Sleep Related Enuresis
Introduction
Up to the fifth year of life, urinary incontinence is regarded as a physiological phenomenon, even if many children develop complete continence well before this age.1 According to the International Children’s Continence Society, enuresis is classified as either primary – when the child has never achieved nighttime dryness, or secondary – when nocturnal enuresis occurs after a period of dryness of at least 6 months.
Among the known risk factors for the occurrence of nocturnal enuresis, significant associations between sleep-disordered breathing and SRE have emerged both in children and in adults over the last decade.2–6 It has become apparent that increased upper airway resistance during sleep manifesting either as habitual snoring (HS) or as documented obstructive sleep apnea syndrome (OSAS) leads to increases in the risk of SRE. Most importantly, after successful treatment of the respiratory disorder during sleep, SRE can be reduced in frequency or severity, and even eliminated. Thus, careful evaluation of sleep-disordered breathing in enuretic patients is important, especially in those children with concomitant daytime incontinence.6
Epidemiology
The epidemiology of bedwetting is complicated by the variety of definitions used in studies (Box 13-1).
Children develop stable bladder control in the third to sixth year of life – initially during the day and later also during the night. At age 7 years, approximately 10% still have nocturnal enuresis, and 2–9% are affected during the day.8 Similar results were reported by the Avon Longitudinal Study, a prospective and large longitudinal cohort from birth that examined a variety of developmental trajectories specifically assessing growth and pediatric milestones. Another epidemiological study in Hong Kong, which defined bedwetting as the occurrence of one wet night over a 3-month period, reported a prevalence of 16.1% at age 5 years, 10.1% at 7 years and 2.2% at 19 years.9 In all studies, the prevalence is markedly greater for boys than for girls at all ages, with an average ratio of 3 : 1.9–12 Children tend to outgrow SRE, with a spontaneous remission rate of about 14–15% annually among bedwetters, with 3% remaining enuretic into adulthood.8,10,11 Male gender and age younger than 9 years are considered major contributors to sleep-related enuresis in children.12
Interestingly, in a recent population-based study made in 6147 children by Su and collaborators, the prevalence of nocturnal enuresis (NE) was not greater in children with OSA, but was increased with increasing severity of OSA in girls only, demonstrating, for the first time, a sex-associated prevalence of NE in relation to increasing OSA severity.13
Etiology
Important risk factors for SRE include family history, nocturnal polyuria, impaired sleep arousal and nocturnal bladder dysfunction. Nocturnal enuresis has been linked to chromosomes 13, 12, 8 and 22, with a predominantly autosomal dominant inheritance.14
In two-thirds of children with SRE, disturbed circadian rhythms in ADH release and nocturnal polyuria have been reported.15 Defects in sleep arousal have also been associated with SRE.16 As many as a third of children with SRE may have nocturnal detrusor overactivity along with reduced functional bladder capacity. Interestingly, these children have normal detrusor activity and a normal functional bladder capacity when they are awake, but a reduced functional bladder capacity with detrusor hyperactivity when asleep.7
Other risk factors for sleep-related enuresis include constipation,17 developmental delay and other neurological dysfunction,18 attention deficit hyperactivity disorder (ADHD),19 upper airway resistance,20,21 and sleep-disordered breathing.2–6,22
Pathophysiology
Physiological Urinary Incontinence
This term clarifies urinary incontinence as a symptom that is regarded as a normal feature during the first few years of life, and is considered as pathological only after the fifth year of life. The range of normal continence development is, however, very wide, such that one can assume that many children experience ‘physiological’ urinary incontinence beyond the completed fifth year of life (‘late developers’). The clinical and diagnostic test findings in such children are negative and reveal the absence of any pathological features.7
Organic Urinary Incontinence
This form of urinary incontinence is rare. However, special efforts have to go into the detection of possible organic causes, particularly among treatment-refractory cases. The permanent leaking of small amounts of urine during the day and at night is typical for girls with duplex kidney and ectopic ureter implantation. Malformations of the urethra may also be the cause of organic urinary incontinence. Polyuric renal disease – such as tubulopathies, chronic renal failure, or diabetes insipidus – can also manifest as treatment-refractory enuresis.
Neurogenic Disorders
In congenital diseases (e.g., myelomeningocele/spina bifida) or acquired neoplastic or inflammatory disorders of the nervous system, the innervation of the bladder is often affected. Occult spinal dysraphisms (for example, spina bifida occulta, tethered cord syndrome, sacral agenesis) often remain undetected for a long time and can manifest as treatment-resistant SRE.1
Manifestations of the Symptoms of Functional Urinary Incontinence
Monosymptomatic Enuresis Nocturna (MEN)
There are children who present nocturnal polyuria, with or without vasopressin deficiency. These children usually have no associated daytime bladder dysfunction,23 and wet their beds because nocturnal urine output exceeds the amount of urine that the bladder can accommodate. In general, they sleep too deeply to wake up when the bladder is full – high arousal thresholds. Experts have chosen to call this subtype of MEN as diuresis-dependent enuresis.24
There is a second group of children with SRE and MEN who suffer from detrusor overactivity.23,24 Many of these children have daytime symptoms such as urgency and/or incontinence, or are constipated,10 and they wet their beds because of uninhibited detrusor contractions that fail to awaken the child from sleep. The term detrusor-dependent enuresis is commonly used to define this MEN subgroup.24 There are also children who exhibit signs of both diuresis-dependent and detrusor-dependent SRE.25
Nocturnal Polyuria
The findings by Nørgaard et al. showing that many enuretic children have nocturnal polyuria (due to the lack of the physiological nocturnal peak of vasopressin secretion) causing nocturnal urine production and exceeding their functional bladder capacity26 have been replicated27,28 and contradicted.29 The possibility has also been put forward that polyuria is not necessarily always caused by vasopressin deficiency.16
Detrusor Overactivity
Support for the detrusor overactivity hypothesis is provided by the finding that children with enuresis go to the toilet more often than dry children, that they void smaller volumes, and that urgency symptoms are more common in this group.17,18 However, the European Bladder Dysfunction Study (EBDS) did not find any correlation between clinical urge symptoms and cystomanometric detrusor overactivity.24 It is likely that the overactive bladder in children is not pathophysiologically identical to the better-understood overactive bladder in adults. The cardinal symptom of overactive bladder is an imperative urinary urge. By intentionally restricting fluid intake and paying frequent visits to the toilet many children remain continent during the day, but once these control mechanisms are absent, for example, during sleep, such children manifest enuresis, a very different situation from that seen in adults.1
Sleep-Disordered Breathing
Over the last decade, a significant correlation between SRE and sleep-disordered breathing (SDB) has been firmly established. Habitual snoring is the most common clinical manifestation of SDB in children, a condition that ranges from primary snoring to severe OSAS.30 Studies on the epidemiology and symptoms of sleep-disordered breathing have reported an increased frequency of enuresis in children with habitual snoring. Wang and colleagues reported that 46% of children with OSAS diagnosed by polysomnography had nocturnal enuresis.31
In a European population questionnaire-based study, Kaditis and colleagues showed that 23.3% of children with SRE were habitual snorers.32 In a recent questionnaire-based survey of a community sample of children in Greece by the same authors, children with HS reported more often the concurrent presence of SRE than those children without HS.21 Similar results were reported by a North American population-based study, in which 26.9% of habitual snorers presented with enuresis.33 The existence of a significant association between enuresis and SDB has been further supported by the decreases in frequency of SRE or even complete resolution of nocturnal enuresis after successful treatment of the breathing disorder during sleep.
As a general recommendation, mouth breathing and nasal congestion during sleep should be more carefully evaluated in cases of children with NE who do not respond to standard treatment and present with SDB.4
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
