Printer Friendly

Risk Factors of Nocturnal Enuresis in Children with Attention Deficit Hyperactivity Disorder.

1. Introduction

Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder in children, which is manifested by impulsive, hyperactive, and inattentive behaviors.[1] The worldwide prevalence of ADHD in children is about 5%, with no significant difference among different geographic regions.[2] It is reported that 50 % of children with ADHD suffer from psychiatric comorbidities that often continue into adulthood.[3,4]

Children with ADHD commonly experience sleep problems such as resistance towards going to bed and night awakenings.[5,6] These problems are usually originated from non-biological causes, but can also be the result of undiagnosed biological sleep problems such as restless leg syndrome (RLS), sleep disordered breathing (SDB) or nocturnal enuresis (NE),[7] which are associated with poorer daily functioning.[6] NE is defined as urinary incontinence during sleep in children older than 5 years after excluding organic causes.[8]

The prevalence of NE in patients with ADHD has been estimated to be 28-32%.[9,10] The association between NE and ADHD has been investigated in several previous studies.[11-16] The etiology of NE has been demonstrated to be associated with neurological maturation. Previous studies have reported that children with NE had a higher incidence of delayed language and gross motor development.[17-21] It was shown that the presence of ADHD had a negative effect on the resolution of incontinence and treatment of urinary incontinence in children with ADHD compared to those without ADHD.[22]

Although, different studies demonstrated the role of neonatal sepsis,[23] head injury,[24] low birth weight,[25] prematurity and gestational age[25,26] as risk factors for ADHD, there are few studies which investigated the risk factors of NE in patients with ADHD. This study was conducted to investigate the prevalence of NE and its risk factors in children with ADHD.

2. Methods

2.1 Participants

This study was approved by the Research Council and Ethical Committee of the Kermanshah University of Medical Science and carried out between September 2014 and August 2015. Written informed consent was obtained from all participants' parents. During the study period, we consecutively enrolled 344 children, aged 6 to 10 years, diagnosed as having ADHD as well as children with confirmed ADHD who presented for the follow-up in the Psychiatric Clinics of Farabi Hospital, Kermanshah, Iran. Children with other mental disorders such as mental retardation, intellectual disability (i.e., IQ<70), pervasive developmental disorder, seizure, and urinary tract infection/disorders were excluded from the study.

The diagnosis of ADHD was confirmed by an experienced child and adolescent psychiatrist according to DSM-IV-TR[27] and the ADHD rating scale (ADHD-RS).[28] The ADHD-RS includes 18 items that each shows one ADHD symptom according to DSM-IV-TR criteria. It may be used for ages ranging from 5 to 18 years and is useful for differentiation of ADHD and healthy children, and differentiates attention deficit symptoms from hyperactivity and impulsivity symptoms. The ADHD-RS has been used extensively in Iran and the reliability of this instrument showed alpha Cronbach's as 0.81.[28]

NE was defined as nighttime wetting with or without daytime incontinence, at least twice a week over a period of 3 months or longer in children 5 years old and older without anatomical abnormalities. NE was diagnosed by a pediatric urologist and was examined by urinalysis, renal sonography, and interview with children and their parents. Details on demographic data, perinatal history, medical history and developmental history were collected from parents or medical records.

2.2 Statistical analysis

Statistical analysis was conducted using SPSS version 19.0. The Student t-test and [chi]2 test were used to compare the variables between the groups. A p value of less than 0.05 was regarded as significant.

3. Results

During the 11 month study period, from 344 children with ADHD, 13 children were excluded from the study and the 331 remaining children with a diagnosis of ADHD were enrolled in this study. Mean (sd) age of study participants was 7.9 (1.3) years (range 6-11 years) and 205 of them were boys. A total of 49 children were diagnosed with the inattentional subtype (14.8%), 104 with the hyperactive/impulsive subtype (31.4%) and 178 with the combined subtype (53.8%) according to the DSM-IV-TR criteria (Table 1). The prevalence of NE among the 331 children with ADHD was 33.5% (111/331). So, we divided the children with ADHD into two groups according to presence of NE and assessed risk factors between the two groups.

The mean (sd) age of ADHD diagnosis was slightly higher in the NE group, but did not reach statistical significance (5.7 (1.9) in NE group vs. 5.2 (1.9) in non-NE group; p=0.055, t=2.48). Furthermore, compared with the non-NE group, significantly more children with NE were boys (p=0.007, t=7.28).

Among children with enuresis, there was a significantly higher rate of history of familial enuresis (26% vs. 18 %, p<0.001, t=16.9), cesarean delivery (47% vs. 33%, p=0.019, t=5.84) as well as history of neonatal sepsis (16% vs. 7%, p=0.018, t=5.62) compared to non-NE children. Moreover, patients with NE had a lower birth weight than non-NE patients (2.93 (0.65) vs. 3.09 (0.46), p=0.026, t=2.51). Regarding parents education level, our results showed that low parental education was associated with increase in the rate of NE (p<0.001, t=56.17) (Table 2).

There was a significant difference between the non-NE and NE groups with respect to ADHD subtype. Most of the ADHD patients with inattentional subtype (38/49 patients (77.5%)) had NE, compared to 33/104 patients (31.7%) in hyperactive/Impulsive and 40/178 patients (22.5%) in combined subtypes (p<0.001, t=42.7) (Table 2).

There were no significant differences in terms of gestational age at birth, history of neonatal icter, and motor or language developmental delay, between the NE and non-NE groups. Furthermore, the rate of Ritalin use was more among non-NE children compared with NE, however, this difference did not reach statistical significance (49% in NE group vs. 59% in non-NE group; p=0.084, t=2.99) (Table 2).

Enuresis was most common in children 7 to 9 years of age. Incidence of NE was the following: children aged <7 years, 52 children (46.8%), aged 7-7.9 years, 20 children (18%), children aged 8-8.9 years, 26 children (23.4%) , children aged 9-9.9 years, children aged >10 years, only 8 (7.2%) and 5 (4.5%) children had enuresis, respectively.

4. Discussion

4.1 Main findings

The aim of this study was to better understand the correlation between nocturnal enuresis and ADHD as well as the risk factors of NE in children with ADHD. Comorbidity of ADHD and nocturnal enuresis has been shown in several studies.[9-13] In our study, the prevalence of NE in children with ADHD was 33.5%. This is roughly in agreement with other studies which reported 32% and 28.3% prevalence rate of NE in children with ADHD.[9-10] The exact pathogenesis of the high incidence of NE in ADHD children is not clear. It has been suggested that delay in maturation of the central nervous system could account for the association between enuresis and ADHD.[18-20] Also, a brainstem inhibition deficit in children with enuresis, could explain why they are unable to remain dry at night.[18] Several previous studies have suggested that primary NE happens when a child with ADHD can't wake up when the urinary bladder is full or be awake enough to get up and go to the toilet when there is an urge to urinate.[19-21]

In our study, most of the enuretic children were 6-8 years old. In a study of the prevalence of ADHD in enuretic children in Belgium, the older children (9 to 12 years), had a higher prevalence of ADHD.[21] However, in a study by Yang et al in Taiwan, the mean (sd) ages of enuretic and nonenuretic children with ADHD were 7.53 (1.06) and 7.26 (1.03) respectively, which was not a statistically significant difference (p=0.04).[9]

Yang et al found no association between NE and birth weight, gestational age, type of delivery, neonatal icter, and maternal education in children with ADHD. [9] However we found a significant correlation between birth weight as well as type of delivery and NE in ADHD. Our data revealed that children with NE had lower birth weight than non-NE children, and also, children who were given birth by caesarian had a higher risk for developing NE. It has been shown that low birth weight was significantly associated with delay in achieving all developmental milestones including walking alone, meaning speech, and bedwetting cessation.[29] We also investigated the correlation between parental education and NE and concluded that the lower parental educational level was associated with higher prevalence of NE in ADHD children.

In our study, children who had a history of neonatal sepsis had a higher risk for developing NE compared with children without a history of neonatal sepsis. Although the association of neonatal sepsis and NE is not clear and the origin of sepsis in our cases was unknown, some studies showed that a history of infection, especially urinary tract infection, was significantly associated with NE. It may be due to the negative effects of infection on the lower urinary tract. It has been shown that vesicoureteral reflux (VUR) might be more frequent in children with NE with intermittent daytime incontinence.[30]

In the present study, a meaningful association was seen between family history of NE and developing NE in patients with ADHD. This may indicate the role of genetics in NE in children with ADHD. Norgaard et al., in their review reported that when both parents were enuretic as children, their offspring had a 77% risk of having nocturnal enuresis. The risk was 43% when one parent was enuretic and 15% when neither parent was enuretic.[31] Furthermore, Bailey et al., reported a positive family history enurenesis in 65-85% of children with NE. If the father or the mother was enuretic as a child, the relative risk for his/her child was 7.1 and 5.2, respectively.[32] In addition, certain chromosomal loci (5, 13, 12, and 22) have been implicated in nocturnal enuresis,[33, 34] of which suggestive linkage to chromosomes 12 and 13 were shown in children with ADHD.[35]

In our study, 77.5% of ADHD children with inattentional subtype had NE, compared to 31.7% in the hyperactive/Impulsive subtype and 22.5% in the combined subtype. Baeyens et al showed that 15% of all enuretic children were diagnosed with the full syndrome of ADHD, an additional 22.5% and 2.5% met the DSM-IV criteria of the ADHD predominantly inattentive and predominantly hyperactive impulsive subtypes, respectively. Their study revealed a brainstem inhibition deficit in children with enuresis, which could explain why they are unable to remain dry at night. When additional attention is allocated to specific trials in the task, children with attention deficit hyperactivity disorder of the predominantly inattentive subtype, failed to optimize sensory gating. With respect to enuresis, this could result in an identification problem of bladder signals, leading to an inadequate or absent arousal effect in attention deficit hyperactivity disorder of the predominantly inattentive subtype.[36]

4.2 Limitations

The main limitation of this study is that the findings were based on interviews with children and their parents and in using this retrospective method some details may have been overlooked.

4.3 Implications

The investigation of the risk factors of NE in patients with ADHD provides useful information about neonatal, familial and environmental factors oaffecting the prevalence of NE in ADHD patients.

5. Conclusions

Children with ADHD have a high prevalence of NE. factors like male sex, low educational level of parents, history of neonatal sepsis, positive family history of NE, low birth weight and caesarian delivery may be risk factors for NE in ADHD children. Most of the children diagnosed as having ADHD inattentional subtype had NE.

Funding statement

No funding was obtained for this study.

Conflict of interest statement

The authors declare no conflict of interest related to this manuscript.

Ethical approval

All procedures were approved by the institutional ethics committee of the Kermanshah University of Medical Sciences (KUMS)

Informed consent

Written consent and/or assent were obtained from the parents.

Authors' contributions

Study design: HK & HA

Assessments: HK, FE, HA & MRM

Data analysis: MRG

Questionnaire evaluation: HK, MRG, FE, HA & MRM

Manuscript writing: HK & MRG

[phrase omitted]


[1.] American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, fifth edition. DC, Washington: American Psychiatric Association; 2013. P. 271-272

[2.] Polanczyk G, Delima Ms, Horta BL, Biderman J, Rohde LA. The worldwide prevalence of ADHD: A systematic review and met regression analysis. Am J Psychiatry. 2007; 169(6): 924-980. doi:

[3.] Gillberg C, Gillberg IC, Rasmussen P, Kadesjo B, Soderstrom H, Ristam M, et al. Co-existing disorders in ADHD-implications for diagnosis and intervention. Eur Child Adolesc Psychiatry. 2004; 13(1): 80-92. doi:

[4.] Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler 0, et al. The prevalence and correlates of adult ADHD in the United States: results from the national comorbidity survey replication. Am J Psychiatry. 2006; 163(4): 716-723. doi:

[5.] Cortese S, Faraone SV, Konofal E, Lecendreux M. Sleep in children with attention-deficit/hyperactivity disorder: metaanalysis of subjective and objective studies. J Am Acad Child Adolesc Psychiatry. 2009; 48(9): 894-908. doi:

[6.] Sung V, Hiscock H, Sciberras E, Efron D. Sleep problems in children with attention-deficit/hyperactivity disorder: prevalence and the effect on the child and family. Arch Pediatr Adolesc Med. 2008; 162(4): 336-342. doi:

[7.] Cortese S, Lecendreux M, Mouren M-C, Konofal E. ADHD and insomnia. J Am Acad Child Adolesc Psychiatry. 2006; 45(4): 384-385. doi:

[8.] Austin PF, Bauer SB, Bower W, Chase J, Franco I, Hoebeke P, et al. The standardization of terminology of lower urinary tract function in children and adolescents: update report from the standardization committee of the international children's continence society. J Urol. 2014; 191: 1863-1865. doi:

[9.] Yang TK, Huang KH, Chen SC,Chang HC, Yang HJ, Guo YJ. Correlation between clinical manifestations of nocturnal enuresis and attentional performance in children with attention deficit hyperactivity disorder (ADHD). J Formos Med Assoc. 2013; 112: 41-47. doi:

[10.] Robson WL, Jackson HP, Blackhurst D, Leung AK. Enuresis in children with attention-deficit hyperactivity disorder. South Med J. 1997;90:503-505

[11.] Baeyens D, Roeyers H, Demeyere I, Verte S, Hoebeke P, Vande Walle J. Attention-deficit/hyperactivity disorder (ADHD) as a risk factor for persistent nocturnal enuresis in children: a two-year follow-up study. Acta Paediatr. 2005; 94: 1619-1625. doi:

[12.] Baeyens D, Roeyers H, D'Haese L, Pieters F, Hoebeke P, Vande Walle J. The prevalence of ADHD in children with enuresis: comparison between a tertiary and non-tertiary care sample. Acta Paediatr. 2006; 95: 347-352. doi:

[13.] Baeyens D, Roeyers H, Van Erdeghem S, Hoebeke P, Vande Walle J. The prevalence of attention deficit hyperactivity disorder in children with non mono symptomatic nocturnal enuresis: a 4-year follow-up study. J Urol. 2007; 178: 2616-2620. doi:

[14.] Duel BP, Steinberg-Epstein R, Hill M, Lerner M. A survey of voiding dysfunction in children with attention deficit hyperactivity disorder. J Urol. 2003; 170: 1521-1523. doi:

[15.] Elia J, Takeda T, Deberardinis R, Burke J, Accardo J, Ambrosini PJ, et al. Nocturnal enuresis: a suggestive endophenotype marker for a subgroup of inattentive attention deficit/hyperactivity disorder. J Pediatr. 2009; 155: 239-244. doi:

[16.] Burgu B, Aydogdu 0, Gurkan K, Uslu R, Soygur T. Lower urinary tract conditions in children with attention deficit hyperactivity disorder: correlation of symptoms based on validated scoring systems. J Urol. 2011; 185: 663-668. doi:

[17.] Baeyens D, Roeyers H, Naert S, Hoebeke P, Vande Walle J. The impact of maturation of brainstem inhibition on enuresis: a startle eye blink modification study with 2-year followup. J Urol. 2007; 178: 2621-2625. doi:

[18.] Baeyens D, Roeyers H, Hoebeke P, Antrop I, Mauel R, Walle JV. The impact of attention deficit hyperactivity disorders on brainstem dysfunction in nocturnal enuresis. J Urol. 2006; 176: 744-748. doi:

[19.] Bosson S, Holland PC, Barrow S. A visual motor psychological test as a predictor to treatment in nocturnal enuresis. Arch Dis Child. 2002; 87: 188-191. doi:

[20.] Butler RJ, Holland P, Gasson S, Norfolk S, Houghton L, Penney M. Exploring potential mechanisms in alarm treatment for primary nocturnal enuresis. Scand J Urol Nephrol. 2007; 41: 407-413. doi:

[21.] Chertin B, Koulikov D, Abu-Arafeh W, Mor Y, Shenfeld OZ, Farkas A. Treatment of nocturnal enuresis in children with attention deficit hyperactivity disorder. J Urol. 2007; 178: 1744-1747. doi:

[22.] Crimmins CR, Rathbun SR, Husmann DA. Management of urinary incontinence and nocturnal enuresis in Attention-Deficit Hyperactivity Disorder. J Urol. 2003; 170:1347-1350. doi:

[23.] Ree M, Tanis J, Van Braeckel K, Bos A, Roze E. Functional impairments at school age of preterm born children with late-onset sepsis. Early Hum Dev. 2011; 87: 821-826. doi:

[24.] Schachar R, Levin H, Max J, Purvis K, Chen S. Attention Deficit Hyperactivity Disorder Symptoms and Response Inhibition After Closed Head Injury in Children: Do Preinjury Behavior and Injury Severity Predict Outcome? Dev Neuropsychol. 2004; 25(1-2): 179-198. doi:

[25.] Linnet KM, Wisborg K, Agerbo E, Secher N, Thomsen P, Henriksen T. Gestational age, birth weight, and the risk of hyperkinetic disorder. Arch Dis Child. 2006; 91: 655-660. doi:

[26.] Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, Chang WH, et al. Is neonatal jaundice associated with autism spectrum disorder, attention deficit hyperactivity disorder, and other psychological development? A nationwide prospective study. Res Autism Spectr Disord. 2014; 8: 625-632. doi:

[27.] American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC & London: American Psychiatric Association; 2000

[28.] Amiri S, Shafiee-Kandjani AR, Fakhari A, Abdi S, Golmirzaei J, Akbari Rafi Z, et al. Psychiatric comorbidities in ADHD children: an Iranian study among primary school students. Arch Iran Med. 2013; 16(9): 513-517. doi:

[29.] Liu X, Sun Z, Neiderhiser JM, Uchiyama M, Okawa M. Low birth weight, developmental milestones, and behavioral problems in Chinese children and adolescents. Psychiatry Res. 2001; 101(2): 115-129. doi:

[30.] Boybeyi O, Asian MK, Durmus EG, Ozmen i, Soyer T. A comparison of dysfunctional voiding scores between patients with nocturnal enuresis and healthy children. Turk J Med Sci. 2014; 44(6): 1091-1094

[31.] Norgaard JP, Djurhuus JC, Watanabe H, Stenberg A, Lettgen B. Experience and current status of research into the pathophysiology of nocturnal enuresis. Br J Urol. 1997; 79: 825-835. doi:

[32.] Bailey JN, Ornitz EM, Gehricke JG, Gabikian P, Russell AT, Smalley SL. Transmission of primary noctur nal enuresis and attention deficit hyperactivity disorder. Acta Paediatr. 1999; 88: 1364-1368. doi:

[33.] Djurhuus JC. Definitions of subtypes of enuresis. Scan J Urol Nephrol Suppl. 1999; 202: 5-7

[34.] Fergusson DM, Horwood L J, Shannon FT. Factors related to the age of attainment of nocturnal bladder control: an 8-year longitudinal study. Pediatrics. 1986; 78: 884-890

[35.] Frazier-Wood AC, Bralten J, Arias-Vasquez A, Luman M, Ooterlaan J, Sergeant J, et al. Neuropsychological intra-individual variability explains unique genetic variance of ADHD and shows suggestive linkage to chromosomes 12, 13, and 17. Am J Med Genet B Neuropsychiatr Genet. 2012; 159(2): 131-140. doi:

[36.] Baeyens D, Roeyers H, Hoebeke P, Verte S. Hoeck E, Vande Walle J. Attention deficit/hyper activity disorder in children with nocturnal enuresis. J Urology. 2004; 171: 2576-2579. doi:

Habibolah KHAZAIE, Farshid EGHBALI, Houshang AMIRIAN, Mahmoud Reza MORADI, Mohammad Rasoul GHADAMI (*)

Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

(*) correspondence: Mohammad Rasoul Ghadami. Mailing address: Sleep Disorders Research Center, Farabi Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran. Postcode: PO Box 6719851151. E-Mail:

Dr. Habibolah Khazaie obtained his speciality of Psychiatry from Tabriz University of Medical Sciences, Tabriz, Iran in 2002. He has been working in the Department of Psychiatry, Kermanshah University of Medical Sciences, Kermanshah, Iran since 2002 and now is a professor. He is also the head of the Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. His research interest is sleep disorders.

Table 1. Demographic data of participants (n=331)

Mean (sd) age in years    7.9 (1.3)
Sex (m)                 205 (61.9)
ADHD subtype
Inattentional            49 (14.8)
Hyperactive/Impulsive   104 (31.4)
Combined                178 (53.8)

Data presented as mean (SD) or number (%)

Table 2. Comparison of risk factors between groups

                                      Non-NE group (n=220)

Age (mean [sd])                         5.2(1.9)
Sex (Male)                            125 (56.8)
ADHD subtype (%)
 Inattentional (n=49)                  11 (22.5)
 Hyperactive/Impulsive (n=104)         71 (68.3)
 Combined (n=178)                     138 (77.5)
Familial history of NE(%)              20 (9)
Delivery by cesarean section (%)       73 (33.1)
Birth weight (mean [sd])                3.09 (0.46)
Gestational age at birth (mean [sd])   37 (1.2)
History of neonatal icter (%)          62 (28.1)
History of neonatal sepsis (%)         17 (7)
Motor or language developmental         9 (4)
delay (%)
Ritalin use (%)                       131 (59)
Parents education (%)
 Illiterate                             2 (1)
 Elementary school                     77 (35)
 High school                           99 (45)
 Academic                              42 (19)

                                      NE group (n=111)  Statistics

Age (mean [sd])                        5.7(1.9)         t= 2.48
Sex (Male)                            80 (72)           [X.sup.2]=7.28
ADHD subtype (%)
 Inattentional (n=49)                 38 (77.5)         [X.sup.2]=42.71
 Hyperactive/Impulsive (n=104)        33 (31.7)
 Combined (n=178)                     40 (22.5)
Familial history of NE(%)             29 (26.1)         [X.sup.2]=16.97
Delivery by cesarean section (%)      52 (46.8)         [X.sup.2]=5.84
Birth weight (mean [sd])               2.93 (0.65)      t=2.51
Gestational age at birth (mean [sd])  37 (0.5)          t=0.78
History of neonatal icter (%)         36 (32.4)         [X.sup.2]=0.64
History of neonatal sepsis (%)        18 (16.2)         [X.sup.2]=5.62
Motor or language developmental       10 (9)            [X.sup.2]=3.29
delay (%)
Ritalin use (%)                       55 (49)           [X.sup.2]=2.99
Parents education (%)
 Illiterate                           18 (16)
 Elementary school                    33 (30)           [X.sup.2]=56.17
 High school                          59 (53)
 Academic                              1 (1)


Age (mean [sd])                        0.055
Sex (Male)                             0.007
ADHD subtype (%)
 Inattentional (n=49)                 <0.0001
 Hyperactive/Impulsive (n=104)
 Combined (n=178)
Familial history of NE(%)             <0.0001
Delivery by cesarean section (%)       0.019
Birth weight (mean [sd])               0.026
Gestational age at birth (mean [sd])   0.938
History of neonatal icter (%)          0.424
History of neonatal sepsis (%)         0.018
Motor or language developmental        0.069
delay (%)
Ritalin use (%)                        0.084
Parents education (%)
 Elementary school                    <0.0001
 High school

[Please note: Some non-Latin characters were omitted from this article]
COPYRIGHT 2018 Shanghai Mental Health Center
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2018 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Khazaie, Habibolah; Eghbali, Farshid; Amirian, Houshang; Moradi, Mahmoud Reza; Ghadami, Mohammad Ras
Publication:Shanghai Archives of Psychiatry
Article Type:Report
Date:Feb 1, 2018
Previous Article:The Study of White Matter Hyperintensity (WMH) and Factors Related to Geriatric Late-Onset Depression.
Next Article:Defects of Gamma Oscillations in Auditory Steady-State Evoked Potential of Schizophrenia.

Terms of use | Privacy policy | Copyright © 2021 Farlex, Inc. | Feedback | For webmasters |