD Height, cm, mean SD Weight, kg, mean SD BMI, kg m 2, mean SD BMI z score, mean SD Boys Paternal education level Primary level or below Up to secondary level Tertiary level or above Maternal education level Primary level or below Up to secondary level Tertiary level or above Respiratory diseases Allergic rhinitis Nasosinusitis Asthma Tonsillitis Pharyngitis or laryngitis
Without NE (n = 5862)
With NE (n = 285)
9.2 1.7 133.7 12.8 30.8 9.1 16.9 3.1 0.22 1.14 49.6%
8.4 1.6 128.9 12.7 27.9 8.0 16.4 2.9 0.10 1.20 73.3%
18.2% 66.0% 15.7%
12.0% 65.6% 22.4%
19.1% 71.0% 9.9%
14.3% 69.2% 16.5%
41.9% 1.9% 4.4% 9.8% 48.8%
47.4% 2.1% 8.1% 11.9% 58.6%
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PSG. Among the 597 children who underwent PSG, the prevalence of NE was 9.2% (55/597). More boys than girls were affected (11.5% [44/382] vs 5.1% [11/215]; P < .01). Overall, 257 children were found to have OSA. The prevalence of NE did not differ in the children with OSA and those without OSA (9.7% [25/258] vs 8.8% [30/339]; P = .725); however, there was a significant difference in the prevalence of NE in girls with increasing OSA severity (2.1% for those with OAHI <1 vs 8.8% for OAHI 1-5 vs 20.0% for OAHI >5; P < .01). This increased prevalence of NE with increasing severity of OSA was not seen in boys (13.8% for those with OAHI <1 vs 8.8% for OAHI 1-5 vs 10.2% for OAHI >5; P = .278) (Table II). OAHI was significantly higher in girls with NE than in controls (median [range], 1.8 [0.1-5.9] vs 0.4 [0-1.3]; P = .026). Arousal index, sleep efficiency, and proportion of each sleep stage (S1, S2, and S3+4) were similar in children with and without NE (Table III; available at www.jpeds.com). Seventeen items in the questionnaire were categorized into 5 factors—morning or daytime symptoms, nocturnal symptoms, anxiety or insomniac symptoms, symptoms of parasomnias, and respiratory symptoms—by factor analysis (Table IV). The total variance explained by this 5-factor model was 47.5%, and the factor scores were calculated using the regression method. In the first logistic regression model with 5403 subjects, several risk factors were found to be significantly associated with NE, including age (OR, 0.761; P < .0001); male sex (OR, 2.568; P < .0001); morning and daytime symptoms, including feeling unrefreshed in the morning, daytime fatigue, and difficulty getting up in the morning (OR, 2.644; P < .0001); nocturnal symptoms, including restless sleep, prone position, bruxism, and night sweats (OR, 0.648; P < .0001); respiratory symptoms, including breathing difficulty, gasping for breath or cessation of breathing during sleep, and mouth breathing (OR, 1.460; P < .0001); symptoms of parasomnias (OR, 1.188; P = .008); and habitual snoring (OR, 0.550; P = .030). In the second logistic model that included only subjects who had undergone PSG, female sex (OR, 0.092; P = .001), morning or daytime symptoms (OR, 1.914; P < .0001), nocturnal symptoms (OR, 0.715; P = .037), respiratory symptoms (OR, 1.331; P = .032), symptoms of parasomnias (OR, 1.305; P = .016) with OAHI in girls (OR, 1.530; P =
Vol. 159, No. 2 .004), and slow-wave sleep (OR, 1.021; P = .039) were associated with NE (Table V).
Discussion This systematic study of the association of NE with OSA and other sleep-related symptoms in a community-based population found a prevalence of NE of 4.6% in our cohort of 6- to 11-year-old children, with no difference in rate between children with OSA and those without OSA. A novel finding was the differential sex response to OSA in the prevalence of NE, with a higher prevalence of NE in girls with increasing OSA severity. NE was defined using different cutoff values in previous studies, giving rise to a wide range of reported prevalence rates.3-10 The present study’s prevalence of 4.6% is comparable with that from studies that used the same NE definition and involved ethnic Chinese children of similar age range. Two studies from the Middle East reported an NE prevalence of >10%,9,10 and a study involving Malaysians6 reported a rate twice that of ours. Locally, 2 groups of researchers have examined the prevalence of NE using different cutoff values, and accordingly found different prevalence rates. Ng et al23 reported a prevalence of 5.1% in 3047 children aged 6 to 12 years using $1 episodes/week to define NE. Yeung et al24 reported a prevalence of 3.1% using a definition of 1 wet night every 3 months. A consistent finding in all studies is that younger boys have the highest rate of NE, and that prevalence decreases with increasing age. Various causative mechanisms for NE have been proposed, including delayed maturation of the nervous system controlling bladder function, delayed development of bladder function and size, and decreased nighttime secretion of antidiuretic hormone.25,26 Our study also found longer slow-wave sleep in children with NE. This finding is compatible with previous studies suggesting that children with NE tend to sleep more deeply and are more difficult to awaken.27,28 The relationship between NE and OSA is controversial, and studies reporting both positive and negative associations have been published.12-17 These discrepant findings might be related to different study designs and varying sample sizes. In the present study, a large sample of children underwent PSG, the current gold standard for diagnosing OSA, allowing us to accurately classify the subjects into an OSA group and
Table II. Prevalence of NE in children with OSA and without OSA using different cutoffs (n = 597) Girls (n = 215)
NE frequency Never <1/month 12/month 1-2/week >2/week >1/month
240
Boys (n = 382)
Overall
OAHI <1
OAHI 1-5
OAHI >5
OAHI <1
OAHI 1-5
OAHI >5
OAHI <1
OAHI ‡1
OAHI 1-5
OAHI >5
(n = 143)
(n = 57)
(n = 15)
(n = 196)
(n = 136)
(n = 49)
(n = 339)
(n = 257)
(n = 193)
(n = 64)
111 (77.6%) 29 (20.3%) 1 (0.7%) 1 (0.7%) 1 (0.7%) 3 (2.1%)
49 (86.0%) 3 (5.3%) 5 (8.8%) 0 (0.0%) 0 (0.0%) 5 (8.8%)
8 (53.3%) 4 (26.7%) 2 (13.3%) 0 (0.0%) 1 (6.7%) 3 (20.0%)
129 (65.8%) 40 (20.4%) 14 (7.1%) 3 (1.5%) 10 (5.1%) 27 (13.8%)
94 (69.1%) 30 (22.1%) 8 (5.8%) 2 (1.5%) 2 (1.5%) 12 (8.8%)
34 (69.4%) 10 (20.4%) 4 (8.2%) 0 (0.0%) 1 (2.0%) 5 (10.2%)
240 (70.8%) 69 (20.4%) 15 (4.4%) 4 (1.2%) 11 (3.2%) 30 (8.8%)
185 (75.5%) 47 (17.0%) 19 (4.2%) 2 (1.1%) 4 (2.2%) 25 (9.7%)
143 (74.1%) 33 (17.1%) 13 (6.8%) 2 (1.0%) 2 (1.0%) 17 (8.8%)
42 (65.6%) 14 (21.9%) 6 (9.4%) 0 (0.0%) 2 (3.1%) 8 (12.5%)
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Table IV. Summary of items and factor loadings for the 5 identified factors Item
Factor loading
Factor 1: Morning/daytime symptoms Feeling unrefreshed in the morning Daytime fatigue Difficulty getting up in the morning Factor 2: Nocturnal symptoms Restless sleep Prone position Bruxism Night sweats Factor 3: Anxiety/insomnia symptoms Rocking or head banging Feeling anxious or afraid when falling asleep Difficulty falling asleep Factor 4: Parasomniac symptoms Sleep walking Sleep talking Nightmares Sudden awakening during sleep Factor 5: Respiratory symptoms Breathing difficulty Gasping for breath or inability to breathe during sleep Mouth breathing
0.770 0.742 0.631 0.666 0.593 0.555 0.489 0.680 0.510 0.438 0.656 0.524 0.512 0.464 0.635 0.625 0.578
a non-OSA group. We found no difference in the prevalence of NE between subjects with OSA and those without OSA. In studies that demonstrated improvements in NE following adenotonsillectomy or other interventions, the subjects—unlike ours—were recruited from hospital cases.14,15 This might explain the negative association found in the present study. We also found a significant sex difference in the prevalence of NE in relation to OSA severity, with girls with more severe OSA more likely to have NE. Some studies have found that compared with males, females are more protected against adverse renal consequences secondary to hypoxia and ischemiareperfusion injury.29-31 Whether this or other hormonal effects might play a role in the differential sex response to OSA in the prevalence of NE merits further evaluation.
We used factor analysis to correlate different sleep-related symptoms into common factors, and found that NE was positively associated with morning or daytime symptoms, nocturnal and respiratory symptoms, and symptoms of parasomnias. This finding suggests that sleep-related symptoms should be investigated in children with NE. In the present study, we failed to establish an association between habitual snoring and NE in logistic regression analysis. This finding is in contrast to previous studies reporting a positive association between habitual snoring and NE.32,33 Differening definitions for NE might have contributed to this discrepancy. The present study has some limitations. First, the response rate to our questionnaire survey was only modest, at 70%. This could have introduced a degree of selection bias whereby only parents whose child had sleep symptoms or problems were more likely to return the questionnaire. Another potential source of selection bias is the high number of subjects with NE who underwent PSG in second phase despite our strict inclusion criteria. Comparing the demographic and socioeconomic data of respondents and nonrespondents reveals no significant differences between the 2 groups. We believe that overall, our study cohort represents the sample population. Second, the survey questionnaire was completed by parents who often did not sleep in the same room as their child and thus were not aware of the child’s actual sleep behavior. This is an intrinsic problem known to be associated with the use of questionnaire surveys. There is also a lack of real-time association of NE and PSG, and so the sleep variables may more closely reflect the trait rather than state phenomenon. However, a study of preschool children showed a significant and independent association between parentally reported and objectively measured sleep symptoms.34 Furthermore, the reliability of our screening questionnaire has been demonstrated previously.20 Finally, the lack of correlation between NE and severity of OSA might be related to the fact that boys are more likely to have other
Table V. Associations between independent factors and NE Model 2 (n = 480)†
Model 1 (n = 5403)*
Age, years Male sex Female sex Breast-feeding BMI z score Anxiety/insomnia symptoms Morning/daytime symptoms Nocturnal symptoms Respiratory symptoms Symptoms of parasomnias Habitual snoring OAHI, /h OAHI*female sex REM sleep Stage 1 sleep Stage 2 sleep Slow-wave sleep
OR
95% CI
P
OR
95% CI
P
0.761 2.568
0.689-0.841 1.826-3.610
<.0001 <.0001
0.807
0.626-1.042
.100
1.122 0.933 1.154 2.644 0.648 1.460 1.188 0.550
0.811-1.553 0.817-1.066 0.991-1.343 2.266-3.084 0.548-0.766 1.300-1.638 1.047-1.347 0.320-0.944
.487 .311 .065 <.0001 <.0001 <.0001 .008 .030
0.092 1.199 0.962 1.199 1.914 0.715 1.331 1.305 1.959 0.998 1.530 0.992 1.018 1.001 1.021
0.021-0.400 0.536-2.685 0.677-1.365 0.858-1.676 1.339-2.734 0.521-0.981 1.026-1.726 1.050-1.621 0.805-4.767 0.924-1.079 1.148-2.039 0.976-1.009 0.989-1.048 0.990-1.012 1.001-1.042
.001 .659 .826 .287 <.0001 .037 .032 .016 .138 .961 .004 .377 .234 .833 .039
*Model 1 included all subjects with a completed questionnaire. †Model 2 included only subjects with a completed questionnaire and PSG results.
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factors, such as a familial predisposition to NE, which could dilute the relationship between NE and OSA. Strengths of this study include the large number of subjects and the use of a validated and reliable locally applicable questionnaire. Furthermore, all subjects who agreed to take part in the second phase of this study underwent PSG to ascertain their OSA status, allowing an accurate comparison of NE prevalence in subjects with OSA and those without OSA. In summary, we found a NE prevalence rate similar to that reported in previous studies performed in ethnic Chinese. We did not find a higher NE prevalence in children with OSA, but did note a differential sex response in NE prevalence with increasing OSA severity. Children with NE tended to spend more time in deep sleep and were more likely to have other sleep-related symptoms. n We thank the staff of Shatin Hospital’s Sleep Assessment Unit for their logistical support, and all participating schools, children, and parents for their cooperation. Submitted for publication Jun 5, 2010; last revision received Nov 22, 2010; accepted Jan 19, 2011. Reprint requests: Albert M. Li, MCRP, MD, Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. E-mail: [email protected]
References 1. Butler RJ. Annotation. Night wetting in children: psychological aspects. J Child Psychol Psychiatry 1998;39:453-63. 2. Thiedke CC. Nocturnal enuresis. Am Fam Physician 2003;67:1499-506. 3. Cher TW, Lin GJ, Hsu KH. Prevalence of nocturnal enuresis and associated familial factors in primary school children in Taiwan. J Urol 2002; 168:1142-6. 4. Chiozza ML, Bernardinelli L, Caione P, Del Gado R, Ferrara P, Giorgi PL, et al. An Italian epidemiological multicentre study of nocturnal enuresis. Br J Urol 1998;81(Suppl 3):S86-9. 5. Kajiwara M, Inoue K, Mutaguchi K, Usui T. The prevalence of overactive bladder and nocturnal enuresis in Japanese early adolescents: a questionnaire survey. Hinyokika Kiyo 2006;52:107-11. 6. Kanaheswari Y. Epidemiology of childhood nocturnal enuresis in Malaysia. J Paediatr Child Health 2003;39:118-23. 7. Spee-van der Wekke J, Hirasing RA, Meulmeester JF, Radder JJ. Childhood nocturnal enuresis in the Netherlands. Urology 1998;51:1022-6. 8. Wen JG, Wang QW, Chen Y, Wen JJ, Liu K. An epidemiological study of primary nocturnal enuresis in Chinese children and adolescents. Eur Urol 2006;49:1107-13. 9. Ozkan KU, Garipardic M, Toktamis A, Karabiber H, Sahinkanat T. Enuresis prevalence and accompanying factors in schoolchildren: a questionnaire study from southeast Anatolia. Urol Int 2004;73:149-55. 10. G€ ur E, Turhan P, Can G, Akkus S, Sever L, G€ uzel€ oz S, et al. Enuresis: prevalence, risk factors and urinary pathology among school children in Istanbul, Turkey. Pediatr Int 2004;46:58-63. 11. Brooks LJ. Enuresis and sleep apnea. Pediatrics 2005;116:799-800. 12. Brooks LJ, Topol HI. Enuresis in children with sleep apnea. J Pediatr 2003;142:515-8. 13. Barone JG, Hanson C, DaJusta DG, Gioia K, England SJ, Schneider D. Nocturnal enuresis and overweight are associated with obstructive sleep apnea. Pediatrics 2009;124:e53-9. 14. Basha S, Bialowas C, Ende K, Szeremeta W. Effectiveness of adenotonsillectomy in the resolution of nocturnal enuresis secondary to obstructive sleep apnea. Laryngoscope 2005;115:1101-3.
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Vol. 159, No. 2 15. Weissbach A, Leiberman A, Tarasiuk A, Goldbart A, Tal A. Adenotonsilectomy improves enuresis in children with obstructive sleep apnea syndrome. Int J Pediatr Otorhinolaryngol 2006;70:1351-6. 16. Rittig S, Knudsen UB, Nørgaard JP, Gregersen H, Pedersen EB, Djurhuus JC. Diurnal variation of plasma atrial natriuretic peptide in normals and patients with enuresis nocturna. Scand J Clin Lab Invest 1991;51:209-17. 17. Sans Capdevila O, Crabtree VM, Kheirandish-Gozal L, Gozal D. Increased morning brain natriuretic peptide levels in children with nocturnal enuresis and sleep-disordered breathing: a community-based study. Pediatrics 2008;121:e1208-14. 18. Chan JY, Li AM, Au CT, Lo AF, Ng SK, Abdullah VJ, et al. Cardiac remodelling and dysfunction in children with obstructive sleep apnoea: a community-based study. Thorax 2009;64:233-9. 19. Li AM, Au CT, Sung RY, Ho C, Ng PC, Fok TF, et al. Ambulatory blood pressure in children with obstructive sleep apnoea: a community-based study. Thorax 2008;63:803-9. 20. Li AM, Cheung A, Chan D, Wong E, Ho C, Lau J, et al. Validation of a questionnaire instrument for prediction of obstructive sleep apnea in Hong Kong Chinese children. Pediatr Pulmonol 2006;41: 1153-60. 21. Li AM, Wing YK, Cheung A, Chan D, Ho C, Hui S, et al. Is a 2-night polysomnographic study necessary in childhood sleep-related disordered breathing? Chest 2004;126:1467-72. 22. American Thoracic Society. Cardiorespiratory sleep studies in children: stablishment of normative data and polysomnographic predictors of morbidity. Am J Respir Crit Care Med 1999;160:1381-7. 23. Ng DK, Kwok KL, Cheung JM, Leung SY, Chow PY, Wong WH, et al. Prevalence of sleep problems in Hong Kong primary school children: a community-based telephone survey. Chest 2005;128:1315-23. 24. Yeung CK, Sreedhar B, Sihoe JD, Sit FK, Lau J. Differences in characteristics of nocturnal enuresis between children and adolescents: a critical appraisal from a large epidemiological study. BJU Int 2006;97:1069-73. 25. Bakwin H. The genetics of enuresis. In: Kalvin J, MacKeith RC, Meadow SR, eds. Bladder Control and Enuresis. Lavenham, England: Lavenham Press; 1973. p. 73-88. 26. Mammen AA, Ferrer FA. Nocturnal enuresis: medical management. Urol Clin North Am 2004;31:491-8. 27. Wolfish NM, Pivik RT, Busby KA. Elevated sleep arousal thresholds in enuretic boys: clinical implications. Acta Paediatr 1997; 86:381-4. 28. Hunsballe JM. Increased delta component in computerized sleep electroencephalographic analysis suggests abnormally deep sleep in primary monosymptomatic nocturnal enuresis. Scand J Urol Nephrol 2000;34: 294-302. 29. Sharma PK, Thakur MK. Estrogen receptor alpha expression in mice kidney shows sex differences during aging. Biogerontology 2004;5:37581. 30. Fekete A, Vannay A, Ver A, Vasarhelyi B, M€ uller V, Ouyang N, et al. Sex differences in the alterations of Na+, K+-ATPase following ischaemia-reperfusion injury in the rat kidney. J Physiol 2004;555: 471-80. 31. Saez F, Reverte V, Salazar F, Castells MT, Llinas MT, Salazar FJ. Hypertension and sex differences in the age-related renal changes when cyclooxygenase-2 activity is reduced during nephrogenesis. Hypertension 2009;53:331-7. 32. Alexopoulos EI, Kostadima E, Pagonari I, Zintzaras E, Gourgoulianis K, Kaditis AG. Association between primary nocturnal enuresis and habitual snoring in children. Urology 2006;68:406-9. 33. Ersu R, Arman AR, Save D, Karadag B, Karakoc F, Berkem M, et al. Prevalence of snoring and symptoms of sleep-disordered breathing in primary school children in Istanbul. Chest 2004;126:19-24. 34. Castronovo V, Zucconi M, Nosetti L, Marazzini C, Hensley M, Veglia F, et al. Prevalence of habitual snoring and sleep-disordered breathing in preschool-aged children in an Italian community. J Pediatr 2003;142: 377-82.
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Table III. Comparison of PSG parameters between children with NE and without NE according to sex Girls (n = 179)
OAHI, /h Arousal index, /h Sleep efficiency, % Sleep stage REM, min Sleep stage 1, min Sleep stage 2, min Slow wave sleep, min Total sleep time, min
Boys (n = 301)
Controls
NE
P*
Controls
NE
P*
0.4 (0-1.3) 6.1 (5.0-8.0) 84.2 (76.8-90.0) 103 (83-119) 30 (22-38) 240 (208-266) 109 (91-124) 483 (444-515)
1.8 (0.1-5.9) 7.3 (5.0-12.9) 83.1 (69.8-91.0) 96 (68-128) 39 (22-45) 222 (163-249) 110 (88-132) 474 (399-524)
.026 .242 .725 .657 .132 .112 .610 .746
0.4 (0.1-0.9) 7.0 (5.4-9.1) 83.0 (74.8-89.6) 103 (81-121) 33 (25-43) 225 (195-254) 110 (94-124) 475 (429-514)
0.3 (0-0.9) 6.3 (4.6-8.5) 82.5 (78.1-87.2) 91 (82-108) 28 (22-41) 229 (198-240) 118 (98-131) 471 (448-502)
.107 .118 .581 .101 .153 .800 .079 .868
Values are median (range). *Without NE versus with NE.
Nocturnal Enuresis in Children: Prevalence, Correlates, and Relationship with Obstructive Sleep Apnea
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Study design Parents of children aged 6-11 years completed a questionnaire eliciting information on sleeprelated symptoms, demography, and family and past medical history. Children screened due to high risk for OSA, along with a randomly chosen low-risk group, underwent overnight polysomnography (PSG). Results A total of 6147 children (3032 girls) were studied. The overall prevalence of NE ($1 wet night/month) was 4.6% (6.7% of boys and 2.5% of girls). Boys had a significantly greater prevalence across all age groups. In 597 children (215 girls) who underwent PSG, the prevalence of NE was not greater in children with OSA, but was increased with increasing severity of OSA in girls only. Boys with NE had longer deep sleep duration. Sex and sleep-related symptoms were associated with NE. Conclusions This community-based study demonstrated a sex-associated prevalence of NE in relation to increasing OSA severity. (J Pediatr 2011;159:238-42).
N
octurnal enuresis (NE) is a common problem that can cause much distress to affected families.1 In general, NE is not considered a significant clinical problem when the number of wet nights is fewer than 1 per month.2 Using 1 or >1 episode per month as a cutoff, the reported prevalence rate for NE varies from 3.8-13.0%.3-10 This variance is related in part to age. NE occurs when a child is unable to suppress nocturnal bladder contractions. Evidence suggests a possible association with sleep-disordered breathing.11 Several studies have reported a close relationship between obstructive sleep apnea (OSA) and NE.12-15 Children with OSA have increased negative intrathoracic pressure as a result of increased inspiratory effort during sleep. The continual swing in intrathoracic pressure causes cardiac distention that can lead to release of atrial natriuretic peptide, triggering enuresis.16 However, a recent study did not support a positive relationship between OSA and NE.17 It is important to note that previous studies were limited by their patient selection and lack of matched control subjects for comparison.12-17 In the present study, we aimed to identify the prevalence, sleep study characteristics, and risk factors associated with NE in children, and to compare the prevalence of NE in children with and those without OSA.
Methods First Phase: Sleep Questionnaire This study was part of an epidemiologic study examining the prevalence of OSA in Hong Kong Chinese children.18,19 The study protocol was approved by the pertinent Institutional Ethics Review Committee. Parents of children aged 6-11 years in 13 randomly selected primary schools were invited to participate. They attended an education forum where details of the study were explained. A validated parent-completed OSA screening questionnaire (the Hong Kong Children Sleep Questionnaire [HK-CSQ])20 and a personally addressed letter asking for consent were then distributed with the help of school teachers. Parents who failed to return the HK-CSQ questionnaire within 1 week were sent another copy along with a self-addressed envelope to facilitate its return. The HK-CSQ sought information regarding sleep habits and problems of the participants in the past 12 months. The information obtained included nocturnal From the Department of Respiratory Medicine, Wenzhou OSA symptoms (ie, snoring, witnessed apnea, labored breathing, and mouth Medical College Affiliated Second Hospital–Yuying BMI HK-CSQ NE OAHI OSA PSG REM
Body mass index Hong Kong Children Sleep Questionnaire Nocturnal enuresis Obstructive apnea hypopnea index Obstructive sleep apnea Polysomnography Rapid eye movement
Children’s Hospital, Zhejiang, People’s Republic of China (M.S.); and Department of Pediatrics, Prince of Wales Hospital (A.L., H.S., C.A.) and Department of Psychiatry, Shatin Hospital (C.H., Y.W.), The Chinese University of Hong Kong, Shatin, Hong Kong *Contributed equally to this work. Supported by funding from the Research Grants Council of the Hong Kong Special Administrative Region (CUHK4161/02M). The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2011.01.036
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Vol. 159, No. 2 August 2011 breathing), symptoms of parasomnias (ie, presence and frequency of NE, night terrors, nightmares, somnambulism, sleep talking, and bruxism), and daytime symptoms (ie, morning headache, recurrent upper airway infections, daytime sleepiness in different situations, and hyperactivity). Parents provided answers on a 5-point frequency scale (0, ‘‘never’’; 1, ‘‘rarely,’’ 0-1 night per month; 2, ‘‘sometimes,’’ 1-2 nights per month; 3, ‘‘often,’’ 1-2 nights per week; and 4, ‘‘frequently,’’ 3 nights or more per week), along with a ‘‘don’t know’’ option. In addition, the following information was elicited: history of respiratory diseases, including allergic rhinitis, nasosinusitis, asthma, tonsillitis, and pharyngitis or laryngitis; parental education; and physical measurements. Data from 3 survey questions covering snoring, nocturnal mouth breathing, and night sweats were used to classify survey participants as being at high risk or at low risk for potential OSA. It was found that a composite HKCSQ score from the 3 questions (total score, 0-12) of $7 had a sensitivity of 75.4% and specificity of 80.5% in predicting for the presence of OSA.20 All children belonging to the high risk for OSA group and a randomly chosen sample of subjects at low risk for OSA were invited to undergo an overnight polysomnography (PSG) study. Second Phase: Polysomnography A single attended overnight PSG study was performed in a dedicated sleep laboratory with a CNS 1000P polygraph (CNS, Chanhassen, Minnesota).21 All computerized sleep data were manually edited by experienced PSG technologists and clinicians in accordance with standardized criteria.22 Hypopnea was defined as a $50% reduction in the amplitude of the airflow signal. It was counted only if longer than 2 baseline breaths and associated with oxygen desaturation of at least 4% and/or arousals. The obstructive apnea hypopnea index (OAHI) was defined as the total number of obstructive apneic and hypopneic episodes per hour of sleep. The arousal index was defined the total number of arousals per hour of sleep. Definitions of NE and OSA Children aged 6 years and older who were reported to have 1 or more wet nights per month over the past 12 months were defined as having NE. Those who were reported as never having wet nights over the past 12 months served as controls. The children who underwent PSG were separated into OSA cases and non-OSA controls, using an OAHI $1 as the cutoff. Statistical Analysis Descriptive data are presented as percentages for discrete variables and as means (SD) or medians (IQR) for continuous variables. The c2 test and Mann-Whitney U test were used to compare variables between children with and without NE. Exploratory factor analysis was used to identify the underlying patterns among the various sleep-related symptoms. Correlation coefficients were analyzed by principal component analysis and subsequent rotation according to the standard varimax criterion. In this type of analysis, the
correlation between parameters was attributed to their common dependence on independent entities, called ‘‘factors.’’ The coefficients that link parameters to factors are called ‘‘factor loadings;’’ the number of factors was chosen to be as small as possible but large enough to account for most of the variation within the data. It was decided a priori that the number of factors in the varimax rotation would be based on the number of eigenvalues >1.0 in the principal component analysis. Logistic regression analysis was used to determine the association between NE and risk factors that were found to be significant on univariate analysis. For the first logistic regression model, a total of 5403 children were included. NE was the dependent variable, and age, male sex, body mass index (BMI) z score, and sleep-related symptoms were the independent variables. The second logistic model included only subjects who had undergone overnight PSG. A P value < .05 was considered significant. All analyses were performed using SPSS version 15.0 (SPSS Inc, Chicago, Illinois).
Results A total of 6147 completed questionnaires for 3032 girls and 3115 boys aged 6 to 11 years were analyzed (Table I). The overall prevalence of NE was 285/6147 (4.6%), with boys 3 times more likely than girls to be affected (209/3115 [6.7%] vs 76/3032 [2.5%]). The prevalence of NE declined gradually with increasing age, from 9.0% at age 6 years to 1.9% at age 11 years. In each age group, the prevalence of NE was significantly greater in boys than in girls. Based on the completed questionnaires, 568 children (9.2%; 396 boys and 172 girls) were identified to be at high risk for OSA, of whom 397 (70%; 279 boys and 118 girls) agreed to take part in the second phase of our study. Two hundred children (103 boys and 97 girls) identified to be at low risk for OSA also were invited to undergo overnight Table I. Characteristics of the study subjects without NE and with NE Age, years, mean SD Height, cm, mean SD Weight, kg, mean SD BMI, kg m 2, mean SD BMI z score, mean SD Boys Paternal education level Primary level or below Up to secondary level Tertiary level or above Maternal education level Primary level or below Up to secondary level Tertiary level or above Respiratory diseases Allergic rhinitis Nasosinusitis Asthma Tonsillitis Pharyngitis or laryngitis
Without NE (n = 5862)
With NE (n = 285)
9.2 1.7 133.7 12.8 30.8 9.1 16.9 3.1 0.22 1.14 49.6%
8.4 1.6 128.9 12.7 27.9 8.0 16.4 2.9 0.10 1.20 73.3%
18.2% 66.0% 15.7%
12.0% 65.6% 22.4%
19.1% 71.0% 9.9%
14.3% 69.2% 16.5%
41.9% 1.9% 4.4% 9.8% 48.8%
47.4% 2.1% 8.1% 11.9% 58.6%
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PSG. Among the 597 children who underwent PSG, the prevalence of NE was 9.2% (55/597). More boys than girls were affected (11.5% [44/382] vs 5.1% [11/215]; P < .01). Overall, 257 children were found to have OSA. The prevalence of NE did not differ in the children with OSA and those without OSA (9.7% [25/258] vs 8.8% [30/339]; P = .725); however, there was a significant difference in the prevalence of NE in girls with increasing OSA severity (2.1% for those with OAHI <1 vs 8.8% for OAHI 1-5 vs 20.0% for OAHI >5; P < .01). This increased prevalence of NE with increasing severity of OSA was not seen in boys (13.8% for those with OAHI <1 vs 8.8% for OAHI 1-5 vs 10.2% for OAHI >5; P = .278) (Table II). OAHI was significantly higher in girls with NE than in controls (median [range], 1.8 [0.1-5.9] vs 0.4 [0-1.3]; P = .026). Arousal index, sleep efficiency, and proportion of each sleep stage (S1, S2, and S3+4) were similar in children with and without NE (Table III; available at www.jpeds.com). Seventeen items in the questionnaire were categorized into 5 factors—morning or daytime symptoms, nocturnal symptoms, anxiety or insomniac symptoms, symptoms of parasomnias, and respiratory symptoms—by factor analysis (Table IV). The total variance explained by this 5-factor model was 47.5%, and the factor scores were calculated using the regression method. In the first logistic regression model with 5403 subjects, several risk factors were found to be significantly associated with NE, including age (OR, 0.761; P < .0001); male sex (OR, 2.568; P < .0001); morning and daytime symptoms, including feeling unrefreshed in the morning, daytime fatigue, and difficulty getting up in the morning (OR, 2.644; P < .0001); nocturnal symptoms, including restless sleep, prone position, bruxism, and night sweats (OR, 0.648; P < .0001); respiratory symptoms, including breathing difficulty, gasping for breath or cessation of breathing during sleep, and mouth breathing (OR, 1.460; P < .0001); symptoms of parasomnias (OR, 1.188; P = .008); and habitual snoring (OR, 0.550; P = .030). In the second logistic model that included only subjects who had undergone PSG, female sex (OR, 0.092; P = .001), morning or daytime symptoms (OR, 1.914; P < .0001), nocturnal symptoms (OR, 0.715; P = .037), respiratory symptoms (OR, 1.331; P = .032), symptoms of parasomnias (OR, 1.305; P = .016) with OAHI in girls (OR, 1.530; P =
Vol. 159, No. 2 .004), and slow-wave sleep (OR, 1.021; P = .039) were associated with NE (Table V).
Discussion This systematic study of the association of NE with OSA and other sleep-related symptoms in a community-based population found a prevalence of NE of 4.6% in our cohort of 6- to 11-year-old children, with no difference in rate between children with OSA and those without OSA. A novel finding was the differential sex response to OSA in the prevalence of NE, with a higher prevalence of NE in girls with increasing OSA severity. NE was defined using different cutoff values in previous studies, giving rise to a wide range of reported prevalence rates.3-10 The present study’s prevalence of 4.6% is comparable with that from studies that used the same NE definition and involved ethnic Chinese children of similar age range. Two studies from the Middle East reported an NE prevalence of >10%,9,10 and a study involving Malaysians6 reported a rate twice that of ours. Locally, 2 groups of researchers have examined the prevalence of NE using different cutoff values, and accordingly found different prevalence rates. Ng et al23 reported a prevalence of 5.1% in 3047 children aged 6 to 12 years using $1 episodes/week to define NE. Yeung et al24 reported a prevalence of 3.1% using a definition of 1 wet night every 3 months. A consistent finding in all studies is that younger boys have the highest rate of NE, and that prevalence decreases with increasing age. Various causative mechanisms for NE have been proposed, including delayed maturation of the nervous system controlling bladder function, delayed development of bladder function and size, and decreased nighttime secretion of antidiuretic hormone.25,26 Our study also found longer slow-wave sleep in children with NE. This finding is compatible with previous studies suggesting that children with NE tend to sleep more deeply and are more difficult to awaken.27,28 The relationship between NE and OSA is controversial, and studies reporting both positive and negative associations have been published.12-17 These discrepant findings might be related to different study designs and varying sample sizes. In the present study, a large sample of children underwent PSG, the current gold standard for diagnosing OSA, allowing us to accurately classify the subjects into an OSA group and
Table II. Prevalence of NE in children with OSA and without OSA using different cutoffs (n = 597) Girls (n = 215)
NE frequency Never <1/month 12/month 1-2/week >2/week >1/month
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Boys (n = 382)
Overall
OAHI <1
OAHI 1-5
OAHI >5
OAHI <1
OAHI 1-5
OAHI >5
OAHI <1
OAHI ‡1
OAHI 1-5
OAHI >5
(n = 143)
(n = 57)
(n = 15)
(n = 196)
(n = 136)
(n = 49)
(n = 339)
(n = 257)
(n = 193)
(n = 64)
111 (77.6%) 29 (20.3%) 1 (0.7%) 1 (0.7%) 1 (0.7%) 3 (2.1%)
49 (86.0%) 3 (5.3%) 5 (8.8%) 0 (0.0%) 0 (0.0%) 5 (8.8%)
8 (53.3%) 4 (26.7%) 2 (13.3%) 0 (0.0%) 1 (6.7%) 3 (20.0%)
129 (65.8%) 40 (20.4%) 14 (7.1%) 3 (1.5%) 10 (5.1%) 27 (13.8%)
94 (69.1%) 30 (22.1%) 8 (5.8%) 2 (1.5%) 2 (1.5%) 12 (8.8%)
34 (69.4%) 10 (20.4%) 4 (8.2%) 0 (0.0%) 1 (2.0%) 5 (10.2%)
240 (70.8%) 69 (20.4%) 15 (4.4%) 4 (1.2%) 11 (3.2%) 30 (8.8%)
185 (75.5%) 47 (17.0%) 19 (4.2%) 2 (1.1%) 4 (2.2%) 25 (9.7%)
143 (74.1%) 33 (17.1%) 13 (6.8%) 2 (1.0%) 2 (1.0%) 17 (8.8%)
42 (65.6%) 14 (21.9%) 6 (9.4%) 0 (0.0%) 2 (3.1%) 8 (12.5%)
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Table IV. Summary of items and factor loadings for the 5 identified factors Item
Factor loading
Factor 1: Morning/daytime symptoms Feeling unrefreshed in the morning Daytime fatigue Difficulty getting up in the morning Factor 2: Nocturnal symptoms Restless sleep Prone position Bruxism Night sweats Factor 3: Anxiety/insomnia symptoms Rocking or head banging Feeling anxious or afraid when falling asleep Difficulty falling asleep Factor 4: Parasomniac symptoms Sleep walking Sleep talking Nightmares Sudden awakening during sleep Factor 5: Respiratory symptoms Breathing difficulty Gasping for breath or inability to breathe during sleep Mouth breathing
0.770 0.742 0.631 0.666 0.593 0.555 0.489 0.680 0.510 0.438 0.656 0.524 0.512 0.464 0.635 0.625 0.578
a non-OSA group. We found no difference in the prevalence of NE between subjects with OSA and those without OSA. In studies that demonstrated improvements in NE following adenotonsillectomy or other interventions, the subjects—unlike ours—were recruited from hospital cases.14,15 This might explain the negative association found in the present study. We also found a significant sex difference in the prevalence of NE in relation to OSA severity, with girls with more severe OSA more likely to have NE. Some studies have found that compared with males, females are more protected against adverse renal consequences secondary to hypoxia and ischemiareperfusion injury.29-31 Whether this or other hormonal effects might play a role in the differential sex response to OSA in the prevalence of NE merits further evaluation.
We used factor analysis to correlate different sleep-related symptoms into common factors, and found that NE was positively associated with morning or daytime symptoms, nocturnal and respiratory symptoms, and symptoms of parasomnias. This finding suggests that sleep-related symptoms should be investigated in children with NE. In the present study, we failed to establish an association between habitual snoring and NE in logistic regression analysis. This finding is in contrast to previous studies reporting a positive association between habitual snoring and NE.32,33 Differening definitions for NE might have contributed to this discrepancy. The present study has some limitations. First, the response rate to our questionnaire survey was only modest, at 70%. This could have introduced a degree of selection bias whereby only parents whose child had sleep symptoms or problems were more likely to return the questionnaire. Another potential source of selection bias is the high number of subjects with NE who underwent PSG in second phase despite our strict inclusion criteria. Comparing the demographic and socioeconomic data of respondents and nonrespondents reveals no significant differences between the 2 groups. We believe that overall, our study cohort represents the sample population. Second, the survey questionnaire was completed by parents who often did not sleep in the same room as their child and thus were not aware of the child’s actual sleep behavior. This is an intrinsic problem known to be associated with the use of questionnaire surveys. There is also a lack of real-time association of NE and PSG, and so the sleep variables may more closely reflect the trait rather than state phenomenon. However, a study of preschool children showed a significant and independent association between parentally reported and objectively measured sleep symptoms.34 Furthermore, the reliability of our screening questionnaire has been demonstrated previously.20 Finally, the lack of correlation between NE and severity of OSA might be related to the fact that boys are more likely to have other
Table V. Associations between independent factors and NE Model 2 (n = 480)†
Model 1 (n = 5403)*
Age, years Male sex Female sex Breast-feeding BMI z score Anxiety/insomnia symptoms Morning/daytime symptoms Nocturnal symptoms Respiratory symptoms Symptoms of parasomnias Habitual snoring OAHI, /h OAHI*female sex REM sleep Stage 1 sleep Stage 2 sleep Slow-wave sleep
OR
95% CI
P
OR
95% CI
P
0.761 2.568
0.689-0.841 1.826-3.610
<.0001 <.0001
0.807
0.626-1.042
.100
1.122 0.933 1.154 2.644 0.648 1.460 1.188 0.550
0.811-1.553 0.817-1.066 0.991-1.343 2.266-3.084 0.548-0.766 1.300-1.638 1.047-1.347 0.320-0.944
.487 .311 .065 <.0001 <.0001 <.0001 .008 .030
0.092 1.199 0.962 1.199 1.914 0.715 1.331 1.305 1.959 0.998 1.530 0.992 1.018 1.001 1.021
0.021-0.400 0.536-2.685 0.677-1.365 0.858-1.676 1.339-2.734 0.521-0.981 1.026-1.726 1.050-1.621 0.805-4.767 0.924-1.079 1.148-2.039 0.976-1.009 0.989-1.048 0.990-1.012 1.001-1.042
.001 .659 .826 .287 <.0001 .037 .032 .016 .138 .961 .004 .377 .234 .833 .039
*Model 1 included all subjects with a completed questionnaire. †Model 2 included only subjects with a completed questionnaire and PSG results.
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factors, such as a familial predisposition to NE, which could dilute the relationship between NE and OSA. Strengths of this study include the large number of subjects and the use of a validated and reliable locally applicable questionnaire. Furthermore, all subjects who agreed to take part in the second phase of this study underwent PSG to ascertain their OSA status, allowing an accurate comparison of NE prevalence in subjects with OSA and those without OSA. In summary, we found a NE prevalence rate similar to that reported in previous studies performed in ethnic Chinese. We did not find a higher NE prevalence in children with OSA, but did note a differential sex response in NE prevalence with increasing OSA severity. Children with NE tended to spend more time in deep sleep and were more likely to have other sleep-related symptoms. n We thank the staff of Shatin Hospital’s Sleep Assessment Unit for their logistical support, and all participating schools, children, and parents for their cooperation. Submitted for publication Jun 5, 2010; last revision received Nov 22, 2010; accepted Jan 19, 2011. Reprint requests: Albert M. Li, MCRP, MD, Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. E-mail: [email protected]
References 1. Butler RJ. Annotation. Night wetting in children: psychological aspects. J Child Psychol Psychiatry 1998;39:453-63. 2. Thiedke CC. Nocturnal enuresis. Am Fam Physician 2003;67:1499-506. 3. Cher TW, Lin GJ, Hsu KH. Prevalence of nocturnal enuresis and associated familial factors in primary school children in Taiwan. J Urol 2002; 168:1142-6. 4. Chiozza ML, Bernardinelli L, Caione P, Del Gado R, Ferrara P, Giorgi PL, et al. An Italian epidemiological multicentre study of nocturnal enuresis. Br J Urol 1998;81(Suppl 3):S86-9. 5. Kajiwara M, Inoue K, Mutaguchi K, Usui T. The prevalence of overactive bladder and nocturnal enuresis in Japanese early adolescents: a questionnaire survey. Hinyokika Kiyo 2006;52:107-11. 6. Kanaheswari Y. Epidemiology of childhood nocturnal enuresis in Malaysia. J Paediatr Child Health 2003;39:118-23. 7. Spee-van der Wekke J, Hirasing RA, Meulmeester JF, Radder JJ. Childhood nocturnal enuresis in the Netherlands. Urology 1998;51:1022-6. 8. Wen JG, Wang QW, Chen Y, Wen JJ, Liu K. An epidemiological study of primary nocturnal enuresis in Chinese children and adolescents. Eur Urol 2006;49:1107-13. 9. Ozkan KU, Garipardic M, Toktamis A, Karabiber H, Sahinkanat T. Enuresis prevalence and accompanying factors in schoolchildren: a questionnaire study from southeast Anatolia. Urol Int 2004;73:149-55. 10. G€ ur E, Turhan P, Can G, Akkus S, Sever L, G€ uzel€ oz S, et al. Enuresis: prevalence, risk factors and urinary pathology among school children in Istanbul, Turkey. Pediatr Int 2004;46:58-63. 11. Brooks LJ. Enuresis and sleep apnea. Pediatrics 2005;116:799-800. 12. Brooks LJ, Topol HI. Enuresis in children with sleep apnea. J Pediatr 2003;142:515-8. 13. Barone JG, Hanson C, DaJusta DG, Gioia K, England SJ, Schneider D. Nocturnal enuresis and overweight are associated with obstructive sleep apnea. Pediatrics 2009;124:e53-9. 14. Basha S, Bialowas C, Ende K, Szeremeta W. Effectiveness of adenotonsillectomy in the resolution of nocturnal enuresis secondary to obstructive sleep apnea. Laryngoscope 2005;115:1101-3.
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Vol. 159, No. 2 15. Weissbach A, Leiberman A, Tarasiuk A, Goldbart A, Tal A. Adenotonsilectomy improves enuresis in children with obstructive sleep apnea syndrome. Int J Pediatr Otorhinolaryngol 2006;70:1351-6. 16. Rittig S, Knudsen UB, Nørgaard JP, Gregersen H, Pedersen EB, Djurhuus JC. Diurnal variation of plasma atrial natriuretic peptide in normals and patients with enuresis nocturna. Scand J Clin Lab Invest 1991;51:209-17. 17. Sans Capdevila O, Crabtree VM, Kheirandish-Gozal L, Gozal D. Increased morning brain natriuretic peptide levels in children with nocturnal enuresis and sleep-disordered breathing: a community-based study. Pediatrics 2008;121:e1208-14. 18. Chan JY, Li AM, Au CT, Lo AF, Ng SK, Abdullah VJ, et al. Cardiac remodelling and dysfunction in children with obstructive sleep apnoea: a community-based study. Thorax 2009;64:233-9. 19. Li AM, Au CT, Sung RY, Ho C, Ng PC, Fok TF, et al. Ambulatory blood pressure in children with obstructive sleep apnoea: a community-based study. Thorax 2008;63:803-9. 20. Li AM, Cheung A, Chan D, Wong E, Ho C, Lau J, et al. Validation of a questionnaire instrument for prediction of obstructive sleep apnea in Hong Kong Chinese children. Pediatr Pulmonol 2006;41: 1153-60. 21. Li AM, Wing YK, Cheung A, Chan D, Ho C, Hui S, et al. Is a 2-night polysomnographic study necessary in childhood sleep-related disordered breathing? Chest 2004;126:1467-72. 22. American Thoracic Society. Cardiorespiratory sleep studies in children: stablishment of normative data and polysomnographic predictors of morbidity. Am J Respir Crit Care Med 1999;160:1381-7. 23. Ng DK, Kwok KL, Cheung JM, Leung SY, Chow PY, Wong WH, et al. Prevalence of sleep problems in Hong Kong primary school children: a community-based telephone survey. Chest 2005;128:1315-23. 24. Yeung CK, Sreedhar B, Sihoe JD, Sit FK, Lau J. Differences in characteristics of nocturnal enuresis between children and adolescents: a critical appraisal from a large epidemiological study. BJU Int 2006;97:1069-73. 25. Bakwin H. The genetics of enuresis. In: Kalvin J, MacKeith RC, Meadow SR, eds. Bladder Control and Enuresis. Lavenham, England: Lavenham Press; 1973. p. 73-88. 26. Mammen AA, Ferrer FA. Nocturnal enuresis: medical management. Urol Clin North Am 2004;31:491-8. 27. Wolfish NM, Pivik RT, Busby KA. Elevated sleep arousal thresholds in enuretic boys: clinical implications. Acta Paediatr 1997; 86:381-4. 28. Hunsballe JM. Increased delta component in computerized sleep electroencephalographic analysis suggests abnormally deep sleep in primary monosymptomatic nocturnal enuresis. Scand J Urol Nephrol 2000;34: 294-302. 29. Sharma PK, Thakur MK. Estrogen receptor alpha expression in mice kidney shows sex differences during aging. Biogerontology 2004;5:37581. 30. Fekete A, Vannay A, Ver A, Vasarhelyi B, M€ uller V, Ouyang N, et al. Sex differences in the alterations of Na+, K+-ATPase following ischaemia-reperfusion injury in the rat kidney. J Physiol 2004;555: 471-80. 31. Saez F, Reverte V, Salazar F, Castells MT, Llinas MT, Salazar FJ. Hypertension and sex differences in the age-related renal changes when cyclooxygenase-2 activity is reduced during nephrogenesis. Hypertension 2009;53:331-7. 32. Alexopoulos EI, Kostadima E, Pagonari I, Zintzaras E, Gourgoulianis K, Kaditis AG. Association between primary nocturnal enuresis and habitual snoring in children. Urology 2006;68:406-9. 33. Ersu R, Arman AR, Save D, Karadag B, Karakoc F, Berkem M, et al. Prevalence of snoring and symptoms of sleep-disordered breathing in primary school children in Istanbul. Chest 2004;126:19-24. 34. Castronovo V, Zucconi M, Nosetti L, Marazzini C, Hensley M, Veglia F, et al. Prevalence of habitual snoring and sleep-disordered breathing in preschool-aged children in an Italian community. J Pediatr 2003;142: 377-82.
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Table III. Comparison of PSG parameters between children with NE and without NE according to sex Girls (n = 179)
OAHI, /h Arousal index, /h Sleep efficiency, % Sleep stage REM, min Sleep stage 1, min Sleep stage 2, min Slow wave sleep, min Total sleep time, min
Boys (n = 301)
Controls
NE
P*
Controls
NE
P*
0.4 (0-1.3) 6.1 (5.0-8.0) 84.2 (76.8-90.0) 103 (83-119) 30 (22-38) 240 (208-266) 109 (91-124) 483 (444-515)
1.8 (0.1-5.9) 7.3 (5.0-12.9) 83.1 (69.8-91.0) 96 (68-128) 39 (22-45) 222 (163-249) 110 (88-132) 474 (399-524)
.026 .242 .725 .657 .132 .112 .610 .746
0.4 (0.1-0.9) 7.0 (5.4-9.1) 83.0 (74.8-89.6) 103 (81-121) 33 (25-43) 225 (195-254) 110 (94-124) 475 (429-514)
0.3 (0-0.9) 6.3 (4.6-8.5) 82.5 (78.1-87.2) 91 (82-108) 28 (22-41) 229 (198-240) 118 (98-131) 471 (448-502)
.107 .118 .581 .101 .153 .800 .079 .868
Values are median (range). *Without NE versus with NE.
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