Nocturnal Enuresis in Children

All children start life being incontinent of urine both by day and night and, as neurological maturation occurs, voluntary control of the bladder is gained first by day and then by night. Very few never gain control of the bladder unless there is obvious neurological disease, including gross mental handicap. In most cases, nocturnal enuresis in children should be seen not as a disease but as a variation of the normal rate of neurological maturation.

Three factors are commonly involved: a disorder of sleep arousal, a low nocturnal bladder capacity and nocturnal polyuria. Constipation may be an additional aggravating condition.¹

Definitions²

• Primary nocturnal enuresis. This is the recurrent involuntary passage of urine during sleep by a child aged 5 years or older, who has never achieved consistent night-time dryness. This may further be subdivided into children who have enuresis only at night and those who also have daytime symptoms (urgency, frequency, or daytime wetting).
• Secondary nocturnal enuresis. This is is the involuntary passage of urine during sleep by a child who has previously been dry for at least 6 months.

Primary enuresis most often represents developmental delay which resolves in time. In secondary enuresis the patient regresses after a period of incontinence which requires the exclusion of underlying pathology, e.g. a urinary infection.

Figures about the prevalence of nocturnal enuresis in children have to be taken with great caution as different studies use different criteria for definition. What is clear is that the prevalence of not being reliably dry at night falls as age rises and girls tend to be a little ahead of boys in terms of achieving control.

The Diagnostic and Statistical Manual of Mental Disorders (fourth edition) defines nocturnal enuresis as wetting at least twice a week. A large cohort study found that, using this criterion, the prevalence at seven years old was 2.6%.³ This represented 3.3% of boys and 2.3% of girls. A total of 15.5% were not totally reliably dry and occasionally still wet the bed.

Even by the teens, 1 or 2% occasionally wet the bed.

One study of school-age children found one in six 5-year-olds, at least one in fifty 7-year-old boys and one in a hundred 7-year-old girls, wet the bed more than once a week. Moreover, in some children, the problem can persist, with around 0.8% of girls and 1.6% of boys aged 15-16 years wetting at least once every 3 months.⁴

Risk factors

There are a number of factors that predispose to persistent nocturnal enuresis.

• There is a genetic predisposition.⁵ As an illustration, it is said that the risk of nocturnal enuresis is 15% if neither parent was affected, 40% if one parent was affected and 75% if both had the condition.⁶ One study found that patients with a family history of primary nocturnal enuresis had a higher incidence of small bladder capacity or outflow obstruction than controls.⁵
• 23% of nocturnal enuresis is associated with encopresis and daytime incontinence.⁷
• Enuresis is to be expected as a manifestation of developmental delay, in those with global developmental delay, with or without an associated syndrome such as Down's syndrome. Even without gross developmental delay, there is more likely to be persistent bed-wetting in children with delayed developmental milestones, premature delivery or behavioural disorders such as hyperactivity or inattention deficits.^8,9
• There may be neurological problems such as spina bifida or cerebral palsy. Those with physical problems are more likely to have daytime enuresis or trouble with encopresis. Physical problems are a rare cause of nocturnal enuresis per se.
• Constipation can cause bladder problems.¹⁰ In an American series, those with severe constipation even causing encopresis, benefited from treatment of constipation and cured about two thirds of nocturnal enuresis.¹¹ There was also a high rate of urinary tract infection (UTI), affecting 3% of boys and 33% of girls.
• Other risk factors include disturbed sleep,¹² mother aged less than 20 at time of birth, mother smokes at least 10 cigarettes a day at home and not being first born.¹³ In that survey, only 50% of parents had consulted a doctor about enuresis. Afro-Caribbean children seem to have a slightly higher incidence than white children and only 35% of the families had consulted a doctor. These risk factors have not changed in 45 years.
• Airways obstruction with snoring increases risk.
• Drinks containing methylxanthines (e.g. caffeine and theophylline found in 'high-energy' drinks) can aggravate the situation by their diuretic action. These include tea, coffee, cola and chocolate.
• There is no evidence that early potty training prevents bed-wetting.
• Stresses in the child's life such as an admission to hospital with separation from the mother, or bullying, are more likely to cause secondary enuresis. The older the child, the more likely it is that psychological problems are the result of enuresis and not the cause.

When a parent presents with a child with the complaint of persistent nocturnal enuresis, it is interesting to find what has prompted the consultation. There may have been talk amongst parents and the mother is embarrassed to find that her child is less advanced than his peers. There may be problems of "sleep overs" in a friend's house or going to camp with a youth group. Generally, those who run such camps are very familiar and competent about the problem, especially as disturbed sleep and great excitement is to be expected. However, it can be a great source of embarrassment and teasing. Children can be very cruel. Holidays can also be difficult if a relatively large child still wets the bed.

• Note the age of the child. Most management protocols are aimed at children who have passed their 7th birthday.The older the child, the more seriously the complaint should be taken.
• Elicit the nature of the problem. Is the child wet every night or most nights? Is the child wet perhaps just once a week or often more than once a night? This indicates the severity of the problem. If it is near to solution, perhaps minor adjustments are necessary or just patience is required as maturation occurs.
• Has the child ever been reliably dry? Primary and secondary enuresis are two separate matters.
• At what age were siblings reliably dry? Were the parents late in achieving nocturnal control? If it appears that all family members are late but everyone gets control in the end, this is reassuring.
• Check that there is good control of urine by day.
• Ask about bowel habits. Constipation is a common cause of urinary problems.
• Is there polyuria or polydypsia?
• If other urinary symptoms are present, consider other conditions such as overactive bladder.¹⁴
• What have the parents been doing in terms of management? They may be restricting fluids or lifting the child from bed to the toilet before they retire at night themselves.

Unless the child is less than 5 years old or has only occasional enuresis, a mid-stream specimen of urine (MSU) should be sent for culture. UTI in children is an uncommon cause of either primary or secondary enuresis but, when it does occur, it is important that diagnosis be made with referral for appropriate investigations. Many protocols for treatment will demand a negative MSU before commencement.

If the child drinks a great deal, check the urine. This is a very uncommon presentation of diabetes mellitus at this age but check for glucose. Also check the specific gravity of an early morning specimen. Diabetes insipidus may be incomplete and failure of enhanced ADH production overnight can be a problem. Check for albumin too. Chronic renal failure can present with failure of concentration. If the child is growing normally and doing well at school, it is unlikely that there are any serious physical problems.

Arginine vasopressin deficiency can be assessed by measuring the nocturnal urine volume, although this may not be easy to arrange in primary care.¹⁵

Ultrasound can be used to assess bladder capacity and predict response to treatment but is not currently used routinely in uncomplicated primary enuresis.¹⁶

Basic principles

It is important to understand that the child does not wet the bed out of malevolence or defiance. It may help to explain to the parents that primary enuresis occurs because the volume of urine produced at night exceeds the capacity of the bladder to hold it and the sensation of a full bladder does not wake the child. Enuresis will thus resolve when bladder capacity increases and/or night-time urine volume is reduced and/or the child wakes in response to a full bladder. It is therefore important to try not to be angry with the child, although this may be difficult at times. Stress aggravates the problem. Instead, reinforce success.

All children with daytime symptoms should be referred for specialist assessment and management to exclude congenital disorders, neurological disease or overactive bladder syndrome or stress incontinence.²

Primary enuresis

• If the child is less than 5 years old, then reassurance and waiting is in order. This may also be true with a slightly older child if there is a family history of late acquisition of control or if wetting occurs only occasionally and it appears that reliable control is imminent.
• The child should empty their bladder before going to bed. This is common sense and what adults do.
• One study found that children with low voidance frequency have an increased incidence of diurnal urinary incontinence and should be reminded to go to the toilet at regular intervals.¹⁷
• Fluid restriction is not recommended, especially as the problem may be inadequate response to ADH. On the other hand, drinking freely before bedtime is not sensible and, in the evening, avoid drinks containing methylxanthines.
• Waterproof undersheets are a sensible precaution to avoid ruining mattresses.

• Urine for culture is extremely important as the chance of UTI in this group is much higher than with primary enuresis.
• Loss or impairment of bladder control by day is possible with UTI but other problems, such as clumsiness or falls, may suggest a neurological problem. This demands neurological examination and referral.
• An extremely important cause of regression is emotional upset. This tends to occur at times when continence has not been established for very long and so it is less often the problem in older children or adolescents. It is said that the psychopathology is a desire to regress to the times when the child was younger and did not have to cope with such problems. Problems may include troubles in the family, such as parental separation or illness, bullying at school or sexual abuse.
• It may not be easy to elicit the cause of the problem and, if the doctor is convinced that there is such a problem that needs to be uncovered and addressed, referral to a professional such as a child psychologist may be required.

Lifting

Many parents choose to take the child to the toilet before they go to bed, so that the child may empty his bladder and, in effect, have a shorter night in which to need control. The child is gently lifted, taken to the toilet to pass urine and then put back to bed. A refinement of this is to ask the child to say a password to ensure that they are awake.This technique is very commonly used and is recommended by such authorities as the Royal College of Psychiatrists.¹⁸ One study found that lifting without a password had better short- and long-term results (measured after three years) than a reward system or placebo.¹⁹

Behavioural modification

This takes 3 main forms.

Star charts
The aim is to reinforce success rather than to punish failure. Remember that the child does not choose to wet the bed at night. The star chart requires a calendar and some sticky stars. Every time that the child has a dry night, a star is placed on that date. If it is not a dry night, that date is ignored. The star is a reward. There is no punishment. Perhaps a run of success, such as 7 consecutive stars, may merit a treat.

For this to be viable, the child must have a significant number of dry nights already. The natural history of the condition is that it will improve and it is difficult to be sure that the technique is really accelerating achievement of control, rather than just acting as psychotherapy for the parent. The value of simple interventions is not clearly demonstrated.²⁰

Enuresis alarms

• Alarms are the treatment of choice for the long-term management of nocturnal enuresis. Most providers of buzzers and pads insist that the child should be at least 7 years old and have been checked for UTI. The device should be used for 3-5 months.
• The buzzer and pad have been in use for around 50 years and efficacy has been demonstrated.^21,22 The aim is to wake the child as they start to urinate, so that they will stop, go to the toilet and learn to recognise the nocturnal sensation of a full bladder.
• The structure of the system is that above the waterproof sheet over the mattress is a mesh pad. A normal sheet is on top of this and another mesh pad on top of that. Both pads are at around the level where the child's pelvis and thighs will be. There is a further sheet on top of the upper pad. The pads are on each end of a circuit that includes a battery and a buzzer. When the child starts to urinate, the urine, that contains electrolytes and is a good conductor, will sink down and complete the electric circuit between the pads, and the buzzer will sound. At this, the child wakes and goes to the toilet to finish passing urine. Older children are expected to strip the wet sheets, remake the bed and reset the buzzer.
• A common cause of nocturnal enuresis is that the child sleeps so deeply that he does not respond to the sensation of a full bladder. There are many stories of children who sleep so deeply that the buzzer has awakened the whole family with the exception of the one it is supposed to wake.
• 65% of children become dry with treatment although, after 6 months, 50% tend to relapse. 'Over-learning' (increasing fluid intake beyond that normally expected, to train the bladder) may help reduce this.
• Failure of an enuresis alarm may be an indication for referral to confirm the diagnosis and obtain specialist advice regarding management.

Alternative medicine

A Cochrane review found poor evidence to support hypnosis, psychotherapy, acupuncture and chiropractic.²⁴ Each case was supported by single small trials, some of dubious methodological rigour. There is no logic to the use of any of these.

Drugs

For comprehensive information about the drugs in this section see the British National Formulary for Children.²⁵
Desmopressin^4,26

• Intermittent oral desmopressin is the treatment of choice for nocturnal enuresis. An analogue of vasopressin, it acts selectively on the V1 receptors in the kidney to increase water but not electrolyte absorption within the distal collecting tubules and collecting ducts. The result is therefore a reduction in urine volume and intravesicular pressure.
• Recent studies suggest that patients who respond best to desmopressin have a larger than average nocturnal urine excretion rate and a pronounced arginine vasopressin deficiency.¹⁵
• The risk of hyponatraemia may be greater with nasal preparations than oral; the nasal route has been removed from this indication as a safety precaution.²⁷
• Cochrane review evidence shows that desmopressin rapidly reduces the number of wet nights per week experienced by children but there was some evidence that the benefit was not sustained once treatment had finished.²⁸ Not all children respond to desmopressin; factors predicting a good response are the child being aged 8 or over and fewer initial wet nights (<3/4). Relapse rates are high (50-95%).²
• When compared to imipramine, it had a similar efficacy but was more expensive and had fewer side-effects.²⁸
• Usually, desmopressin is used as a short-term treatment to allow a child to recover confidence (sometimes when family stress and conflict have developed around the enuresis) or as a temporary measure to help the child for nights spent away from home.
• Desmopressin may also be a helpful adjunct to alarm treatment. Alarms are more effective than desmopressin in producing a sustained response.²⁹
• Cystic fibrosis, renal impairment, raised intracranial pressure and cardiac insufficiency are noteworthy contra-indications in children.²⁶
• Usually desmopressin is well-tolerated. Most common side-effects are abdominal cramp, nausea and vomiting.²⁶ The most serious side-effect is hyponatraemia and risk of associated convulsions. Patients must be advised to avoid fluid overload, including swallowing too much water when swimming, and stop desmopressin during illness with vomiting and diarrhoea.³⁰ Hyponatraemia secondary to the use of desmopressin in children is more common in younger children and particularly at the outset of treatment, so keep to recommended starting doses.³¹ Other notable side-effects are hypersensitivity reactions and anaphylaxis and vasoconstriction.

Long-term treatment with desmopressin should not be instituted in primary care without specialist advice, due to the dangers of fluid overload and hyponatraemia; furthermore, the evidence from Cochrane is that there is a higher recurrence rate with this treatment than with an alarm.² One study found that the incidence of recurrence was reduced if structured withdrawal was initiated, rather than sudden cessation of treatment.³² Poor compliance may play a part in long-term treatment failures.³³

Other drugs
A Cochrane review found 28 other drugs that had been used but none had good supporting evidence or was as effective as desmopressin.³⁴ Pseudoephedrine was used in the past to lighten sleep but this is not a licensed indication and it was recognised that it can cause sleep disturbance, nightmares and behavioural problems. Tricyclic antidepressants such as imipramine have fallen out of favour due to their anticholinergic effects. Their toxicity in overdosage has led for calls for them never to be prescribed to children in primary care. Ironically, recent research suggests that long-acting cholinergics may be useful in combination with desmopressin in enuretic children who are resistant to desmopressin alone.³⁵

Measuring success

As mentioned earlier, there are many different statistics for the prevalence of nocturnal enuresis at various ages, depending upon the criteria used for definition. The definition of success is similarly varied. A successful outcome should be taken as one in which the child is reliably dry rather than invariably dry. To some people, success is not simply achieving a dry night but responding to the stimulus of a full bladder and getting up to empty it without wetting the bed. Most people sleep all through the night but, if the stimulus arises, it is important to respond appropriately.

• Bedwetting can be very distressing, especially for older children and it may lead to social isolation, bullying and low self-esteem. Whilst an expectant approach is appropriate for younger children, older children need a more active approach.
• If enuresis persists into adult life, there may be severe psychosocial problems affecting self-esteem, careers, social life and personal relationships. It is unpleasant to sleep with a bedwetter.
• Parents have extra work and cost of extra laundry along with the additional stress of caring for a child with enuresis. Up to 30% of parents become intolerant of the enuresis and consequently also of their child.

The majority of patients who do not have a serious neurological defect or severe learning difficulties can expect to achieve nocturnal continence sooner or later. Primary enuresis without daytime symptoms resolves in approximately 15% of children each year.² Even after dry nights have been reliably achieved, the occasional "accident" is still to be expected and is no cause for concern unless there is apparent regression. Those with a family history of late nocturnal continence, those with behavioural disorders and those with developmental delay will take longer. Boys tend to take longer than girls but all cases are highly variable.

In 1% of patients enuresis will persist into adulthood² and one study found that children with the most severe form of bed-wetting are likely to persist with the problem and to have the more complex form (non-monosymptomatic) which persists into adolescence.³⁶ A typical scenario is after a night of heavy consumption of beer. The alcohol causes deep sleep and the volume puts the bladder under great stress. Those at risk need to be more restrained in their drinking habits.

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• ERIC (Education and Resources for Improving Childhood Continence) Enuresis resources for patients and professionals