Incontinence in children

To pee or not to pee? If only the question were that simple. There is a wide range of normal when
it comes to child development and urinary continence. Anne Tait, Starship Children’s Hospital
general paediatrician, provides an overview of childhood wetting and the appropriate management
approaches, with a focus on monosymptomatic nocturnal enuresis

Learning
objectives

  • Describe
    the difference between
    primary or secondary
    nocturnal enuresis
  • Identify
    factors that contribute to
    monosymptomatic
    nocturnal enuresis
  • Describe
    non-pharmacological
    and pharmacological
    treatment options for
    nocturnal enuresis

Enuresis (involuntary wetting) – whether it be daytime
or night-time – is a common symptom presenting to
health professionals and can be a source of frustration,
embarrassment and psychological distress for children and
their caregivers. It can also bring a heavy financial burden for
families, with the cost of pull-ups and the frequently required
washing of sheets, as well as the time involved. There is also a
variety of differing expectations across different cultures as to
when children should be continent and how to achieve that.
For daytime incontinence, bladder control is normally
obtained at between two and five years of age and, at night,
by seven years of age. Approximately 20 per cent of five-yearolds
have nocturnal enuresis, with that falling to 10 per cent
of seven and eight-year-olds, and 2 to 3 per cent of 12-yearolds.
Beyond this, up to 1 to 2 per cent of young adults have
ongoing difficulties with enuresis. There is a 15 per cent rate
of spontaneous resolution per year.
Nocturnal enuresis is subdivided into monosymptomatic
enuresis (MNE) and non-monosymptomatic enuresis
(NMNE), according to whether urinary tract symptoms are
absent or present.1 More than 80 per cent of children with
nocturnal enuresis are monosymptomatic.

Some authors, however, do feel that the reported lower rate of lower urinary tract (LUT) symptoms is inaccurate because of a lack of recognition by caregivers and practitioners (note 2)
It has been shown that children with MNE are a different group, clinically, compared with those children with concomitant symptoms of LUT malfunction, and, therefore, they need to be assessed and managed in a different clinical manner. Children with LUT symptoms (ie, NMNE) are a more complex subgroup and usually require secondary paediatric evaluation and treatment of their urinary tract symptoms.
The in-depth assessment and treatment of daytime enuresis is beyond the scope of this article. Having a standardised treatment and  referral approach to enuresis, as well as knowing what is normal, is helpful in the management of children with all forms of urinary incontinence.

This article describes what is normal, addresses the different forms of enuresis, explains the different terminology used and takes readers through the treatment approaches of MNE in children.


Is enuresis primary or secondary, and monosymptomatic or not?

Children presenting to their GP with nocturnal enuresis are initially assessed to determine whether the enuresis is primary or secondary. Primary nocturnal enuresis means the child has either never been dry overnight or not been dry consistently for more than six months. Secondary nocturnal enuresis means the child has been dry consistently for more than six months, then restarted having nocturnal enuresis. Primary nocturnal enuresis is twice as common as the secondary form, with boys outnumbering girls two-to-one.

The next part of the history the GP will address involves whether there are LUT symptoms during the daytime (ie, NMNE); these are listed in Panel 1.
Most experts state that treatment of daytime symptoms must occur first, before the treatment of nocturnal enuresis.

PANEL 1. Lower urinary tract symptoms 

  • increased (eight or more times a day) or decreased
    (three or fewer times a day) voiding frequency
  • daytime incontinence
  • urgency
  • hesitancy
  • straining
  • weak stream
  • intermittency
  • holding manoeuvres
  • genital or LUT pain

PANEL 2. Red flags for organic causes of enuresis

  • excessive fluid intake (day and/or night time)
  • secondary enuresis
  • elevated blood pressure
  • blood and/or protein in the urine
  • poor growth
  • recurrent headaches

Factors that contribute to monosymptomatic nocturnal enuresis

Once the assessment has managed to exclude LUT symptoms, the problem of MNE and the contributing factors are addressed. Educating the parents/caregivers on the genetic, (patho)physiological and anatomical basis for MNE can be helpful.

Genetics
Genetic predisposition plays a strong role in MNE;

there is a 45 per cent chance of nocturnal enuresis occurring in children where one parent had enuresis,
and 75 per cent where both parents had enuresis beyond seven years of age
.

Linkage studies have implicated loci on chromosome 8, 12 and 13.

Sleep
The contribution of aspects of sleep to MNE is debatable. Most parents of children with primary MNE commonly state their children could “sleep through World War III” and are very difficult to wake. Some studies have shown that attempts at arousal from sleep are more successful in control subjects compared with those with enuresis (44 per cent vs 9 per cent). However, other studies show enuretic children to be light sleepers, leading some to propose that chronic overstimulation of the arousal centre from sleep because of a full bladder leads to downregulation of the voiding centre.3 Screening for obstructive sleep apnoea (OSA) is important in this group, as treatment by way of an adenotonsillectomy can result in the resolution of enuresis in a number of children.

Nocturnal polyuria
Normally, antidiuretic hormone (ADH) secretion is higher at night compared with daytime, leading to up to 50 per cent less urine iroduction at night. However, a high nocturnal urine production is one of the key factors in the pathophysiology of enuresis.
There is often a discordance between nocturnal urine production and bladder capacity. Parents often recognise this with comments that their enuretic child passes “spa pool amounts” of urine at night. Nocturnal polyuria is thought to occur in 66 per cent of children with MNE. This can be determined through the use of a night-time bladder diary, which is often recommended by many authors but, practically,
is often not used. This author’s practice is, if standard treatment approaches (ie, bed alarm and/or desmopressin spray) have not proved successful and the child/caregiver is very keen for dryness, to recommend a nocturnal bladder diary to determine whether the child has nocturnal polyuria or not.

Small bladder capacity
Studies in enuretic children have shown some to have small maximum-voided volumes (<65 per cent of expected bladder capacity for age). This is a functional effect rather than an anatomical one, and can occur in the absence of daytime LUT symptoms. Other associated conditions. Enuretic children have been shown to have higher rates of language delay and attention deficit hyperactivity disorder (2.88 increased odds). Treatment of ADHD can result in improved nocturnal enuresis symptoms in some children. Some medications (eg,
sodium valproate) can result in secondary nocturnal enuresis.

Other associated conditions
Enuretic children have been shown to have higher rates of language delay and attention deficit hyperactivity disorder (2.88 increased odds). Treatment of ADHD can result in improved nocturnal enuresis symptoms in some children. Some medications (eg, sodium valproate) can result in secondary nocturnal enuresis.

Organic causes
Most MNE is physiological (see figure); however, rarely, organic causes can occur (Panel 2). Anatomical causes, such as ectopic ureters, typically present with constant incontinence. Polyuric renal disease from tubulopathies, chronic renal failure or diabetes insipidus can present with enuresis. Typically, these children drink a lot of fluids, especially at night. Spinal cord abnormalities and brain tumours can also present with enuresis as can, rarely, renal anatomic malformations.

PANEL 3    Enuresis terminology

Incontinence: ….. uncontrolled leakage of urine
Continuous: ….. constant urine leakage, usually due to congenital issues
Intermittent:….. urine leakage in discrete amounts, whichcan occur in daytime and/or night-time
Daytime: ….. used instead of “diurnal”, which is ambiguous
Overactive bladder: ….. all children with complaints of urgency and frequency with or without incontinence
Nocturnal enuresis: ….. used for wetting at night in children over seven years of age
Primary: ….. enuresis in a child who has previouslybeen dry for less than six months
Secondary: ….. enuresis in a child who has previously been dry for more than six months
Monosymptomatic: ….. nocturnal enuresis in a child without any daytime symptoms
Non-monosymptomatic: ….. enuresis in a child with other lower urinary tract symptoms (eg, daytime incontinence, urgency, holding manoeuvres)
Expected bladder capacity: …… (age in years + 1) × 30 = … mL
Polyuria: ….. 130 per cent of expected bladder capacity
Residual urine: ….. ≥5–20ml remains in bladder after voiding


Primary care assessment overview

It helps to begin by providing the child and parent/caregiver with initial reassurance and a discussion of the issues. Inform them it is a common problem, although people rarely discuss it. Provide parents/caregivers with information from websites such as www.kidshealth.org.nz

The overview below is an assessment of a child with nocturnal enuresis, adapted from case-based assessments by Donald Baird and colleagues.5 The use of the correct terminology with other healthcare professionals, patients and families is encouraged (Panel 3). There have been many different terminologies used over the years, and in different countries, which have contributed to confusion among practitioners and parents and, therefore, confusion in approaches to treatment. The International Children’s Continence Society has worked to standardise the terminology.6

General
•   What is the child’s age? Children younger than seven years are best observed, as there is a 15 per cent resolution rate annually.
•   Is the child bothered by the enuresis? If not, then wait until they seven or older and are concerned about it.
•   Has there been any period of dryness of more than six months? Secondary enuresis needs to prompt consideration for organic causes or psychosocial stressors.
• Have any therapies been trialled previously (ie, fluid restriction, lifting at night, alarm)?
• Is the child a deep sleeper? Deep sleep can indicate arousal difficulties in response to a full bladder.
• Is there any family history of enuresis, and what age of resolution? This gives a possible indication of prognosis.

Enuresis characteristics
• What is the frequency of enuresis? Multiple episodes of enuresis per night indicate a small bladder capacity.
• Are pull-ups being soaked through, or large volumes of enuresis occurring? This would indicate nocturnal polyuria.
• Does the child pass a large amount of urine first thing in the morning? This would indicate nocturnal polyuria.
• How much fluid does the child drink? Polydipsia may be psychogenic but may indicate diabetes mellitus or insipidus. Polydipsia is an absolute contraindication to the use of desmopressin.

Complicating factors
• Are there any specific daytime symptoms indicating LUT (see Panel 1). If there is any suggestion of them, parents will likely be asked by the GP to do a three-day bladder diary. Other investigations will be warranted.
• Does the child have dysuria? The GP will request a urinalysis for microscopy, culture and sensitivity as well as the protein/creatinine ratio.
• Bowel habit review – are there any symptoms of constipation that need to be actively treated?
• Is there polyuria, polydipsia and/or weight loss? These may be indicators of organic causes and need paediatric review.
• Are there sleep problems? Assessment for obstructive sleep apnoea is warranted. The GP may consider referral for ENT assessment.

The primary care practitioner would typically go on to conduct a physical examination of the child, comprising growth and blood pressure assessment, and abdominal, genitalia, ENT and neurological examinations. Investigations for monosymptomatic nocturnal enuresis

Dr Anne Tait, Paediatrician

Most children with MNE do not require investigations other than a simple urinalysis; the GP will take a thorough history and examination to determine the treatment approach. However, in children in whom there is some confusion about whether they have MNE or NMNE, a daytime and night-time bladder diary can be helpful.

The GP will also consider a lateral neck x-ray if there is suspicion of sleep-disordered breathing and the child does not have enlarged tonsils, and screening for constipation. Treatment approaches Treatment approaches depend on the child’s and caregiver’s motivation. Some families are not overly bothered by MNE and may be happy to continue with observation, given the 15 per cent spontaneous
resolution rate per year. Pull-ups do help as they usually mean the bed sheets do not need to be washed unless there is overflow.
However, pull-ups do impose a financial burden on families, which can be quite significant. In addition, sleepovers, school camps and other events pose challenges to those children concerned about their peers finding out about their wetting. Behavioural interventions
Simple evening/night-time behavioural interventions can be used initially, particularly in younger children or those who are not particularly bothered by MNE. Measures can include:

•   limiting fluid intake in the several hours prior to bed, although this has not been studied as to how effective it is
•   avoiding high amounts of protein and/or salt in the evening, as these induce solute diuresis
•   voiding before bedtime, which is recommended
•   lifting the child from sleep to go to the toilet in the later part of the evening (eg, 10pm) can be helpful for some families.
In addition, during the daytime, bladder training exercises to increase bladder capacity (ie, urotherapy) and the use of reward charts may be helpful. A 2013 Cochrane review showed these nighttime behavioural and daytime training interventions appear to be more effective than no treatment but are less effective than the bed alarm. Needless to say, negative consequences for bedwetting need to be totally avoided.

Bed alarm
The bed alarm is the approach with the best evidence base and should be first-line therapy for MNE. The alarm is triggered when a sensor in the sheets or night clothes becomes wet. This wakes the child, who should cease voiding and get out of bed to go to the toilet. The alarm needs to be worn every night and, generally, should be used for two to three months or if the child is dry for 14 consecutive
nights. There is no one type of alarm that is better than the others, although vibration alarms may be better for children with noise sensitivity (ie, autism spectrum disorder). Bed alarms can be provided by local public health nursing teams, with the advantage
of a nurse home visit to show families how to use the alarm and give further information about fluid intake, toileting, etc. There are a number of online providers now, some of which just provide an alarm, although others do provide an online coaching service for a fee.
The main issue with the alarm is it can be significantly disruptive for the entire family. Some children are such deep sleepers they sleep through the alarm. The alarm may not be culturally appropriate, and particularly if children are sharing the room with other family members.
A 2005 Cochrane review involving 576 patients showed the relative risk of treatment failure with an alarm (relative risk 0.38) was less than with no intervention, with 50 per cent remaining dry after stopping the alarm. The alarm is probably more effective in those children who are not deep sleepers, and who have a smaller-than-expected bladder capacity. For children who do respond to the alarm, over-learning strategies may help reduce the relapse rate. This is where children who do respond to the alarm, and while still using it, are given extra fluids at bedtime until they achieve a further 14 days of consistently dry nights.

Desmopressin
Desmopressin is a synthetic version of ADH. It acts on renal vasopressin V2 receptors, resulting in the resorption of water in the distal convoluted tubules and collecting ducts, to reduce the volume of urine produced overnight. Generally, children with nocturnal polyuria are reported to be more sensitive to desmopressin. In New Zealand, desmopressin is commonly prescribed as a nasal spray although oral medication can be used.
Typically, desmopressin should only be used in children above seven or eight years of age who have failed to stay dry with the bed alarm and are very keen to be dry. Other indications include short-term use for sleep overs or school camps.

If desmopressin is used long term, it should be discontinued for one week every three months to check whether the nocturnal enuresis has resolved. However, a 2002 Cochrane review of 119 patients showed the relative risk of enuresis recurring after discontinuing desmopressin was 1.42, compared with discontinuing alarm therapy. Patients treated with desmopressin had an average of 1.21 more dry nights per week compared with placebo. Its success rate is generally quoted as 70 per cent. The dose of desmopressin spray starts at 10μg (one spray) up to a maximum of 40μg (four sprays). There is a tablet formulation, the dose being 200μg, initially, increasing up to 400μg if this is not effective. In some countries, a “melt” formulation is available. Expert international opinion recommends the initial
duration of desmopressin treatment should be two to six weeks. The main risk with desmopressin use is that of hyponatraemia as a result of water intoxication. Therefore, desmopressin is contraindicated in those children who have polydipsia. Guidelines recommend restricting fluid intake for at least one hour prior to use and for eight hours after administration. Care also needs to be taken if other medications present a risk of inducing syndrome of inappropriate
antidiuretic hormone secretion (SIADH) – ie, tricyclic antidepressants, selective serotonin reuptake inhibitors, carbamazepine and NSAIDs (see The New Zealand formulary for children at www.nzfchildren.org.nz).

Other treatments
Tricyclic antidepressants, used previously for enuresis, went out of favour many years ago because of their side effects and the potential for cardiac toxicity in the advent of accidental overdose. Their effectiveness is low.
Diclofenac and indomethacin do improve enuresis but are not as effective as desmopressin.
Anticholinergic agents have been used alone and in combination with desmopressin, but they are often associated with adverse effects, particularly constipation and dry mucous membranes. Anticholinergics tend to be used for those children with a small bladder capacity and daytime symptoms, and in whom constipation has been actively excluded. The practice of this author is to not use any of these treatments, despite, occasionally being asked about them by parents.

Alarm or desmopressin – which one?
With regards to which children respond best to an alarm, expert international opinion generally recommends that children with a normal urine output during the night-time and a normal bladder capacity can use either an alarm or desmopressin. Children with a smaller-than-expected bladder capacity for age are more likely to be desmopressin-resistant and, therefore, would respond better to an alarm.
Children with nocturnal polyuria and a normal bladder volume are more sensitive to desmopressin. Some children have both an excessive urine output and reduced bladder capacity and, in this situation, the combination of a bed alarm and desmopressin may be successful.
In clinical practice, most children are treated with the bed alarm as the first option. However, if there is treatment failure, some thought about which category the child comes under can help in recommending further treatment strategies. Treatment failure Treatment failure may be due to a variety of reasons. Generally, with bed alarms, their use should be attempted again every six months or so.
For children who fail to respond to both the bed alarm and desmopressin therapy, a visit to the GP to retake a history to determine whether there are any daytime symptoms is strongly recommended. This is because subtle daytime symptoms may become apparent with a careful history and the judicious use of investigations: symptoms not immediately apparent on the first consultation.
There is consensus opinion that, for children with NMNE, the daytime symptoms are treated before nocturnal enuresis is addressed as without them being addressed, there are less favourable outcomes with both alarm and desmopressin therapy. Secondary referral is highly recommended, even considered mandatory by some experts.7

 


The role of the pharmacist
Parents/caregivers may use a pharmacist as the first point of care, and then have ongoing contact should a GP prescribe desmopressin under specialist guidance. The pharmacist can initially reassure the child and their parent/caregiver by informing them that although it is seldom talked about, nocturnal bedwetting is a common problem. Points provided in the primary care assessment section in this article can be used for parent/caregiver education and to advise on the need to visit their GP. In addition, provide parents/caregivers with information from websites such as www.kidshealth.org.nz Ensure the patient/parent/caregiver knows the correct use of desmopressin (spray/tablets), and is aware of potential drug interactions and the side effects for which action must be taken (ie, fluid retention, allergic
reaction). Also provide the information sheets on desmopressin from the New Zealand formulary for children website at  https://bit.ly/2IYtpFi (nasal spray) and https://bit.ly/2zeH2AA (tablets). Provide advice regarding fluid limitation at night, avoidance of accidental fluid overload (ie, during swimming) and also to discontinue desmopressin if the child is unwell with vomiting, diarrhoea or
significantly reduced fluid intake during illness.

Summary
Nocturnal enuresis is a relatively common presenting complaint in primary care practice. MNE can be managed in primary care with education, basic strategies, judicious use of a bed alarm and/or desmopressin therapy. Daytime LUT symptoms and/or daytime incontinence warrant referral to secondary paediatric care. To illustrate the seismic shifts in expectations and practices around children learning to toilet themselves, here is a taste of my grandmother’s 1940s’ approach. The toilet training of my father involved strapping him by the chest to a table leg while he was sitting on the potty. He was untied when he had passed urine. Needless to say, this is not an evidenced- based approach nor what we recommend nowadays. However, my father claims it worked, and he does not wet his pants now…them’s were the days?

Article first published NZ Doctor and Pharmacy Today

References
1. Vande Walle J, Rittig S, Tekgül S et al. Enuresis: practical guidelines for primary care. Br J Gen Pract 22 May 2017. Available online at https://doi.org/10.3399/bjgp17X691337
2. Nevéus T, von Gontard A, Hoebeke P et al. The standardization of terminology of lower urinary tract function in children and adolescents: Report from the Standardisation Committee of the International Children’s Continence Society. J Urol 2006;176:314–24.
3. Arda E, Cakiroglu B. Thomas DT. Primary nocturnal enuresis: A review. Nephrourol Mon 2016;8(4):e35809.
4. Sinha R, Raut S. Management of nocturnal enuresis – myths and facts. World J Nephrol 2016;5(4):328–88.
5. Baird DC, Seehusen DA, Bode DV. Enuresis in children: A casebased approach. Am Fam Physician 2014;90(8):560–68.
6. Chase J, Austin P, Hoebake P et al. The management of dysfunctional voiding in children: A report from the
Standardisation Committee of the International Children’s Continence Society. J Urol 2010;183:1296–1302.
7. Vande Walle J, Rittig S, Bauer S et al. Practical consensus guidelines for the management of enuresis. Eur J Pediatr 2012;171(6):971–83.