All pediatric clinicians will encounter patients and their parents seeking care for the issue of bedwetting, also known as nocturnal enuresis, which refers to urination while asleep in a child older than age 5 years. Enuresis is classified into “monosymptomatic” and “nonmonosymptomatic” types, with the former referring to bedwetting plus no other symptoms, and the latter referring to bedwetting plus other urinary tract symptoms (daytime incontinence, infections, urinary urgency or retention with holding maneuvers, abnormal urine stream, forced voiding) and bladder dysfunction.1–3 This condition is even further distinguished into primary versus secondary types; secondary refers to bedwetting recurring after bladder control has been achieved for at least 6 months.4
Pediatric clinicians need to be well versed on the current concepts of etiology, comorbid conditions, and management of enuresis, as misconceptions still exist in the 21st century in relation to this issue. Schlomer et al.5 reported that a substantial percentage (42%) of surveyed parents believed that characteristics such as laziness, defiance, and attention seeking were responsible for bedwetting episodes. In the same survey, less than one-third of parents knew that there were effective treatments available for the condition.5 The pediatric clinician has a key role in dispelling these misconceptions when parents seek assistance. An update is provided here to enhance the pediatric clinician's understanding of the etiology, epidemiology, presentation, evaluation, and treatment of enuresis of the primary, monosymptomatic type (Table 1).
Basic Approach to Primary,Monosymptomatic Enuresis Management
Sporadic cases occur, but its familial occurrence reveals that a genetic predisposition exists for enuresis.6 Järvelin et al.7 documented a 77% risk of having nocturnal enuresis if both parents have a history compared to 43% if only one parent had enuresis. The three main factors implicated in the pathophysiology of enuresis include the neurological system with its neurotransmitters and receptors, bladder dysfunction, and the alteration in the circadian rhythm. These three factors contribute to a small nocturnal bladder capacity, increased nocturnal urine production due to a disturbance in the pattern of antidiuretic hormone secretion, and the lack of arousal when the bladder is full.8,9 Although not part of the definition, bladder dysfunction (such as detrusor overactivity) has been found in a minority of children with a history of monosymptomatic nocturnal enuresis who were referred to a pediatric nephrology clinic.10 The contribution of associated conditions, such as behavioral and sleep disorders, to the persistence of enuresis is an area of on-going research.11–13
The reported prevalence of enuresis includes rates of 15.5% in children age 6 to 8 years and 4.1% in children age 10 to 12 years.14,15 These statistics do not differentiate between monosymptomatic and nonmonosymptomatic enuresis. The monosymptomatic type is reportedly more common, as indicated in a study of 111 patients age 5 to 17 years who presented to a pediatric nephrology clinic. Nearly two-thirds of these patients had the diagnosis of monosymptomatic enuresis and approximately 70% were boys.16 A similar predominance of boys was also reported by Fagundes et al.,4 along with the presence of a positive family history of nocturnal enuresis in more than 90% of first- and second-degree relatives, wheras constipation was present in 89.3% and mild to moderate apnea in 40.7%.
The typical presentation of monosymptomatic enuresis involves a parent who is concerned that their school-aged child is still wetting the bed. Monosymptomatic enuresis of the primary variety implies that wetting occurs only when the child is asleep, there has not been more than 6 months of nighttime dryness, and there are no other urinary tract symptoms. The parent and/or child may express emotional distress because of the bedwetting. Because familial occurrences are common, the parent may describe a personal experience and history with enuresis. Children who continue to be enuretic into the late pre-teen years, such as age 11 years and older, experience more psychosocial difficulties,17 and are therefore usually more interested than younger children in seeking treatment for their condition. Enuresis has been reported to be associated with impaired quality of life, anxiety, lower self-esteem, and poor academic performance.14,18,19 Constipation, sleep disorders (including sleep apnea), daytime sleepiness, and attention-deficit/hyperactivity disorder have also been found to be associated with enuresis.19–22
The major goal of the diagnostic evaluation in the primary care pediatrics clinic is to obtain an accurate and thorough history and physical examination to ensure the condition is truly primary and monosymptomatic, and that there are no anatomical abnormalities or comorbidities. Limited diagnostic studies are needed in the evaluation of primary, monosymptomatic enuresis. Particularly important parts of the history include the child's age, growth pattern, daytime elimination habits and symptoms (such as daytime incontinence, urinary urgency or retention with holding maneuvers, abnormal urine stream, forced voiding, constipation, and snoring), neurologic symptoms (such as abnormal gait and weakness), spinal abnormalities (such as sacral dimple, lipoma, or tuft of hair), and psychosocial concerns. The clinician is recommended to thoroughly explore the psychological impact on the patient.21 Parental history of enuresis and age of resolution of parents' symptoms should be elicited. Oguz et al.23 reported that there was a positive correlation between children and their parents regarding the mean ages of spontaneous resolution of enuresis.23 The physical examination should focus on the genitals, spine, and neurologic system.
Besides the history and physical examination, a voiding diary is also a suggested part of the enuresis diagnostic evaluation.24 Diary entries should include the number of wet nights and any other urinary symptoms over a 1- to 2-week time span. The measuring of urine output is recommended,2 but it is not always practical to perform at home, so parents must be provided with careful instruction to increase compliance. Timing and amount of fluid intake may also be recorded and correlated with voiding times and amounts. Obtaining a detailed voiding diary may uncover clues that the child is suffering from nonmonosymptomatic enuresis, and that a more aggressive evaluation would be necessary. Practice consensus guidelines emphasize the importance of voiding diaries, so that bladder capacity and nocturnal urine production can be estimated.25
The only laboratory study recommended for the evaluation of primary, monosymptomatic enuresis is a urinalysis; results are expected to be normal in this specific type.2 Mid-stream, clean-catch urine should be analyzed within 2 hours of collection. Findings that need to be addressed promptly include three or more of the following: proteinuria, pyuria (positive for leukocyte esterase, >5 white blood cells per high powered field), gross or microscopic hematuria (>5 red blood cells per high powered field), and glucosuria especially with ketonuria.26 The finding of a urine specific gravity of <1.021 can be indicative of low vasopressin secretion or excessive hydration prior to sleep; thus, it is important to obtain that first morning void,27 which should be typically concentrated at a specific gravity of greater than 1.020. Renal and bladder ultrasounds are not routinely required in the primary care pediatrics clinic, but would be considered in the specialist's office for patients referred with monosymptomatic enuresis who have been resistant to available treatments.24 Urodynamic studies are also not ordered by the general pediatric clinician, although Naseri and Hiradfar10 reported that 41.2% (n = 17) of their patients with monosymptomatic nocturnal enuresis had evidence of detrusor overactivity. Testing beyond the urinalysis should be left to a specialist who should be consulted when the interventions described below have been unsuccessful.
Treatments in the Primary Care Clinic
Because bedwetting can be a source of distress and disturbed sleep for the child and the family, and it can lead to social withdrawal and reduced self-esteem in the patient, providing effective treatment is a top priority for the pediatric clinician. Approximately one-half of surveyed parents (55%) reported that they would seek professional medical care for their child who suffers from enuresis.5 Parents may not seek treatment because of lack of awareness of effective remedies; parents also know that enuresis is typically self-limiting. It is commonly reported that without treatment, enuresis has a spontaneous cure rate of about 15% each year.28 Enuresis can persist into adulthood with prevalence rates of 1% to 3%.15,25
The first steps of therapy for primary monosymptomatic enuresis include education, behavior modification, and reassurance (Table 2). The educational goal includes providing families with accurate information about the condition and the evidence-based treatments to combat it.25 Per practice consensus guidelines,25 behavioral modifications include dietary manipulations of the elimination of excessive evening fluid intake, the elimination of caffeinated beverages, and the avoidance of high protein foods and salt. Staying well-hydrated during the daytime and voiding before bedtime are also part of the published consensus guidelines.25 Parents should be educated that limiting fluids should never take precedence over adequate hydration.29 It should be kept in mind that Cederblad et al.30 warned that the recommendation to employ basic bladder advice (BBA) as first-line therapy should be reassessed. BBA consisting of specific instructions regarding the number of voids per day, sound drinking habits, good voiding posture, and discontinuation of ineffective therapies such as waking the child at night has been found to not significantly decrease the number of wet nights when implemented alone or with alarm therapy.30 On the contrary, a Cochrane Review of 16 eligible trials revealed some efficacy with the use of simple behavioral modifications such as reward systems, waking the child at night to void, bladder training, and fluid restriction.31 Implementation of simple behavior modifications resulted in fewer wet nights, higher full response rates, and lower relapse rates in comparison to controls. Overall, behavior modification techniques were more effective than no treatment, but were inferior to alarm therapy and medication therapy.31 Reassurance should be offered and consist of emphasizing that enuresis is a common problem, that there are others within the child's peer group that experience enuresis, and that effective therapies do exist.25 Parents should be educated that punishment is not an acceptable treatment for enuresis.29
Enuresis Treatments Initiated in the Primary Care Clinic
Regarding treatment success, the combination of a motivated child and a cooperative family is the greatest predictor of a good outcome, as reported by Elsayed et al.32 Part of the treatment involves gauging the degree to which the child and the parents are interested in treatment. The physician must assess the degree to which the child appears to be bothered by enuresis.29
Along with providing the first steps of education, behavior modification and reassurance, the primary care pediatric clinician has two other first-line treatment options for the management of primary monosymptomatic enuresis: alarm therapy and desmopressin.2,25 Information gathered from the voiding diaries and patients' preference will be considered when determining the optimal treatment. Practice guidelines describe four patient scenarios, and their respective suggested treatments are as follows: for normal night-time urine output and bladder capacity, treatment with an alarm or desmopressin; for small bladder capacity, treatment with an alarm; for excessive night-time urine output, treatment with desmopressin; and for excessive night-time urine output plus small bladder capacity, treatment with both an alarm and desmopressin.25
The enuresis alarm is a long-studied device composed of a sensor that sounds when it comes in contact with the wetness caused by urine. Ideally, the sound of the alarm should awaken the child at the start of urination, and then once awake, the child should walk to the toilet to complete the void. Families must be motivated to participate fully in the use of this therapy as children often turn off the alarm and go back to sleep if left alone. Poor compliance and insufficient duration of therapy are common with alarm therapy.25 Alarms are effective and have a high response rate and low relapse rate in families that comply with this treatment modality for an adequate amount of time.25 As an improved response is not immediate, the patient and/or family may get discouraged. Warning families that effective treatment requires consistent use every night for 2 to 3 months or until the child is dry for 14 consecutive days may curb the discouragement. The mechanism of alarm therapy is not well understood, but successful resolution of enuresis is thought to be due to changes in sleep arousal associated with voiding. Increased bladder capacity with the consistent use of an alarm has also been demonstrated.29 The process of overlearning has been shown to further reduce relapse rates.33 Overlearning involves liberalizing bedtime fluid intake in a child who has had a positive response to alarm therapy while continuing to use the enuresis alarm. Overlearning relapse is often responsive to re-introduction of alarm therapy.34 Along with the use of alarms, it is recommended that children participate in the changing of soiled bedding.29
Desmopressin is the synthetic analogue of the pituitary hormone, arginine vasopressin, and it is approved for the treatment of primary enuresis in children age 6 years and older.35 Its antidiuretic effect occurs at the renal collecting tubule resulting in increased water absorption. When this medication is administered at bedtime, it results in decreased nocturnal urine production.33 Therefore, desmopressin is effective in children with nocturnal polyuria, which is defined as urine production exceeding 130% of the expected bladder capacity for age.34 Desmopressin was first trialed in a tablet form in 1972.33 A fast-melting formulation became available in 2005,36 and it is the formulation most preferred by children younger than age 12 years. Intranasal desmopressin has not been recommended for use for primary enuresis since 2007 due its potential side effects of hyponatremia and seizures.37 A Cochrane Review reported that the administration of desmopressin resulted in dryness in 20% to 30% of patients, and approximately 40% had a partial response.38 Unlike alarms, which can take weeks to produce a response, desmopressin works immediately. However, it is only effective on the night in which it is administered. Patients must adhere to a daily treatment regimen and avoid water intoxication and hyponatremia by abstaining from fluids 1 hour before and 8 hours after treatment.25 Montaldo et al.39 suggest starting with a dose of 120 mcg on a fast-melting form or with 0.2 mg tablets in doses of 0.2 to 0.6 mg nightly.39 The medication should be given for at least 2 to 6 weeks to assess effectiveness and maintained for 3 months before weaning.40 If the patient is therapy resistant or a partial responder, the dose can be doubled by the primary care physician who will monitor efficacy closely. However, in their study, Montaldo et al.39 found no significant difference between the two doses of desmopressin. Withdrawal of this medication results in high relapse rates. Studies suggest that a tapered withdrawal of desmopressin reduces the relapse rates.36,41 No matter which treatment is initiated, reassessment at 2 weeks is prudent, and then depending on progress, follow-up appointments will be determined on a case-by-case basis.
Other medications, such as imipramine (and its potential cardiac side effects) and anticholinergics, are not used routinely in the primary care office34 so they will not be highlighted in this article. Children with bedwetting that is not responsive to the first-line treatments described above should be referred to a specialist after the treatments have been maximized. Researchers continue to study interventions for resistant cases; for example, a combination treatment of desmopressin plus indomethacin has been found to reduce night-time urine output, but without reduction in frequency of nighttime wetting.42 At this time, there is insufficient evidence to recommend hypnosis, acupuncture, or chiropractic care as effective therapies for treatment of enuresis.29
The general pediatric clinician must obtain a thorough history to properly diagnose a child's bedwetting condition as either monosymptomatic or nonmonosymptomatic and primary or secondary. Specific interventions are recommended for each type, and the recommended management of primary monosymptomatic enuresis has been detailed in this article. Care from specialists should be sought if the child's condition is resistant to treatment, especially if associated with psychosocial concerns or other urinary or systemic symptoms.
- Franco I, von Gontard A, De Gennaro MInternational Children's Continence Society. Evaluation and treatment of non-monosymptomatic nocturnal enuresis: a standardized document from the International Children's Continence Society. J Pediatr Urol. 2013;9:234–243. doi:10.1016/j.jpurol.2012.10.026 [CrossRef]
- Neveus T, Eggert P, Evans J, et al. Evaluation of and treatment for monoymptomatic enuresis: a standardized document from the International Children's Continence Society. J Urology. 2010;183:441–447. doi:. doi:10.1016/j.juro.2009.10.043 [CrossRef]
- Chang SJ, Van Laecke E, Bauer SB, et al. Treatment of daytime urinary incontinence: a standardized document from the International Children's Continence Society. Neurourol Urodyn. 2017;36(1):43–50. doi:. doi:10.1002/nau.22911 [CrossRef]
- Fagundes SN, Lebl AS, Soster LA, et al. Monosymptomatic nocturnal enuresis in pediatric patients: multidisciplinary assessment and effects of therapeutic intervention. Pediatr Nephrol. 2016;25;31(8):1295–1303. doi:. doi:10.1007/s00467-016-3316-6 [CrossRef]
- Schlomer B, Rodriquez E, Weiss D, Copp H. Parental beliefs about nocturnal enuresis causes, treatments and the need to seek professional medical care. J Pediatric Urol. 2013;9:1043–1048. doi:. doi:10.1016/j.jpurol.2013.02.013 [CrossRef]
- Ferrara P, De Angelis MC, Caporale O, et al. Possible impact of comorbid conditions of persistence of nocturnal enuresis: results of a long-term follow-up study. Urol J. 2014;11(4):1777–1781.
- Järvelin MR, Vikeväinen-Tervonen L, Moilanen I, Hutunen NP. Enuresis in seven-year-old children. Acta Paediatr Scand. 1988;77:148–153. doi:10.1111/j.1651-2227.1988.tb10614.x [CrossRef]
- Fatouh AA, Motawie AA, Abd Al-Aziz AM, et al. Anti-diuretic hormone and genetic study in primary nocturnal enuresis. J Pediatric Urol. 2013;9:831–827. doi:. doi:10.1016/j.jpurol.2012.11.009 [CrossRef]
- Kim JM, Park JW, Lee CS. Evaluation of nocturnal bladder capacity and nocturnal urine volume in nocturnal enuresis. J Pediatric Urol. 2014;10:559–563. doi:. doi:10.1016/j.jpurol.2013.11.020 [CrossRef]
- Naseri M, Hiradfar M. Abnormal urodynamic findings in children with nocturnal enuresis. Indian Pediatr. 2012;49:401–403. doi:10.1007/s13312-012-0083-8 [CrossRef]
- Alexopoulos EI, Malakasioti G, Varlami V, Miligkos M, Gourgoulianis K, Kaditis AG. Nocturnal enuresis is associated with moderate-to-severe obstructive sleep apnea in children with snoring. Pediatr Res. 2014;76(6):558–559. doi:. doi:10.1038/pr.2014.137 [CrossRef]
- Soster LA, Alves R, Fagundes SN, Koch VHK, Bruni O. Sleep disturbances associated with sleep enuresis: a questionnaire study. Eur J Paediatr Neurol. 2016;20:282–285. doi:. doi:10.1016/j.ejpn.2015.11.014 [CrossRef]
- Somuk BT, Bozkurt H, Göktaş G, Demir O, Gürbüzler L, Eyibilen A. Impact of adenotosillectomy on ADHS and nocturnal enuresis in children with chronic adenotonsillar hypertrophy. Am J Otolaryngol. 2016;37:27–30. doi:. doi:10.1016/j.amjoto.2015.08.003 [CrossRef]
- Srivastava S, Srivastava KL, Shingla S. Prevalence of monosymptomatic nocturnal enuresis and it correlate in school going children of Lucknow. Indian J Pediatr. 2013;80(6):488–491. doi:. doi:10.1007/s12098-012-0870-1 [CrossRef]
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
- Naseri M, Hiradfar M. Monosymptomatic and non-monosymptomatic nocturnal enuresis: a clinical evaluation. Arch Iran Med. 2012;15(11):702–706. doi:0121511/AIM.0011 [CrossRef].
- Tai TT, Tai BT, Chang Y, Huang K. Parents have different perceptions of bed-wetting than children from 6 to 15 years of age. Acta Paeditriaca. 2015;104:e466–e472. doi:. doi:10.1111/apa.13101 [CrossRef]
- Üçer O, Gümüş B. Quantifying subjective assessment of sleep quality, quality of life and depressed mood in children with enuresis. World J Urol. 2014;32:239–243. doi:. doi:10.1007/s00345-013-1193-1 [CrossRef]
- Phung P, Kelsberg G, Safranke S. Clinical inquiry: does primary nocturnal enuresis affect children's self-esteem. J Fam Pract. 2015;64(4):250–259.
- Abdou-Khadra MK, Amin OR, Ahmed D. Association between sleep and behavioral problems among children with enuresis. J Paediatr Child Health. 2013;49:E160–E166. doi:. doi:10.1111/jpc.12017 [CrossRef]
- Van Herzeele C, De Bruyne P, De Bruyne E, Vande Walle JV. Challenging factors for enuresis treatment: psychological problems and non-adherence. J Pediatr Urol. 2015;11:308–313. doi:. doi:10.1016/j.jpurol.2015.04.035 [CrossRef]
- Van Herzeele C, Dhondt K, Roels SP, et al. Neuropsychological functioning related to specific characteristics of nocturnal enuresis. J Pediatr Urol. 2015;11(4):208.e1–208.e6. doi:. doi:10.1016/j.jpurol.2015.04.033 [CrossRef]
- Oguz U, Aykac A, Demirelli E, et al. The time of spontaneous resolution of monosymptomatic nocturnal enuresis (MNE) is familial. Urol Int. 2015;94:459–463. doi:. doi:10.1159/000370166 [CrossRef]
- Kovacevic L, Wolfe-ChristensenMirkovic J, Yih J, Lakshmanan Y. Renal bladder ultrasound evaluation in monosymptomatic primary nocturnal enuresis: is it really necessary?Pediatr Nephrol. 2014;29:1189–1194. doi:. doi:10.1007/s00467-013-2742-y [CrossRef]
- Vande Walle J, Rittig S, Bauer S, Eggert P, Marschall-Kehrel D, Tekgul SAmerican Academy of PediatricsEuropean Society for Paediatric UrologyEuropean Society for Paediatric NephrologyInternational Children's Continence Society. Practical consensus guidelines for the management of enuresis. Eur J Pediatr. 2012;17:971–983. doi:. doi:10.1007/s00431-012-1687-7 [CrossRef]
- Simmerville JA, Maxted WC, Pahira JJ. Urinalysis: a comprehensive review. Am Fam Physician. 2005;71(6):1153–1162.
- Eberdt-Golabek B, Zmyslowska K, Slowik M, Hozyasz K. Etiology and own experience in the primary monosymptomatic nocturnal enuresis in children. Pol Merkur Lekarski. 2015;38(226):196–202.
- Merks BT, Burger H, Willemsen J, van Gool JD, de Jong TP. Melatonin treatment in children with therapy-resistant mono symptomatic nocturnal enuresis. J Pediatr Urol. 2012;8:416–420. doi:. doi:10.1016/j.jpurol.2011.08.012 [CrossRef]
- Bayne AP, Skoog SJ. Nocternal enuresis: an approach to assessment and treatment. Pediatr Rev. 2014;35:327–334. doi:. doi:10.1542/pir.35-8-327 [CrossRef]
- Cederblad M, Sarkadi A, Engvall G, Neveus T. No effect of basic bladder advice in enuresis: a randomized controlled trial. J Pediatr Urol. 2015;11:153.e1–153.e5. doi:. doi:10.1016/j.jpurol.2015.03.004 [CrossRef]
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- Elsayed ER, Abdalla MM, Eladl M, Gabr A, Siam AG, Abdelrahman HM. Predictors of severity and treatment response in children with monosymptomatic nocturnal enuresis receiving behavior therapy. J Pediatr Urol. 2012;8:29–34. doi:. doi:10.1016/j.jpurol.2010.12.011 [CrossRef]
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Basic Approach to Primary,Monosymptomatic Enuresis Management
Obtain history (features should include age 5 years or older, bedwetting only, lack of other urinary symptoms, possible constipation, psychological and sleep abnormalities, possible family history)
Perform thorough physical examination (findings should be normal, particularly of the urogenital and neurologic systems and spine)
Perform urine studies (findings should be normal)
Keep voiding diary to estimate bladder capacity and urine output
Treatment (see Table 2 for further details)
Education, behavior modification, and reassurance (use for all patients)
Enuresis alarm (can consider use in all patients, but especially in patients with normal or small bladders and normal nighttime urine output)
Desmopressin (can consider use in all patients age 6 years or older, but especially in those patients with excessive nighttime urine output)
Enuresis Treatments Initiated in the Primary Care Clinic
||Various methods employed such as the institution of a reward system for dry nights, waking child to void, bladder training31
||Behavioral modification is superior to no treatment, but inferior to alarm therapy and drug therapy. Cochrane Review concluded that behavioral therapy can be employed, but strong evidence supporting efficacy is lacking31
||Consistent daily use for 2 to 3 months or until 14 consecutive dry nights
||Two-thirds of children had a positive response. Relapse is low compared to other therapies43
||Tablet (dosage, 0.2–0.4 mg) or fast-melt (dosage, 120–360 mcg). Initial treatment duration 2 to 6 weeks. If effective, treatment can be continued for additional 3 months. Trials off medication should be instituted to determine if break-through enuresis occurs. Nasal preparation should not be used due to side effects25, 35, 37
||Success rates are as follows: 30% full response, 40% partial response. Use of desmopressin reduced bedwetting events by 1 to 2 nights per week compared to placebo. Patients receiving desmopressin were 2 times as likely to experience 14 consecutive dry nights. High relapse rates of 60% to 70% upon discontinuation38