AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• DIFFERENTIALS
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• DIFFERENTIALS
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The word enuresis is derived from a Greek word that means "to make water." In North America, the term is used to refer to wetting by night or day, and nighttime wetting is referred to as nocturnal enuresis (NE). NE can be divided into primary nocturnal enuresis (PNE) and secondary nocturnal enuresis (SNE). If the child has experienced a minimum 6-month period of continence before the onset of the bed-wetting, the NE is considered SNE.

Psychological and social impact

In PNE, psychological problems are almost always the result and only rarely the cause. By contrast, in SNE, psychological problems are a possible cause. The comorbidity of behavioral problems is 2-4 times higher for children with NE in all epidemiologic studies. The emotional impact of NE on a child and family can be considerable. Children with NE are commonly punished and are at significant risk of emotional and physical abuse. Numerous studies report feelings of embarrassment and anxiety in children with enuresis; loss of self-esteem; and effects on self-perception, interpersonal relationships, quality of life, and school performance.¹ A significant negative impact on self-esteem is reported even in children with enuretic episodes as infrequent as once per month.

Pathophysiology

Normal achievement of continence

Dryness at night usually follows achievement of continence by day. The table below shows the percentage of American children who achieve day and nighttime continence at varying ages.

During the second year of life, children start to develop the ability to voluntarily relax the external urethral sphincter and initiate voiding even in the absence of the desire to void. By approximately age 4 years, all children with normal bladder function should have acquired this ability.

Table 1. Percent of Children Dry by Day and Night at Various Preschool Ages

Genetics

Numerous studies report varying but high prevalence of the condition in other family members. The highest reported familial prevalence rates concluded that 56% of fathers, 36% of mothers, and 40% of siblings experienced a problem with NE. NE is reported in 43% of children of enuretic fathers, 44% of children of enuretic mothers, and 77% of children when both the mother and father had NE. A family history of bed-wetting is found in approximately 50% of children with SNE.

NE is usually transmitted in an autosomal dominant fashion. Chromosome 22 was identified as the site of NE locus in a Danish family in 1995.² Subsequent reports link NE in other families to loci chromosomes 8, 12, and 16.³

Frequency

United States

The prevalence of PNE in the United States depends on age. By age 4 years, 25% of children frequently wet the bed. By age 7 years, only 5-10% still wet the bed. Less that 5% of children wet the bed by age 10 years. The resolution rate of PNE is approximately 15% per year; by the late teenaged years, very few patients have the condition.

International

The prevalence of PNE seems to be the same throughout the world, although no true global evaluation of the incidence of bed-wetting has been made on a global basis.

Mortality/Morbidity

No mortality due to enuresis has ever been reported, but the morbidity, in terms of psychosocial stress, has been recognized in the psychiatric literature. Enuresis can also be associated with significant family stress. Punishment may also be a morbid consequence of enuresis.

Race

Enuresis has no racial predisposition.

Sex

• NE may more common in young males, but the incidence may be the same later in adolescence.
• Reported prevalence in boys aged 7 and 10 years is 9% and 7%, respectively, compared with 6% and 3%, respectively, in girls.

Age

• Prevalence gradually declines during childhood. Of children aged 5 years, 23% have NE. During elementary school years, the problem remains common, with 10% of 7-year-old children and 4% of 10-year-old children still experiencing NE. Of persons aged 18 years and older, approximately 1-2% remain enuretic.
• When PNE and SNE are reported, a secondary onset accounts for approximately one fourth of patients. The prevalence of SNE as a percent of all cases of NE increases with age. In a cohort of New Zealand children, 7.9% developed SNE by the time they were aged 10 years.⁴
• The incidence in adulthood may be 0.5-3%.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• DIFFERENTIALS
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• The best time to investigate nocturnal enuresis (NE) is when the parent first raises the issue in the office.
• The most important aspect of the investigation is a meticulous history, which can establish the diagnosis, lead to more precise treatment recommendations, and minimize the need for invasive and costly investigations.
• The history should include fluid intake, daytime voiding frequency, pattern, and volume, and number and time of episodes of bed-wetting. When the history is not clear, request that the family record fluid intake, daytime voiding, and episodes of bed-wetting for a 2-week period.
• A sleep history should include the times the child goes to bed, falls asleep, and awakens in the morning. Parents should be asked to subjectively comment on the depth of sleep of the child, offering examples of why they consider their child to be or not to be in deep sleep. The presence of restless sleep, snoring, and the type and frequency of nocturnal arousals (eg, nightmares, sleep terrors, sleepwalking) should be determined.
• The timing and number of wetting episodes should be determined.
• Whether the child has experienced periods of dryness and the circumstances of these episodes should also be determined.
• A diet history should include the timing, quantity, and type of fluid and solid food intake during the day and after supper.
• An assessment of the emotional impact on the child is important. Information should be solicited from both the parents and the child. Basic and revealing information includes whether the child has experienced teasing by family or friends or has self-restricted participation in school, sleepovers, or trips.
• Presence of common underlying problems is indicated by the following:
• • Patients with urge syndrome (overactive bladder) or dysfunctional voiding usually present with frequency, urgency, squatting behavior, the sensation of the need to void again immediately after voiding, and daytime as well as nighttime wetting. Constipation and cystitis are common associated problems in patients with urge syndrome or dysfunctional voiding.
  • Symptoms of cystitis include dysuria; cloudy, foul-smelling urine; visible blood in the urine; frequency; urgency; and day and nighttime wetting.
  • Constipation manifests with infrequent and painful passage of hard wide stool, encopresis, and colicky periumbilical pain.
  • Bowel-related problems and gait abnormalities are often present in patients with neurogenic bladder.
  • Symptoms of sleep disordered breathing (SDB) include snoring, mouth breathing, lack of restful sleep, and tiredness the following morning.
  • The hallmark symptoms of urethral obstruction are the need to wait or push to initiate voiding and a weak or interrupted stream.
  • When bed-wetting is a feature of a major motor seizure, parents may hear nocturnal sounds associated with abnormal muscle movements.
  • Girls with ectopic ureter are always wet.
  • Symptoms of diabetes mellitus include polyuria, polydipsia, and weight loss notwithstanding a voracious appetite.
  • Patients with diabetes insipidus present with polyuria, polydipsia, and symptoms related to the underlying hypothalamic or renal causes.

Physical

• A comprehensive physical examination is important. The examination should include the following:
• • Measurement of blood pressure
  • Inspection of external genitalia
  • Palpation in the renal and suprapubic areas to look for enlarged kidneys or bladder
  • Thorough neurologic examination of the lower extremities including gait, muscle power, tone, sensation, reflexes, and plantar responses.
  • Inspection and palpation of the lumbosacral spine
• Abnormal physical findings are usually not present in children when NE is the sole symptom and are not necessarily present in children with urge syndrome/dysfunctional voiding.
• Abnormal physical findings may be found in patients with cystitis, constipation, neurogenic bladder, urethral obstruction, ectopic ureter, obstructive sleep apnea (OSA), and hyperthyroidism.
• A spinal defect, such as a dimple, hair tuft, or skin discoloration, might be visible in approximately 50% of patients with an intraspinal lesion.
• Assessment of the anal wink or the ability of a patient to stand on the toes is a satisfactory test of the integrity of the S2-4 spinal reflex arc.
• In some situations, observing the child void is helpful to assess the urinary stream. If the child grunts audibly or uses the abdominal muscles to push or if the stream is weak or interrupted, a urethral obstruction might be present.
• In girls with ectopic ureter, a constant moistness is observed in the introitus, and regular drying with tissue reveals the persistent leak of urine.
• Tonsillar size in a child examined in the awake and sitting position may not correlate with OSA symptoms. Examination of the child in the prone position and during sleep may be necessary to visibly document obstruction.
• Palpation of the thyroid is important if hyperthyroidism is suspected.

Causes

Table 2. Causes of Primary and Secondary Nocturnal Enuresis

• Idiopathic: If no cause can be identified, the important pathophysiologic factors include a disorder of sleep arousal, nocturnal polyuria, and a low nocturnal bladder capacity.
• Disorder of sleep arousal
• • Studies reveal that children with NE do not wake up normally in response to an auditory signal; these studies confirm a defect in arousal.
  • Arousal to the sensation of a full or contracting bladder involves interconnected anatomic areas including the cerebral cortex, reticular activating system (RAS), locus ceruleus (LC), hypothalamus, pontine micturition center (PMC), spinal cord, and bladder. The RAS controls depth of sleep, the LC controls arousal, and the PMC initiates the command for a detrusor contraction. Various neurotransmitters are involved, including noradrenaline, serotonin, and antidiuretic hormone (ADH).
• Nocturnal polyuria
• • Factors that cause nocturnal polyuria in children with NE include the following:
  • • Fluid ingestion before bedtime
    • Food consumption before bedtime
    • Low nocturnal secretion of ADH
    • Increased nocturnal solute excretion
  • Studies reveal nocturnal polyuria in some but not all children with NE.
  • Although nocturnal polyuria is important in the pathophysiology of NE, overproduction of urine per se cannot be the sole causal factor. Nocturnal polyuria does not explain why children with NE do not wake up to the sensation of a full or contracting bladder or enuresis that occurs during daytime naps.
  • Nocturnal polyuria likely has multiple causes.
  • Ingestion of fluids prior to bedtime is a common cause. Solid food ingestion is also a cause because excretion of solute by the kidney is accompanied by an obligate amount of water.
  • Production of urine is controlled by several factors, including ADH, which directly controls water absorption, and atrial natriuretic peptide (ANP) and aldosterone, which control solute and, therefore, indirectly affect water excretion.
  • Norgaard et al were the first to report absence of the expected nocturnal increase in ADH secretion in children with NE.⁵ Subsequent reports suggest that low nocturnal secretions of ADH are present in some but not all children with NE.
  • Urine sodium and potassium excretion are increased in some children with NE, but the reasons for these observations are not clear. Rittig et al report that secretion of ANP in children with NE shows a normal circadian rhythm, and the renin-angiotensin-aldosterone system is intact.⁶
  • Bladder distension may influence nocturnal secretion of ADH. Some studies report that ADH secretion is increased in response to bladder distension and reduced with bladder emptying. If ADH secretion falls with bladder emptying, the observed low nocturnal blood levels of ADH may be a consequence rather than a cause of NE.
• Low nocturnal bladder capacity
• • Small functional bladder capacity is a long-suspected pathophysiologic factor for NE. Until recently, this theory was considered a less likely explanation for NE in children without daytime symptoms. The literature includes reports of normal and reduced functional bladder capacity, but few studies report on carefully selected patients with only NE. Daytime urodynamic studies in carefully selected children with NE but without daytime symptoms have reported results within the reference range; however, urodynamic studies during sleep reveal that some of these children have a low nocturnal bladder capacity. The reasons for the diurnal-nocturnal difference are not clear.
  • In a study by Mattsson and Lindstrom, functional bladder capacity (FBC) was positively correlated with nighttime urine output.⁷ Children with NE possibly maintain a smaller nocturnal bladder volume, and this situation may condition the detrusor to contract at a lower volume. According to this theory, the low nocturnal bladder capacity is a consequence rather than a cause of NE.
  • Bloom et al suggest a problem with the external urethral sphincter as a possible cause of low nocturnal bladder capacity.⁸ These authors suggest that the control of voiding rests at the external urethral sphincter, where constant activity is present as a guarding reflex to preserve continence. They speculate that the activity of the external urethral sphincter might fall below a critical level during sleep and thereby trigger a detrusor contraction.
• Urge syndrome/dysfunctional voiding
• • Urge syndrome/dysfunctional voiding is more common in preschool- and elementary school–aged girls and usually presents with urinary frequency, urgency, squatting behavior, daytime wetting, and NE.
  • Squatting behavior, a common and distinct symptom of urge syndrome/dysfunctional voiding, is a learned response and an attempt to suppress an unexpected and unwelcome detrusor contraction. The squatting posture elicits a bulbar detrusor inhibitory reflex.
  • In some children, a period of normal voiding occurs, and the onset of the bed-wetting is compatible with SNE.
  • If NE is present, the cause is presumed to be a low nocturnal bladder capacity, but a disorder of arousal may also be present.
  • Symptoms tend to improve or resolve with time and are less common after puberty. Vesicoureteral reflux is more common in these children, and cystitis and constipation are frequent complicating problems. Urodynamic studies reveal unstable detrusor contractions early in the filling phase.
• Cystitis
• • Cystitis is a common cause of NE and an aggravating factor associated with other causes. Cystitis associated with NE might present at any age.
  • Cystitis causes uninhibited detrusor contractions that can lead to episodes of day and nighttime wetting.
  • If cystitis is the only cause of NE, other symptoms of infection are usually present, and the wetting resolves with an appropriate antibiotic.
  • Cystitis is more common in children with urge syndrome/dysfunctional voiding, neurogenic bladder, urethral obstruction, ectopic ureter, and diabetes mellitus. In these conditions, daytime symptoms do not resolve completely with antibiotic treatment.
• Psychological causes
• • Various common situations predispose to a psychological cause, including birth of a new sibling, parental divorce or separation, a death in the family, child abuse, or any other cause of social dysfunction at home or school.
  • von Gontard et al found that children with SNE have a significantly higher rate of behavioral disorders, life events, and continuous psychosocial stress than those with PNE.⁹
  • Stressful life events and psychiatric diagnoses are reported to precede the diagnosis of SNE. The later the onset of SNE, the more likely the possibility of preceding psychological stress.
• Constipation
• • Constipation can cause both PNE and SNE and is a common aggravating factor that should be considered when other causes are present.
  • Although the mechanism is not clear, the pressure effect of stool in the descending or sigmoid colon possibly can trigger an uninhibited detrusor contraction. Constipation is usually present in children with neurogenic bladder and is more common in those with urge syndrome and dysfunctional voiding.
• Sleep disordered breathing
• • SDB is a disorder associated with both an abnormality in arousal and NE. The most common cause of SDB in childhood is adenotonsillar hypertrophy, which has a peak incidence in children aged 2-5 years.
  • The dramatic resolution of NE following surgical treatment of airway obstruction suggests SDB influences a critical pathophysiologic factor. A disorder of sleep arousal is suggested as the most likely factor. Nocturnal polyuria is reported in individuals with OSA and is another possible causative factor. A decrease in nocturnal secretion of ADH and increase in ANP are possible explanations for nocturnal polyuria.
• Neurogenic bladder
• • A neurogenic bladder can develop because of a lesion at any level in the nervous system, including the cerebral cortex, the spinal cord, or the peripheral nerves. As many as 37% of children with cerebral palsy have NE.
  • Patients with myelomeningocele almost always have NE. Other spinal cord abnormalities, such as caudal regression syndrome, tethered cord, tumors, anterior spinal artery syndrome, and spinal cord trauma, can cause NE.
  • Specific dysfunction in the external urethral sphincter can develop after pelvic extirpative surgery, radiation therapy for pelvic malignancy, pelvic fracture, and incontinence surgery.
  • Sacral agenesis can be associated with a neurogenic bladder. As many as 5% of patients with an imperforate anus have a neurogenic bladder, and most patients also have a lumbosacral anomaly.
• Urethral obstruction
• • Urethral obstruction can be congenital, such as with posterior urethral valves, congenital stricture, or urethral diverticula, or acquired because of a traumatic or infectious stricture. Traumatic strictures may develop after a traumatic urethral catheterization, a foreign body in the urethra, or pelvic trauma.
  • Infectious strictures are a complication of purulent urethritis due to bacteria such as Neisseria gonorrhoeae.
  • Meatal stenosis is a common cause of distal urethral obstruction in circumcised males.
• Seizure disorder
• • SNE may be a symptom of an unobserved overnight major motor convulsion in a child with a known seizure disorder.
  • New-onset seizures rarely occur only at night, and bed-wetting is, therefore, a rare manifestation.
• Ectopic ureter
• • This rare congenital abnormality is due to the insertion of the ureter in a location other than the lateral angle of the bladder trigone. Enuresis results when the insertion is distal to the external urethral sphincter.
  • Ectopic ureter is 3-4 times more common in girls than in boys and only causes incontinence in females.
  • The most common site of the ectopic orifice is adjacent to the external urethral meatus and is below the external sphincter in females.
• Diabetes mellitus
• • NE is usually not the presenting complaint in a child with new-onset diabetes mellitus. Conventional symptoms of insulin deficiency usually overshadow the presence of bed-wetting.
  • SNE in a child with established diabetes mellitus may be a symptom of suboptimal control with nocturnal polyuria due to hyperglycemia. Although nocturnal polyuria is presumed to be the cause of the bed-wetting, a disorder of arousal is also likely present because most school-aged patients develop nocturia but maintain a dry bed.
  • Diabetes mellitus is also associated with abnormalities in the afferent sensory pathways to the bladder, which may contribute to NE.
• Diabetes insipidus
• • Diabetes insipidus is an uncommon cause of NE. Although nocturnal polyuria is often presumed to be the cause of bed-wetting, a disorder of arousal may also be present.
  • Diabetes insipidus may be central or nephrogenic. Central diabetes insipidus may result from an intracranial tumor, head trauma, encephalitis, or meningitis. Nephrogenic diabetes insipidus may result from any cause of renal failure, diffuse renal cortical or medullary damage, hypokalemia, hypercalcemia, or nephrotoxic drugs.
• Heart block
• • Very rarely, SNE may be secondary to heart block.
  • Berul and Murphy reported a 4-year-old boy with SNE associated with third-degree atrioventricular block.¹⁰ Following implantation of a ventricular demand pacemaker, the bed-wetting resolved. The authors speculated that the SNE was due to a problem with arousal consequent to nocturnal bradycardia and hypoxia.
• Hyperthyroidism: Kozeny and Wood reported a 17-year-old boy with hyperthyroidism and SNE.¹¹ The SNE resolved with attainment of a euthyroid state.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• DIFFERENTIALS
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to Be Considered

See Causes.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• DIFFERENTIALS
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Urinalysis
• • Urinalysis is the most important screening test in a child with nocturnal enuresis (NE).
  • Children with cystitis usually have WBCs or bacteria evident in the microscopic urinalysis.
  • Children with urge syndrome or dysfunctional voiding, urethral obstruction, neurogenic bladder, ectopic ureter, or diabetes mellitus are predisposed to cystitis.
  • If the urinalysis findings suggest cystitis, urine should be sent for culture and sensitivity.
  • Urethral obstruction may be associated with RBCs in the urine.
  • The presence of glucose suggests diabetes mellitus.
  • A random or first-morning specific gravity greater than 1.020 excludes diabetes insipidus.
• Blood tests: These are usually not needed, unless some other condition is suspected.

Imaging Studies

No imaging is needed if PNE is suspected. However, if other conditions are considered, then radiologic evaluation may be warranted. Some of the testing may involve the following:

• Ultrasonography of the kidneys and bladder (prevoiding and postvoiding)
• • Failure to empty the bladder is a significant risk factor for cystitis and is common in patients with urge syndrome, dysfunctional voiding, neurogenic bladder, and urethral obstruction. Portable bladder ultrasonography is available to assess residual urine when the patient is in the office. The residual volume of urine is normally less than 5 mL.
  • Diagnostic imaging studies are not routinely indicated; however, patients with coincidental daytime voiding symptoms should undergo an ultrasound of the bladder and kidneys. In patients with significant daytime symptoms for whom the ultrasound result is normal, more invasive investigations should be deferred pending a 3-month period during which the voiding routine and emptying are improved, cystitis is treated or prevented, and constipation is treated.
• Voiding cystourethrography
• • If the bladder wall is thickened or trabeculated or a significant postvoid residual volume of urine is noted, consider performing voiding cystourethrography (VCUG).
  • Perform VCUG for patients in whom a neurogenic bladder is suspected.
  • • The lumbosacral spine should be visualized during the VCUG to look for sacral agenesis or spinal dysraphism.
    • The classic radiologic feature of a neurogenic bladder is a trabeculated bladder with a Christmas tree or pine cone configuration.
  • If urethral obstruction is suspected based on an abnormal urinary stream or ultrasonography findings, VCUG should be performed.
• Urodynamic studies and cytoscopy
• • Urodynamic studies help to clarify the diagnosis of neurogenic bladder.
  • A video urodynamic study measures filling phase parameters, such as bladder capacity, presence or absence of unstable detrusor contractions, bladder compliance, and the state of the bladder neck, and voiding phase parameters, such as voiding pressures, bladder emptying, and the state of the external urethral sphincter.
  • Urodynamic studies and cystoscopy should be reserved for patients with urethral obstruction and neurogenic bladder, and for patients with dysfunctional voiding who do not improve after 3 months of therapy.
• MRI
• • MRI of the spine is indicated in any patient with an abnormal neurologic examination finding of the lower extremities; a visible defect in the lumbosacral spine; or the triad of encopresis, gait abnormality, and daytime symptoms.
  • Consider MRI in patients with significant daytime voiding dysfunction that does not improve with treatment, even if neurologic and orthopedic examination findings are normal.
• Radiography: If OSA is suspected, consider lateral radiography of the neck or referral to a pediatric otolaryngologist for direct visualization of the nasopharynx; also consider referral to a pediatric sleep specialist.

Other Tests

• Uroflowmetry
• • Uroflowmetry is a simple, noninvasive measurement of urine flow that is helpful to screen patients for neurogenic bladder and urethral obstruction.
  • Children are instructed to void into a special toilet with a pressure-sensitive device at the base. A normal uroflow study shows a single bell-shaped curve with a normal peak and average flow rate for age and size.
  • Patients with urethral obstruction and a neurogenic bladder have prolonged curves or an interrupted series of curves and low peak and average urine flow rates.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• DIFFERENTIALS
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The most important reason to treat nocturnal enuresis (NE) is to minimize the embarrassment and anxiety of the child and the frustration experienced by the parents. Most children with NE feel very much alone with their problem. Family members with a history of NE should be encouraged to share their experiences and offer moral support to the child. The knowledge that another family member had and outgrew the problem can be therapeutic.

A positive attitude and motivation to be dry are important components of treatment. Children with NE benefit from a caring and patient attitude by their parents; punishment has no role. A positive approach by the physician, also, is important to instill confidence and enhance compliance. Many children have given up on the concept of dryness, and an optimistic attitude should be encouraged. Behavioral modification with positive reinforcement may enhance treatment results. Consistent follow-up is important to gauge the therapeutic results.

An explanation of the probable cause of the NE is important for every family. If a child has no daytime symptoms or has experienced significant dry spells in the past, the presence of a structural abnormality as a cause of the NE is unlikely. This should be explained to the parents to allay any fears about other causes and to reassure that invasive investigations are not necessary. Parents should be asked to provide specific examples of potential causes that have them worried, so that these often irrational fears can be discussed and relieved.

Keen attention to a normal daytime voiding pattern is important. The child should be encouraged to void on awakening, approximately every 1.5-2 hours, before leaving home or school for any reason, and always before bed. Holding the urine to the last minute should be discouraged. With voiding, the child should relax, use optimal posture, and take time to completely empty the bladder.

Children should be instructed not to drink liberal amounts during the day, not to drink to in excess with the evening meal, and to minimize fluid intake afterward. Common sense modifications of fluid intake are necessary to maintain hydration in children who play sports or who are otherwise physically active in the evening after mealtime. Fluid restriction should not be presented in a fashion that could be construed by the child as punishment.

Parents should be asked to take the child to the bathroom to void prior to bedtime. Because this therapeutic measure is designed only to minimize the quantity of fluid in the bladder, full wakefulness is neither necessary nor desirable. Careful monitoring by a parent is necessary for the trip from bed to bathroom and back. Children should go to bed at an hour calculated to offer the optimal hours of sleep for their age.

If attention to the above preliminary management program for up to 3 months does not result in dryness, then either alarm or pharmacologic therapy should be considered. Since no single therapy has been consistently superior, the clinical setting, family preference, and experience of the practitioner should suggest the preliminary choice.

• Alarm therapy
• • Alarm therapy offers the possibility of sustained improvement of NE and should be considered for every patient. Alarm therapy is reported to improve bedwetting by increasing nocturnal bladder capacity or by enhanced arousal. Alarm therapy does not reduce nocturnal urine output. Some successfully treated children replace NE with nocturia, and others sleep dry without the need to void at night. Some improve within the first 2 weeks of treatment and others only after several months. The volume of enuretic urine may diminish progressively until dryness is achieved, or the improvement can be more sudden. Analysis of 25 reported studies suggests an average success rate of 68%.¹²
  • A number of practical considerations limit the usefulness of alarm therapy and should be discussed with the family before selecting this approach. Optimal results occur when the child is well motivated. Older children have better developed motivation. Parental motivation is also critical. The parent should believe the approach is worthwhile and should be prepared to participate every night for at least 3 consecutive months. The impact on other family members should be considered. If the alarm might interrupt the sleep of an infant sibling or similar-aged sibling in the same bedroom, shift-working parent, or live-in grandparent, alarm therapy may not be suitable. Numerous alarms are available. The alarm should be attached at bedtime to the underwear or pajamas in a position chosen to promptly sense wetness.
  • Although most children with NE do not awaken to the alarm, they stop emptying the bladder. When the alarm sounds, a parent must assist the child to the bathroom to finish voiding. The child need not be awakened to full consciousness. After changing the sheets and underwear or pajamas, the child should be returned to bed and the alarm reset.
  • Close biweekly follow-up care is important to sustain motivation, troubleshoot technical problems, and otherwise monitor the therapy. In successfully treated children, alarm therapy should be continued for at least 3 months after sustained dryness. Relapses are common, develop in 29-66% of children, and may respond to further alarm therapy. If the child is still wet after a minimum of 3 months of consecutive use, alarm therapy can be discontinued and considered unsuccessful. Failure does not preclude future successful treatment in an older, more motivated child.
• Desmopressin acetate therapy
• • Desmopressin acetate (DDAVP) is the preferred medication to treat children with NE. Numerous studies report total dryness in 38-55% of children treated with DDAVP. Although most authorities suggest the therapeutic benefit of DDAVP is because of a reduction in the nocturnal production of urine, effects on arousal may be important.
  • The tablet, oral disintegrating tablet (not available in the United States), and nasal spray formulations have similar efficacy. The more recently approved melt and tablet formulations have a better safety profile and are preferred.
  • The intranasal formulation is no longer recommended for NE because of the risk for severe hyponatremia that can cause seizures and death.
  • DDAVP tablets or oral disintegrating tablets should be administered at bedtime or 1 hour before bedtime. The recommended starting dose for the tablet is 0.2 mg, and the drug can be titrated as necessary to a maximum of 0.6 mg. The equivalent starting dosage for the melt is 120 mcg and the maximum dose is 360 mcg. The immediate onset of action of DDAVP allows the flexibility of intermittent administration for special occasions or long-term use to maintain dryness. For long-term use, DDAVP can be prescribed in 3-month quantities and discontinued between prescriptions to determine if the wetting persists and, therefore, to justify continued use.
  • The safety profile of DDAVP is favorable, and many studies have documented low rates of adverse effects.
  • • For the tablet, incidence of minor adverse events is not significantly different from a placebo.
    • The most frequently reported adverse events with the nasal spray are nasal discomfort, epistaxis, abdominal pain, and headache.
    • The only serious adverse effect reported in patients with NE treated with desmopressin is seizure or other CNS symptoms due to water intoxication. A review of case reports of water intoxication associated with desmopressin confirmed excess fluid intake was a feature in at least 6 of 11 individuals. This serious adverse effect is preventable with careful patient education not to consume an excess of fluids on any evening that desmopressin is administered. A maximum of 1 cup of fluid should be offered at the evening meal, no more than 1 cup between mealtime and bedtime, and nothing to drink within 2 hours prior to bedtime. Early symptoms of water intoxication include headache, nausea, and vomiting. If these symptoms develop, the medication should be discontinued and the child promptly assessed by a physician.
    • As of December 2007, the US Food and Drug Administration (FDA) reviewed 61 postmarketing cases of hyponatremic-related seizures associated with the use of desmopressin. Fifty-five cases reported sodium levels ranging from 104-130 mEq/L during the seizure event. In 2 cases, the patients died (both patients experienced hyponatremia and seizures). Thirty-six cases were associated with intranasal formulations, of which 25 cases occurred in pediatric patients younger than 17 years. The most commonly reported indication of use in these 25 pediatric cases was nocturnal enuresis. Thirty-nine of the 61 cases were associated with at least one concomitant drug or disease that is also associated with hyponatremia, seizures, or both.
  • Combination of alarm therapy with DDAVP is reported to result in dryness not achievable with either therapy alone.
• Anticholinergic therapy
• • An anticholinergic medication may be helpful in some patients, especially those with urge syndrome, dysfunctional voiding, or neurogenic bladder. These medications reduce uninhibited detrusor contractions, increase the threshold volume at which an uninhibited detrusor contraction occurs, and enlarge the functional bladder capacity. Oxybutynin chloride (Ditropan) and tolterodine (Detrol) are commonly prescribed medications. Oxybutynin chloride also has antispasmodic and analgesic properties. Anticholinergic adverse effects include dry mouth, blurred vision, facial flushing, constipation, poor bladder emptying, and mood changes.
  • These medications should not be administered during a fever because a decrease in sweating is an anticholinergic effect. Similarly, these medications should be used cautiously in children who exercise or play strenuously, especially on hot days.
  • The dosage of oxybutynin is 2.5-5 mg administered at bedtime. A long-acting preparation is available but has not been approved for use in children. Tolterodine is not approved for use in children younger than 12 years. Flavoxate HCl (Urispas), a urinary spasmolytic, may be helpful in some patients with urge syndrome and dysfunctional voiding but is approved only for children older than 12 years. The combination of DDAVP and oxybutynin chloride may be efficacious in children with urge syndrome or dysfunctional voiding who respond to anticholinergic therapy with improved daytime symptoms but who continue to wet at night.
• Imipramine therapy
• • Treatment with imipramine results in dryness in 5-40% of children. The relapse rate is high when the medication is discontinued. The usual dose, taken 1-2 hours before bedtime, is 25 mg for patients aged 6-8 years and 50-75 mg for older children and adolescents.
  • Adverse effects include constipation, difficulty initiating voiding, irritability, drowsiness, reduced appetite, and personality changes. Imipramine overdose can be fatal, and a cautionary warning is necessary with every prescription. Because of the unfavorable adverse effect profile and significant risk of death with overdose, the World Health Organization (WHO) does not recommend imipramine for the treatment of NE.

Surgical Care

Ectopic ureter, OSA, and heart block respond to specific surgical interventions.

Consultations

Referral to a pediatric otolaryngologist or a pediatric sleep specialist may be appropriate if OSA is suspected.

Diet

Children should be instructed not to drink a liberal amount during the day but not to drink to excess with the evening meal and to minimize fluid intake after mealtime. Common sense modifications of fluid intake are necessary to maintain hydration in children who play sports or who are otherwise physically active in the evening after mealtime.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• DIFFERENTIALS
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Pharmacologic management plays an important role in the treatment of bed-wetting. Three pharmacologic approaches are currently considered: desmopressin, anticholinergic medications, and imipramine.

Drug Category: Vasopressin Analog

Secretion of vasopressin at night reduces urine output. Water is conserved and concentrated by increasing the flow in the kidney through the collecting tubules to the medullary interstitium.

Desmopressin is a synthetic analog of ADH. The first reported use of desmopressin to treat a child with bed-wetting was in the 1960s. The mechanism of action was presumed to be a reduction in the overnight production of urine. Later studies demonstrated that some children with bed-wetting had lower nocturnal levels of ADH than children who were dry at night. This provided a scientific rational for desmopressin use; however, not all children with bed-wetting have lower levels of ADH at night, overproduce urine at night, or respond to desmopressin. In addition, not all children who respond to desmopressin have lower levels of ADH or overproduce urine at night prior to treatment with the medication. The mechanism of action of desmopressin possibly involves factors other than control of the production of urine.

Because ADH is also a neurotransmitter, a CNS-mediated action, perhaps on arousal pathways, is speculated as a possible factor.

Drug Category: Anticholinergic agents

Some children with bed-wetting have a small functional bladder capacity at night. Other children with bed-wetting also have daytime symptoms of frequency and urgency. These children may benefit from treatment with an anticholinergic medication that allows the bladder to hold more urine. In the absence of these situations, treatment with an anticholinergic medication is not likely to decrease the incidence of bed-wetting.

Drug Category: Tricyclic antidepressants

Imipramine was first prescribed for bed-wetting in an era when psychological causes were considered common. The modern understanding is that psychological causes are not a common cause of PNE. The mechanism whereby imipramine improves bed-wetting is not clear. Current theories include CNS- or local bladder-related effects.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• DIFFERENTIALS
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

Patients with primary nocturnal enuresis (PNE) are asked to keep a diary and should return for evaluation on a monthly basis to assess their progress. Once the child has achieved dryness, then the follow-up intervals can be spaced out.

Complications

Relapse of the enuresis is the most common complication and requires restarting the treatment that resulted in an improvement or cure of the condition.

Prognosis

• The most important reason to treat children with NE is to improve the loss of self-esteem and other secondary psychological or behavioral problems that develop consequent to NE. Improvement in self-esteem is noted with all therapies and to levels comparable to children without NE after only 6 months of treatment. The spontaneous cure rate for children who are not treated is reportedly approximately 15% per year.
• When NE is the sole symptom, treatment with DDAVP results in total dryness in as many as 55% of children and improvement in dryness in approximately 75% of children.
• When daytime symptoms are also present, the prognosis depends on the underlying cause.
• • The prognosis is excellent when NE is due to cystitis, ectopic ureter, OSA, diabetes mellitus, diabetes insipidus, seizure disorder, heart block, or hyperthyroidism.
  • • NE due to cystitis should resolve with appropriate antibiotic therapy.
    • Ectopic ureter, OSA, and heart block respond to specific surgical interventions.
    • Diabetes mellitus, diabetes insipidus, and hyperthyroidism respond to specific medical interventions.
  • NE due to urge syndrome or dysfunctional voiding usually resolves, but daytime symptoms continue after puberty and into adulthood in as many as 20% of patients.
  • The prognosis for NE due to neurogenic bladder depends on the neurologic cause and whether a surgical solution is possible.

Patient Education

• For excellent patient education resources, visit eMedicine's Children's Health Center and Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Bedwetting, Bladder Control Problems, and Understanding Bladder Control Medications.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• DIFFERENTIALS
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Punishment has no role in the treatment of NE. The impact on self-esteem and on the emotional health of the child is significant enough without the added insult of punishment for a problem beyond the child's control. Punishment can be subtle and unrecognized by an otherwise well-meaning parent. A child easily interprets fluid restriction and requests to wear diaper training pants or to launder sheets and clothes as punishment. Parents should be very sensitive to how they present these requests in order to minimize any sense of punishment.
• Bladder training exercises are not recommended. With this therapy, the child is asked to ingest large quantities of fluid and to hold the urine in the bladder without voiding until uncomfortable. Teaching a child not to respond normally to the sensation of a full bladder and prescribing a therapy that is inherently painful seems fundamentally without merit. The results of studies that report on this therapy are either methodologically flawed or show no improvement.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• DIFFERENTIALS
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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