What are the causes of nocturnal enuresis?

Causes of Nocturnal Enuresis

Nocturnal enuresis is primarily caused by a combination of genetic predisposition, sleep arousal dysfunction, nocturnal polyuria (excessive nighttime urine production), reduced functional bladder capacity, and detrusor overactivity, with secondary causes including underlying medical conditions such as obstructive sleep apnea, diabetes mellitus, constipation, and neurological disorders. 1, 2, 3

Primary Mechanisms in Monosymptomatic Nocturnal Enuresis

The pathophysiology involves four core mechanisms that often coexist 2, 3, 4:

• Sleep arousal disorder: Children cannot awaken from sleep in response to bladder fullness, with a brainstem-level mechanism likely underlying this dysfunction 3, 4
• Nocturnal polyuria: Overproduction of urine at night, potentially related to alterations in vasopressin secretion 2, 5, 4
• Reduced functional bladder capacity: Small bladder storage capacity limits the volume that can be held overnight 2, 6
• Detrusor overactivity: Uninhibited bladder contractions occur before the enuretic episode, with no arousal to bladder distention in this subgroup 1, 4

Genetic Factors

There is a clear hereditary component 1:

• 44% of children are enuretic when one parent was enuretic 1
• 77% of children are enuretic when both parents were enuretic, compared to only 15% incidence in children from non-enuretic families 1
• Genetic data link specific chromosomal foci to enuresis 1

Sleep-Related Causes

Sleep disorders play a significant role 1, 7, 8:

• Obstructive sleep apnea (OSA) causes nocturnal enuresis through increased arousals and light sleep proportion, with upper airway obstruction specifically associated with bedwetting 1, 7, 8
• Wetting occurs randomly across all sleep stages in proportion to time spent in each stage, not preferentially in deep sleep 1
• The European Association of Urology identifies OSA as a key medical condition in the "SCREeN" framework for evaluating nocturia and enuresis 8

Medical Conditions (Secondary Causes)

Several underlying conditions must be ruled out 1, 2, 3:

Endocrine Disorders

• Diabetes mellitus: Loss of glucose in urine increases urine production 1, 3
• Diabetes insipidus: Impaired urine concentrating mechanism (morning urine osmolarity <600 mosm/L after overnight fluid avoidance confirms diagnosis) 1, 3
• Thyroid disease: Both overactive and profoundly underactive thyroid can contribute 1

Renal Disease

• Chronic kidney disease: Night-time natriuresis and impaired urine concentrating mechanism in the renal medulla 1, 3

Gastrointestinal

• Constipation and fecal impaction: Mechanical pressure on the bladder from stool impaction is a frequently overlooked cause 1, 3

Neurological Disorders

• Neurologic abnormalities: Spinal cord anomalies, autonomic failure, or other neurological diseases affecting bladder control 1
• New-onset severe symptoms, numbness, weakness, gait disturbance, or cognitive impairment warrant direct neurology referral 1

Cardiovascular

• Congestive heart failure: Daytime retention of salt and water with nighttime diuresis causes peripheral edema and nocturnal polyuria 1

Psychological and Developmental Factors

Psychological factors are contributory in a minority of children 1:

• Secondary enuresis (resumption after ≥6 months of dryness) often follows identifiable stressors: parental divorce, school trauma, sexual abuse, or hospitalization 1
• The enuresis represents a regressive symptom in response to stress or trauma 1
• Developmental immaturity in motor and language milestones is relevant for some children, though the mechanism remains unknown 1
• Family disorganization or neglect resulting in inadequate toilet training is rare but should be considered when other signs of neglect are evident 1

Medication-Induced Causes

Certain medications contribute to nocturnal enuresis 1:

• Diuretics: Timing of doses relative to bedtime affects nighttime urine production 1
• Medications causing xerostomia (dry mouth) increase fluid intake: anxiolytics, antidepressants, antimuscarinics, antihistamines, decongestants, antiparkinsonians, pain medicines, and antipsychotics 1, 9
• Calcium channel blockers, lithium, and NSAIDs may also contribute 1, 9

Common Pitfalls to Avoid

When evaluating nocturnal enuresis 9, 8:

• Do not assume deep sleep is the primary cause—wetting occurs across all sleep stages proportionally 1
• Screen for OSA even in younger patients without other urinary symptoms, as it is frequently missed 8
• Always check for constipation, as occult fecal impaction is a treatable cause often overlooked 1, 4
• Do not attribute enuresis to psychological factors without evidence of specific stressors, as this is only relevant in a minority of cases 1
• Review all medications, including over-the-counter drugs that may cause xerostomia or diuresis 9