Prevalence of nocturnal enuresis, risk factors, associated familial factors and urinary pathology among school children in Iran

Journal of Pediatric Urology (2007) 3, 443e452

Prevalence of nocturnal enuresis, risk factors, associated familial factors and urinary pathology among school children in Iran Mohammad R. Safarinejad* Urology and Nephrology Research Center, Shaheed Beheshti University of Medical Sciences, P.O. Box 19395-1849, Tehran, Iran Received 23 March 2007; accepted 11 June 2007 Available online 13 August 2007

KEYWORDS Enuresis; School children; Associated factors; Urinary pathology; Epidemiology

Abstract Aim: To estimate the prevalence of enuresis in school-age children in Iran and determine associated factors. Materials and methods: A total of 7562 children, aged 5e18 years, enrolled in this crosssectional study. Using a standard questionnaire, data on demographic characteristics, and familial and physical conditions were obtained from the parents by interview. The ICD-10 definition of enuresis was used. In the case of enuretics, a detailed history was taken, and physical and ultrasonographic examinations, urinalysis and urine culture were performed. Results: The overall prevalence of enuresis was 6.8%. A significant relationship was found between the prevalence of enuresis and age (P Z 0.001), educational level of parents (P Z 0.001), number of family members (P Z 0.028), positive family history of enuresis (P Z 0.001), parenting methods (P Z 0.001), and deep sleep (P Z 0.001). Birth weight (P Z 0.07), monthly income (P Z 0.322), employment status of parents (P Z 0.08), ethnic differences (P Z 0.09), delayed development (P Z 0.062), drinking (P Z 0.072) or urination habit before sleep (P Z 0.06), and stool incontinence (P Z 0.062) were not significantly associated with enuresis. Prevalence of urinary tract pathology was 2.9% in enuretics. Conclusions: This study provides a quantitative estimate of the prevalence and main risk factors for enuresis in Iranian children. ª 2007 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Introduction Epidemiology has been defined as the study of the distribution and determinants of disease frequency in man [1].

* Tel.: þ98 21 22454499; fax: þ98 21 22456845. E-mail address: [email protected]

Enuresis is an important public health problem that can cause considerable distress to children and their parents [2e4], which has mandated population-based studies concerning the prevalence, determinants and consequences of this disorder. Despite recent advances in the understanding of the pathophysiology of enuresis, few population-based estimates of the prevalence in different ethnic groups are available. Enuresis prevalence may vary

1477-5131/$30 ª 2007 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2007.06.001

444 according to cultural, racial and health variables among countries. Several studies have been done in various countries worldwide to determine the prevalence of enuresis, but few were population-based and used probabilistic samples representative of the general population. Studies addressing associated family and risk factors are even scarcer. Enuresis prevalence is characterized by great geographical variability. Prevalence depends on the age group examined, the definition of enuresis, geographical areas involved, the composition of the population studied, the selection criteria and the method of study used. In European countries [5], the reported rate of prevalence of nocturnal enuresis is 9%e19% at 5 years, 7%e22% at 7 years, 5%e13% at 9 years, and 1%e2% at 16 years. A study in the United States [6] reported somewhat higher prevalence rates of 33% at 5 years, 18% at 8 years, 7% at 11 years, and 0.7% at 17 years. The prevalence of enuresis has been reported to be 18.6% in India [7], 3.8% in Italy [8], 9.2% in Korea [9], 8% in Malaysia [10], 5.5% in Taiwan [11], 4.2% in Thailand [12], 12.4% in Turkey [13], 18.9% in Australia [14], 15% in Saudi Arabia [15], 3.5% in Hong Kong [16], 6% in The Netherlands [17], 7.4% in New Zealand [18] and 13.7% in Sudan [19]. These reports indicate that rates vary between different cultural and ethnic groups, perhaps reflecting variations in attitudes and expectations towards the problem [16]. The Iranian population comprises a multiracial society that is culturally different from the communities in Asian and Middle-Eastern countries previously studied. The epidemiological study of enuresis has not been reported from Iran. Epidemiological data represent an invaluable tool for the development of strategies and allocation of adequate resources for providing assistance in a population. The present study was conducted to address this issue, and to identify the associated family and risk factors that contribute to enuresis.

Materials and methods This study was performed at kindergartens, elementary schools, guidance schools and high schools in Tehran, Iran. This geographical situation as well as the willingness of the general population to participate in medical programs caused the launch of a study. The study population comprised children in regular classrooms in kindergarten and first to twelfth grade. There are 20 educational areas in Tehran, and nearly 7000 schools (kindergartens, elementary schools, guidance schools and high schools). Roughly 1 300 000 students attend the different schools in Tehran. Because Tehran is a large city, a probabilistic two-stage cluster random sampling design was used, with stratification of the primary sampling units. The potential sampling frame covers 97% of all children in Tehran in this age range. The primary sampling units were educational areas, the secondary sampling units were schools, and the final sampling units were subjects. The secondary sampling units or schools were selected using the random route procedure and a computerized generated random number list. Extensive discussion of the sampling design and evaluations of sample and data quality are found in Laumann et al. [20]. Seventy-eight schools were chosen from these educational

M.R. Safarinejad areas. Every 100th children was included in the selection until the desired sample size was completed. The subjects were divided into four age groups, including ages 5e7, 8e10, 11e14 and 15e18 years. Sample sizes were determined for the 95% confidence interval with a design effect of 1.1. Using this assumption, a sample size of 6806 would be required. With a projected subject drop-out rate of 10% the total number of subjects required was determined to be 7562. Using a standard questionnaire, data were obtained from children’s parents by interviewers. Parents were approached during registration for the new school year. Interviewers were educators who had been instructed in the method of use by the author. Data were obtained using a questionnaire consisting of two parts, which was completed by the educators. The first section determined socio-demographic factors such as age, sex, ethnicity, parents’ marital status, parental educational level and employment status, parental relationship, father’s occupation, birth order of subject, socioeconomic status of the family, birth weight, family size, family history of enuresis, sleeping arrangements within the family home, child’s level of arousability from sleep, and presence of stressful and worrying events. This was followed by a question on the occurrence of bedwetting. The World Health Organization (ICD-10) definition of at least one wet night per month for three consecutive months was used. The second section classified the type of enuresis, being applicable only to those considered enuretic. Items included here were the presence of daytime wetting, night-time wetting, frequency of wetting, determinants of primary and secondary wetting, soiling, family history of wetting, UTI, medical illness, constipation, encopresis, behavioral problems such as thumb sucking, nail biting, hair pulling and teeth grinding, social problems such as aggression, attention deficit and learning problems, and previous therapies. Indicators of parental attitudes towards their enuretic child, including water restriction in the evening, getting the child to void before bedtime, willingness for future therapy, whether the child was embarrassed by his wetting, waking the child up at night to void, seeking physician advice, allowing for the child’s natural physiological process to mature, punishment and reward were also assessed. Primary enuresis was defined as a child who has never established urinary continence, while a child with secondary enuresis has had at least 6 months of uninterrupted dryness. The frequency of enuresis was divided into five groups: >5, 4e5, 2e3, 1 and <1 wet nights per week. To assess factors associated with the severity of enuresis, the children with enuresis were divided into those with >3 or 3 wet nights per week. Monthly incomes of the families were classified according to the minimum salary in Iran (2006) as follows: low (up to two times the minimum salary), medium (twoefour times the minimum salary) and high (five times the minimum salary or above). The child’s level of arousability from sleep (by asking whether he/she is a deep sleeper or not) was classified as high or low. Birth weight was categorized as low (<2.5 kg) and normal (>2.5 kg). A visual analog scale (VAS) was used to measure the variables of parental concern, child distress and management outcome. The variables of parental concern and child

Nocturnal enuresis and associated factors distress ranged from 0 (no concern) to 10 (high level of concern), and of outcome from 0 (not improved at all) to 10 (completely dry indefinitely). Parental and child concern was categorized into three groups: 1e3, minimal concern; 4e7, moderate concern; and 8e10, great concern. The baseline category was 1e3. The cut-off value for a great deal of parental concern and child distress was >7. Enuretic children and their parents were invited to the outpatient clinic for further evaluation. A detailed history was taken and a through physical examination was done by the author. Urine specimens were analyzed and urine cultures were performed. Ultrasonographic examination of the urinary system was performed in all children. Pyuria is defined as more than 10 leukocytes per high-power field under microscopic examination. Children with abnormal urine analysis, urine culture and ultrasonographic findings underwent further evaluation, including VCUG, IVU and DMSA scintigraphy.

Statistical analysis Data were summarized according to the cross-sectional design. After the sample was weighted according to the specified design, the prevalence and population estimates of the degree of enuresis in the population were obtained to construct 95% confidence intervals (CI). The clustered structure of the sample was taken into account in the calculation of CIs. Factors associated with enuresis were statistically analyzed using contingency table analysis, and the Chi-square and Fisher exact tests to determine independence. For assessing the prevalence of enuresis across demographic characteristics, logistic regressions were performed for each symptom. This approach produced adjusted odds ratios (ORs). The effect of factors and covariates on enuresis and the potential effect of interactions among factors and covariates on enuresis were also studied. Statistical significance was at P < 0.05. Statistical analysis was performed using SPSS/10.0 (SPSS, Chicago, IL, USA) and SAS/6.4 (SAS Institute Cary, NC, USA).

Results Study population Of the 7562 parents interviewed, 673 (8.9%) were excluded from analysis due to missing data (572) and response not completed personally (101). Baseline average age of the 6889 children in the analysis sample was 11.2  2.7 years (range 5e18) (95% CI: 3.41e7.12). Those children excluded from study did not significantly differ from the study group in regard to socio-demographic characteristics. There were 3341 (48.5%) males and 3548 (51.5%) females. Seventy-eight percent (5373) of the questionnaires were completed by the mothers, while response by the fathers accounted for the other 22% (1516).

Prevalence of enuresis and impact of age and sex Of the 6889 parents who provided information, 6.8% (468) (95% CI: 6.1e7.7) reported enuresis, comprising 4.8% (330) for nocturnal enuresis alone, 1.1% (76) for diurnal enuresis

445 Table 1

Prevalence of enuresis

Group Number Nocturnal Diurnal Boys Girls

3341 3548

166 (5) 161 (4.5)

Age group (years) 5e7 1748 156 8e10 1696 116 11e14 1744 35 15e18 1701 20 Total

6889

(9) (6.9) (2) (1.2)

327 (4.8)

Combined Total

39 (1.2) 32 (1) 38 (1.1) 32 (0.9)

237 (7.1) 231 (6.5)

37 27 8 5

224 166 49 29

(2.1) 32 (1.8) (1.6) 24 (1.4) (0.5) 6 (0.3) (0.3) 4 (0.2)

77 (1.1) 64 (0.9)

(12.8) (9.8) (2.8) (1.7)

468 (6.8)

Values are n (%).

alone and 0.9% (62) for combined day and night wetting (Table 1). Of all enuretic children 74.5% (349) had primary enuresis and 25.5% (119) had secondary enuresis. The most frequent category of bedwetting was ‘‘once a week’’. The severity of enuresis for the five categories of frequency (>5 to <1 wet night per week) was 3%, 5%, 28%, 49% and 15%, respectively; 8% of the 330 children had >3 wet nights per week. The prevalence of enuresis decreased with age (Chisquared linear test of trend 208.114, one degree of freedom, P Z 0.001). Table 1 lists the distribution of enuresis prevalence by age group. The prevalence decreased from 12.8% in children aged 5e7 years to 1.7% in those 15e18 years (test for trend, P Z 0.001). The youngest cohort of children (age 5e7 years) is more likely to experience enuresis in comparison to children aged 15e18 years (OR: 4.6; 95% CI: 2.6e6.4). Enuresis was slightly more frequent in males (7.1%) than females (6.5%) giving a male-to-female ratio of 1.2:1 (OR: 1.04; 95% CI: 0.67e1.36; P Z 0.722). Nocturnal, diurnal and combined day and night wetting were also slightly more common in boys than girls, but again this difference was not significant statistically (P Z 0.71).

Factors associated with enuresis For assessing the effect of different risk factors, univariate regression analysis was done. Enuresis was significantly associated with a positive family history of enuresis (Table 2). The odds ratio (OR) was highly significant (OR: 3.4; 95% CI: 1.9e5.4) for a family history of enuresis in siblings. A family history of enuresis was found in 48.5% (227/468) of enuretic children compared to 19.4% (1246/6421) in the non-enuretic group (P Z 0.001). A positive family history of enuresis was one of the strongest predictors in the logistic model. Soiling was also analyzed as an outcome variable. The difference between primary and secondary enuresis was significant for soiling: secondary enuretic children had a significantly higher rate of soiling (OR: 2.15; 95% CI: 1.70e3.36; P Z 0.03). Soiling had a negative association with age (OR: 0.87; 95% CI: 0.55e1.35; P Z 0.03). The prevalence for soiling tended to be lower in girls than in boys (OR: 2.16; 95% CI: 1.15e3.35; P Z 0.032). No positive association was found between soiling and parental education (OR: 0.91; 95% CI: 0.69e1.33; P Z 0.08), social class (OR: 1.17; 95% CI: 0.68e1.92; P Z 0.074), motor co-ordination (OR: 1.68; 95%

446

Table 2

M.R. Safarinejad

Prevalence of enuresis by demographic characteristics and risk factors surveyed

Variable

All cases, n (%)

Enuretic cases, n (%)

P-value

OR

95% CI

Age (years) 5e7 8e10 11e14 15e18

1748 1696 1744 1701

224 166 49 29

0.001 0.01 0.03 e

4.6 2.3 1.6 Reference

2.6e7.4 1.6e4.1 1.3e2.9 e

Sex Boys Girls

3341 (48.5) 3548 (51.5)

237 (7.1) 231 (6.5)

0.72 e

1.04 Reference

0.67e1.36 e

Family history Yes No

1473 (21.4) 5416 (78.6)

227 (15.4) 241 (4.4)

0.001 e

3.4 Reference

1.9e5.4 e

Father’s education (years) 12 5146 (74.7) >12 1743 (25.3)

320 (6.2) 148 (8.5)

0.001 e

2.86 Reference

1.9e4.3 e

Mother’s education (years) 12 4781 (69.4) >12 2108 (30.6)

156 (3.3) 312 (14.8)

0.001 e

0.8 Reference

0.61e1.12 e

No. of children Single child 2e4 children 5

599 (8.7) 6021 (87.4) 269 (3.9)

42 (7) 405 (6.7) 21 (7.8)

0.03 e 0.006

1.64 Reference 1.64

1.25e2.94 e 1.46e2.91

Father’s occupational status Yes 5725 (83.1) No 1164 (16.9)

388 (5.6) 80 (6.9)

e 0.063

Reference 1.27

e 0.90e1.72

Mother’s occupational status Yes 2184 (31.7) No 4705 (68.3)

145 (6.6) 323 (6.9)

e 0.08

Reference 1.14

e 0.81e1.77

Monthly income Low Medium High

304 (6.8) 112 (6.7) 52 (7.3)

0.322 0.41 e

1.14 0.89 Reference

0.47e1.46 0.62e1.55 e

Family marital status Married 5670 (82.3) Divorced 923 (13.4) Separated 296 (4.3)

364 (6.4) 73 (8) 31 (10.4)

e 0.001 0.03

Reference 4.21 1.84

e 2.75e5.77 1.42e2.70

Father raising style Democratic Rigid Permissive Combination

3629 623 1134 284

(64) (11) (20) (5)

203 70 73 18

(5.6) (11.2) (6.4) (6.3)

e 0.001 0.043 0.044

Reference 2.21 1.64 1.77

e 1.27e3.13 1.22e2.87 1.42e291

Mother raising style Democratic Rigid Permissive Combination

4423 340 567 440

(78) (6) (10) (6)

254 22 76 32

(5.7) (6.5) (13.4) (7.3)

e 0.037 0.001 0.041

Reference 1.41 2.74 1.67

e 1.17e2.73 1.82e3.67 1.44e282

e 0.062

Reference 1.18

e 0.75e1.91

(25.4) (24.6) (25.3) (24.7)

4499 (65.3) 1674 (24.3) 716 (10.4)

Developmental history On time 6324 (91.8) Delayed 565 (8.2)

(12.8) (9.8) (2.8) (1.7)

430 (6.8) 38 (6.7)

Nocturnal enuresis and associated factors

447

Table 2 (continued ) Variable

All cases, n (%)

Enuretic cases, n (%)

P-value

OR

95% CI

Drinking before sleep Yes 1977 (28.7) No 4912 (71.3)

131 (6.6) 337 (6.9)

0.072 e

1.22 Reference

0.83e2.13 e

Urination before sleep Yes 5291 (76.8) No 1598 (23.2)

355 (6.7) 113 (7)

e 0.06

Reference 1.62

e 0.81e2.73

Stool incontinence Yes No

117 (1.7) 6772 (98.3)

8 (6.8) 460 (6.8)

0.062 e

1.27 Reference

0.91e1.76 e

Menstruation Yes No

2050 (57.8) 1498 (42.2)

102 (5) 129 (8.6)

0.01 e

0.52 Reference

0.30e1.42 e

Reference Z the category used as the standard or reference point, with an OR of 1.0.

CI: 0.83e2.91; P Z 0.08), non-verbal reasoning (OR: 1.49; 95% CI: 0.80e2.63; P Z 0.08), and body mass index (OR: 1.44; 95% CI: 0.74e2.53; P Z 0.08). The present study does not support the presence of ethnic differences in the common risk factors for enuresis (OR: 1.16; 95% CI: 0.67e1.95; P Z 0.072). Maternal and paternal educations were analyzed together in a logistic model. The percentage of fathers and mothers who had received more than 12 years of education was 25.3% and 30.6%, respectively. Educational level was also determined and divided into three groups: (1) elementary school, (2) high school and (3) university graduate. The multivariate analysis was used to identify parental education levels with regard to enuresis. The baseline/comparison group was education level > 12. There was an increasing trend of enuresis in children with increasing mother education level. The OR was 1 for elementary school, 1.91 for high school and 3.11 for university graduate. Also, there was an increasing trend of enuresis in children with increasing father education level, with an OR of 1 for primary school, 1.46 for high school and 2.74 for university graduate. Stratified analyses were performed to examine the interactive effects of maternal and paternal education levels on the risk of childhood enuresis. A higher relative risk of enuresis was demonstrated in families with a father with a low educational level and a mother with a relatively higher education level (OR: 2.95; 95% CI: 1.70e5.33; P Z 0.001). When the father had an elementary school education, the OR was as high as 3.07 for the children of a mother with a high-school education. When the father had a high-school education and the mother was university graduate, the children were at as high as a 6.32-fold risk of enuresis compared to those with two parents with a primary school education. Of the recruited subjects, 82.4% were living in a family with two to three children. A positive correlation was found between the prevalence of enuresis and the total number of family members (3 or >3) (OR: 3.07; 95% CI: 2.17e4.25; P Z 0.028). The prevalence of enuresis was noted to be highest in single-child families (OR: 1.64; 95% CI: 1.25e 2.94; P Z 0.03) and in those with five or more children (OR: 1.64; 95% CI: 1.46e2.91; P Z 0.006) compared to the

average sized (two to four children) families (OR: 0.6; 95% CI: 0.3e1.6; P Z 0.042). In other words, there was a descending order of risk for enuresis as the rank of parity increased from first to fifth parity. Enuresis was significantly higher in children who slept in their own bedroom instead of a shared bedroom (OR: 2.84; 95% CI: 1.61e4.15; P Z 0.03), but whether the child’s bed was shared was not significant (OR: 1.22; 95% CI: 0.84e1.74; P Z 0.071). The fathers and mothers with employment were 83.1% and 31.7%, respectively. No positive association was found between enuresis and unemployment status of father (OR: 1.27; 95% CI: 0.90e1.72; P Z 0.063) or mother (OR: 1.14; 95% CI: 0.81e1.77; P Z 0.08). Monthly incomes were low in 65.3%, medium in 24.3%, and high in 10.4% of the families. A significant correlation between the prevalence of enuresis and monthly income was not found. The OR for the contrast between low and high monthly income was 1.14 (95% CI: 0.47e1.46; P Z 0.322). Parental raising methods were also assessed, and were divided into four major types: rigid, democratic, permissive and a combination of these methods. Paternal and maternal raising methods were democratic in 64% and 78%, rigid in 11% and 6%, permissive in 20% and 10%, and a combination of these methods in 5% and 6%, respectively. Fathers with a rigid style had the highest incidence of enuresis in their children (OR: 2.21; 95% CI: 1.27e3.13; P Z 0.001). The highest risk of enuresis was also seen in children with a mother who raised them permissively (OR: 1.76; 95% CI: 1.53e2.53; P Z 0.02). In this study, father and mother authoritarian raising styles caused a high incidence of enuresis. The OR for enuresis was 3.6 compared to families with two democratic parents. Enuresis was significantly associated with deep sleep (OR: 2.36; 95% CI: 1.38e3.75; P Z 0.04), divorced parents (OR: 4.21; 95% CI: 2.75e5.77; P Z 0.001) and separated family (OR: 1.84; 95% CI: 1.42e2.70; P Z 0.03). Low birth weight (OR: 1.19; 95% CI: 0.89e1.31; P Z 0.07), delayed development (OR: 1.18; 95% CI: 0.75e1.91; P Z 0.062), drinking (OR: 1.22; 95% CI: 0.83e2.13; P Z 0.072) or urination habit before sleep (OR: 1.62; 95% CI: 0.81e2.73; P Z 0.06), and stool incontinence (OR: 1.27; 95% CI: 0.91e1.76; P Z 0.062) were not significantly associated with enuresis.

448 Table 3 children

M.R. Safarinejad The perceived impact of enuresis on parents and

Grade of concern

No.

%

Parents 1e3 4e7 8e10

226 110 132

48.2 23.6 28.2

Children 1e3 4e7 8e10

137 57 226

32.5 13.5 54

Of the factors associated with the severity of enuresis, only deep sleep was associated in children with >3 wet nights per week (OR: 2.42; 95% CI: 1.3e4.24; P Z 0.001). The occurrence of menstruation was significant, having a protective effect (OR Z 0.52), suggesting that the hormonal changes at puberty may ameliorate enuresis.

Visual analog scale (VAS) The mean VAS for parental concern about wetting was 3.7 (Table 3). When parents were asked to grade their concern about their child’s enuresis and to specify how much distress it caused them, only 28.2% reported a ‘‘great deal’’ of concern. The baseline category was 1e3. There was a significant association between high level of parental concern (>7) and frequency of wetting (nocturnal enuresis, OR: 3.18; 95% CI: 2.27e4.15; P Z 0.008; diurnal enuresis, OR: 1.48; 95% CI: 1.28e2.21; P Z 0.014). Child distress related to wetting was assessed by parental report. The mean score for perceived child distress was 2.8. Fifty-four percent of enuretic children were significantly concerned about the impact of enuresis. The mean VAS for the outcome of management was 6.7. An inverse association existed between the outcome score and the frequency of enuresis (OR: 2.62; 95% CI: 1.42e4.68; P Z 0.02).

Parental strategies for managing enuresis Parents were asked to indicate their strategies towards their child’s bedwetting (Table 4). There was belief that Table 4

Methods and outcome of management

Strategies

No. (%) of children

VAS score for outcome

Family Restricting fluids Waking to void Urination before sleep Reward charts Wait for maturity

337 122 355 64 86

(72) (26) (75.9) (13.7) (18.4)

6 4 6 3 6

Professional Counseling Medication Bedwetting alarm Bladder training

21 368 32 47

(4.5) (78.6) (6.8) (10.1)

4 6 7 5

the child should become dry at a very early age: the mean anticipated age of dryness was 4.32 years. The distribution of enuretics according to what the parents viewed as the cause of the problem demonstrated that psychologic problems were primary. The causes that parents believed to be responsible for their child’s wetting were: psychologic problems 42.5%, deep sleep 36.4%, organic problem 31.6% and familial problem 38.2%. Most mothers had a rather tolerant strategy, but 68% of the mothers of children with severe enuresis had consulted a doctor, mainly a general practitioner or a pediatrician. Twelve percent of mothers showed an attitude expressed as ‘‘maternal intolerance’’. These mothers are certain that their child is wetting on purpose. They think the child is capable of controlling the bedwetting; they get angry with their child and even punish them. The rate of punishment in this study was 26%. Most of the physicians did not consider the child’s enuresis a problem and proposed no solution or a ‘‘wait and see strategy’’; when a treatment was proposed, it was a drug rather than an alarm, and mainly imipramine. Seventyeight percent of the mothers stated that most doctors do not pay enough attention to enuresis. Still, a majority of school health educators and teachers considered that enuresis could have a negative impact on children, influencing their social relationships and quality of life, and that more consideration should be paid to the problem.

Associated medical factors Of 468 enuretic children invited for further evaluation, 417 (89.1%) completed the whole study protocol: 310 children (74.3%) had nocturnal enuresis, 70 (16.8%) had diurnal enuresis only, and 37 (8.9%) had combined day and night wetting. Of these children, 314 (75.3%) were defined as primary and 103 (24.7%) as secondary enuretics. The distribution according to specialist and type of tests recommended showed that all specialists recommended urinary tests, with urine culture; sophisticated examinations were mostly requested by nephrologists and urologists. Physical examination of all the enuretics revealed no abnormal finding. Sixteen children (12 girls and four boys) had documented UTIs (positive urine cultures); 12 with nocturnal and four with diurnalenocturnal enuresis. Of these 16 children, nine had history of recurrent lower UTI, and ultrasonographic findings that were compatible with chronic cystitis (increase in urinary bladder wall thickness  10 mm). Ultrasonographic examination of the urinary tract revealed bilateral grade II hydronephrosis in five and unilateral grade II hydronephrosis in seven. Six children with secondary nocturnal enuresis had been diagnosed as having a PUJ obstruction and underwent an operation. Further investigations of the remaining seven cases with hydronephrosis revealed no anatomical or functional underlying urinary abnormalities. Overall prevalence of urinary pathology was 2.9% (12 cases) as identified by ultrasonographic examination.

Discussion Although enuresis is recognized as a widespread health problem, some controversy exists regarding its prevalence.

Nocturnal enuresis and associated factors Large differences are present in the prevalence of enuresis between countries. They may reflect medical and psychological factors, particularly in the setting of possible, socioeconomic, cultural and racial differences, the geographical areas involved, the composition of the population studied, the clinical definition used for enuresis, the type of trial performed (self-applicable questionnaire, mailed questionnaire, interview by phone, personal interview), and the characteristics of the samples (general population versus health clinics) studied. Population prevalence data are scarcer. In this study, a questionnaire designed with local characteristics and language in mind was administered. History taking was performed with great care. To minimize any embarrassment to children, the parents were assessed directly to obtain the information. The questionnaires were completed by trained interviewers. The questionnaire also recorded factors useful for establishing a familial connection with enuresis. The likelihood of sample bias was decreased as the questionnaires were anonymous until the parents had agreed to take part in the study. The prevalence of enuresis was found to be 6.8%. Studies on the epidemiology of enuresis often have a selection bias and sample sizes have frequently been too small to allow any definite conclusion. The present study used a random cluster sampling method, with an adequate sample size to estimate prevalence with acceptable accuracy. A comparison between the present results and those of other epidemiological studies show lower but more consistent values in this study. Definitions ranging from one wet episode in 6 months to two wet nights per week (DSM IV) have been used [8,9,21]. The definition of the frequency of wetting also differs considerably. Definitions of nocturnal enuresis range from one wet episode in 12 months [6], 6 months [21], 3 months [16] or 1 month [9,10,14,15,17,22], to two wet nights per week [17]. Studies from different countries show the prevalence rate for some degree of nocturnal enuresis in children aged 6e11 years to be 1.4%e28% [2,7e14,23e29]. The prevalence of enuresis in Iranian children in the present study was 6.8%; this is lower than in reports from Japan, Korea, Turkey and Western countries [2,6,8,9,14,22,23,28,30e35], but higher than that of China [36], Hong Kong [16] Italy [8] and Thailand [12]. The difference with the Hong Kong study possibly comes up because nocturnal enuresis was defined as at least one wet night every 3 months, which is more rigid than the present definition. The prevalence rate in this study was significantly lower compared to most reported series in other countries [9e12,14,15,19,22,37]. The previous studies on enuresis have revealed a wide variation in prevalence rates. This may be explained by the variation in selection criteria and definitions of enuresis used; whether differences in genetic predisposition or cultural background have an effect requires further investigation. The prevalence of bedwetting declines with age. In a community-based study in Baltimore, Oppel et al. [26] reported that among 5-year-old children 20% of the boys wet their beds at least once a month, compared to 21% of the girls, and by the age of 12 years only 5% of boys and 4% of girls wet their beds monthly. Likewise, a community-based study on the Isle of Wight, UK [38] demonstrated that

449 among 5-year-old children, 13.4% of boys and 13.9% of girls were bedwetters; the prevalence decreased to 3% among boys and 1.7% among girls by the age of 14 years. In this study the prevalence decreased from 12.8% in children aged 5e7 years to 1.7% in those 15e18 years. This finding is similar to those of all the previous studies in different countries [7e15,17e19,21,22,37], except the study in China [36] where the prevalence was nearly unchanged between 6 and 16 years of age. Enuresis is associated with male gender. There is a slightly higher prevalence in males than females in many studies [8,9,14e17,19,21,22,36,39]. Few studies did not reveal a similar preponderance [10,18], and some other studies demonstrated a female preponderance [2,23,40,41]. In the present study, gender does not have a significant effect on the prevalence of enuresis (P Z 0.72), with a prevalence of 7.1% in boys and 6.5% in girls. Some researchers believe that, since general continence is clearly linked with developmental maturity, perhaps females experience fewer problems in this area because they mature faster on average than males [42]. To determine the contribution of genetic factors in the etiology of enuresis concordance rates of mono- and dizygotic twins (MZ and DZ, respectively) have been compared. The rates were: 68% (36/53) for MZ and 36% for DZ twin pairs, and 46% for MZ and 19% for DZ twins [43]. The most common mode of transmission is autosomal dominant with high (90%) penetrance. Some genetic studies [44e46] reported that chromosome 4p (D4S2960) [47], 8q (D8S260, D8S257) [45], 12q (D12S80, D12S43, D12S86) [44e47], 13q (D13S291, D13S263) [46,48], and 22q (D22S446, D22S156, D22S257) [49] had a relationship with enuresis. Yet, the sex chromosome has not been found to be part of this association. Other linkage studies have defined different ‘‘loci’’ or ‘‘chromosome intervals’’ on, for example, chromosomes 12, 13 and 22 [50]. This phenomenon is recognized as ‘‘locus heterogeneity’’ which means that genes on different chromosomes can lead to the same disorder. There was no obvious relationship of any of the identified loci with any type of enuresis [51]. All possible candidate genes for nocturnal enuresis have been excluded [52]. Enuresis is one of the most common developmental disorders among children [53], and often leads to great concern and distress in affected children and their parents [2,40,54]; it may cause secondary emotional and social problems in children who continue to wet their bed [4]. In the present study, enuretic children and their parents were significantly distressed by the enuresis (54% and 28%, respectively). Haque et al. [40] reported that in the USA 61% of parents believed bedwetting to be a major problem and that one third dealt with it by punishment. Foxman et al. [2] also reported that two thirds of a large, representative sample of American parents were concerned about the symptom, and over half the children were distressed by the problem. In the present study familial factors associated with enuresis seemed to be family size, positive family history, child ranking, and the raising style and education level of the parents. Rona et al. reported that, in England and Scotland, primary nocturnal enuresis was more likely in a child who was not the first born in the family [55]. In this study,

450 also, birth order was a significant determinant of enuresis. When subject parity in the family was ranked first, the child was at higher risk for enuresis (P Z 0.03). In addition, there was a descending order of risk for enuresis as the rank of parity increased from first parity. Other studies have established an association between higher nocturnal enuresis and lower parental education level [35]. The present series showed a greater prevalence rate in children with mothers of a higher educational status. Positive family history in enuretic children has been reported in most of the previous studies [8,10,15,16, 18,21,22,56,57] as well. In one study, the recurrence risk for a child to be affected by enuresis was 40% if one parent and 70% if both parents had been enuretic [58]. In a clinical population study, a positive family history was found in 63.2% of the families, 22.2% of the fathers, 23.9% of the mothers and 16.5% of the siblings being affected [59]. In another cross-sectional epidemiological study, the risk for enuresis was five to seven times higher if one parent had a history of enuresis. If both parents had been affected, the risk ratio was 11.3 in comparison to healthy families [8]. In the present study, a family history of enuresis was found in 48.5% of enuretic children compared to 19.4% in the non-enuretic group (P Z 0.001). Family factors, such as low socioeconomic status [8,11] low educational level of parents [11,13,35,57], family size [13,56e60], birth order [11,15] and deep sleep [15,16,21, 61e63], were reportedly associated with enuresis, in agreement with this study. On the other hand, Spee-van der Wekke et al. [17] reported that the educational level of parents was not significantly related to the prevalence of nocturnal enuresis. In the present study, a higher relative risk of enuresis in children was demonstrated in families with a father with a lower education and a mother with a relatively higher education (P Z 0.001). Gu ¨r et al. [13] reported that nocturnal enuresis was more common in the children of unemployed mothers while diurnal enuresis was more common in the children of unemployed fathers. The present results do not show a positive association between enuresis and unemployment status of father (P Z 0.063) or mother (P Z 0.08). The prevalence of enuresis was significantly higher among children of larger families i.e. those with five or more children, compared to the average sized (two to four children) families (P Z 0.006). This is in agreement with the related literature. No positive association was found between enuresis and monthly income (P Z 0.322), consistent with the results of the Taiwanese [21], Italian and Turkish studies [8,35]. Deep sleep has been reported to be associated with enuresis in multiple studies [6,8,14,21,30,35], as in the present study (P Z 0.04). Watanabe and Kawauchi [64] demonstrated that the arousal centre was activated to turn deep sleep into light sleep when the bladder was distended. Irrespective of the cause of the inequality between nocturnal urine production and bladder reservoir function after sleep at night, bedwetting will not occur unless there is also an associated failure of conscious arousal in response to bladder fullness. Graham [65] concluded that it is uncertain whether enuretic children are more or less easy to wake than those who are not enuretic; apparently nocturnal enuresis can occur in both deep and lighter sleepers

M.R. Safarinejad [66]. In the present study, 72% of parents reported that their child was a deep sleeper. Parents who were worried about enuresis were more likely to attempt to treat it themselves, using medical intervention as a last resort. This practice is similar to that of some other countries [10,12,14,22,61]. They were more likely to restrict fluid intake and wake the child at night to void than were parents in either New Zealand [29] or the USA [67]. Pharmacological intervention was used by 78.6% of parents, while American, Irish and New Zealand children were treated by medication in 28%, 28% and 48% of cases, respectively [25], and Australian children in 4.7% of cases [14]. In this study the parents were less likely to be offered bladder training or counseling. Rona and Devlin reported that <50% of the parents in their samples had consulted a doctor regarding their child’s enuresis [25,55]. In the present study, 78.2% of parents said they would be willing to bring their child forward for assessment and treatment. The forms of therapy for nocturnal enuresis available in Iran are counseling, positive reinforcement, pharmacotherapy with tricyclic antidepressants or desamino-D-arginine vasopressin analogs and alarm systems. Common behavioral techniques used for the management of enuresis are restriction of fluid intake, waking the child at night to void, waiting for maturity and counseling [9,12,22]. The present results show these same behavioral strategies being used by parents. Most parents used the techniques of voiding before bedtime (75.9%) and waking the child at night to void (26%). This study does not support the presence of ethnic differences in the common risk factors for enuresis. This agrees with a Turkish study [13] but disagrees with a Malaysian study [10]. In contrast to monosymptomatic nocturnal enuresis, careful history taking and physical examination may reveal the possibility of any underlying definable and perhaps treatable cause. Any child with non-monosymptomatic bedwetting, or with physical signs of neurological or anatomical anomalies, or with persistent UTIs, should be referred for further urological evaluation. In this sample overall prevalence of urinary pathology was 2.9% (12 cases) as identified by ultrasonographic examination. Documented UTI was present in 3.8% (16 cases).

Conclusion This was the first large population-based study of the prevalence of enuresis in Iran. The relatively low prevalence rate found compared to those reported from other countries may be due to differences in genetic predisposition, psychosocial or environmental conditions, and traditional and cultural background. It would be desirable to conduct more population-based studies throughout the world with a consensus on working definitions to obtain more accurate epidemiological data on enuresis, and to compare studies and therapeutic responses. An agreement regarding the age range of participants would also be worthwhile.

Acknowledgments Thanks to many coordinators, project managers and data reviewers who assisted in this study.

Nocturnal enuresis and associated factors The expert secretarial assistance Safarinejad is highly appreciated.

451 by

Miss

Shiva

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