Chapter XIII.10. Enuresis
Daniel M. Bender, MA
August 2022

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The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Potenciano Reynoso Paredes. This current third edition chapter is a revision and update of the original author’s work.

A 4.5 year old male presents to the office with his mother with a chief complaint of bedwetting twice a week. He is healthy except for an occasional cough and fever that his mother attributes to exposure to other children with colds. Urinary incontinence occurs only at night, he must wear diapers to bed. His mother is worried since his brothers and sisters were all toilet-trained by this age. There is no history of dysuria, intermittent daytime wetness, polyuria, or polydipsia.

His past medical history is unremarkable. Family history is significant for his father being a bedwetter. His child development is normal.

Exam: VS T 37C, P 110, R 20, BP 107/64, Ht 102 cm (25th percentile), Wt 16.2 kg (25th percentile). He is alert and active, in no distress. His appearance is non-toxic. HEENT and neck exams are negative. His lungs are clear bilaterally. His heart has a normal rate and rhythm, normal S1and S2, and no murmurs or rubs. No masses, organomegaly, or tenderness are appreciated on exam of his abdomen. Bowel sounds are present. He has no inguinal hernias. He has a circumcised penis of normal size. The meatus is normally placed, without discharge. No phimosis is present. His testes are descended bilaterally and are of normal size (Tanner stage 1). His back is straight with normal posture and no scoliosis, tenderness, or midline defects. His extremities and muscle tone are normal. His gait is normal. He can hop, skip, and stand on each foot for 5 seconds, copy a square, and get dressed without help. His speech and behavior are age appropriate.

You reassure his mother that bladder control is usually attained between the ages of 1 and 5 years and bedwetting becomes less frequent with each passing year. You recommend that she be supportive of her son's dry nights and avoid criticism of wet nights. You also recommend avoiding excessive fluid intake two hours before bedtime and emptying his bladder at bedtime. He returns to your office after 6 months and his mother feels that the bed-wetting problem has improved significantly. On his next appointment (4 months later) his mother reports the resolution of his bedwetting problems.

Enuresis, commonly known as bedwetting, is one of the most common childhood urologic complaints encountered by pediatricians. Nocturnal enuresis (NE) refers to the involuntary passage of urine during sleep in a child at least 5 years of age. It affects about 20% of 5 year old children, 10% of 7 year old children, and 5% of 10 year old children and is more common in boys (1,2). Enuresis can be subdivided as primary or secondary, and monosymptomatic or nonmonosymptomatic. Primary enuresis is the term used when a child never stopped bedwetting for any lengthy period, whereas secondary enuresis is acquired after being dry or continent for at least 6 months. When the only symptom is nighttime bedwetting, the enuresis is referred to as monosymptomatic. This contrasts with nonmonosymptomatic enuresis, which is associated with additional symptoms of urgency, hesitancy, frequency, and/or daytime incontinence. Primary monosymptomatic enuresis affects the large majority (75%) of children with enuresis (2).

The pathogenesis of primary enuresis is multifactorial. Several important contributing factors include delayed maturation of voluntary cortical control of the micturition reflex, reduced nighttime antidiuretic hormone production, decreased bladder capacity, and impaired sleep arousal. Epidemiologic studies have shown that approximately 15% of enuresis cases resolve spontaneously each year, supporting delayed neurodevelopmental maturation as the main etiology (1). Decreased functional bladder capacity has also been shown in those with nocturnal enuresis as compared to normal peers. The average bladder capacity in children can be approximated by the formula: volume in mL = (2 + age in years) × 30. A normal 5 year old child would therefore have an estimated bladder capacity of 210 ml. By comparison, the adult bladder capacity is 250 to 400 ml (2).

Interestingly, family studies show a strong genetic predisposition for enuresis. A child has a 44% risk of developing enuresis if one parent was affected; the likelihood jumps to 77% if both parents were enuretic (3). More recent genome-wide association studies have identified localized risk variants for the development of primary NE to chromosomes 6 and 13. Potential genes of interest at these loci include PRDM13, SIM1, and EDNRB, which are important for the balance of neuronal excitation and inhibition, regulation of ADH neurons, and smooth muscle contraction, respectively (4).

Organic causes of bedwetting account for a small minority of cases, mostly due to urinary tract infections. Other less frequent organic causes include diabetes mellitus, diabetes insipidus, nocturnal seizures, genitourinary anomalies, sickle cell disease, medications, or emotional stress. These children should be identified and treated accordingly. In some children, severe constipation may compress the bladder and present with bedwetting. There is also a connection between enuresis and obstructive airway disease, with studies showing a 50% or greater resolution rate of enuresis after airway surgery (1).

The office evaluation of nocturnal enuresis must exclude any organic causes. The history should include the pattern of wetting, developmental milestones, fevers, polydipsia, polyuria, and prior urinary infections. Questioning about sickle cell disease, constipation, and obstructive sleep apnea is occasionally helpful. Special attention should also be paid to the child’s stressors and family dynamics, since these may uncover relevant psychological factors at play. Identifying potential sources of psychological stress is especially important in the workup of secondary nocturnal enuresis (3).

Because most cases of primary enuresis are monosymptomatic, the physical examination will typically be normal. Therefore, the examination should primarily focus on identifying secondary or nonmonosymptomatic causes of enuresis. Special attention should be given to the neurological, genital, bladder, and bowel exams. A neurological examination should assess gait, muscle tone, strength, and perineal sensation. The lumbosacral spine should be inspected for midline defects, occult abnormalities, and spinal cord dysfunction. Examination of external genitalia for abnormalities such as labial adhesions, meatitis, epispadias, and hypospadias should also be performed. The abdomen should be assessed for evidence of fecal impaction, organomegaly, or bladder distention. Additionally, tracking height and weight for signs of growth delay and assessing the oropharynx for enlarged adenoids and tonsils may prove to be useful (5).

The purpose of initial laboratory tests is to rule out infectious and metabolic etiologies. A urine specific gravity of 1.015 or greater rules out diabetes insipidus and the absence of glycosuria rules out type 1 diabetes mellitus. In cases in which urinary tract obstruction or neurogenic bladder are suspected, a voiding cystourethrogram may be warranted.

At present, no treatment modality is 100% successful. Parents need to be reminded that a majority of bedwetting is due to maturational delay and is not under conscious control. Therefore, the most important aspects of treatment are reassurance and protecting the child's self-esteem. It is important that bedwetting not be perceived as a bad behavior since punishment not only lowers the child’s self-esteem but also does nothing to improve symptoms. Early education of the parents in regard to maturational delay, the role of genetics, and the importance of a supportive toilet training practice may ease the difficult period. Since there is a 15% chance of spontaneous remission every year, some advocate an approach of reassurance and watchful waiting. Simple behavioral modifications such as fluid restriction before bedtime, voiding at bedtime, daytime bladder training, and waking children in the middle of the night may be tried initially. However, none of these strategies are curative and evidence supporting their efficacy is lacking (6). Additionally, this conservative approach (which requires patience) can lead to suffering and frustration for the patient and family. Instead, a combination of behavior modification with an alarm system and pharmacologic therapy can be implemented.

Behavioral therapy with an auditory or vibratory alarm is most effective in the treatment of nocturnal enuresis. Urination acts as a stimulus for the alarm and wakes the patient from sleep, conditioning a cerebral response to the nocturnal urge. Enuresis alarms have a success rate of 50% to 70% and a lower relapse rate compared to pharmacotherapy (7,8). The only drawback is that the child and family must be highly motivated to stay committed to these conditioning methods. The alarm is typically worn every night until 14 consecutive dry nights have been achieved. It typically takes between 5 and 24 weeks to achieve this response, with most children responding 12 to 16 weeks into treatment (3).

The other established first-line therapy for nocturnal enuresis is desmopressin (DDAVP), a synthetic analog of vasopressin. The drug works by stimulating water retention and urine concentration, thereby reducing urine volume. DDAVP is administered as an oral tablet one hour before bedtime and must be accompanied by nighttime fluid restriction. Approximately 60% to 80% of patients with monosymptomatic enuresis will have a good or intermediate response to DDAVP therapy (1). Desmopressin may be preferred over alarm therapy in those with nocturnal polyuria, or for use during important nights, such as a child going to a sleepover. The sole contraindication to DDAVP therapy is polydipsia, which can precipitate water intoxication and hyponatremia. An important drawback is the high relapse rate (65%) with drug cessation (3). Some studies suggest tapering the dose over several months may help to reduce the relapse rate, although more evidence is needed (8).

Additional pharmacologic options exist for children with enuresis that is resistant to alarms and desmopressin. Anticholinergics, such as oxybutynin and tolterodine, are considered second-line and may be indicated in children with symptoms of an overactive bladder. These drugs primarily work by decreasing detrusor muscle contractions. Anticholinergics are rarely used as monotherapy; they are typically added to desmopressin therapy. Clinically relevant side effects of anticholinergics to be aware of in the pediatric population include constipation, postvoid residual urine, and dry mouth. These can result in worsening of lower urinary tract symptoms and increased risk of urinary tract infections and dental caries (8).

Imipramine, a tricyclic antidepressant, has also been FDA-approved for the treatment of nocturnal enuresis and is considered third line. The drug has several effects in enuretic patients, including decreased REM time, increased ADH production, and detrusor muscle relaxation (3). However, the drug carries a serious risk of side effects (insomnia, dry mouth, anxiety) and toxicity (especially cardiac), restricting its use to patients who have failed to respond to other therapies. Among therapy-resistant enuretic children, 30% to 50% respond favorably to imipramine treatment. The success rate increases with the addition of desmopressin (8).

1. At what age do parents usually become concerned about bedwetting?
2. True/False: Most nocturnal enuresis is due to organic causes.
3. Which drug for nocturnal enuresis is cardiotoxic?
4. What laboratory test should be done to evaluate a child with enuresis?
5. What is the bladder capacity of children?
6. In evaluating a chronic bedwetting child, what should you look for in an abdominal exam?
7. True/False: Enuresis alarms produce excellent results if the child wakes up spontaneously when the alarm goes off.

1. Haid B, Tekgül S. Primary and Secondary Enuresis: Pathophysiology, Diagnosis, and Treatment. Eur Urol Focus. 2017;3(2-3):198-206. doi:10.1016/j.euf.2017.08.010
2. Elder, JS. Enuresis and Voiding Dysfunction. In: Kliegman RM, St. Geme JW, Blum NJ, et al (eds). Nelson Textbook of Pediatrics, 21st edition. 2020, Elsevier, Philadelphia, PA. pp. 2816-2821.
3. Savoy M, Walker R. Nocturnal Enuresis. In: Primary Care: Clinics in Office Practice. Vol 46. 2. 2019, Elsevier, Philadelphia, PA. pp. 243-248.
4. Jørgensen CS, Horsdal HT, Rajagopal VM, et al. Identification of genetic loci associated with nocturnal enuresis: a genome-wide association study. Lancet Child Adolesc Health. 2021;5(3):201-209. doi:10.1016/S2352-4642(20)30350-3
5. Baird DC, Seehusen D, Bode DV. Enuresis in Children: A Case-Based approach. American Family Physician. Published October 15, 2014. Accessed March 28, 2022.
6. Caldwell PHY, Nankivell G, Sureshkumar P. Simple behavioural interventions for nocturnal enuresis in children. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD003637. DOI: 10.1002/14651858.CD003637.pub3. Accessed 28 March 2022.
7. Caldwell PHY, Codarini M, Stewart F, Hahn D, Sureshkumar P. Alarm interventions for nocturnal enuresis in children. Cochrane Database of Systematic Reviews 2020, Issue 5. Art. No.: CD002911. DOI: 10.1002/14651858.CD002911.pub3. Accessed 28 March 2022.
8. Nevéus T, Fonseca E, Franco I, et al. Management and treatment of nocturnal enuresis-an updated standardization document from the International Children's Continence Society. J Pediatr Urol. 2020;16(1):10-19. doi:10.1016/j.jpurol.2019.12.020

Answers to questions
1. Typically at age 5 or 6 years.
2. False.
3. Imipramine.
4. Urinalysis with specific gravity, glucose, protein, blood, and white cells.
5. Most adults have a bladder capacity between 250 to 400 ml, but the average bladder capacity in children can be approximated by the formula: volume (mL) = (2 + age in years) x 30.
6. The abdominal exam should assess for masses secondary to enlarged urinary organs (bladder, kidney) and evidence of palpable stool in the colon suggesting fecal impaction.
7. True.

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