Nocturnal Enuresis: Current Concepts

Objectives After completing this article, readers should be able to: Nocturnal enuresis affects approximately 5 to 7 million children in the United States, making it the most common pediatric urologic complaint encountered by primary care physicians. Despite its prevalence, nocturnal enuresis remains incompletely understood, which can frustrate patients, family members, and physicians. Appropriate intervention is justified for the affected child because of the potential consequences of family stress, social withdrawal, and poor self-esteem.Enuresis refers to the persistence of inappropriate voiding of urine beyond the age of anticipated bladder control (age 4 to 5 y at the latest). The development of bladder control is a multidimensional process that requires sensory awareness of bladder fullness by the child, capacity for storage of urine, voluntary control of the bladder sphincter, psychological desire for control, and a positive training experience. Diurnal enuresis is involuntary leaking of urine during waking hours. Nocturnal enuresis refers to involuntary passage of urine during sleep and is classified as primary (no prior period of sustained dryness) or secondary (recurrence of nighttime wetting after 6 mo or longer of dryness). Recent urology literature describes another classification of nocturnal enuresis based on the presence or absence of other bladder symptoms. Monosymptomatic nocturnal enuresis (MNE) is defined as a normal void occurring at night in bed in the absence of any other symptoms referable to the urogenital tract, and it precludes any daytime symptomatology. It is the focus of this article. Polysymptomatic nocturnal enuresis (PNE) is bed-wetting associated with other bladder symptoms such as urgency, frequency,instability, or voiding dysfunction. Investigations of patients who have MNE reveal that they are clearly different from patients who have PNE.The spontaneous resolution rate of nocturnal enuresis is approximately 15% per year, with 1% of teenagers at 15 years of age still wetting the bed (Fig. 1). Parents may become concerned about nocturnal enuresis when their child reaches 5 to 6 years of age and is preparing to enter school. Most children are not concerned until 7 to 8 years of age. Approximately 80% to 85% of children who have nocturnal enuresis have MNE. Another 5% to 10% of cases meet the definition of PNE, with daytime wetting or other bladder symptoms. Organic causes are responsible for nocturnal enuresis in fewer than 5% of cases. Such organic causes must be searched for and ruled out if the history suggests their presence. There is a slight male predominance (about 60% overall) for nocturnal enuresis. Etiologic factors contributing to MNE include genetics, sleep arousal dysfunction,urodynamics, nocturnal polyuria, psychological components, and maturational delay. That the condition probably is multifactorial, with various contributing factors in any one patient, confounds attempts to base therapeutic approaches on etiology.A hereditary basis for nocturnal enuresis has been suspected for years. Studies of twins show a concordance rate of 43% to 68% for monozygotic and 19% to 36% for dizygotic twins. Seventy percent of children who have enuresis have a parent who has a history of the disorder. Studies indicate that if one parent had enuresis, the probability of a child having it is approximately 40% to 45%. If both parents were affected, the probability of a child having the condition increases to 70% to 77%. If neither parent had enuresis, only 15% of offspring will have enuresis. Chromosomes 12q, 13q, and 22 all have been named as possible locations of a gene(s) resulting in enuresis, but a specific mechanism for enuresis related to a gene locus is not known.The association between the presence of a full bladder and the sensation in the brain of a full bladder occurs in most children by the age of 5 years,which correlates with the normative standard in the United States for nocturnal dryness in 85% of 5-year-olds. Concurrently, by this age the child's pattern of several sleep/wake cycles daily, known as multiphasic sleep, has changed to a single period of sleep daily, known as monophasic sleep. Daytime urination control usually occurs first,followed by learning to arouse during sleep to the sensation of a full bladder. Many parents report that a child who has enuresis is more difficult to arouse from sleep than are other children in the home, but sleep studies have not documented a convincing association between a child’s sound sleep and a nocturnal wetting episode.The relationship of sleep patterns with enuresis is an area of active research. In some studies, the enuretic event seemed to occur during nonREM sleep and could occur during any part of the night. In others,enuresis reportedly was caused by a mild disturbance in arousal, based on the finding that activation of the arousal center proceeded correctly, but the transition from light sleep to complete awakening was not achieved properly. In a subset of patients, the arousal center in the brain failed to activate, despite proper full bladder sensation. There is conflicting evidence that children who have enuresis may exhibit other parasomnias, such as sleepwalking and night terrors. A recurrent theme in sleep research is the child’s inability to recognize the sensation of a full bladder during sleep and failure to awaken from sleep to urinate in an appropriate place. There appears to be a maturational pattern of progressive central nervous system “recognition” of bladder fullness and control over the micturition reflex.Some children who have enuresis may have a small bladder capacity. Functional bladder capacity in children may be estimated by the formula: age in years plus 2, which gives bladder capacity in ounces. By adolescence, this no longer applies; adult bladder capacity is approximately 10 to 15 oz. Children who have small bladder capacities probably represent a subgroup of patients who have MNE and presumably cannot hold the normal amount of urine produced at night. They are more likely to report frequent daytime voiding,some nights with multiple episodes of enuresis per night, and no history of attaining dryness.In some children who have normal bladder capacities,urgency may play a role in nocturnal enuresis. These children exhibit daytime urgency, but they can maintain bladder control during the day. They have a pattern of partial emptying of the bladder that results in frequent daytime urination to maintain continence and enuresis occurring at night when they cannot void as often. No evidence supports abnormal urodynamics in children who have MNE. Involuntary nighttime voiding in those who have MNE occurs with a urodynamically normal bladder at functional capacity. Because most patients who have abnormal urodynamics as an underlying cause for their nighttime enuresis also have daytime symptoms, asking patients about daytime voiding patterns in the initial history is important.Polyuria is defined as excessive urine production. It may be associated with chronic illnesses such as diabetes mellitus and diabetes insipidus. Caffeine,alcohol, and medications also may cause it. Factors such as irregular food and drink intake and staying up late also may contribute. It seems reasonable to limit fluid intake several hours prior to bedtime because the most common cause of polyuria is habit polydipsia.Since first described in 1985, the theory that MNE is due to nocturnal polyuria with relative nocturnal deficiency of pituitary-produced antidiuretic hormone(ADH) has been controversial. Early studies reported that the plasma level of ADH did not increase during sleep in those who had enuresis compared with a rise in ADH among unaffected children, resulting in relative nocturnal polyuria as a factor in enuresis. Studies documenting the percentage of children who have enuresis and lack a nocturnal surge in ADH ranges from 25% to 100%, suggesting the presence of other factors. New research about polyuria and enuresis theorizes that a full bladder might communicate with the kidneys to reduce urine production. Some recent investigations also suggest abnormal osmoregulatory function in the kidney, with higher solute excretion among those who have enuresis.Most children who have enuresis have no psychological disorder. The dated concept that enuresis frequently is due to anxiety or stress is unproven. On the contrary, enuresis creates psychosocial problems for the bed-wetting child, including poor self-esteem,family stress, and social isolation. Secondary enuresis commonly has been attributed to psychological factors. Recent studies show no major psychological differences between children who have secondary enuresis and children who have no enuresis. If a child reverts to bed-wetting during treatment for enuresis or has increased episodes of bed-wetting during times of stress, it is more likely due to poor compliance with treatment. Children who have enuresis not only have lower self-esteem than unaffected children, but they have lower self-esteem than children who have chronic,debilitating illnesses. These study results both emphasize the profound impact that enuresis may have and justify a careful evaluation of psychosocial symptoms in the family and the patient.The fact that most children who have enuresis become dry in time with or without intervention supports maturational delay as a factor in MNE. At age 5 years,15% of children occasionally wet the bed compared with only 10% at 6 years of age. Perhaps development of central nervous system recognition of and response to the sensation of a full bladder is delayed, a concept that correlates strongly with the arousal dysfunction theory. Proposed abnormal urodynamic factors also may normalize as the child becomes older. A similar process of maturation over time is seen in other milestones of normal development,such as the age range of 9 to 15 months at which a child begins to walk. Maturational delay may be the most plausible and unifying concept among proposed etiologic factors in MNE.In addition to a detailed toilet training history, a family history of enuresis should be sought because it rarely is volunteered, even when known by a parent. Other pertinent details of a history include the onset and pattern of wetting, voiding behavior, sleep pattern, parasomnias, medical conditions, daytime urinary symptoms, bowel habits, and psychosocial factors. It also is important to assess both the family’s and the patient’s attitude toward the bed-wetting and their readiness to initiate and continue treatment. Questions about voiding patterns may reveal urgency or a history of small, frequent voids that suggests bladder instability or small bladder capacity. Organic causes of enuresis may be apparent by a history of dysuria (urinary tract infection),polyuria and polydipsia (diabetes insipidus or mellitus), encopresis (constipation), abnormal urine stream (lower obstructive lesions), gait disturbances(spinal cord pathology), or nighttime snoring(adenoidal hypertrophy). A thorough and thoughtful history is the means by which the infrequent organic causes of enuresis are separated from the majority of cases that have no organic etiology (TableT1). Most children who have nocturnal enuresis will have normal findings on physical examination. In addition to assessing the child’s height, weight, and blood pressure, perform a complete examination, paying careful attention to the urogenital, neurologic, and gastrointestinal systems. A palpable bladder or palpable stool may be present on abdominal examination, ectopic ureter or signs of sexual abuse on urogenital examination, or abnormal gait apparent during neurologic examination. Cremasteric, anal, abdominal,and deep tendon reflexes that reflect spinal cord function all should be tested. The skin of the lower back should be inspected for the presence of a sacral dimple, hair patches, or vascular birthmarks, which can be clues to spinal dysraphism. Mouth breathing may suggest sleep apnea with associated enuresis due to adenoidal hypertrophy. Direct observation of the urinary stream in the office is important, especially if findings on the history suggest an abnormality. The family can measure bladder capacity at home prior to the initial evaluation or it can be measured in the office by having the child drink 12 oz of fluid on arrival, then voiding into a calibrated cup.All children who have enuresis should have urinalysis of a clean-catch midstream urine specimen (Fig 2). The ability to concentrate urine to 1.015 or greater rules out diabetes insipidus and the absence of glucose rules out diabetes mellitus as causes of nocturnal enuresis. Further laboratory testing is unnecessary for MNE. A urine culture should be obtained for symptoms suggestive of urinary tract infection on history or findings on urinalysis. Routine radiologic or ultrasonographic imaging studies of the urinary tract or cystoscopy are not recommended for children who have MNE. PNE may require further evaluation with voiding cystourethrography (VCUG), renal and bladder ultrasonography, or urodynamic testing. When enuresis is resistant to treatment and the history suggests a sleep disorder, a sleep study may be useful to look for sleep apnea or parasomnias.An important factor in any pediatric treatment is the child’s motivation and acceptance. Parents also must support the child and the treatment program for maximal effectiveness. The child’s age is a critical factor when formulating a treatment plan. Consideration of treatment is guided by the clinician’s understanding of the changing prevalence of enuresis in school-age children and the effect of enuresis on the child’s self-esteem and family function. Timing of the intervention should be tailored to the individual child and family.Although a child’s self-esteem can be harmed by MNE, even at early school age, the effects are variable. Some school-age children and their parents are not bothered by the child’s enuresis; others experience anxiety and stress. It is reasonable to discuss MNE during a health supervision visit and for of patients at 6 or 7 years of age. The maturational of nighttime awakening to void should be to parents and to other milestones that occur over a range of time than at a specific age. plausible medical a family history of enuresis, and its prevalence may the on the Parents should that or is both in the enuresis and in the child’s children and who are bothered by the child’s intervention is recommended by age 8 years at the In MNE should be and begins with parents and the child about enuresis, a process that usually with can the parents and the child to the can be by up a or to and a system to the child for night that or is The child should be out of or training and to the bladder prior to to The child should in as a of The of secondary psychological to the child’s self-esteem is by from and by a excessive fluid intake bedtime can cause increased nocturnal urine as can and for hours prior to bedtime is The child should to fluid than having it The rate of complete resolution of enuresis with is estimated to be only but up to 70% of children who have MNE have some in the of wet dry nights are the reported rate is is a reasonable especially with the If after a of to 6 a different treatment program should be training and an enuresis also may be part of a program to enuresis. an of the brain and bladder the out of enuresis by the and and having the child of awakening to urinate in the toilet or staying dry all night. It can be with an office are until the is that the child can at may be to a or may be if the primary care not have the training or time for this training described by and in waking the child on a progressive at over several the child and if wet or to the toilet when voiding is in the of the is to have the child to a rate is reported with this by the it is a more and process than most are to have the rate of any treatment. 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These medications may play a role in the treatment of a condition that has no single etiology and various factors in any one patient, it is not that a single of nocturnal enuresis is of that more than one treatment may response children and their and about enuresis are of They must that nocturnal wetting is not the child’s There is no for or a to the by described and that the child in waking to void and that dryness this age children who still have nocturnal enuresis at this age and for the child and family an the enuresis gives the results in of response rate and also is the age at which of such as can be useful for such as an at a home or a of the impact of bed-wetting in adolescence, intervention is If of an enuresis not or reduce the wetting of is justified as treatment. 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