Nocturnal enuresis, or bedwetting, is a common condition which children usually grow out of. Advice to parents on simple behavioural strategies is usually the first step. The use of bed alarms with support offers the best chance of long-term success. The occasional, short-term use of desmopressin is also discussed.
         
        
        
	
		
		
			
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			Expert Reviewer: Associate Professor David Reith, Department of Women's and Children's Health,
					Dunedin School of Medicine, University of Otago
		
            
            
            
            
		
			
				| Key Concepts | 
			
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						Nocturnal enuresis is common and children usually grow out of it
						Simple advice regarding fluids and use of rewards may be appropriate in the first instance
						If the child and their family are motivated to try treatment, then the use of bed alarms with support offer the
							best chance of long-term success
						Desmopressin can be prescribed with caution for occasional short term use
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		Considerations:
		
			- At what age is bedwetting abnormal?
- What is it normally due to?
- Are any investigations needed?
- What advice can I give to parents?
- When should I refer?
- What non-drug treatments are recommended?
- What medications are recommended?
    
            
            
            
		Defining bedwetting
		Primary nocturnal enuresis is bedwetting in a child who has never been consistently dry at nights for
			a period of six months.
		Secondary nocturnal enuresis is bedwetting in a child who has previously had a period of at least six
			months of dryness.
		Bedwetting can place considerable stress on the individuals affected and their families. Although this article is aimed
			mainly at children, similar principles apply to adolescents and adults who are still bedwetting.
		At what age is bedwetting abnormal?
		The International Children's Continence Society defines nocturnal enuresis as:1
		
			- A child five to six years old with two or more bedwetting episodes per month
- A child over six years old with one or more bedwetting episodes per month
However, most management strategies are aimed at children aged seven years or older, as this is when bedwetting is usually
			considered to be a problem by both the child and their family.
		Bedwetting is common but reduces with age. It affects approximately:
		
			- 15% of 5 year olds
- 5% of 10 year olds
- 2% of 15 year olds
- 1% of adults
Spontaneous remission occurs in about 15% of affected children each year and is more likely to occur if there is a family
			history of nocturnal enuresis.2
		A recent study found that children with the most frequent bedwetting were more likely to persist with the problem.3
		It is thought that fewer than half of parents with a child with nocturnal enuresis, consult their doctor about the problem.4
             
            
            
            
		Causes of bedwetting
            
		The exact cause of nocturnal enuresis is unknown. It appears to be a neurodevelopmental problem which is probably multifactorial.
			Discussion with patients and parents may centre around the following:
		
			- Sleep polyuria
- Reduced night-time bladder capacity
- Lack of arousal from sleep
- Psychosocial factors
- Genetics
 
            
		Sleep polyuria
		Nocturnal polyuria can result from a deranged circadian rhythm of antidiuretic hormone (ADH) secretion which occurs
			in approximately 70% of children with bedwetting.5 ADH, also known as vasopressin, is a peptide secreted from
			the posterior pituitary and plays a key role in the control of urine production. Usually ADH secretion increases during
			the night to concentrate the urine and this in turn helps to produce low volumes of urine.
                 
            
		Reduced night-time bladder capacity
		A recent Chinese study included ultrasound examination of 500 children with nocturnal enuresis and showed a reduced
			functional bladder capacity in approximately 40% of children with nocturnal enuresis.6
                 
            
		Lack of arousal from sleep
		Sleep and arousal is one of the least understood factors in the pathophysiology of enuresis. Many parents will comment
			that their child with bedwetting is a "deep sleeper". A 1999 study using EEG analysis suggested that both deeper sleep
			and impaired arousal is more common in children with enuresis,7 however other studies have conflicting results.
                 
            
		Psychosocial factors
		Psychological problems are rarely the cause of primary nocturnal enuresis but teasing, bullying or punishment can be
			the result of it. Secondary nocturnal enuresis is more likely to be due to a psychosocial stressor such as parental separation,
			a new baby in the family, sickness or problems at school.
                 
            
		Genetics
		Genetic factors are strongly implicated in the etiology of primary nocturnal enuresis, so it is worthwhile taking a
			family history of bedwetting.
		Approximately 70% of children with bedwetting have a sibling or parent who was late in becoming dry. Children with one
			parent who had enuresis have a 44% risk of nocturnal enuresis and those with two affected parents have a 77% risk.4
		Most inherited nocturnal enuresis exhibits an autosomal dominant mode of transmission with high penetrance (90%). However,
			a third of all cases are sporadic, and the difference between sporadic and familial forms is not known.8
                 
             
            
            
            
		Differential diagnosis - what else might it be?
		When a child presents with bedwetting, enquire about the presence of daytime symptoms, which could indicate that the
			bedwetting is secondary to other causes.
		
			- UTI and other acute illness might cause short periods of bedwetting in someone who has previously been dry.
- Diabetes mellitus, diabetes insipidus or renal failure may cause bedwetting but there are usually other symptoms e.g.
				daytime polyuria, excessive thirst.
- Chronic constipation may result in bladder instability, a careful history of bowel pattern is required.
- Bladder instability can cause daytime and night-time incontinence.
- Caffeinated drinks may irritate the bladder.
     
            
            
            
		Investigation of bedwetting
		A careful history is important
		
			- Distinguish between children with nocturnal enuresis (the majority) and children who also have episodes of enuresis
				during the daytime.
- Distinguish between primary and secondary nocturnal enuresis.
- Ask about the pattern of voiding, the number of dry nights in the past week or month, fluid intake at bedtime, intake
				of caffeine at bedtime (e.g. tea, coffee, cola, chocolate).
- Discuss practical issues such as can the child reach the toilet, do they need a light on to see their way to the toilet,
				any night time fears.
- Ask about any possible stressors at home, school or with friends.
- Discuss what has been tried already, including punishments and rewards.
- Elicit previous medical history, such as previous UTIs.
The examination of the abdomen, perineum, spine and nervous system is normal in a child with nocturnal enuresis. Any
			abnormalities found would lead to additional investigation.
		Ultrasound examination of the kidneys and urinary tract to exclude anatomical abnormalities is only recommended in children
			who are wet during the day, after UTI or when nocturnal enuresis is unresponsive to treatment.9
		Investigation with urine dipstick and culture can be helpful.4 However, checking specific gravity is usually
			not.10
             
            
            
            
		Treatment options for bedwetting
            
		Waiting
		Most children will outgrow bedwetting. For this reason most treatments are delayed until the child is at least seven
			years old. However treatment might begin earlier if the situation is perceived to be damaging the child's self esteem
			or relationships with family and friends.
                 
            
		Behavioural strategies
		Parents could be advised to:
		
			- Ensure that the child empties their bladder well at bedtime.
- Improve the child's access to the toilet (e.g. have them sleep on the bottom bunk, have a torch within reach).
- Use waterproof covers on mattress and duvet (especially for boys) and then absorbent layers over the mattress cover. 
- Shower/bathe the child in the morning prior to attending school to remove odour.
- Do not restrict fluids. The child should have about eight drinks per day, spaced out throughout the day, the last
				one about an hour before bed. Avoid caffeine in night-time food and drink (e.g. tea, coffee, cola, chocolate).4
- Treat constipation if present.
- Reward systems.11 Advise use of positive reinforcement to encourage a desired behaviour. The aim is to
				positively reinforce dry nights (or any steps towards that) and to reduce the negative emphasis on wet beds.
- Scheduled wakening is preferable to "lifting" a child. Scheduled wakening involves waking the child periodically (one
				to three times) at night and walking them to the toilet to pass urine. Eventually the time between awakenings is stretched
				until the child can go a full night without wetting the bed. Lifting is thought to be counterproductive in some children
				as the child is denied the opportunity to learn the sensation of a full bladder and is encouraged to urinate without
				wakening.4
- Older individuals may use an alarm clock to wake themselves before their usual time of enuresis.12
 
            
		When should GPs refer?
		If after initial advice, more active treatment is sought, then referral to a paediatrician, enuresis clinic (if available
			in your area) or a continence advisor might be the next step to working out a programme most suited to the child. The
			programme would usually centre on the use of bed alarms.
                 
            
		Supported bed alarm programmes
		Enuresis alarms emit a loud tone when moisture is sensed, so that the child is awoken as soon as they begin to wet the
			bed. They are considered a good long-term and safe treatment. 
		Bed alarms have a 65 to 80% success rate when used with support (such as an enuresis nurse) and if the child is motivated
			to become dry.4 They help "condition" the child to wake at the sensation of a full bladder. Efficacy is better
			than behavioural treatments alone and relapse rate is lower than with pharmacological treatments.4
		Alarms are usually needed for three to five months. When dryness has been achieved for 14 nights, children should be
			encouraged to drink extra fluid (up to 500mL of water in the hour prior to bedtime), and continue with this until there
			have been another seven to 14 consecutive dry nights. This form of challenge is used in conjunction with the bed alarm
			and is known as "overlearning". This reduces the rate of relapse from 50% to 25%.4
		Children who relapse should be promptly offered the supported alarm programme again.
                 
            
		Desmopressin
		Desmopressin is a synthetic analogue of ADH and is the only available antidiuretic drug. It works by reducing the volume
			of urine produced during the night but only on the nights it is used, so does not cure the problem in the long term. 
		In most situations, before considering this medication, it would be appropriate to have tried a bed alarm programme.
                 
            
		Safety concerns about desmopressin
		In April 2007 the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued a drug safety alert stating that
			hyponatraemia, water intoxication and convulsions were associated with the use of desmopressin nasal spray. Following
			this, the nocturnal enuresis indication has been withdrawn from desmopressin nasal spray in the UK.
		In December 2007 US drug regulators, the FDA, stated that they no longer approved desmopressin nasal spray for use in
			nocturnal enuresis after two deaths and a review of data that showed that 41% of hyponatraemic-related seizures occurred
			in people younger than 17 years old, using desmopressin most commonly for primary nocturnal enuresis.
		The BNF 2008 states: "The Committee on Safety of Medicines has advised that patients should stop taking desmopressin
			during an episode of vomiting or diarrhoea (until fluid balance normal). The risk of hyponatraemic convulsions can also
			be minimised by keeping to the recommended starting dose and by avoiding concomitant use of drugs which increase secretion
			of vasopressin e.g tricyclic antidepressants".13
                 
            
		Occasional short term use of desmopressin
		Desmopressin intranasal spray is currently available fully funded on specialist recommendation. The tablets are not
			currently funded. GPs might be asked to consider prescribing desmopressin for short-term use such as for school camps
			or sleepovers. Desmopressin can also be offered as an adjunct to alarm therapy if required to assist family coping.4
		A Cochrane review of desmopressin concluded that it was effective in reducing bedwetting compared with placebo. When
			desmopressin is used, most of the children have fewer wet nights (one night less on average per week) and more become
			dry (19% compared with 2% using placebo treatment in five trials involving 288 children).14
		The usual dose of desmopressin is 20 to 40 micrograms intranasally or 200 to 400 micrograms orally, at bedtime. Fluid
			intake should be restricted one hour before to at least eight hours after the dose, and patients or parents should be
			told to report symptoms of water retention and hyponatraemia e.g. headache, nausea, vomiting, weight gain or convulsions.
		There is insufficient data to reliably assess whether a higher dose is any more effective than a lower dose, so to minimise
			side effects and costs, the lowest effective dose should be used.4
                 
            
		Other drug options?
		Oxybutynin can be useful in daytime enuresis and may also improve nocturnal enuresis. It can be considered in patients
			with bladder instability or in children who do not respond to desmopressin.
		Tricyclic antidepressants are contraindicated for use in children for nocturnal enuresis. Tricyclic antidepressants,
			most commonly imipramine, have historically been used for the treatment of nocturnal enuresis and have evidence of effectiveness
			but with safety concerns.15 A particular concern is overdose, which can be fatal.
		Indomethacin, diclofenac and diazepam are not recommended as initial therapy for children with nocturnal enuresis.
                 
             
            
            
            
            
		
			Useful resources
			KEEA - Kiwi Enuresis Encopresis Association - www.keea.org.nz
			KEEA was registered as a charity in New Zealand in 2001 and helps with information and advice on bedwetting and soiling.
				They have a useful database which shows who to contact in your area for a bed alarm, what costs may be involved, the
				waiting list length and whether a GP referral is necessary.
			
			
			This website covers a range of information on child and youth health - use ‘bedwetting' as a search term.
			
			NZCA (The New-Zealand Continence Association) - www.continence.org.nz
			The NZCA has a children's continence section on it's website.
			Patient information leaflets are also available - Incontinence in children, and Adults and bedwetting. Email: 
			jan@continence.org.nz 
				or call free 0800 650 659
			
			
			This is a support service for parents of children with a range of conditions and can put parents in touch with other
				parents experiencing similar situations.
			
			
			The society has published a best practice evidence-based guideline. 
             
		 
            
            
            
            
            
		 
		
			References
			
				- Norgaard J, van Gool J, Hjalmas K et al. Standardisation and definitions in lower urinary tract dysfunction in children.
					International Children's Continence Society. Br J Urol 1998; 81(Suppl 3):1-16.
- Mikkelsen EJ. Enuresis and encopresis: ten years of progress. J Am Acad Child Adolesc Psychiatry 2001;40(10):1146-58.
- Butler RJ, Heron J. The prevalence of infrequent bedwetting and nocturnal enuresis in childhood. Scand J Urol Nephrol
					2008;42(3): 257-64.
				
- Paediatric Society New Zealand. Best Practice Evidence Based Guideline. Nocturnal Enuresis "Bedwetting". 2005. Available
					from www.paediatrics.org.nz Accessed May 2008.
- Rittig S, Knudsen UB, Sorensen S et al. Abnormal diurnal rhythm of plasma vasopressin and urinary output in patients
					with enuresis. Am J Physiol 1989;56:664-71.
- Lui YL, Wen FQ, Sun F. Functional bladder capacity in 1500 children with nocturnal enuresis. Zhongguo Dang Dai Er
					Ke Za Zhi. 2008 Apr;10(2):170-172. Article in Chinese, abstract available on PubMed. 
- Hunsballe JM. Sleep studies based on electroencephalogram energy analysis. Scand J Urol Nephrol 1999; 33(Suppl 202):28-30.
- Von Gontard A, Schaumburg H, Hollmann E, et al. The genetics of enuresis: A review. J Urol 2001;166(6): 2438-43.
- Hjalmas K, Arnold T, Bower W, et al. Nocturnal Enuresis: an International evidence based management strategy. J Urol
					2004;171(6):2545-61.
- Sailta M, Macknin M, Medendorp SV, Jahnke D. First-morning urine specific gravity and enuresis in preschool children.
					Clin Pediatr (Phila). 1998 Dec:37(12):719-24.
- Glazener C, Evans J, Cheuk D. Complementary and miscellaneous interventions for nocturnal enuresis in children. Cochrane
					Database Syst Rev 2005;2:CD005230.
- Lynth N, Bosson S. Nocturnal enuresis. Clin Evid 2004;12:508-17.
- British National Formulary (BNF). BMJ Publishing Group and Royal Pharmaceutical Society of Great Britain. March 2008.
- Glazener C, Evans J. Desmopressin for nocturnal enuresis in children. Cochrane Database Syst Rev 2000;2:CD002112.
- Glazener C, Evans J, Peto R. Tricyclic and related drugs for nocturnal enuresis in children. Cochrane Database Systematic
					Rev 2000;2:CD002117.