- Email: [email protected]
Risk Factors for Nocturnal Enuresis in School-Age Children
Risk Factors for Nocturnal Enuresis in School-Age Children Premala Sureshkumar,* Mike Jones, Patrina H. Y. Caldwell and Jonathan C. Craig From the School of Public Health, University of Sydney (PS, PHYC, JCC), Department of Psychology, Macquarie University (MJ) and Center for Kidney Research, NHMRC Center for Clinical Research Excellence, Children’s Hospital at Westmead, Sydney, Australia
Purpose: Although nocturnal enuresis is common in children, its etiology is multifactorial and not fully understood. We evaluated potential risk factors for presence and severity of nocturnal enuresis. Materials and Methods: A validated, reproducible questionnaire was distributed to 8,230 school children in Sydney, Australia. Nocturnal enuresis was defined as any wetting in the previous month and categorized as mild (1 to 6 nights), moderate (7 or more nights but less than nightly) or severe (nightly). Results: Parents of 2,856 children (mean ⫾ SD age 7.3 ⫾ 1.3 years) completed the questionnaire (response rate 35%). Overall prevalence of nocturnal enuresis was 18.2%, with 12.3% of patients having mild, 2.5% moderate and 3.6% severe enuresis. Multivariate analysis showed that daytime incontinence (OR 4.8, 95% CI 2.9 to 7.9), encopresis (OR 2.7, 95% CI 1.6 to 4.4), bladder dysfunction (OR 3.6, 95% CI 2.4 to 5.3) and male gender (OR 2.0, 95% CI 1.3 to 3.1) were associated with severe nocturnal enuresis after adjustment for age. Emotional stressors (OR 2.3, 95% CI 1.2 to 4.2) and social concerns (OR 2.4, 95% CI 1.2 to 4.5) were associated with moderate nocturnal enuresis only. Conclusions: Encopresis and daytime incontinence are significant modifiable risk factors for nocturnal enuresis. Expressed as population attributable risk, 23% of nocturnal enuresis is associated with encopresis and daytime incontinence. Psychosocial factors appear to contribute to moderate but not severe nocturnal enuresis.
Abbreviations and Acronyms ADHD ⫽ attention deficit hyperactivity disorder MNE ⫽ monosymptomatic nocturnal enuresis NMNE ⫽ nonmonosymptomatic nocturnal enuresis UTI ⫽ urinary tract infection Submitted for publication April 9, 2009. Supported by grants from Ramaciotti Foundation for Children (RN005/01) and Financial Markets Foundation for Children (143-2004). Study received approval of ethics committee of Children’s Hospital at Westmead and New South Wales Department of School Education. * Correspondence: Center for Kidney Research, Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia (telephone: 61-2-9845-1474; FAX: 61-2-9845-1491; e-mail: [email protected]).
Key Words: child, nocturnal enuresis, questionnaires, risk factors NOCTURNAL enuresis is a common pediatric problem. The prevalence varies in epidemiological studies from 3.8% to 25% according to patient age and the definition used.1– 8 At age 5 years 15% to 25% of children experience nocturnal enuresis.8 Prevalence of nocturnal enuresis decreases with increasing age, with about 15% of children spontaneously achieving nighttime bladder control annually.9 In adults the prevalence of nocturnal enuresis is estimated at 1% to 2%. The etiology of nocturnal enuresis is multifactorial and hypothesized to be related to problems with arousal, small
bladder capacity and large overnight urine production.10 ADHD, constipation, encopresis, developmental problems, male gender and young age are also reportedly associated with nocturnal enuresis.11–15 However, previous studies have not evaluated whether these associations of risk factors vary with severity. Nocturnal enuresis is a heterogeneous disorder. The spectrum of severity is wide but important from a management perspective, with older children (older than 7 years) who wet frequently requiring treatment. We sought to determine independent risk factors for nocturnal enuresis for each
0022-5347/09/1826-2893/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 182, 2893-2899, December 2009 Printed in U.S.A. DOI:10.1016/j.juro.2009.08.060
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stratum of severity, with particular focus on the most severe cases.
MATERIALS AND METHODS Participant Recruitment Recruitment occurred between May 2003 and December 2004. A random sample of children from the first 4 years of elementary schools in Sydney was chosen. Further details of questionnaire development, validation and recruitment have been described previously.16 A validated parent questionnaire with high reproducibility was used to collect information on age, gender, birth weight, gestation, medication taken during pregnancy, developmental milestones, developmental concerns, circumcision, ADHD, and urinary and bowel history.
Measurement of Risk Factors and Outcomes Parents were asked to estimate the frequency of nocturnal enuresis in the month before the survey. Severity was defined according to frequency, with 1 to 6 nights defined as mild, 7 or more but less than nightly moderate and nightly severe. This series was part of a large cohort study that looked at other urinary tract problems such as urinary tract infections and daytime urinary incontinence. We collected potential risk factors for these outcomes as well as for nocturnal enuresis. We believed that the causal pathways for enuresis were not well established, with causality not 100% explained. Male gender, young age, constipation, encopresis, daytime incontinence, developmental problems and ADHD are reportedly associated with nocturnal enuresis.11–15 Birth weight, prenatal history and kidney problems are also thought to be associated with nocturnal enuresis. By limiting our study to established risk factors we would have limited the capacity to identify novel risk factors. For this reason we have included all potential risk factors in our tables. We assessed several potential risk factors for each category of severity (see Appendix). Perinatal risk factors measured included birth weight, gestation, newborn hospitalization and any medication that the mother took during pregnancy. Developmental concerns regarding fine motor skills, speech, learning skills at school and social behavior were also elicited. Medical history included ADHD, emotional stressors, encopresis and kidney problems. Constipation was measured using the Rome II scale.16 Urinary history included daytime urinary incontinence and symptoms of bladder dysfunction (urinary frequency, urgency, holding postures and post-void incontinence).
Data Analysis Data were analyzed using SPSS®, version 13.0 and SAS®, version 9.1.3 software. Continuous variables such as developmental milestones were categorized according to the Denver II Training Manual.17 Birth weight was categorized into less than 2.5 kg, 2.5 to 4 kg and greater than 4 kg, which are commonly used pediatric thresholds. Age was analyzed as continuous in the multivariate model but is presented as categorical for ease of interpretation. Prevalence values for each risk factor were reported with 95% confidence intervals. Polychotomous logistic re-
gression analysis was used to identify risk factors for each category of nocturnal enuresis. In this approach odds ratios for each risk factor applied to each severity category were estimated simultaneously. Absence of nocturnal enuresis was used as a reference category. The relationship between the risk factors and nocturnal enuresis of all severity levels was expressed in terms of population attributable risk and calculated with the formula, population attributable risk ⫽ [F(OR-1)/1⫹(F(OR-1))]⫻100, where F is prevalence of exposure in the population of interest and OR is odds ratio.18 Potential interaction effects between risk factors were also analyzed. Due to the excessive number of potential interactions, only a limited subset, thought to be of a priori interest, was considered, which included gender, encopresis, constipation, emotional stressors, daytime incontinence and symptoms of bladder dysfunction.
Ethical Approval The study was approved by the ethics committee of the Children’s Hospital at Westmead, Sydney, Australia and the New South Wales Department of School Education. Written consent was obtained from parents of the participating children.
RESULTS Characteristics of Respondents Of 83 schools invited 60 agreed to participate in the study (72% response rate). A total of 2,856 parents of primary school children (47.4% girls) with a mean ⫾ SD age of 7.3 ⫾ 1.3 years completed the questionnaire (overall response rate 35%). Daytime incontinence was reported in 17% of children, constipation in 5.7% and encopresis in 10%. Parents reported UTI in 12.7% of children, of whom 3.6% had microbiologically confirmed UTI. Further details of patient demographic and baseline characteristics have been published previously.19 Frequency of Nocturnal Enuresis Overall 18.4% (95% CI 16.8% to 19.6%) of children had at least 1 episode of nocturnal enuresis in the last month, with 12.3% having mild, 2.5% moderate and 3.6% severe frequency. Table 1 demonstrates the frequency of different severities of nocturnal enuresis and nonenuresis in all children. We stratified the data according to severity of enuresis for children with an identified risk factor. For example, of patients with daytime incontinence 10.0% had severe, 6.0% moderate, 23.3% mild and 60.7% no enuresis. The risk of severe nocturnal enuresis was increased 3-fold in children with daytime urinary incontinence. Daytime urinary incontinence with or without nocturnal enuresis was reported in 16.9% of children, and 6.6% (95% CI 5.7 to 7.6) of children had nocturnal enuresis and daytime incontinence. Nocturnal enuresis decreased with age. Of children 4.8 to 6.2 years old 27.8% (95% CI 24.6 to 31.1) experienced nocturnal enuresis compared to
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Table 1. Prevalence of nocturnal enuresis stratified by severity
Overall Gender: M F Birth wt (kg): Less than 2.5 2.5–4.0 More than 4.0 Age (yrs): Younger than 6 6–6.9 7–7.9 8–8.9 9–9.9 10–12.8 Newborn hospitalization Premature birth Medication during pregnancy Age at sitting (mos): Younger than 7 Older than 7 Age at walking (mos): Younger than 15 Older than 15 Developmental concerns: Fine motor Speech Learning skills at school Social Constipation Encopresis ADHD Emotional stressor Kidney problems Daytime incontinence* UTI: Definite Possible Bladder dysfunction:† Frequency Urgency Holding postures Post-void incontinence
OR Severe (95% CI)
OR Moderate (95% CI)
OR Mild (95% CI)
OR Absent (95% CI)
3.6 (2.9–4.3)
2.5 (1.9–3.1)
12.3 (11.1–13.5)
81.6 (80.0–83.2)
4.2 (3.3–5.4) 3.0 (2.1–4.0)
2.9 (2.1–3.9) 2.0 (1.4–3.0)
14.6 (12.8–16.4) 9.8 (8.3–11.5)
78.3 (76.2–80.4) 85.2 (83.3–87.1)
4.4 (2.0–8.6) 3.9 (3.1–4.8) 1.7 (0.6–4.4)
2.2 (0.6–5.6) 2.5 (1.9–3.2) 3.1 (1.1–5.4)
14.2 (9.7–20.6) 12.1 (10.7–13.4) 13.9 (10.2–18.7)
79.2 (73.3–85.1) 81.5 (80.0–83.2) 81.3 (76.7–85.7)
6.2 (4.9–9.6) 4.5 (3.1–6.3) 2.5 (1.4–3.9) 1.7 (0.8–3.1) 2.1 (0.8–4.5) 5.3 (0.1–26.0) 5.3 (3.1–7.5) 3.2 (1.0–5.4) 4.7 (2.5–6.9)
2.4 3.7 2.0 1.9 2.1 Not 3.5 3.6 2.5
(1.4–4.3) (2.4–5.4) (1.1–3.4) (0.9–3.3) (0.8–4.5) estimable (1.7–5.3) (1.3–5.9) (0.9–4.1)
20.6 (17.1–24.1) 13.0 (10.5–15.5) 11.3 (8.9–13.7) 8.3 (6.2–10.8) 7.0 (4.4–10.7) 5.3 (0.1–26.0) 12.0 (8.8–15.2) 13.9 (9.6–18.2) 12.2 (8.8–15.6)
70.7 (67.0–74.4) 78.8 (75.7–82.0) 84.2 (81.5–86.9) 88.1 (85.6–90.8) 88.8 (85.1–92.5) 89.5 (75.7–103.3) 79.2 (75.2–83.2) 79.3 (74.3–84.3) 80.6 (76.5–84.5)
3.3 (2.5–4.1) 5.0 (2.9–7.1)
2.5 (1.8–3.2) 1.4 (0.3–2.5)
12.5 (11.1–13.9) 11.8 (8.7–14.9)
81.7 (80.1–83.3) 81.6 (78.0–85.4)
3.4 (2.8–4.2) 7.2 (3.5–12.8)
2.4 (1.8–3.0) 5.0 (2.1–10.1)
12.2 (10.9–13.4) 15.1 (9.6–22.2)
82.0 (80.5–83.5) 72.7 (65.3–80.1)
5.2 (2.3–10.0) 4.3 (2.4–7.0) 2.8 (1.2–5.5) 5.8 (3.2–9.5) 3.1 (1.0–7.1) 7.6 (4.8–11.2) 7.0 (2.6–14.6) 4.9 (2.5–8.3) 3.3 (0.4–11.5) 10.0 (7.4–13.0)
3.3 (1.1–7.5) 2.6 (1.2–4.9) 3.9 (2.0–6.9) 6.6 (3.8–10.5) 3.7 (1.4–7.9) 5.5 (3.2–8.8) 3.5 (0.7–9.9) 4.9 (2.5–8.3) 1.7 (0.04–8.9) 6.0 (4.1–8.5)
20.0 (14.2–27.5) 15.0 (11.2–18.7) 18.4 (13.9–23.0) 19.0 (14.1–24.0) 9.2 (5.3–14.8) 20.6 (16.0–25.3) 17.4 (10.1–27.1) 18.6 (13.8–23.5) 15.0 (7.1–26.6) 23.3 (19.5–27.1)
71.5 78.1 74.9 68.6 84.0 66.3 72.1 71.7 80.0 60.7
6.8 (2.8–13.5) 4.1 (1.7–8.3)
4.9 (1.6–11.0) 1.8 (0.4–5.1)
14.6 (8.4–22.9) 7.1 (3.7–12.0)
73.8 (65.3–82.3) 87.1 (82.1–92.1)
4.4 3.2 4.0 5.8
18.3 (15.8–20.9) 15.0 (13.4–16.6) 16.3 (14.2–18.5) 24.9 (19.6–30.2)
69.3 77.6 74.1 57.1
7.3 (5.7–9.3) 4.2 (3.3–5.2) 5.6 (4.4–7.2) 12.1 (8.1–16.0)
(3.2–5.9) (2.5–4.1) (2.9–5.3) (3.3–9.4)
(64.0–78.4) (73.8–82.5) (69.7–79.9) (62.8–74.5) (78.4–89.7) (60.9–71.7) (62.6–81.6) (66.1–77.3) (69.9–90.1) (56.3–65.1)
(66.9–72.9) (75.7–79.5) (71.6–76.7) (51.2–63.3)
Frequency (OR, 95% CI) in patients with each risk factor present. * Any reported daytime incontinence in previous 6 months. † Reference category, “None of the time.”
10.9% (95% CI 8.7 to 13.2) of those 8.4 to 12.8 years old. Risk Factors for Nocturnal Enuresis Univariate analysis revealed that daytime incontinence, encopresis, social concerns, delayed age at walking (after 15 months) and symptoms of bladder dysfunction were significantly predictive of severe nocturnal enuresis (table 2). We did not find a significant association between constipation and severe nocturnal enuresis (OR 0.7, 95% CI 0.3 to 1.9). Age adjusted independent risk factors for severe nocturnal enuresis were male gender, encopresis, daytime incontinence and symptoms of bladder dysfunction
(table 3). Males exhibited a doubling of risk and children with encopresis a tripling of risk for severe nocturnal enuresis. Daytime incontinence and urinary frequency were also significantly associated (OR 4.8, 95% CI 2.9 to 7.9 and OR 3.6, 95% CI 2.4 to 5.3, respectively). Severe nocturnal enuresis in this population was associated with daytime incontinence in 7.1% of patients, urinary frequency in 5.8%, encopresis in 1.5% and male gender in 1%. There was a statistically significant interaction between daytime incontinence and urgency in risk of nocturnal enuresis (p ⬍0.0001). There was a 2-fold increased risk of severe nocturnal enuresis in chil-
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Table 2. Risk factors for nocturnal enuresis stratified by severity (unadjusted odds ratios)
Male gender Birth wt (kg): Less than 2.5 2.5–4.0 More than 4.0 Newborn hospitalization Premature birth Medication during pregnancy Age at sitting (mos): Younger than 7 Older than 7 Age at walking (mos): Younger than 15 Older than 15* Developmental concerns: Fine motor Speech Learning skills at school Social* Constipation Encopresis* ADHD Emotional stressor Kidney problems Daytime incontinence† Microbiologically confirmed UTI: Definite Possible Bladder dysfunction:*,‡ Frequency Urgency Holding postures Post-void incontinence
OR Severe (95% CI)
OR Moderate (95% CI)
OR Mild (95% CI)
1.6 (1.0–2.3)
1.5 (1.0–2.3)
1.6 (1.3–2.0)*
1.00 0.9 (0.4–2.1) 0.6 (0.2–1.8) 1.7 (1.0–2.9) 0.9 (0.5–1.9) 1.4 (0.9–2.3)
1.00 0.9 (0.3–2.2) 1.0 (0.3–3.4) 1.6 (0.9–2.9) 1.5 (0.8–2.9) 1.1 (0.5–2.1)
1.00 0.8 (0.5–1.3) 0.9 (0.4–1.8) 1.0 (0.8–1.5) 1.3 (0.9–1.9) 0.9 (0.6–1.4)
1.00 1.3 (0.7–2.4)
1.00 0.7 (0.3–1.7)
1.00 1.0 (0.7–1.4)
1.00 2.3 (1.2–4.4)
1.00 3.7 (1.5–9.2)
1.00 1.8 (1.1–3.0)
1.7 (0.9–3.5) 1.3 (0.7–2.3) 0.9 (0.4–1.7) 1.8 (1.1–3.4) 0.7 (0.3–1.9) 3.5 (2.2–5.5) 2.2 (0.9–5.2) 1.6 (0.8–3.0) 0.9 (0.3–3.6) 6.2 (4.2–9.4)*
1.5 (0.6–3.7) 1.1 (0.5–2.2) 1.9 (1.0–3.4) 3.7 (2.2–6.5) 1.5 (0.7–3.6) 3.0 (1.6–5.6) 1.2 (0.3–4.9) 2.6 (1.3–5.1)* 0.7 (0.1–4.8) 4.8 (3.0–7.8)*
2.0 (1.3–2.9)* 1.3 (0.9–1.8) 1.7 (1.3–2.5)* 1.8 (1.5–2.6) 0.7 (0.4–1.2) 2.3 (1.6–3.1) 1.6 (1.0–2.7) 1.8 (1.3–2.5)* 1.2 (0.6–2.5) 3.4 (2.6–4.3)*
2.2 (1.0–5.1) 1.1 (0.6–2.3)
2.2 (0.9–5.6) 0.7 (0.2–2.1)
1.3 (0.8–2.2) 0.5 (0.3–0.9)
4.8 (3.4–6.8) 2.0 (1.2–3.3) 3.0 (2.0–4.4) 6.2 (3.9–9.9)
3.5 (2.0–6.1) 3.7 (1.9–7.3) 3.1 (1.9–5.0) 3.7 (2.0–6.9)
2.4 (1.9–3.1) 2.7 (1.9–3.7) 2.0 (1.6–2.5) 3.3 (2.3–4.7)
Reference category, “No nocturnal enuresis.” * p ⬍0.05. † Any reported daytime incontinence in previous 6 months. ‡ Reference category, “None of the time.”
dren with daytime incontinence who had urgency compared to those without urgency (OR 5.2 vs 2.3, table 4). Table 3. Risk factors for nocturnal enuresis stratified by severity (adjusted odds ratios)
Male gender* Encopresis Emotional stressor Daytime incontinence* Social concerns Bladder dysfunction*,†
OR Severe (95% CI)
OR Moderate (95% CI)
OR Mild (95% CI)
2.0 (1.3–3.1) 2.7 (1.6–4.4)* 1.2 (0.5–2.7) 4.8 (2.9–7.9) 0.7 (0.3–1.8) 3.6 (2.4–5.3)
1.8 (1.1–3.1) 2.1 (1.1–4.3)* 2.3 (1.2–4.2)* 2.6 (1.3–5.2) 2.4 (1.2–4.5)* 2.4 (1.4–4.4)
2.1 (1.6–2.8) 1.6 (1.0–2.4) 1.3 (0.9–2.0) 3.0 (2.1–4.2) 1.3 (0.9–1.8) 2.0 (1.5–2.7)
Adjusted for age and all other variables in final model. Reference category, “No nocturnal enuresis.” * p ⬍0.05. † Reference category, “None of the time.”
Table 4. Risk factors for nocturnal enuresis demonstrating significant interaction terms
Constipation ⫹ frequency: Frequency No frequency Constipation ⫹ urgency: Urgency No urgency Constipation ⫹ holding postures: Holding postures No holding postures Daytime incontinence ⫹ urgency: Urgency* No urgency Urgency ⫹ daytime incontinence: Daytime incontinence No daytime incontinence
OR Severe (95% CI)
OR Moderate (95% CI)
OR Mild (95% CI)
0.6 (0.2–2.2) Not estimable
3.6 (1.1–12.3)* 0.9 (0.3–3.6)
0.8 (0.3–2.9) 0.5 (0.2–1.1)
0.3 (0.1–1.3) Not estimable
1.9 (0.8–5.1) Not estimable
0.6 (0.3–1.2) 0.7 (0.2–3.4)
0.4 (0.1–1.8) Not estimable
1.8 (0.6–5.3) 1.4 (0.3–6.1)
0.4 (0.2–1.2) 0.9 (0.4–2.7)
5.2 (2.9–9.2) 2.3 (0.6–9.5)
2.7 (1.3–5.6) Not estimable
2.9 (2.0–4.3) 2.3 (0.9–6.0)
1.8 (0.4–8.5) 0.6 (0.3–1.3)
Not estimable 1.0 (0.5–2.0)
1.6 (0.6–4.3) 1.4 (0.9–2.2)
Interaction expressed as simple effects of risk factors stratified by demographics. Reference category, “Nonexposed.” * p ⬍0.0001.
Univariate analysis showed that daytime incontinence, symptoms of bladder dysfunction, encopresis, social concerns, delayed age at walking and emotional stressors were positively associated with moderate frequency of enuresis (table 2). There was no association between constipation and moderate nocturnal enuresis (OR 1.5, 95% CI 0.7 to 3.6). Age adjusted independent risk factors for moderate nocturnal enuresis were male gender, encopresis, emotional stressors, daytime incontinence, social concerns and voiding frequency (table 3). About 6.5% of moderate nocturnal enuresis can be attributed to male gender, daytime incontinence, encopresis, emotional stressors, social concerns or urinary frequency. There was a statistically significant interaction between constipation and voiding problems (urinary frequency) in predicting moderate nocturnal enuresis (table 4). However, we were unable to interpret this apparent effect due to numerous small cell frequencies. Univariate analysis demonstrated that male gender, delayed age at walking and other developmental concerns (fine motor/learning skills, social concerns), encopresis, emotional stressors, daytime incontinence and symptoms of bladder dysfunction were significantly positively associated with mild nocturnal enuresis (table 2). There was no significant association of constipation with mild nocturnal enuresis. Age adjusted independent risk factors for mild nocturnal enuresis were male gender, daytime incontinence and urine frequency (table 3). About
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18.6% of mild nocturnal enuresis can be attributed to these 3 factors. The effect of daytime incontinence on mild nocturnal enuresis depended on the presence or absence of urgency. Interaction between daytime incontinence and urgency predicted about a 3-fold increased risk of mild nocturnal enuresis compared to a 2-fold risk when urgency was not present (table 4). Although the focus of this study was not to look at MNE and NMNE separately, we compared the frequency of severe nocturnal enuresis in children with MNE and NMNE because they are commonly believed to be separate entities. The NMNE group had more severe nocturnal enuresis. When we compared risk factors separately for MNE and NMNE bladder and bowel symptoms were more pronounced in children with NMNE.
DISCUSSION In this large, randomly selected population of school-age children the prevalence of nocturnal enuresis was 12.3%, 2.5% and 3.6% for mild, moderate and severe enuresis, respectively. After adjustment for age daytime incontinence, encopresis, male gender and symptoms of bladder dysfunction were important predictors of nocturnal enuresis. Emotional stressors and social concerns were positively associated with moderate nocturnal enuresis only. These findings suggest that at the population level the frequency of nocturnal enuresis could be reduced by about 20% with the elimination of 2 potentially modifiable risk factors, ie encopresis and daytime incontinence. The relationship between daytime and nighttime incontinence is complex. Of all risk factors daytime incontinence, a symptom of bladder dysfunction, was the strongest predictor for all categories of nocturnal enuresis but the concordance of both conditions in the same child was variable. We identified daytime incontinence in a third of patients with nocturnal enuresis but the test for agreement between these 2 risk factors revealed poor concordance (weighted kappa 0.25), which confirms that it is a separate entity that should be evaluated and treated separately from nocturnal enuresis. Additionally the effect of daytime incontinence on the risk of nocturnal enuresis is inconstant and varies with the presence of urgency, which presumably delineates the group with more severe bladder dysfunction. Other findings are in keeping with established knowledge. Males have a higher risk of nocturnal enuresis and encopresis. This risk is well recognized and may be related to the differing rate of development and age of attaining successful toilet training between the genders (being later in males).20 –22 In
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our study encopresis was a risk factor for nocturnal enuresis, while constipation was not associated with nocturnal enuresis. This finding indicates that parental reporting may be unreliable, since parents poorly recognize constipation in their children with nocturnal enuresis.23 While our observed prevalence of nocturnal enuresis (18.4%) confirms it is a common childhood problem, previous cross-sectional studies have resulted in varying prevalence estimates (3.8% to 25%). This variability could be explained by nonstandardized definitions of nocturnal enuresis. Unlike previous studies, we sought to distinguish between different categories of enuresis severity, recognizing that treatment algorithms are likely to be used only in the more severe cases. Our finding that severe nocturnal enuresis was strongly represented in NMNE compared to MNE is similar to previous studies.2,24 Strengths of this study are the population based design of subject selection, use of a validated and reproducible questionnaire, and risk factor analysis with severity of nocturnal enuresis. Unlike previous studies, we considered all of the well-known confounders, which allowed us to identify how the effect of a given risk factor is modified by another patient characteristic. Addressing some of the modifiable risk factors identified (encopresis, daytime incontinence, urinary urgency) may reduce the risk of nocturnal enuresis. Our study has limitations. The response rate was low (35%) but in keeping with current school based population surveys.25,26 The response bias may limit the generalizability of the results, and is likely to be an issue only for estimating the prevalence of disease and not for estimating potential causal relationships.27,28 Another limitation is the cross-sectional setting, which means that we cannot predict how these risk factors change the outcome through time. Further longitudinal studies are required to evaluate causal associations between risk factors and nocturnal enuresis.
CONCLUSIONS Our findings provide new information for treating patients with all degrees of nocturnal enuresis. The results suggest that daytime incontinence, encopresis and urgency are significant modifiable risk factors for nocturnal enuresis. Longitudinal cohort studies are necessary to confirm these potential causal relationships, and randomized controlled trials are required to show the effectiveness of treatment of daytime incontinence, encopresis and urgency in children with nocturnal enuresis.
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APPENDIX Definition of Risk Factors for Nocturnal Enuresis Variable Perinatal factors: Premature birth Newborn hospital admission Medication during pregnancy Developmental milestones: Sitting Walking Developmental concerns: Fine motor skills Speech Learning at school Social Encopresis Constipation Attention deficit hyperactivity syndrome (ADHD) Emotional stressors Kidney problems Urinary tract infection (UTI): Definite/probable Possible Negative Daytime urinary incontinence Symptoms of bladder dysfunction: Frequency Urgency Holding postures Post-micturition incontinence
Definition Gestational age ⬍37 weeks Whether the child was in a special care nursery or intensive care after he/she was born Did the mother of the child receive any medication during the pregnancy Age at sitting without support Age at starting to walk at least 3 steps without help Parental concerns about the child’s fine motor skills Parental concerns about the child’s speech Parental concerns about the child’s learning skills at school Parental concerns about the child’s social behavior Soiling of pants with more than a smear in a period of three months Present if the child had two or more of the following: straining more than 25% of the time in passing stool lumpy or hard stools more than 25% of the time in passing stool having fewer than three bowel movements per week Diagnosis with ADHD Any frightening or emotionally stressful events that affected the child in the past six months Any anatomical abnormalities related to urinary system excluding urinary tract infection Microbiologically confirmed definite or probable UTI with parental reporting of positive UTI Parental reporting of a positive UTI but unable to confirm with a microbiological result Microbiologically normal results Daytime incontinence with a frequency of more than once in the past 6 months Micturating more than two times in a two hour period Rushing to the toilet to urinate Adopting any characteristic postures to avoid incontinence Having wet pants within half an hour of having passed urine
REFERENCES 1. Foxman B, Valdez RB and Brook RH: Childhood enuresis: prevalence, perceived impact, and prescribed treatments. Pediatrics 1986; 77: 482.
8. Wan J, Greenfield S: Enuresis and common voiding abnormalities. Pediatr Clin North Am 1997; 44: 1117.
2. Chiozza ML, Bernardinelli L, Caione P et al: An Italian epidemiological multicentre study of nocturnal enuresis. Br J Urol, suppl., 1998; 81: 86.
9. Forsythe WI and Redmond A: Enuresis and spontaneous cure rate. Study of 1129 enuretics. Arch Dis Child 1974; 49: 259.
3. Bower WF, Moore KH, Shepherd RB et al: The epidemiology of childhood enuresis in Australia. Br J Urol 1996; 78: 602.
10. Butler RJ, Robinson JC, Holland P et al: Investigating the three systems approach to complex childhood nocturnal enuresis—medical treatment interventions. Scand J Urol Nephrol 2004; 38: 117.
4. Hellstrom A, Hanson E, Hansson S et al: Association between urinary symptoms at 7 years old and previous urinary tract infection. Arch Dis Child 1991; 66: 232.
11. Baeyens D, Roeyers H, Hoebeke P et al: Attention deficit/hyperactivity disorder in children with nocturnal enuresis. J Urol 2004; 171: 2576.
5. Hansen A, Hansen B and Dahm TL: Urinary tract infection, day wetting and other voiding symptoms in seven- to eight-year-old Danish children. Acta Paediatr 1997; 86: 1345.
12. Cayan S, Doruk E, Bozlu M et al: The assessment of constipation in monosymptomatic primary nocturnal enuresis. Int Urol Nephrol 2001; 33: 513.
6. Jarvelin MR, Vikevainen-Tervonen L, Moilanen I et al: Enuresis in seven-year-old children. Acta Paediatr Scand 1988; 77: 148.
13. Kalo BB and Bella H: Enuresis: prevalence and associated factors among primary school children in Saudi Arabia. Acta Paediatr 1996; 85: 1217.
7. Kajiwara M, Inoue K, Kato M et al: Nocturnal enuresis and overactive bladder in children: an epidemiological study. Int J Urol 2006; 13: 36.
14. Jarvelin MR: Developmental history and neurological findings in enuretic children. Dev Med Child Neurol 1989; 31: 728.
15. Touchette E, Petit D, Paquet J et al: Bed-wetting and its association with developmental milestones in early childhood. Arch Pediatr Adolesc Med 2005; 159: 1129. 16. Sureshkumar P, Cumming RG and Craig JC: Validity and reliability of parental report of frequency, severity and risk factors of urinary tract infection and urinary incontinence in children. J Urol 2006; 175: 2254. 17. Frakenburg WK, Dodds JB, Archer P et al: Denver II Training Manual. Denver, Colorado: Denver Developmental Materials Inc 1992. 18. Hennekens CH and Buring JE: Epidemiology in Medicine. Boston: Little, Brown and Co 1987; p 90. 19. Sureshkumar P, Jones M, Cumming RG et al: A population based study of 2,856 school-age children with urinary incontinence. J Urol 2009; 181: 808. 20. Largo RH, Molinari L, von Siebenthal K et al: Development of bladder and bowel control: significance of prematurity, perinatal risk factors, psychomotor development and gender. Eur J Pediatr 1999; 158: 115.
RISK FACTORS FOR NOCTURNAL ENURESIS IN CHILDREN
21. Schum TR, Kolb TM, McAuliffe TL et al: Sequential acquisition of toilet-training skills: a descriptive study of gender and age differences in normal children. Pediatrics 2002; 109: E48. 22. Schum TR, McAuliffe TL, Simms MD et al: Factors associated with toilet training in the 1990s. Ambul Pediatr 2001; 1: 79. 23. McGrath KH, Caldwell PH and Jones MP: The frequency of constipation in children with noctur-
nal enuresis: a comparison with parental reporting. J Paediatr Child Health 2008; 44: 19. 24. Butler RJ and Heron J: The prevalence of infrequent bedwetting and nocturnal enuresis in childhood. A large British cohort. Scand J Urol Nephrol 2008; 42: 257. 25. Blunden SL and Chervin RD: Sleep problems are associated with poor outcomes in remedial teaching programmes: a preliminary study. J Paediatr Child Health 2008; 44: 237.
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26. Salmon J, Salmon L, Crawford DA et al: Associations among individual, social, and environmental barriers and children’s walking or cycling to school. Am J Health Promot 2007; 22: 107. 27. Austin MA, Criqui MH, Barrett-Connor E et al: The effect of response bias on the odds ratio. Am J Epidemiol 1981; 114: 137. 28. Maclure M and Hankinson S: Analysis of selection bias in a case-control study of renal adenocarcinoma. Epidemiology 1990; 1: 441.
EDITORIAL COMMENT The authors report the results of a large epidemiological study addressing the risk factors for nocturnal enuresis. They conclude that patients with NMNE (those with daytime symptoms and encopresis) have the more severe condition compared to those with MNE. This is the first known epidemiological study to calculate this risk, and it confirms the impression of caretakers of children with NE that patients with NMNE have a more severe condition. Taken together with the results of a large epidemiological study by Yeung et al,1 who observed
that patients with frequent bed-wetting have a more severe and longer lasting condition than those with low frequency bed-wetting, we now have more insight into the risk of this so-called benign disease, allowing us to identify the patient at risk for a long lasting condition. For these patients intensified therapy should be advised. Piet Hoebeke Department of Urology Ghent University Hospital Gent, Belgium
REFERENCE 1. Yeung CK, Sreedhar B, Sihoe JD et al: Differences in characteristics of nocturnal enuresis between children and adolescents: a critical appraisal from a large epidemiological study. BJU Int 2006; 97: 1069.
Purpose: Although nocturnal enuresis is common in children, its etiology is multifactorial and not fully understood. We evaluated potential risk factors for presence and severity of nocturnal enuresis. Materials and Methods: A validated, reproducible questionnaire was distributed to 8,230 school children in Sydney, Australia. Nocturnal enuresis was defined as any wetting in the previous month and categorized as mild (1 to 6 nights), moderate (7 or more nights but less than nightly) or severe (nightly). Results: Parents of 2,856 children (mean ⫾ SD age 7.3 ⫾ 1.3 years) completed the questionnaire (response rate 35%). Overall prevalence of nocturnal enuresis was 18.2%, with 12.3% of patients having mild, 2.5% moderate and 3.6% severe enuresis. Multivariate analysis showed that daytime incontinence (OR 4.8, 95% CI 2.9 to 7.9), encopresis (OR 2.7, 95% CI 1.6 to 4.4), bladder dysfunction (OR 3.6, 95% CI 2.4 to 5.3) and male gender (OR 2.0, 95% CI 1.3 to 3.1) were associated with severe nocturnal enuresis after adjustment for age. Emotional stressors (OR 2.3, 95% CI 1.2 to 4.2) and social concerns (OR 2.4, 95% CI 1.2 to 4.5) were associated with moderate nocturnal enuresis only. Conclusions: Encopresis and daytime incontinence are significant modifiable risk factors for nocturnal enuresis. Expressed as population attributable risk, 23% of nocturnal enuresis is associated with encopresis and daytime incontinence. Psychosocial factors appear to contribute to moderate but not severe nocturnal enuresis.
Abbreviations and Acronyms ADHD ⫽ attention deficit hyperactivity disorder MNE ⫽ monosymptomatic nocturnal enuresis NMNE ⫽ nonmonosymptomatic nocturnal enuresis UTI ⫽ urinary tract infection Submitted for publication April 9, 2009. Supported by grants from Ramaciotti Foundation for Children (RN005/01) and Financial Markets Foundation for Children (143-2004). Study received approval of ethics committee of Children’s Hospital at Westmead and New South Wales Department of School Education. * Correspondence: Center for Kidney Research, Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia (telephone: 61-2-9845-1474; FAX: 61-2-9845-1491; e-mail: [email protected]).
Key Words: child, nocturnal enuresis, questionnaires, risk factors NOCTURNAL enuresis is a common pediatric problem. The prevalence varies in epidemiological studies from 3.8% to 25% according to patient age and the definition used.1– 8 At age 5 years 15% to 25% of children experience nocturnal enuresis.8 Prevalence of nocturnal enuresis decreases with increasing age, with about 15% of children spontaneously achieving nighttime bladder control annually.9 In adults the prevalence of nocturnal enuresis is estimated at 1% to 2%. The etiology of nocturnal enuresis is multifactorial and hypothesized to be related to problems with arousal, small
bladder capacity and large overnight urine production.10 ADHD, constipation, encopresis, developmental problems, male gender and young age are also reportedly associated with nocturnal enuresis.11–15 However, previous studies have not evaluated whether these associations of risk factors vary with severity. Nocturnal enuresis is a heterogeneous disorder. The spectrum of severity is wide but important from a management perspective, with older children (older than 7 years) who wet frequently requiring treatment. We sought to determine independent risk factors for nocturnal enuresis for each
0022-5347/09/1826-2893/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 182, 2893-2899, December 2009 Printed in U.S.A. DOI:10.1016/j.juro.2009.08.060
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stratum of severity, with particular focus on the most severe cases.
MATERIALS AND METHODS Participant Recruitment Recruitment occurred between May 2003 and December 2004. A random sample of children from the first 4 years of elementary schools in Sydney was chosen. Further details of questionnaire development, validation and recruitment have been described previously.16 A validated parent questionnaire with high reproducibility was used to collect information on age, gender, birth weight, gestation, medication taken during pregnancy, developmental milestones, developmental concerns, circumcision, ADHD, and urinary and bowel history.
Measurement of Risk Factors and Outcomes Parents were asked to estimate the frequency of nocturnal enuresis in the month before the survey. Severity was defined according to frequency, with 1 to 6 nights defined as mild, 7 or more but less than nightly moderate and nightly severe. This series was part of a large cohort study that looked at other urinary tract problems such as urinary tract infections and daytime urinary incontinence. We collected potential risk factors for these outcomes as well as for nocturnal enuresis. We believed that the causal pathways for enuresis were not well established, with causality not 100% explained. Male gender, young age, constipation, encopresis, daytime incontinence, developmental problems and ADHD are reportedly associated with nocturnal enuresis.11–15 Birth weight, prenatal history and kidney problems are also thought to be associated with nocturnal enuresis. By limiting our study to established risk factors we would have limited the capacity to identify novel risk factors. For this reason we have included all potential risk factors in our tables. We assessed several potential risk factors for each category of severity (see Appendix). Perinatal risk factors measured included birth weight, gestation, newborn hospitalization and any medication that the mother took during pregnancy. Developmental concerns regarding fine motor skills, speech, learning skills at school and social behavior were also elicited. Medical history included ADHD, emotional stressors, encopresis and kidney problems. Constipation was measured using the Rome II scale.16 Urinary history included daytime urinary incontinence and symptoms of bladder dysfunction (urinary frequency, urgency, holding postures and post-void incontinence).
Data Analysis Data were analyzed using SPSS®, version 13.0 and SAS®, version 9.1.3 software. Continuous variables such as developmental milestones were categorized according to the Denver II Training Manual.17 Birth weight was categorized into less than 2.5 kg, 2.5 to 4 kg and greater than 4 kg, which are commonly used pediatric thresholds. Age was analyzed as continuous in the multivariate model but is presented as categorical for ease of interpretation. Prevalence values for each risk factor were reported with 95% confidence intervals. Polychotomous logistic re-
gression analysis was used to identify risk factors for each category of nocturnal enuresis. In this approach odds ratios for each risk factor applied to each severity category were estimated simultaneously. Absence of nocturnal enuresis was used as a reference category. The relationship between the risk factors and nocturnal enuresis of all severity levels was expressed in terms of population attributable risk and calculated with the formula, population attributable risk ⫽ [F(OR-1)/1⫹(F(OR-1))]⫻100, where F is prevalence of exposure in the population of interest and OR is odds ratio.18 Potential interaction effects between risk factors were also analyzed. Due to the excessive number of potential interactions, only a limited subset, thought to be of a priori interest, was considered, which included gender, encopresis, constipation, emotional stressors, daytime incontinence and symptoms of bladder dysfunction.
Ethical Approval The study was approved by the ethics committee of the Children’s Hospital at Westmead, Sydney, Australia and the New South Wales Department of School Education. Written consent was obtained from parents of the participating children.
RESULTS Characteristics of Respondents Of 83 schools invited 60 agreed to participate in the study (72% response rate). A total of 2,856 parents of primary school children (47.4% girls) with a mean ⫾ SD age of 7.3 ⫾ 1.3 years completed the questionnaire (overall response rate 35%). Daytime incontinence was reported in 17% of children, constipation in 5.7% and encopresis in 10%. Parents reported UTI in 12.7% of children, of whom 3.6% had microbiologically confirmed UTI. Further details of patient demographic and baseline characteristics have been published previously.19 Frequency of Nocturnal Enuresis Overall 18.4% (95% CI 16.8% to 19.6%) of children had at least 1 episode of nocturnal enuresis in the last month, with 12.3% having mild, 2.5% moderate and 3.6% severe frequency. Table 1 demonstrates the frequency of different severities of nocturnal enuresis and nonenuresis in all children. We stratified the data according to severity of enuresis for children with an identified risk factor. For example, of patients with daytime incontinence 10.0% had severe, 6.0% moderate, 23.3% mild and 60.7% no enuresis. The risk of severe nocturnal enuresis was increased 3-fold in children with daytime urinary incontinence. Daytime urinary incontinence with or without nocturnal enuresis was reported in 16.9% of children, and 6.6% (95% CI 5.7 to 7.6) of children had nocturnal enuresis and daytime incontinence. Nocturnal enuresis decreased with age. Of children 4.8 to 6.2 years old 27.8% (95% CI 24.6 to 31.1) experienced nocturnal enuresis compared to
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Table 1. Prevalence of nocturnal enuresis stratified by severity
Overall Gender: M F Birth wt (kg): Less than 2.5 2.5–4.0 More than 4.0 Age (yrs): Younger than 6 6–6.9 7–7.9 8–8.9 9–9.9 10–12.8 Newborn hospitalization Premature birth Medication during pregnancy Age at sitting (mos): Younger than 7 Older than 7 Age at walking (mos): Younger than 15 Older than 15 Developmental concerns: Fine motor Speech Learning skills at school Social Constipation Encopresis ADHD Emotional stressor Kidney problems Daytime incontinence* UTI: Definite Possible Bladder dysfunction:† Frequency Urgency Holding postures Post-void incontinence
OR Severe (95% CI)
OR Moderate (95% CI)
OR Mild (95% CI)
OR Absent (95% CI)
3.6 (2.9–4.3)
2.5 (1.9–3.1)
12.3 (11.1–13.5)
81.6 (80.0–83.2)
4.2 (3.3–5.4) 3.0 (2.1–4.0)
2.9 (2.1–3.9) 2.0 (1.4–3.0)
14.6 (12.8–16.4) 9.8 (8.3–11.5)
78.3 (76.2–80.4) 85.2 (83.3–87.1)
4.4 (2.0–8.6) 3.9 (3.1–4.8) 1.7 (0.6–4.4)
2.2 (0.6–5.6) 2.5 (1.9–3.2) 3.1 (1.1–5.4)
14.2 (9.7–20.6) 12.1 (10.7–13.4) 13.9 (10.2–18.7)
79.2 (73.3–85.1) 81.5 (80.0–83.2) 81.3 (76.7–85.7)
6.2 (4.9–9.6) 4.5 (3.1–6.3) 2.5 (1.4–3.9) 1.7 (0.8–3.1) 2.1 (0.8–4.5) 5.3 (0.1–26.0) 5.3 (3.1–7.5) 3.2 (1.0–5.4) 4.7 (2.5–6.9)
2.4 3.7 2.0 1.9 2.1 Not 3.5 3.6 2.5
(1.4–4.3) (2.4–5.4) (1.1–3.4) (0.9–3.3) (0.8–4.5) estimable (1.7–5.3) (1.3–5.9) (0.9–4.1)
20.6 (17.1–24.1) 13.0 (10.5–15.5) 11.3 (8.9–13.7) 8.3 (6.2–10.8) 7.0 (4.4–10.7) 5.3 (0.1–26.0) 12.0 (8.8–15.2) 13.9 (9.6–18.2) 12.2 (8.8–15.6)
70.7 (67.0–74.4) 78.8 (75.7–82.0) 84.2 (81.5–86.9) 88.1 (85.6–90.8) 88.8 (85.1–92.5) 89.5 (75.7–103.3) 79.2 (75.2–83.2) 79.3 (74.3–84.3) 80.6 (76.5–84.5)
3.3 (2.5–4.1) 5.0 (2.9–7.1)
2.5 (1.8–3.2) 1.4 (0.3–2.5)
12.5 (11.1–13.9) 11.8 (8.7–14.9)
81.7 (80.1–83.3) 81.6 (78.0–85.4)
3.4 (2.8–4.2) 7.2 (3.5–12.8)
2.4 (1.8–3.0) 5.0 (2.1–10.1)
12.2 (10.9–13.4) 15.1 (9.6–22.2)
82.0 (80.5–83.5) 72.7 (65.3–80.1)
5.2 (2.3–10.0) 4.3 (2.4–7.0) 2.8 (1.2–5.5) 5.8 (3.2–9.5) 3.1 (1.0–7.1) 7.6 (4.8–11.2) 7.0 (2.6–14.6) 4.9 (2.5–8.3) 3.3 (0.4–11.5) 10.0 (7.4–13.0)
3.3 (1.1–7.5) 2.6 (1.2–4.9) 3.9 (2.0–6.9) 6.6 (3.8–10.5) 3.7 (1.4–7.9) 5.5 (3.2–8.8) 3.5 (0.7–9.9) 4.9 (2.5–8.3) 1.7 (0.04–8.9) 6.0 (4.1–8.5)
20.0 (14.2–27.5) 15.0 (11.2–18.7) 18.4 (13.9–23.0) 19.0 (14.1–24.0) 9.2 (5.3–14.8) 20.6 (16.0–25.3) 17.4 (10.1–27.1) 18.6 (13.8–23.5) 15.0 (7.1–26.6) 23.3 (19.5–27.1)
71.5 78.1 74.9 68.6 84.0 66.3 72.1 71.7 80.0 60.7
6.8 (2.8–13.5) 4.1 (1.7–8.3)
4.9 (1.6–11.0) 1.8 (0.4–5.1)
14.6 (8.4–22.9) 7.1 (3.7–12.0)
73.8 (65.3–82.3) 87.1 (82.1–92.1)
4.4 3.2 4.0 5.8
18.3 (15.8–20.9) 15.0 (13.4–16.6) 16.3 (14.2–18.5) 24.9 (19.6–30.2)
69.3 77.6 74.1 57.1
7.3 (5.7–9.3) 4.2 (3.3–5.2) 5.6 (4.4–7.2) 12.1 (8.1–16.0)
(3.2–5.9) (2.5–4.1) (2.9–5.3) (3.3–9.4)
(64.0–78.4) (73.8–82.5) (69.7–79.9) (62.8–74.5) (78.4–89.7) (60.9–71.7) (62.6–81.6) (66.1–77.3) (69.9–90.1) (56.3–65.1)
(66.9–72.9) (75.7–79.5) (71.6–76.7) (51.2–63.3)
Frequency (OR, 95% CI) in patients with each risk factor present. * Any reported daytime incontinence in previous 6 months. † Reference category, “None of the time.”
10.9% (95% CI 8.7 to 13.2) of those 8.4 to 12.8 years old. Risk Factors for Nocturnal Enuresis Univariate analysis revealed that daytime incontinence, encopresis, social concerns, delayed age at walking (after 15 months) and symptoms of bladder dysfunction were significantly predictive of severe nocturnal enuresis (table 2). We did not find a significant association between constipation and severe nocturnal enuresis (OR 0.7, 95% CI 0.3 to 1.9). Age adjusted independent risk factors for severe nocturnal enuresis were male gender, encopresis, daytime incontinence and symptoms of bladder dysfunction
(table 3). Males exhibited a doubling of risk and children with encopresis a tripling of risk for severe nocturnal enuresis. Daytime incontinence and urinary frequency were also significantly associated (OR 4.8, 95% CI 2.9 to 7.9 and OR 3.6, 95% CI 2.4 to 5.3, respectively). Severe nocturnal enuresis in this population was associated with daytime incontinence in 7.1% of patients, urinary frequency in 5.8%, encopresis in 1.5% and male gender in 1%. There was a statistically significant interaction between daytime incontinence and urgency in risk of nocturnal enuresis (p ⬍0.0001). There was a 2-fold increased risk of severe nocturnal enuresis in chil-
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Table 2. Risk factors for nocturnal enuresis stratified by severity (unadjusted odds ratios)
Male gender Birth wt (kg): Less than 2.5 2.5–4.0 More than 4.0 Newborn hospitalization Premature birth Medication during pregnancy Age at sitting (mos): Younger than 7 Older than 7 Age at walking (mos): Younger than 15 Older than 15* Developmental concerns: Fine motor Speech Learning skills at school Social* Constipation Encopresis* ADHD Emotional stressor Kidney problems Daytime incontinence† Microbiologically confirmed UTI: Definite Possible Bladder dysfunction:*,‡ Frequency Urgency Holding postures Post-void incontinence
OR Severe (95% CI)
OR Moderate (95% CI)
OR Mild (95% CI)
1.6 (1.0–2.3)
1.5 (1.0–2.3)
1.6 (1.3–2.0)*
1.00 0.9 (0.4–2.1) 0.6 (0.2–1.8) 1.7 (1.0–2.9) 0.9 (0.5–1.9) 1.4 (0.9–2.3)
1.00 0.9 (0.3–2.2) 1.0 (0.3–3.4) 1.6 (0.9–2.9) 1.5 (0.8–2.9) 1.1 (0.5–2.1)
1.00 0.8 (0.5–1.3) 0.9 (0.4–1.8) 1.0 (0.8–1.5) 1.3 (0.9–1.9) 0.9 (0.6–1.4)
1.00 1.3 (0.7–2.4)
1.00 0.7 (0.3–1.7)
1.00 1.0 (0.7–1.4)
1.00 2.3 (1.2–4.4)
1.00 3.7 (1.5–9.2)
1.00 1.8 (1.1–3.0)
1.7 (0.9–3.5) 1.3 (0.7–2.3) 0.9 (0.4–1.7) 1.8 (1.1–3.4) 0.7 (0.3–1.9) 3.5 (2.2–5.5) 2.2 (0.9–5.2) 1.6 (0.8–3.0) 0.9 (0.3–3.6) 6.2 (4.2–9.4)*
1.5 (0.6–3.7) 1.1 (0.5–2.2) 1.9 (1.0–3.4) 3.7 (2.2–6.5) 1.5 (0.7–3.6) 3.0 (1.6–5.6) 1.2 (0.3–4.9) 2.6 (1.3–5.1)* 0.7 (0.1–4.8) 4.8 (3.0–7.8)*
2.0 (1.3–2.9)* 1.3 (0.9–1.8) 1.7 (1.3–2.5)* 1.8 (1.5–2.6) 0.7 (0.4–1.2) 2.3 (1.6–3.1) 1.6 (1.0–2.7) 1.8 (1.3–2.5)* 1.2 (0.6–2.5) 3.4 (2.6–4.3)*
2.2 (1.0–5.1) 1.1 (0.6–2.3)
2.2 (0.9–5.6) 0.7 (0.2–2.1)
1.3 (0.8–2.2) 0.5 (0.3–0.9)
4.8 (3.4–6.8) 2.0 (1.2–3.3) 3.0 (2.0–4.4) 6.2 (3.9–9.9)
3.5 (2.0–6.1) 3.7 (1.9–7.3) 3.1 (1.9–5.0) 3.7 (2.0–6.9)
2.4 (1.9–3.1) 2.7 (1.9–3.7) 2.0 (1.6–2.5) 3.3 (2.3–4.7)
Reference category, “No nocturnal enuresis.” * p ⬍0.05. † Any reported daytime incontinence in previous 6 months. ‡ Reference category, “None of the time.”
dren with daytime incontinence who had urgency compared to those without urgency (OR 5.2 vs 2.3, table 4). Table 3. Risk factors for nocturnal enuresis stratified by severity (adjusted odds ratios)
Male gender* Encopresis Emotional stressor Daytime incontinence* Social concerns Bladder dysfunction*,†
OR Severe (95% CI)
OR Moderate (95% CI)
OR Mild (95% CI)
2.0 (1.3–3.1) 2.7 (1.6–4.4)* 1.2 (0.5–2.7) 4.8 (2.9–7.9) 0.7 (0.3–1.8) 3.6 (2.4–5.3)
1.8 (1.1–3.1) 2.1 (1.1–4.3)* 2.3 (1.2–4.2)* 2.6 (1.3–5.2) 2.4 (1.2–4.5)* 2.4 (1.4–4.4)
2.1 (1.6–2.8) 1.6 (1.0–2.4) 1.3 (0.9–2.0) 3.0 (2.1–4.2) 1.3 (0.9–1.8) 2.0 (1.5–2.7)
Adjusted for age and all other variables in final model. Reference category, “No nocturnal enuresis.” * p ⬍0.05. † Reference category, “None of the time.”
Table 4. Risk factors for nocturnal enuresis demonstrating significant interaction terms
Constipation ⫹ frequency: Frequency No frequency Constipation ⫹ urgency: Urgency No urgency Constipation ⫹ holding postures: Holding postures No holding postures Daytime incontinence ⫹ urgency: Urgency* No urgency Urgency ⫹ daytime incontinence: Daytime incontinence No daytime incontinence
OR Severe (95% CI)
OR Moderate (95% CI)
OR Mild (95% CI)
0.6 (0.2–2.2) Not estimable
3.6 (1.1–12.3)* 0.9 (0.3–3.6)
0.8 (0.3–2.9) 0.5 (0.2–1.1)
0.3 (0.1–1.3) Not estimable
1.9 (0.8–5.1) Not estimable
0.6 (0.3–1.2) 0.7 (0.2–3.4)
0.4 (0.1–1.8) Not estimable
1.8 (0.6–5.3) 1.4 (0.3–6.1)
0.4 (0.2–1.2) 0.9 (0.4–2.7)
5.2 (2.9–9.2) 2.3 (0.6–9.5)
2.7 (1.3–5.6) Not estimable
2.9 (2.0–4.3) 2.3 (0.9–6.0)
1.8 (0.4–8.5) 0.6 (0.3–1.3)
Not estimable 1.0 (0.5–2.0)
1.6 (0.6–4.3) 1.4 (0.9–2.2)
Interaction expressed as simple effects of risk factors stratified by demographics. Reference category, “Nonexposed.” * p ⬍0.0001.
Univariate analysis showed that daytime incontinence, symptoms of bladder dysfunction, encopresis, social concerns, delayed age at walking and emotional stressors were positively associated with moderate frequency of enuresis (table 2). There was no association between constipation and moderate nocturnal enuresis (OR 1.5, 95% CI 0.7 to 3.6). Age adjusted independent risk factors for moderate nocturnal enuresis were male gender, encopresis, emotional stressors, daytime incontinence, social concerns and voiding frequency (table 3). About 6.5% of moderate nocturnal enuresis can be attributed to male gender, daytime incontinence, encopresis, emotional stressors, social concerns or urinary frequency. There was a statistically significant interaction between constipation and voiding problems (urinary frequency) in predicting moderate nocturnal enuresis (table 4). However, we were unable to interpret this apparent effect due to numerous small cell frequencies. Univariate analysis demonstrated that male gender, delayed age at walking and other developmental concerns (fine motor/learning skills, social concerns), encopresis, emotional stressors, daytime incontinence and symptoms of bladder dysfunction were significantly positively associated with mild nocturnal enuresis (table 2). There was no significant association of constipation with mild nocturnal enuresis. Age adjusted independent risk factors for mild nocturnal enuresis were male gender, daytime incontinence and urine frequency (table 3). About
RISK FACTORS FOR NOCTURNAL ENURESIS IN CHILDREN
18.6% of mild nocturnal enuresis can be attributed to these 3 factors. The effect of daytime incontinence on mild nocturnal enuresis depended on the presence or absence of urgency. Interaction between daytime incontinence and urgency predicted about a 3-fold increased risk of mild nocturnal enuresis compared to a 2-fold risk when urgency was not present (table 4). Although the focus of this study was not to look at MNE and NMNE separately, we compared the frequency of severe nocturnal enuresis in children with MNE and NMNE because they are commonly believed to be separate entities. The NMNE group had more severe nocturnal enuresis. When we compared risk factors separately for MNE and NMNE bladder and bowel symptoms were more pronounced in children with NMNE.
DISCUSSION In this large, randomly selected population of school-age children the prevalence of nocturnal enuresis was 12.3%, 2.5% and 3.6% for mild, moderate and severe enuresis, respectively. After adjustment for age daytime incontinence, encopresis, male gender and symptoms of bladder dysfunction were important predictors of nocturnal enuresis. Emotional stressors and social concerns were positively associated with moderate nocturnal enuresis only. These findings suggest that at the population level the frequency of nocturnal enuresis could be reduced by about 20% with the elimination of 2 potentially modifiable risk factors, ie encopresis and daytime incontinence. The relationship between daytime and nighttime incontinence is complex. Of all risk factors daytime incontinence, a symptom of bladder dysfunction, was the strongest predictor for all categories of nocturnal enuresis but the concordance of both conditions in the same child was variable. We identified daytime incontinence in a third of patients with nocturnal enuresis but the test for agreement between these 2 risk factors revealed poor concordance (weighted kappa 0.25), which confirms that it is a separate entity that should be evaluated and treated separately from nocturnal enuresis. Additionally the effect of daytime incontinence on the risk of nocturnal enuresis is inconstant and varies with the presence of urgency, which presumably delineates the group with more severe bladder dysfunction. Other findings are in keeping with established knowledge. Males have a higher risk of nocturnal enuresis and encopresis. This risk is well recognized and may be related to the differing rate of development and age of attaining successful toilet training between the genders (being later in males).20 –22 In
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our study encopresis was a risk factor for nocturnal enuresis, while constipation was not associated with nocturnal enuresis. This finding indicates that parental reporting may be unreliable, since parents poorly recognize constipation in their children with nocturnal enuresis.23 While our observed prevalence of nocturnal enuresis (18.4%) confirms it is a common childhood problem, previous cross-sectional studies have resulted in varying prevalence estimates (3.8% to 25%). This variability could be explained by nonstandardized definitions of nocturnal enuresis. Unlike previous studies, we sought to distinguish between different categories of enuresis severity, recognizing that treatment algorithms are likely to be used only in the more severe cases. Our finding that severe nocturnal enuresis was strongly represented in NMNE compared to MNE is similar to previous studies.2,24 Strengths of this study are the population based design of subject selection, use of a validated and reproducible questionnaire, and risk factor analysis with severity of nocturnal enuresis. Unlike previous studies, we considered all of the well-known confounders, which allowed us to identify how the effect of a given risk factor is modified by another patient characteristic. Addressing some of the modifiable risk factors identified (encopresis, daytime incontinence, urinary urgency) may reduce the risk of nocturnal enuresis. Our study has limitations. The response rate was low (35%) but in keeping with current school based population surveys.25,26 The response bias may limit the generalizability of the results, and is likely to be an issue only for estimating the prevalence of disease and not for estimating potential causal relationships.27,28 Another limitation is the cross-sectional setting, which means that we cannot predict how these risk factors change the outcome through time. Further longitudinal studies are required to evaluate causal associations between risk factors and nocturnal enuresis.
CONCLUSIONS Our findings provide new information for treating patients with all degrees of nocturnal enuresis. The results suggest that daytime incontinence, encopresis and urgency are significant modifiable risk factors for nocturnal enuresis. Longitudinal cohort studies are necessary to confirm these potential causal relationships, and randomized controlled trials are required to show the effectiveness of treatment of daytime incontinence, encopresis and urgency in children with nocturnal enuresis.
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RISK FACTORS FOR NOCTURNAL ENURESIS IN CHILDREN
APPENDIX Definition of Risk Factors for Nocturnal Enuresis Variable Perinatal factors: Premature birth Newborn hospital admission Medication during pregnancy Developmental milestones: Sitting Walking Developmental concerns: Fine motor skills Speech Learning at school Social Encopresis Constipation Attention deficit hyperactivity syndrome (ADHD) Emotional stressors Kidney problems Urinary tract infection (UTI): Definite/probable Possible Negative Daytime urinary incontinence Symptoms of bladder dysfunction: Frequency Urgency Holding postures Post-micturition incontinence
Definition Gestational age ⬍37 weeks Whether the child was in a special care nursery or intensive care after he/she was born Did the mother of the child receive any medication during the pregnancy Age at sitting without support Age at starting to walk at least 3 steps without help Parental concerns about the child’s fine motor skills Parental concerns about the child’s speech Parental concerns about the child’s learning skills at school Parental concerns about the child’s social behavior Soiling of pants with more than a smear in a period of three months Present if the child had two or more of the following: straining more than 25% of the time in passing stool lumpy or hard stools more than 25% of the time in passing stool having fewer than three bowel movements per week Diagnosis with ADHD Any frightening or emotionally stressful events that affected the child in the past six months Any anatomical abnormalities related to urinary system excluding urinary tract infection Microbiologically confirmed definite or probable UTI with parental reporting of positive UTI Parental reporting of a positive UTI but unable to confirm with a microbiological result Microbiologically normal results Daytime incontinence with a frequency of more than once in the past 6 months Micturating more than two times in a two hour period Rushing to the toilet to urinate Adopting any characteristic postures to avoid incontinence Having wet pants within half an hour of having passed urine
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21. Schum TR, Kolb TM, McAuliffe TL et al: Sequential acquisition of toilet-training skills: a descriptive study of gender and age differences in normal children. Pediatrics 2002; 109: E48. 22. Schum TR, McAuliffe TL, Simms MD et al: Factors associated with toilet training in the 1990s. Ambul Pediatr 2001; 1: 79. 23. McGrath KH, Caldwell PH and Jones MP: The frequency of constipation in children with noctur-
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26. Salmon J, Salmon L, Crawford DA et al: Associations among individual, social, and environmental barriers and children’s walking or cycling to school. Am J Health Promot 2007; 22: 107. 27. Austin MA, Criqui MH, Barrett-Connor E et al: The effect of response bias on the odds ratio. Am J Epidemiol 1981; 114: 137. 28. Maclure M and Hankinson S: Analysis of selection bias in a case-control study of renal adenocarcinoma. Epidemiology 1990; 1: 441.
EDITORIAL COMMENT The authors report the results of a large epidemiological study addressing the risk factors for nocturnal enuresis. They conclude that patients with NMNE (those with daytime symptoms and encopresis) have the more severe condition compared to those with MNE. This is the first known epidemiological study to calculate this risk, and it confirms the impression of caretakers of children with NE that patients with NMNE have a more severe condition. Taken together with the results of a large epidemiological study by Yeung et al,1 who observed
that patients with frequent bed-wetting have a more severe and longer lasting condition than those with low frequency bed-wetting, we now have more insight into the risk of this so-called benign disease, allowing us to identify the patient at risk for a long lasting condition. For these patients intensified therapy should be advised. Piet Hoebeke Department of Urology Ghent University Hospital Gent, Belgium
REFERENCE 1. Yeung CK, Sreedhar B, Sihoe JD et al: Differences in characteristics of nocturnal enuresis between children and adolescents: a critical appraisal from a large epidemiological study. BJU Int 2006; 97: 1069.