Enuresis

Abstract

After completing this article, readers should be able to: Both day and night wetting can pose a significant problem for children, parents, and medical practitioners. The prevalence of day wetting in 7-year-old children is between 2% and 3% for boys and 3% and 4% for girls. Most cases represent a functional type of incontinence, with only a few cases due to an anatomic, neurologic, or psychiatric cause. Most children typically are trained prior to starting school, but those who continued wetting rated this happening as a significant embarrassment and life stressor. Wetting often is a significant complaint raised during a visit with the pediatrician. Data suggest that children who have prolonged enuresis have lower self-esteem. Primary nocturnal enuresis (PNE) is defined as nocturnal wetting in a child who has never been dry on consecutive nights for longer than 6 months. It is estimated that between 5 and 7 million children and adolescents may suffer from this disorder. The incidence of PNE is based on age. Dryness is expected to be achieved by 5 years of age; if not, the child is diagnosed as having PNE. An estimated 10% to 15% of 7-year-old children still struggle with bedwetting. Nocturnal enuresis resolves at a rate of 15% per year, so 99% of children are dry by age 15 years. The social consequences of nocturnal enuresis lead many to seek medical attention. To clarify day and night wetting, the International Children's Continence Society recently published new standardization for the terminology of enuresis. (1) They define incontinence as uncontrollable leakage of urine that may be intermittent or continuous and occurs after continence should have been achieved. Continuous incontinence means constant urine leakage, as in a child who has an ectopic ureter or iatrogenic damage to the external sphincter. Intermittent incontinence is urine leaking in discrete amounts either during the day, night, or both. Any wetting that occurs in discrete amounts at night is termed enuresis regardless of whether it is associated with daytime symptoms. Leakage that occurs during the day is daytime incontinence (no longer called diurnal enuresis). Dysfunctional voiding is defined by inappropriate muscle contraction during voiding and usually is associated with constipation and is referred to as dysfunctional elimination syndrome.The causes of nocturnal enuresis are not understood completely. Several theories have been proposed, including the role of genetic factors, alterations in vasopressin secretion, sleep factors, and abnormal bladder dynamics. Other mechanisms may include psychological influences, organic disease, and maturational delay.Many parents of children who have enuresis report that their children sleep more deeply and are more difficult to arouse than other children. Early studies supported this controversial hypothesis, but numerous recent studies refute it. Controlled studies have shown no difference between children who do and do not have enuresis. No data support the concept that children who have enuresis wet during “deep” sleep, and wetting has been shown to occur throughout different sleep patterns. An association has been shown between obstructive sleep apnea syndrome and enuresis. Affected patients have increased atrial natriuretic factor, which inhibits the renin-angiotensin-aldosterone pathway, leading to increased diuresis. Tonsillectomy, adenoidectomy, or both have been shown to cure enuresis to a significant extent in this select group.Based on circadian rhythms, nocturnal urine production is approximately 50% less than daytime urine production. As early as the 1950s, children who suffered enuresis were shown to have significantly increased nocturnal urine production compared with unaffected children. Nocturnal polyuria due to alterations in vasopressin release has been shown to be a factor in nocturnal enuresis. This theory is based on studies showing that children who have nocturnal enuresis have abnormal circadian release of antidiuretic hormone (ADH).Bladder dysfunction, as evidenced by diminished bladder capacity and abnormal urodynamics, may play a role in nocturnal enuresis. Patients who have PNE have been shown to have smaller-than-normal functional bladder capacities at night, and urodynamic studies have demonstrated higher bladder instability at night compared with during the day. As expected, patients who have both daytime incontinence and nocturnal enuresis have a higher degree of functional bladder abnormalities and a higher failure rate with conventional treatment than patients experiencing nocturnal enuresis alone. Evidence is strong that genetics plays a role in nocturnal enuresis. Studies have shown that when one parent had enuresis as a child, his or her child had a 44% chance of also experiencing the condition. If both parents were affected, this chance increased to 77%. Interestingly, the parental age of resolution often predicts when the child's enuresis should resolve. Studies of twins support the genetic role, with 68% concordance in monozygotic twins and 36% in dizygotic twins. Psychological factors contribute to PNE. Some studies have shown a higher prevalence of enuresis in children who have attention-deficit/hyperactivity disorder (ADHD) compared with a control population. Surveys show that children who have ADHD have a 30% greater chance of enuretic events. Recent studies reveal that the reason may not, as previously believed, be inattention but may be a neurochemical effect.Maturational delay as a hypothesis for enuresis may be the most unifying of the theories. In a large population study, children who had enuresis had more fine and gross motor clumsiness, perceptual dysfunction, and speech defects than did controls. Patients who had nocturnal enuresis differed less from controls compared with those who had both nocturnal enuresis and daytime incontinence. (2)Secondary enuresis is defined as new-onset nighttime wetting on consecutive nights after a 6-month or greater period of dryness. Although very disturbing, usually this occurrence is not related to an organic cause. In some cases, a stressful event, such as the birth of a sibling, a move, or the death of a parent or grandparent, is the source. Secondary enuresis should be evaluated and treated like PNE; there is no need for additional laboratory work or imaging studies.Evaluation of nocturnal enuresis starts with a history. It is important to determine whether the enuresis is primary or secondary. The pattern of enuresis also must be determined, delineating the number of nights per week and the number of episodes per night. The pattern of nighttime fluid intake should be documented, as should caffeine intake. The evaluation should include questions regarding polyuria, polydipsia, urgency, frequency, dysuria, abnormal urine stream, history of urinary tract infection, constant wetness, and bowel complaints (15% of children who have enuresis also have encopresis). A history of sleep disorders such as sleep apnea or insomnia and a neurologic and developmental history should be obtained. Family history is helpful and should be sought.Most children who have PNE have normal findings on physical examination. Clinicians should focus on the gastrointestinal (GI), urogenital, and neurologic systems. If abnormalities are found, the child most likely does not have an isolated case of nocturnal enuresis. During the abdominal examination, the physician should look for a distended bladder or fecal impaction. The male urologic examination should include evaluation of the phallus and meatus; the female examination should focus on the introitus, looking for labial adhesions or urethral abnormalities. The neurologic examination should assess lower extremity muscle tone and coordination, along with deep tendon reflexes and sensation. The skin over the spine should be inspected, looking for a tuft of hair, vascular marking, or a sacral dimple that might signify occult spinal dysraphism.Laboratory tests, other than a screening urinalysis (UA), are not necessary in evaluating patients who have nocturnal enuresis. Urine specific gravity is measured to evaluate for diabetes insipidus. Glucose spillage may suggest diabetes mellitus, and the presence of bacteria may signify an infection. Urine culture should be obtained if the UA appears to show infection. Patients who have nocturnal enuresis and associated daytime incontinence, with or without encopresis, may warrant additional studies.Urinary tract infection (UTI) in children who suffer enuresis should lead the clinician to consider imaging studies under certain circumstances, specifically renal and bladder ultrasonography and voiding cystourethrography (VCUG). Both studies should be performed in any boy who has a UTI, in girls who have a febrile UTI, in girls who are not toilet-trained who have a UTI without fever, and in girls who are toilet-trained and have recurrent afebrile UTIs (three or more in 6 months). Toilet-trained girls who have afebrile UTIs should undergo ultrasonography. If abnormalities are found, VCUG is indicated. Some clinicians extend the indications for imaging further. Blood testing rarely is needed unless there is associated renal disease or suggestive physical findings.Treatment of nocturnal enuresis includes both behavioral and medical options. Among the behavioral modifications are limiting nighttime fluid intake 2 hours before bedtime, limiting dairy products 4 hours before bedtime (to decrease urine output from osmotic diuresis), and voiding prior to going to sleep. Medical therapy includes desmopressin acetate, anticholinergic agents, imipramine, or combination therapy. Alarm therapy falls into both categories of treatment. Acupuncture and hypnosis are other treatments, but few data support their use.The bedwetting alarm is by far the most effective strategy for curing nocturnal enuresis, having reported success rates as high as 66% to 70%. Alarm therapy, however, is the most difficult method to employ. Its mechanism is unknown, but it is believed to be a conditioned response. The alarm must be used every night for success and may require 3 to 4 months for results. The family needs to be counseled prior to starting treatment and motivated for success to occur. The patient is instructed to wear underwear rather than paper underpants. Usually the patient awakens to the sound of the alarm (triggered by dampness in the device), but if the child does not wake, the parent must awaken and accompany him or her to the bathroom. Many children awaken more than once a night, which can be stressful on the family.Advantages of alarm therapy are that it offers a real cure, with no recidivism and no adverse effects. Disadvantages include significant parental involvement because the alarm may not wake the child at first, with disruption of sleep for all family members. Alarm therapy works better in older children who are motivated to be dry. A patient is considered cured if he or she has worn the alarm for 1 month and it is not triggered because he or she remains dry.Medications often are used in the treatment of nocturnal enuresis to help treat, rather than cure, the problem while awaiting natural resolution. The first-line choice is desmopressin acetate. Desmopressin is a synthetic analog of ADH. It works at the level of the kidney, reducing urine output overnight. Such reduction in urine volume overnight may not make the child completely dry, especially if the child has bladder instability and reduced functional bladder capacity at night. The response rate, as defined by a 50% reduction in wet nights, is 60% to 70%. Success rates generally are better in patients who do not have daytime incontinence and who have normal functional bladder capacities.Desmopressin tablets are well tolerated and have very few reported adverse effects. However, reports of severe hyponatremia associated with seizures and deaths in children who have used the intranasal formulations of desmopressin have caused the United States Food and Drug Administration to advise clinicians not to use desmopressin in that form for treating PNE. (3) Also, desmopressin therapy should be suspended when children experience acute conditions that can cause fluid or electrolyte imbalance, such as fever, recurrent vomiting and diarrhea, or vigorous exercise.Desmopressin has a dose-dependent reaction. The initial dose is one tablet (0.2 mg) taken 30 minutes prior to bedtime on an empty stomach because the polypeptide is absorbed rapidly in the stomach (if patients cannot swallow the tablet, it can be crushed and put in applesauce). The dose may be titrated to a maximum of 0.6 mg to achieve dryness. Desmopressin is maximally effective in 1 hour and is cleared within 9 hours after administration. Therefore, the drug only works on the night it is consumed. We recommend that patients use the medication nightly for 6 months and then stop for 2 weeks to see if the patient has outgrown the problem. Practitioners and patients alike find that desmopressin either “works or it doesn't.” Because the drug controls only one factor, nocturnal urine not all patients to this treatment alone. after treatment is have been used in the treatment of nocturnal enuresis. are especially effective for patients who have associated daytime wetting and or They rarely are effective when used but work well in combination with This combination often is a when the patient has nocturnal enuresis with reduced functional bladder capacity or without daytime and has desmopressin therapy alone. for use in children include in children 5 years or older in the form and in children 6 years and older in the anticholinergic that is not in children is to 4 We have used this medication in with parental and have had is a in the that to be used in the treatment of enuresis. Its is unknown, but it appears to have both a anticholinergic as well as an on the has been to of It has been that the of the by and sleep. in cure rates have been reported to but when therapy is especially only of patients dry are but include gastrointestinal sleep and dry Most adverse are associated with and include and should be of which can be a to as well as to wetting, whether or can have a significant psychological to stressful life one of that children rated wetting their at of stressful events. that parents reported more psychological in their children older than years of age who had daytime wetting compared with children of the age who had no daytime In children who have ADHD are by day and nighttime a 30% incidence of enuresis in children who had ADHD compared with of children who had no Also, children experiencing stressful such as death of family or during the of 2 to 5 years age of have a higher incidence of daytime that children who have daytime wetting and a difficult are at increased for constipation and and the causes of daytime incontinence an of the normal which bladder and bladder and of the bladder are under control of the which the bladder to at while The of while of the bladder and occurs as a of bladder contraction from the voiding of to the bladder that in of the and and from the that to and muscle of the bladder voiding an muscle and an normal urinary wetting has many Most cases from alterations in but it is important to seek specific daytime wetting can be either as a or an problem. some however, a combination of the mechanisms to incontinence. The and treatment of daytime incontinence are after which of the is who have can be into normal children who cannot and urine at abnormal children who have high with children are which in and children who have with or without an are by a failure to empty the bladder on at and with no significant The mechanism may be neurologic, anatomic, or functional by a normal child to the during history is the most in the evaluation of daytime wetting and must include a voiding history. age of pattern of wetting, volume of number of per day the child is whether the child has been dry, of day during incontinence any history of number of per day, any associated nighttime wetting, and prior evaluation and history of bowel is Among the is number of per of presence of or as and presence or of abdominal A social history should focus on the presence of parental wetting, and any psychological that may be physical examination should include to or sacral and the abnormalities that include female labial and which represent a or an ectopic The and should be for an sacral vascular or over the which might spinal The should be for both tone and the presence of a large of fecal examination should assess for and in the The skin should be evaluated for significant evaluation of patients who have daytime wetting with a UA and urine ultrasonography to assess for a is should be measured to evaluate the of bladder of the studies should be performed for children who have the In any child who has both daytime wetting and a UTI should undergo that the urinary both and is the The patient into a with that the rate of A is that on rate and and a is that can in are in such conditions as incontinence, such as or a such as urethral or urethral in testing is for children who have daytime ureter should be considered for female patients who have no history of or nighttime and This should be evaluated by or Patients to have an ectopic ureter should be referred to a because it is a problem. are performed to evaluate children who do not to therapy or patients in a spinal is This should be especially in patients who have daytime incontinence, nocturnal enuresis, and Some however, have syndrome that with no bowel If syndrome is a based either on abnormal or a physical imaging of the is of are as incontinence, incontinence, diurnal enuresis, and urinary or without incontinence, referred to as is by of a strong to by such as and This is caused by bladder and contraction to the amounts of urine are and cause dampness rather than who have syndrome may experience and as well as referred to the bladder capacity but not is for age. incontinence also can be associated with nighttime pattern of daytime wetting that is referred to as incontinence is caused by and This over The bladder and the to is children their of bladder have significantly that need to The of but usually is incontinence is by normal but or especially associated with or The of urine from to Such children who with no that are going to wet leakage The association of in this is of daytime incontinence after continence has been achieved should a to a frequency, generally referred to as urinary of or is a very complaint that is by a need to very to 30 per day. is no dysuria, and no urine Affected patients do not require an occurs in children, usually in those 3 to years of and usually is Interestingly, children often do not to anticholinergic therapy. The cause is believed to be related to psychological of but not are more severe in degree than are conditions are from the to the most as bladder and bladder bladder syndrome a voiding disorder in which children or a day. The bladder and the muscle to Patients must their abdominal to They have a and often intermittent that is at the bladder completely. They have recurrent UTIs that are afebrile or associated with a and may have is inappropriate contraction of the external urethral during bladder an intermittent or type of voiding and often is associated with constipation or due to failure of the to during is by recurrent UTI, leakage, and a and bladder to a external on Affected children are at for or syndrome is the most severe form of voiding this by as a bladder because children often had bladder and renal to children who had but with no neurologic who have syndrome have that can lead to They bladder and if not and treated with mechanisms to empty the to renal or renal of daytime wetting do not as either or incontinence and incontinence is a very form of daytime wetting as bladder with This occurs in to years. The disorder to be in the early but does extend into incontinence does not have other associated voiding abnormalities such as or show a normal and The cause is unknown, but the incontinence is believed to be by a that in patients who have As a patients usually are treated with is associated with urine in the after voiding and leaking when the child This often is in girls and in girls who cannot on the also may be in girls who have The underwear is as is by a examination with a that urine from the Because this is a problem of it is treated by having the patient on the or on the during therapy is the treatment for daytime wetting, regardless of cause. of the child to every 2 voiding also is especially for patients who have Patients are to bladder such as and high and Also, patients should be to on the 30 minutes after a large with their supported for minutes to bowel is important in treating children who have daytime wetting because most of patients have some form of treatment for constipation includes that If the response to this is or medication may be such as with as needed a is achieved. If a bowel and behavioral therapy are other medication may be necessary to help the the patient has a problem that is associated with urinary or or anticholinergic are are most are not for However, have used some of with parental in dysfunctional voiding are the for all anticholinergic and in of dry and that have used include and who have have different needs different is physical therapy for patients who have The therapy on either of the and on the that are to a that the patient the difference between contraction and of the The of this therapy are that it is is very and has no drug adverse effects. Disadvantages include resolution and the need for parent and patient and as well as at for daytime wetting are which were for who had The to work by muscle at the of the bladder and reducing at the lower in to of The include recurrent UTIs due to better Disadvantages include adverse such as and We use of in for treatment of in and for also are used in patients who have because of the of the Such help to the of and and control the of the and nighttime wetting is a significant problem in It is and often because there is no may not the with their It is important for the to the questions at to the presence of such and treatment should be in a to the of laboratory and other should be considered for patients who are to initial therapy.