Alarm interventions for nocturnal enuresis in children

Patrina HY Caldwell; Miriam Codarini; Fiona Stewart; Deirdre Hahn; Premala Sureshkumar

doi:10.1002/14651858.CD002911.pub3

. 2020 May 4;2020(5):CD002911. doi: 10.1002/14651858.CD002911.pub3

Alarm interventions for nocturnal enuresis in children

Patrina HY Caldwell ^1,^2,^✉, Miriam Codarini ³, Fiona Stewart ⁴, Deirdre Hahn ², Premala Sureshkumar ⁵

Editor: Cochrane Incontinence Group

PMCID: PMC7197139 PMID: 32364251

Abstract

Background

Enuresis (bedwetting) affects up to 20% of five‐year‐olds and can have considerable social, emotional and psychological effects. Treatments include alarms (activated by urination), behavioural interventions and drugs.

Objectives

To assess the effects of enuresis alarms for treating enuresis in children.

Search methods

We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In‐Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP, and handsearching of journals and conference proceedings (searched 25 June 2018), and reference lists of relevant articles.

Selection criteria

We included randomised or quasi‐randomised trials of enuresis alarms or alarms combined with another intervention for treating nocturnal enuresis in children between 5 and 16 years old.

Data collection and analysis

Two review authors independently assessed risk of bias and extracted data.

Main results

We included 74 trials (5983 children).

At treatment completion, alarms may reduce the number of wet nights a week compared to control or no treatment (mean difference (MD) −2.68, 95% confidence interval (CI) −4.59 to −0.78; 4 trials, 127 children; low‐quality evidence). Low‐quality evidence suggests more children may achieve complete response (14 consecutive dry nights) with alarms compared to control or no treatment (RR 7.23, 95% CI 1.40 to 37.33; 18 trials, 827 children) and that more children may remain dry post‐treatment (RR 9.67, 95% CI 4.74 to 19.76; 10 trials, 366 children; low‐quality evidence).

At treatment completion, we are uncertain whether there is any difference between alarms and placebo drugs in the number of wet nights a week (MD −0.96, 95% CI −2.32 to 0.41; 1 trial, 47 children; very low‐quality evidence). Alarms may result in more children achieving complete response than with placebo drugs (RR 1.59, 95% CI 1.16 to 2.17; 2 trials, 181 children; low‐quality evidence). No trials comparing alarms to placebo reported the number of children remaining dry post‐treatment.

Compared with control alarms, code‐word alarms probably slightly increase the number of children achieving complete response at treatment completion (RR 1.11, 95% CI 0.97 to 1.27; 1 trial, 353 children; moderate‐quality evidence) but there is probably little to no difference in the number of children remaining dry post‐treatment (RR 0.91, 95% CI 0.79 to 1.05; moderate‐quality evidence). Very low‐quality evidence means we are uncertain if there are any differences in effectiveness between the other different types of alarm.

At treatment completion, alarms may reduce the number of wet nights a week compared with behavioural interventions (waking, bladder training, dry‐bed training, and star chart plus rewards) (MD ‐0.81, 95% CI ‐2.01 to 0.38; low‐quality evidence) and may increase the number of children achieving complete response (RR 1.77, 95% CI 0.98 to 3.19; low‐quality evidence) and may slightly increase the number of children remaining dry post‐treatment (RR 1.39, 95% CI 0.81 to 2.41; low‐quality evidence).

The evidence relating to alarms compared with desmopressin in the number of wet nights a week (MD −0.64, 95% CI −1.77 to 0.49; 4 trials, 285 children) and the number of children achieving complete response at treatment completion (RR 1.12, 95% CI 0.93 to 1.36; 12 trials, 1168 children) is low‐quality, spanning possible harms and possible benefits. Alarms probably slightly increase the number of children remaining dry post‐treatment compared with desmopressin (RR 1.30, 95% CI 0.92 to 1.84; 5 trials, 565 children; moderate‐quality evidence).

At treatment completion, we are uncertain if there is any difference between alarms and tricyclics in the number of wet nights a week, the number of children achieving complete response or the number of children remaining dry post‐treatment, because the quality of evidence is very low.

Due to very low‐quality evidence we are uncertain about any differences in effectiveness between alarms and cognitive behavioural therapy, psychotherapy, hypnotherapy and restricted diet.

Alarm plus desmopressin may reduce the number of wet nights a week compared with desmopressin monotherapy (MD −0.88, 95% CI −0.38 to −1.38; 2 trials, 156 children; low‐quality evidence). Alarm plus desmopressin may increase the number of children achieving complete response (RR 1.32, 95% CI 1.08 to 1.62; 5 trials, 359 children; low‐quality evidence) and the number of children remaining dry post‐treatment (RR 2.33, 95% CI 1.26 to 4.29; 2 trials, 161 children; low‐quality evidence) compared with desmopressin alone.

Alarm plus dry‐bed training may increase the number of children achieving a complete response compared to dry‐bed training alone (RR 3.79, 95% CI 1.85 to 7.77; 1 trial, 80 children; low‐quality evidence). It is unclear if there is any difference in the number of children remaining dry post‐treatment because of the wide confidence interval (RR 0.56, 95% CI 0.15 to 2.12; low‐quality evidence). Due to very low‐quality evidence, we are uncertain about any differences in effectiveness between alarm plus bladder training versus bladder training alone.

Of the 74 included trials, 17 reported one or more adverse events, nine reported no adverse events and 48 did not mention adverse events. Adverse events attributed to alarms included failure to wake the child, ringing without urination, waking others, causing discomfort, frightening the child and being too difficult to use. Adverse events of comparator interventions included nose bleeds, headaches and abdominal pain.

There is probably a slight increase in adverse events between code‐word alarm and standard alarm (RR 1.34, 95% CI 0.75 to 2.38; moderate‐quality evidence), although we are uncertain because of the wide confidence interval. Alarms probably reduce the number of children experiencing adverse events compared with desmopressin (RR 0.38, 95% CI 0.20 to 0.71; 5 trials, 565 children; moderate‐quality evidence). Very low‐quality evidence means we cannot be certain whether the adverse event rate for alarms is lower than for other treatments.

Authors' conclusions

Alarm therapy may be more effective than no treatment in reducing enuresis in children. We are uncertain if alarm therapy is more effective than desmopressin but there is probably a lower risk of adverse events with alarms than with desmopressin. Despite the large number of trials included in this review, further adequately‐powered trials with robust randomisation are still needed to determine the full effect of alarm therapy.

Plain language summary

Alarm interventions for nocturnal enuresis (bedwetting) in children

Review question

Is alarm training an effective treatment for bedwetting in children?

Background

Bedwetting is common in childhood and affects up to 20% of five‐year‐olds. Although children may spontaneously recover from this, bedwetting can have significant social, emotional and psychological effects on the child and their family. Treatments for bedwetting include alarms (activated by urination), behavioural interventions and drugs.

How up‐to‐date is this review?

The evidence is current up to 25 June 2018.

Study characteristics

This review includes 74 trials involving 5983 children.

Study funding sources

Three of the studies included in the review were funded or supported by a pharmaceutical company.

Key results

Alarms may be better than no treatment in terms of reducing the number of wet nights a week and increasing the number of children achieving 14 consecutive dry nights. Alarms may increase the number of children remaining dry after stopping treatment, compared to no treatment.

We are uncertain if there is any difference between alarms and behavioural interventions (such as bladder training), or between alarms and desmopressin medication in terms of reducing the number of wet nights a week, increasing the number of children achieving 14 consecutive dry nights and increasing the number of children remaining dry after stopping treatment.

We are uncertain whether alarms reduce the number of wet nights more than placebo drugs, other types of alarms, tricyclics medication, or various treatments such as hypnotherapy or restricted diet.

Alarm plus desmopressin may reduce the number of wet nights a week compared with desmopressin alone. It may increase the number of children achieving 14 consecutive dry nights and increase the number of children remaining dry after stopping treatment. Alarm plus dry‐bed training may increase the number of children achieving 14 consecutive dry nights compared to dry‐bed training alone, but we are uncertain if the response is maintained after stopping treatment.

Due to very low‐quality evidence, we are uncertain about any differences in effectiveness between alarm plus bladder training versus bladder training alone.

Alarm therapy probably reduces the number of children experiencing adverse events compared with desmopressin. We think there is probably a slight increase in adverse events between code‐word alarms and standard alarms but until we have more evidence from more children we cannot be certain about this. We are uncertain about the safety of alarm therapy compared to other treatments, because the quality of evidence is very low.

Quality of the evidence

The quality of the evidence means that, in general, the level of certainty in our conclusions is low.

Authors' conclusions

Alarm therapy may be more effective than no treatment, but due to the low‐quality evidence we do not know how much alarm therapy is more effective than none at all. Adding alarm therapy to desmopressin may be more effective than desmopressin alone. Despite the large number of trials we identified, the low certainty of the evidence means that we cannot tell from these studies whether or not alarm therapy is better than most other therapies for reducing bedwetting in children. We cannot be sure about its effects until there are better‐designed trials.

Summary of findings

Background

This is one of seven Cochrane Reviews of interventions for enuresis (bedwetting). The others focus on desmopressin (Glazener 2002), tricyclics (Caldwell 2016), drugs other than desmopressin or tricyclics (Deshpande 2012), simple behavioural interventions (Caldwell 2013), complex behavioural and educational interventions (Glazener 2004) and complementary and miscellaneous therapy (Huang 2011).

Description of the condition

Enuresis (or nocturnal enuresis) is the involuntary loss of urine at night, in the absence of organic disease, at an age when a child could reasonably be expected to be dry (by consensus, at a developmental age of five years) (APA 2013; Austin 2014; WHO 1992).

The International Children's Continence Society (ICCS) promotes the use of standardised nomenclature for describing paediatric lower urinary tract function, particularly in research, so that studies can be compared (Austin 2014). With improved understanding about the pathophysiology of bedwetting, enuresis is now subclassified as either monosymptomatic (bedwetting only) or non‐monosymptomatic (bedwetting with lower urinary tract symptoms in the presence or absence of daytime urinary incontinence). This subclassification is important, as the pathophysiology and treatment for both are different. However, many older studies did not distinguish between these groups.

The ICCS has also defined treatment outcomes in terms of change in frequency of wetting compared with baseline frequency (non‐response is less than a 50% reduction in frequency of wetting, partial response is 50% to 99% reduction and complete response is 100% reduction), relapse (more than one symptom recurrence a month after cessation of treatment) and duration of treatment success (initial success is a complete response at the end of treatment, continued success is a complete response for six months after cessation of treatment, and complete success is a complete response for two years after cessation of treatment) (Austin 2014). Unfortunately, most older studies usually did not assess these outcomes or were unclear about their definition of success.

Prevalences and causes

Enuresis is common in children. Estimating the true prevalence of enuresis is difficult because of the variability of diagnostic criteria used in different studies, with very few studies using ICCS definitions (Austin 2014; De Jonge 1973; Krantz 1994). The generally quoted prevalence rates are 15% to 20% of five‐year‐olds, 7% of seven‐year‐olds, 5% of 10‐year‐olds, 2% to 3% of teenagers and 0.5% to 2% of adults, with an annual spontaneous remission rate of about 14% until adolescence (Blackwell 1989; Forsythe 1974; Rutter 1973). The prevalence of enuresis is higher amongst children in residential care and is more persistent in children with severe enuresis (wetting more than three nights a week) (Morgan 1970; Yeung 2006).

Butler 2000 proposed the conceptual model that enuresis occurs when there is a defective arousal response during sleep to the sensation of a full bladder, a lack of inhibition of bladder emptying during sleep, a low capacity or overactive bladder or excessive nocturnal urine production. Other known risk factors for enuresis include:

genetic influences (APA 1980; Bakwin 1971; Bakwin 1973; Eiberg 1995);
delay in attaining bladder control (Jarvelin 1989; Koff 1995);
physiological factors (Djurhuus 1992; Norgaard 1993), for example constipation, faecal incontinence, daytime urinary incontinence and caffeine consumption (Blackwell 1989; Loening‐Baucke 1997; McGrath 2008; O'Regan 1986; Sureshkumar 2009);
sleep apnoea and upper airway obstructive symptoms (Maizels 1993); and
psychological factors (Devlin 1991; Moffatt 1989; Rutter 1973; Shaffer 1977).

These factors are thought to impact on sleep arousal, bladder contraction and overnight urine production.

Description of the intervention

Enuresis alarms

An enuresis alarm is an alarm system activated by micturition. The first enuresis alarms were pads or mats which contained an electrical circuit and were placed on the bed under the child (Mowrer 1938). Urine coming into contact with the pad or mat would complete the circuit, causing a bell to ring (bell and pad alarm). Historically, some bell and pad alarms gave an electric stimulus or shock to the child's skin. More recently, body‐worn alarms were developed where the sensor is placed in the child's underwear (instead of the pad or mat). A code‐word alarm has also been developed which works by delivering a pre‐recorded, personalised message when the child wets the bed; the child is encouraged to remember the word the following morning.

Overlearning

An overlearning procedure may be initiated after successful alarm treatment to reinforce alarm training. The child is given extra drinks at bedtime so that they learn to wake to void with a full bladder. Alarm training is then continued until 14 consecutive dry nights are once again achieved (Blackwell 1989).

How the intervention might work

Enuresis alarms work by conditioning the child to rouse when they wet at night, in response to being woken by the alarm signal when wetting occurs. They learn eventually either to rouse in response to bladder distension and void in the toilet before wetting, or to inhibit voiding by contracting their urethral sphincter if their bladder is not full (Forsythe 1989; Mowrer 1938).

Why it is important to do this review

Although enuresis in itself is pathologically benign and has a high rate of spontaneous remission, it can affect children's quality of life and self‐esteem, as well as impact on their social, emotional and psychological well‐being (Deshpande 2011; Hagglof 1998). More worryingly, enuresis may persist into adulthood, with significant long‐term effects (Fitzwater 1992; Yeung 2004). Enuresis affects the whole family and children with enuresis may experience parental disapproval, sibling teasing and be at an increased risk of emotional and physical abuse (Warzak 1992). Consequently, it is important to identify effective interventions for treating this common condition, as effective treatment can improve self‐esteem and quality of life (Hagglof 1998).

It is important to assess the effectiveness of alarm training both as monotherapy and in combination with other treatments, as it is a non‐pharmacological intervention and therefore has a potentially lower risk of side effects compared with pharmacological interventions.

Objectives

To assess the effects of enuresis alarms for treating enuresis in children.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) or quasi‐randomised trials, including cross‐over trials and cluster RCTs, of alarm training versus any comparable treatments for enuresis. Quasi‐randomised trials use methods of allocating participants to a treatment that is not strictly random, for example by alternate assignment or by replacing dropouts with the next participant.

Types of participants

We included trials of children (as defined by the trialists, but usually from 5 to 16 years of age) with enuresis.

We excluded studies of adults with enuresis, or where participants only had daytime urinary incontinence or an organic cause for their enuresis. We only included studies of children with daytime urinary incontinence if the primary focus of the study was enuresis. As it was often difficult to differentiate between monosymptomatic and non‐monosymptomatic enuresis, we included both types, with subgroup analyses of children with monosymptomatic enuresis if possible.

Types of interventions

We assessed any trial that used an enuresis alarm in at least one arm of the study for this review. Enuresis alarms included standard alarms (a bell and pad alarm that immediately emits a continuous single sound on wetting), or alarms using body‐worn sensors, or alarms of various loudness or that triggered a vibration, light or electric shock. Alarm signals could also be twin‐signal, intermittent or delayed. Alarms could wake the child or the parents. Alarm training could also be combined with another therapy.

We made the following comparisons:

Alarms versus control (non‐functioning) alarms or no treatment;
Alarms versus placebo drug;
Alarms versus other types of alarm;
Alarms versus other behavioural interventions;
Alarms versus drugs;
Alarms versus miscellaneous treatments; and
Alarms combined with another intervention versus other interventions.

We analysed alarm versus control or no treatment separately from alarm versus placebo drug, because placebo could have a different effect from control alarms or no treatment at all.

We identified studies comparing alarms combined with another intervention versus alarm monotherapy, or versus other treatment combinations, but we did not include them in the analysis because they do not directly help to answer the question about the effectiveness of alarm therapy. These comparisons are covered in Appendix 1 and Appendix 2 respectively.

Types of outcome measures

We based the outcomes considered in this review on those used in previous reviews.

Primary outcomes

Mean number of wet nights a week at the end of treatment
Proportion of children achieving 14 consecutive dry nights by the end of treatment

Secondary outcomes

Mean number of wet nights a week at follow‐up after stopping treatment
Proportion of children dry at follow‐up (children maintaining 14 consecutive dry nights after stopping treatment)
Proportion of children with adverse events

Where trials did not specifically report the number of children achieving 14 consecutive dry nights, we interpreted the number of children achieving full response as the number achieving 14 consecutive dry nights.

Main outcomes for 'Summary of findings' tables

We included the following outcomes in the 'Summary of findings' tables (Guyatt 2008).

Mean number of wet nights a week;
Proportion of children achieving 14 consecutive dry nights by the end of treatment;
Proportion of children dry at follow‐up (children maintaining 14 consecutive dry nights after stopping treatment);
Proportion of children with adverse events.

Search methods for identification of studies

We did not impose any language or other limitations on any of the searches described below.

Electronic searches

This review drew on the search strategy developed for Cochrane Incontinence. We identified relevant trials from the Cochrane Incontinence Specialised Register. For more details of the search methods used to build the Specialised Register, please see the Group's webpages where details of the Register's development (from inception) and the most recent searches performed to populate the Register can be found. To summarise, the Register contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In‐Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP, UK Clinical Research Network Portfolio and handsearching of journals and conference proceedings. Many of the trials in the Cochrane Incontinence Specialised Register are also contained in CENTRAL.

The terms used to search the Cochrane Incontinence Specialised Register are given in Appendix 3.

Date of the most recent search of the Register for this review: 25 June 2018.

Searching other resources

The review authors searched the reference lists of relevant articles.

Data collection and analysis

We assessed the studies for this review using the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Selection of studies

At least two review authors checked the titles and, where possible, abstracts of all studies located by the searches to identify those likely to be evaluations of the effects of alarm training for enuresis. We then obtained full papers and assessed them to identify studies that met the inclusion criteria. We settled any differences by discussion with a third review author.

Data extraction and management

We extracted data using a standard form and we processed included trial data as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and contacted study authors for missing information where appropriate.

We converted results to the mean and standard deviation of the number of wet nights a week or the proportion of children achieving a complete response (defined as 14 consecutive dry nights) at the end of the treatment period, or the mean and standard deviation of the number of wet nights a week, or the proportion of children dry at follow‐up after stopping treatment (defined as children who remained dry after stopping treatment). When a mean value was reported with no standard deviation, we entered the data into 'Additional Tables'.

Assessment of risk of bias in included studies

We assessed risk of bias in included studies with Cochrane's 'Risk of bias' tool (Higgins 2017), using the following domains: random sequence generation; allocation concealment; blinding of study participants; blinding of study personnel; blinding of outcome assessors; incomplete outcome data addressed; selective reporting; and other potential bias (e.g. whether there was a washout period in cross‐over trials, and whether appropriate statistical techniques were used).

Where studies did not include the following, we considered them to be at high risk of reporting bias:

whether children with daytime wetting or organic causes of enuresis were specifically excluded;
whether there were baseline differences between groups;
whether adverse events were mentioned;
whether full data sets were given.

Measures of treatment effect

Where possible, we intended to calculate standardised effect sizes and 95% confidence intervals (CIs), mean differences (MDs) where outcomes were continuous variables and risk ratios (RRs) where they were binary. We weighted the mean differences by the inverse of the variance and gave them as differences in number of wet nights a week. Negative values indicated fewer wet nights in the alarm group.

Unit of analysis issues

The unit of allocation was individual participants.

We indicated cross‐over trials by using the symbol '#' after the study ID. For cross‐over trials, we planned to calculate data from paired comparisons to provide information for generic inverse variance analysis but none of the trials provided suitable data. Instead, we chose to tabulate the data as if the data were parallel groups. This approach leads to wider confidence intervals. Hence, statistically significant results using a parallel‐group approach would be significant if correctly analysed as cross‐over studies, but non‐significant results might hide a significant difference.

Dealing with missing data

When intention‐to‐treat analysis was not mentioned in the paper or if some participants were not analysed in the group to which they were randomised, we looked for sufficient information to restore them to the correct group. If participants could not be analysed in their allocated groups, we noted this in the 'Risk of bias' table and in the Risk of bias in included studies section.

Where there were missing outcome data in the included studies, the primary analysis used the number of participants with available data as the denominator (i.e. 'available case' analysis). We also attempted to contact the authors. If there was evidence of differential dropouts from the groups that may have been caused by adverse events or ineffectiveness of the interventions, we stated this in the 'Risk of bias' table. We obtained standard deviations, where not explicitly mentioned, from standard errors, CIs, t values or P values that related to the differences between means in two groups, according to section 7.7.3.3 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Assessment of heterogeneity

We further investigated differences between trials when we noted statistically significant heterogeneity at the 10% probability level or using the I² statistic (Higgins 2003), or if heterogeneity appeared obvious from visual inspection of forest plots. If there was no obvious reason for the heterogeneity, or it persisted despite the removal of outlying trials, we used a random‐effects model for pooling trial results.

Assessment of reporting biases

We investigated the possibility of publication bias and related biases, and produced funnel plots for outcomes measured in 10 or more studies.

Data synthesis

We performed meta‐analysis according to recommendations of the Cochrane Handbook for Systematic Reviews of Interventions if there were sufficient trials for each comparison (Higgins 2011). We used a fixed‐effect model for analysis. If there was substantial heterogeneity, suggesting that treatment effects differed between trials, we used a random‐effects model to produce an overall summary estimate.

Subgroup analysis and investigation of heterogeneity

Where data were available, we conducted subgroup analysis of our two primary outcomes to investigate whether alarms have different effects in children with monosymptomatic nocturnal enuresis (MNE) compared with children with non‐monosymptomatic enuresis (NMNE). We interpreted subgroup analyses using the Chi² statistic, P value and the interaction test I² value.

Sensitivity analysis

We planned to do sensitivity analyses by removing trials with unclear or high risk of bias. However, there were so few trials at low risk of bias that it would not have given meaningful results.

Summary of findings and assessment of the certainty of the evidence

We prepared 'Summary of findings' tables for our main comparisons and presented the results for the four outcomes prespecified for this purpose in the Types of outcome measures.

We adopted the GRADE approach to assess the quality of evidence related to these outcomes (Guyatt 2008). The four levels of evidence certainty are 'high', 'moderate', 'low' or 'very low'. We considered the following factors for assessing the quality of evidence: limitations in the study design, inconsistency of results, indirectness of evidence, imprecision and publication bias.

Results

Description of studies

Results of the search

The literature search produced 493 abstracts and titles for review. We assessed 182 full‐text articles and identified 87 reports for the 74 included studies. In three cases, two different trials were reported within the same paper (Bollard 1981a; Bollard 1981b; Butler 1990a; Butler 1990b; Geffken 1986a; Geffken 1986b). In another, three trials were reported within a single paper (Lovibond 1964a; Lovibond 1964b; Lovibond 1964c).

We identified 92 reports for 89 excluded studies, and two reports of one ongoing study (NCT03389412).

The flow of literature through this assessment process is shown in the PRISMA flowchart (see Figure 1).

Included studies

Design

This review includes 74 randomised or quasi‐randomised trials of alarm training versus any other treatment for enuresis; 40 were parallel‐group studies and 34 were multi‐arm studies. Twenty‐six trials evaluated the effect of enuresis alarms combined with another intervention.

There were two cross‐over studies (Kwak 2010#; Sukhai 1989#). There was also a study where participants were offered the alternate treatment if the first treatment was not effective (Wille 1986).

Sample size

The sample size of studies ranged from 14 to 353 participants (mean 81 participants). There were 30 studies with 50 or fewer participants, 22 studies with 51 to 99 participants, and 22 studies with 100 or more participants.

Setting

Most of the trials were conducted in outpatient settings. Fourteen trials were based in the community (Danquah 1975; Hoseinzadeh 1997), including schools (Kolvin 1972 Turner 1970), community health clinics (Bryant 2003; Nawaz 2002; Ronen 1995; Sacks 1974), from an alarm rental agency (Van Londen 1993), or recruited through the media (Azrin 1974; Azrin 1978; Baker 1969; Fournier 1987; Houts 1986). Some trials used multiple settings (Lovibond 1964a; Lovibond 1964b; Lovibond 1964c; Lynch 1984; Sukhai 1989#; Wagner 1982). Four trials were based in institutional settings (Jehu 1977; Kennedy 1968, Sloop 1973; Wagner 1985). No settings were provided in four trials (Hojsgaard 1979; Ozden 2008; Shakiba 2001; Wright 1974).

Participants

This review included 5983 children. Most trials included children aged between 5 and 16 years. Four trials included older participants: Bollard 1982a included boys up to 17 years of age; McKendry 1975; Scholander 1968 up to 17; and Sloop 1973 up to 18. Seven trials included a few children under the age of five years (Azrin 1974; Azrin 1978; Jehu 1977; Taylor 1975; Wille 1986; Wright 1974; Young 1972). One paper reported two trials (Geffken 1986a; Geffken 1986b) which considered different populations of participants split according to large and small baseline functional bladder capacity.

Duration

The duration of alarm training varied between studies, ranging from two weeks to six months. Most trials incorporated a period of follow‐up, but 22 trials did not report any follow‐up of participants after the end of treatment (Azrin 1978; Azrin 1978; Baker 1969; Butler 1988; Caceres 1982; Caldwell 2015; Elinder 1985; Fagundes 2017; Fournier 1987; Hojsgaard 1979; Kennedy 1968; Lynch 1984; McKendry 1975; Moffatt 1987; Motavalli 1994; Rodriguez 2001; Sacks 1974; Scholander 1968; Tobias 2001; Tuncel 2014; Werry 1965; Wright 1974).

Interventions

Most alarms used in trials were bell and pad (Mowrer) alarms. Some studies used body‐worn alarms with the sensor in the child's underwear (Butler 1990a; Butler 1990b). The enuresis alarm usually activated an audio stimulus such as a bell or buzzer, but other stimuli included vibration and electric shock (Crosby or Uristop alarm) (Lovibond 1964a; Netley 1984; Tobias 2001). Some studies compared variability in the alarm stimulus, such as loudness (Finley 1977), a single versus twin stimulus (Lovibond 1964a; Lovibond 1964c; Turner 1970), immediate versus delayed triggering of the stimulus after wetting (Lynch 1984; Wagner 1985), continuous versus intermittent reinforcement of alarm training (Finley 1973; Taylor 1975), and a stimulus that woke the child only versus the parents as well (Azrin 1974). Other studies compared whether the child was rewarded for being dry, for correct behaviour, or not rewarded at all (Caldwell 2015; Van Londen 1993). There were four studies of overlearning, which is aimed at reducing relapse rates (Houts 1986; Moffatt 1987; Taylor 1975; Young 1972).

Twenty trials compared an enuresis alarm with no treatment or control: 18 with no treatment or wait list (Baker 1969; Bennett 1985; Bollard 1981a; Bollard 1981b; Hojsgaard 1979; Houts 1986; Jehu 1977; Lynch 1984; Moffatt 1987; Nawaz 2002; Ronen 1995; Sacks 1974; Shakiba 2001; Sloop 1973; Wagner 1982; Wagner 1985; Werry 1965; Wright 1974), one with a control (nonfunctioning) alarm (Elinder 1985), and one with a control alarm that rang in the parents' room 20 minutes later (Finley 1973). In standard enuresis alarm training, a sound is immediately triggered when the child wets the bed. Standard alarm training is usually supervised by parents. Non‐standard forms of alarm training that were compared with no treatment included alarms that delivered an electric shock to the child's skin (Elinder 1985; Hojsgaard 1979), had a delayed trigger (Lynch 1984; Wagner 1985), or sounded intermittently (Finley 1973).

Five studies compared alarm to placebo drug (Fournier 1987; Kolvin 1972; Longstaffe 2000; Turner 1970; Wright 1974).

Thirteen studies compared different types of alarms:

bell and pad versus body‐worn alarms (Butler 1990a)
continuous versus intermittent alarms (Finley 1973; Taylor 1975)
immediate versus delayed alarms (Lynch 1984; Wagner 1985)
single‐signal versus twin‐signal alarms (Lovibond 1964b; Lovibond 1964c; Turner 1970)
bell and pad versus electric shock alarms (Lovibond 1964a)
loud versus quiet alarms (Finley 1973; Finley 1977)
audio versus vibration alarms (Tobias 2001)
body‐worn alarm versus code‐word body‐worn alarm (Caldwell 2015)

Ten studies compared alarm training to other behavioural interventions:

waking to void (Azrin 1978; Baker 1969; Fournier 1987; Lovibond 1964b; Turner 1970)
bladder training (Bennett 1985; Bryant 2003)
dry‐bed training (a complex behavioural intervention involving bedtime fluids, hourly waking and cleanliness training) (Bollard 1981b; Caceres 1982)
star chart and rewards (Ronen 1995)

Twenty‐four trials reported on 28 comparisons that compared alarm training to placebo drugs or active drug treatment (including Fournier 1987, Kolvin 1972, Longstaffe 2000 and Wright 1974, which had multiple comparisons):

desmopressin (Ahmed 2013; Bak 2007; Evans 2011; Fagundes 2017; Faraj 1999; Kwak 2010#; Longstaffe 2000; Ng 2005; Onol 2015; Tuncel 2014; Tuygun 2007; Vogt 2010; Wille 1986)
tricyclics (imipramine: Fournier 1987; Hoseinzadeh 1997; Kolvin 1972; McKendry 1975; Motavalli 1994; Netley 1984; Wagner 1982; clomipramine: Motavalli 1994; amitriptyline: Danquah 1975)
combined amphetamine, ephedrine and atropine sulphate (Wright 1974)
placebo drug (Fournier 1987; Kolvin 1972; Longstaffe 2000; Turner 1970; Wright 1974)

Six studies compared alarms to other treatments not classified elsewhere:

cognitive behavioural therapy (Ronen 1995)
psychotherapy (Sacks 1974; Werry 1965)
hypnotherapy (Seabrook 2005)
shaming (traditional Ghanian method for treating enuresis which consisted of the enuretic child being carried from home by a singing mob and being thrown into the lagoon) (Danquah 1975)
restricted diet (McKendry 1975)

Nine studies investigated alarms combined with another treatment versus the other treatment alone:

alarm plus bladder training versus bladder training (Bennett 1985; Bryant 2003)
alarm plus dry‐bed training versus dry‐bed training (Bollard 1981b)
alarm plus desmopressin versus desmopressin (Ahmed 2013; Bak 2007; Fagundes 2017; Ma 2007; Ng 2005)
alarm plus imipramine versus imipramine (Fournier 1987)

Twenty‐two trials reported on 25 comparisons that investigated alarm monotherapy compared with the following combinations of treatments (including Houts 1986, Naitoh 2005 and Taylor 1975, which had multiple comparisons):

alarm plus overlearning (Taylor 1975; Young 1972)
alarm plus dry‐bed training (Bollard 1981b; Nawaz 2002)
alarm plus bladder training (Bennett 1985; Bryant 2003; Fielding 1980; Geffken 1986a; Geffken 1986b; Houts 1986)
alarm plus bladder training plus overlearning (Houts 1986)
alarm plus desmopressin (Ahmed 2013; Bak 2007; Bradbury 1995; Gibb 2004; Leebeek 2001; Naitoh 2005; Ng 2005; Ozden 2008; Rodriguez 2001)
alarm plus imipramine (Fournier 1987; Naitoh 2005)
alarm plus methedrine (Kennedy 1968)
alarm plus reward (Van Londen 1993)
alarm plus pretreatment (Taylor 1975)

As shown in Table 9, 14 trials investigated alarms combined with another treatment compared to no treatment, placebo, one single treatment or combinations of treatment (Bennett 1985; Bollard 1981b; Fournier 1987; Gibb 2004; Houts 1986; Leebeek 2001; Ma 2007; Naitoh 2005; Nawaz 2002; Scholander 1968; Sukhai 1989#; Taylor 1975; Titawee 2000; Van Londen 1993).

1. Studies investigating combination therapies.

Treatment combination: alarm plus other	Comparator	Study
Alarm plus bladder training	No treatment	Bennett 1985; Houts 1986; Nawaz 2002
Alarm plus dry‐bed training		Bollard 1981b
Alarm plus bladder training plus overlearning		Houts 1986
Alarm plus imipramine	Placebo	Fournier 1987
Alarm plus nortriptyline	Placebo	Scholander 1968
Alarm plus behavioural treatment	Desmopressin	Ma 2007
Alarm plus behavioural therapy and desmopressin	Desmopressin	Ma 2007
Alarm plus imipramine	Random waking	Fournier 1987
Alarm plus dry‐bed training	Dry‐bed training	Bollard 1981b
Alarm plus desmopressin	Alarm plus placebo	Gibb 2004; Leebeek 2001; Sukhai 1989#
Alarm plus imipramine		Fournier 1987
Alarm plus nortriptyline		Scholander 1968
Alarm plus behavioural treatment and desmopressin	Alarm plus behavioural treatment	Ma 2007
Alarm plus desmopressin	Alarm plus imipramine	Naitoh 2005
Alarm plus behavioural therapy and desmopressin	Alarm plus behavioural therapy	Ma 2007
Alarm plus behavioural therapy	Fluid restriction and lifting plus behavioural therapy	Titawee 2000
Alarm plus immediate reward	Alarm plus delayed reward	Van Londen 1993
Alarm plus pretreatment A	Alarm plus pretreatment B	Taylor 1975

Trial	Intervention	Mean wet nights a week	Comparator	Mean wet nights a week
Alarm versus control/placebo
Baker 1969	alarm	1.8 (n = 10)	control	5.9 (n = 10)
Bollard 1981b	alarm	0.6 (n = 20)	control	4.4 (n = 20)
Finley 1973	Intermittent alarm	0.2 (n = 10)	control	8 (n = 10)
Jehu 1977	alarm	0.3 (n = 19)	control	5.3 (n = 20)
Wagner 1982	pad‐and‐bell/buzzer	0.58 (n = 12)	control	4.26 (n = 12)
Wagner 1985	delayed alarm	0.38 (n = 13)	control	5.1 (n = 13)
Fournier 1987	alarm	2.5 (n = 8)	placebo	5 (n = 8)
Kolvin 1972	alarm	2.3 (n = 32)	placebo	2.7 (n = 27)
Wright 1974	alarm	1.7 (n = 10)	placebo	3.5 (n = 5)
Alarm versus other types of alarm
Butler 1990a	bell and pad alarm	1.2 (n = 17)	body alarm	1 (n = 18)
Finley 1973	alarm	1 (n = 18)	intermittent alarm	0.6 (n = 10)
Wagner 1985	immediate alarm	0.38 (n =1 3)	delayed alarm	1.45 (n = 13)
Alarm versus other behavioural interventions
Baker 1969	alarm	1.8 (n = 10)	waking	3.1 (n = 10)
Fournier 1987	alarm	2.5 (n = 8)	waking	3.3 (n = 8)
Bryant 2003	alarm	3.0 (n = 34)	bladder training	4.0 (n = 37)
Azrin 1978	alarm	5.32 (n = 27)	dry‐bed training (no alarm)	1.05 (n = 28)
Bollard 1981b	alarm	0.6 (n = 20)	dry‐bed training (no alarm)	3.8 (n = 20)
Alarm versus drugs
Evans 2011	alarm	5.0 (n = 59)	desmopressin	4.28 (n = 192)
Fournier 1987	alarm	2.5 (n = 8)	imipramine	1.9 (n = 8)
Kolvin 1972	alarm	2.3 (n = 32)	imipramine	2.3 (n = 35)
Wagner 1985	alarm	0.58 (n = 12)	imipramine	2.75 (n = 12)
Danquah 1975	alarm	3.2 (n = 10)	amitriptyline	4 (n = 10)
Wright 1974	alarm	1.7 (n = 10)	amphetamine sulphate/Enetrol (ephedrine + atropine)	4.1 (n = 8)
Alarm versus miscellaneous treatments
Danquah 1975	alarm	3.2 (n = 10)	shaming	5.6 (n = 10)
Alarm plus other intervention versus other intervention
Bryant 2003	alarm plus bladder training	4.3 (n = 45)	bladder training	4.0 (n = 37)
Fournier 1987	alarm plus imipramine	1 (n = 8)	imipramine	1.9 (n = 8)
Alarm plus other intervention versus alarm monotherapy
Bryant 2003	alarm plus bladder training	4.3 (n = 45)	alarm	4.0 (n = 37)
Fielding 1980	alarm plus bladder training	1.5 (n = 16)	alarm	0.6 (n = 17)
Bollard 1981b	alarm plus dry bed training	0 (n = 60)	alarm	0.6 (n = 20)
Leebeek 2001	alarm plus desmopressin	2.77 (n = 43)	alarm	2.21 (n = 39)
Naitoh 2005	alarm plus desmopressin	2.5 (n = 35)	alarm	3.1 (n = 37)
Fournier 1987	alarm plus imipramine	1 (n = 8)	alarm	2.5 (n = 8)
Naitoh 2005	alarm plus imipramine	2.15 (n = 33)	alarm	3.1 (n = 37)

Trial	Intervention	Mean wet nights per week	Comparator	Mean wet nights per week
Alarm versus drugs
Evans 2011	alarm	1.5 (n = 59)	desmopressin	2.1 (n = 192)
Kolvin 1972	alarm	2.3 (n = 32)	imipramine	3.4 (n = 35)
Danquah 1975	alarm	1.49 (n = 10)	amitriptyline	3.42 (n = 10)
Alarm versus miscellaneous treatments
Danquah 1975	alarm	1.49 (n = 10)	shaming	5.6 (n = 10)
Alarm plus other intervention versus other intervention
Leebeek 2001	alarm plus desmopressin	2.72 (n = 41)	alarm	1.90 (n = 37)

Alarm compared to control or no treatment for nocturnal enuresis in children
Patient or population: children with nocturnal enuresis Setting: outpatient Intervention: alarm Comparison: no treatment or control
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with no treatment or control	Risk with alarm
Mean number of wet nights a week	The mean number of wet nights a week in the control group ranged from 4.06 to 5.74	Participants in the alarm group experienced 2.68 fewer wet nights a week (4.59 fewer to 0.78 fewer) compared with the control group.	‐	127 (4 RCTs)	⊕⊕⊝⊝ LOW ^{a, b}	‐
Proportion of children achieving 14 consecutive dry nights by the end of treatment	133 per 1000	958 per 1000 (186 to 1000)	RR 7.23 (1.40 to 37.33)	827 (18 RCTs)	⊕⊕⊝⊝ LOW ^{a, c}	826 more childrenper 1000 achieving 14 dry nights with alarm (from 53 more to 1000 more)
Proportion of children dry at follow‐up (maintaining 14 consecutive dry nights post‐treatment)	18 per 1000	177 per 1000 (87 to 361)	RR 9.67 (4.74 to 19.76)	366 (10 RCTs)	⊕⊕⊝⊝ LOW ^{b, d}	159 more childrenper 1000 maintaining 14 dry nights post‐treatment with alarm (from 68 more to 34310 more)
Proportion of children with adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Alarm compared to placebo drug for nocturnal enuresis in children
Patient or population: children with nocturnal enuresis Setting: outpatient Intervention: alarm Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo	Risk with alarm
Mean number of wet nights a week	The mean number of wet nights a week in the placebo group was 4.22	Participants in the alarm group experienced 0.96 fewer wet nights a week (2.32 fewer to 0.41 more) compared with the placebo group	‐	47 (1 RCT)	⊕⊝⊝⊝ VERY LOW^{a, b}	‐
Proportion of children achieving 14 consecutive dry nights by the end of treatment	397 per 1000	632 per 1000 (461 to 862)	RR 1.59 (1.16 to 2.17)	181 (2 RCTs)	⊕⊕⊝⊝ LOW^{c, d}	234 more childrenper 1000 achieving 14 dry nights with alarm (from 64 more to 465 more)
Proportion of children dry at follow‐up (maintaining 14 consecutive dry nights post‐treatment)	Not reported
Proportion of children with adverse events	2 trials collected information related to adverse events but did not report any useable data.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Alarm compared to other behavioural interventions for nocturnal enuresis in children
Patient or population: children with nocturnal enuresis in children Setting: outpatient Intervention: alarm Comparison: other behavioural interventions (waking, bladder training, dry‐bed training, and star chart with rewards)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with other behavioural interventions	Risk with alarm
Mean number of wet nights a week	The mean number of wet nights a week in the comparator groups ranged from 1.11 to 3.75	Participants in the alarm group experienced 0.81 fewer wet nights a week (2.01 fewer to 0.38 more) compared with the behavioural interventions group.	‐	95 (3 RCTs)	⊕⊕⊝⊝ LOW^{a, b}	Behavioural interventions were waking, bladder training, and star chart with rewards
Proportion of children achieving 14 consecutive dry nights by the end of treatment	310 per 1000	548 per 1000 (303 to 987)	RR 1.77 (0.98 to 3.19)	179 (6 RCTs)	⊕⊕⊝⊝ LOW^{a, b}	Behavioural interventions were waking, bladder training, star chart with rewards, and dry‐bed training. 239 more childrenper 1000 achieving 14 dry nights with alarm (from 6 fewer to 678 more)
Proportion of children dry at follow‐up (maintaining 14 consecutive dry nights post‐treatment)	318 per 1000	442 per 1000 (258 to 767)	RR 1.39 (0.81 to 2.41)	89 (3 RCTs)	⊕⊕⊝⊝ LOW^{b, c}	Behavioural interventions were waking,dry‐bed training, and star chart with rewards 124 more childrenper 1000 maintaining 14 dry nights post‐treatment with alarm (from 60 fewer to 449 more)
Proportion of children with adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Alarm compared to drugs for nocturnal enuresis in children
Patient or population: children with nocturnal enuresis Setting: outpatient Intervention: alarm Comparison: desmopressin
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with desmopressin	Risk with alarm	Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
Mean number of wet nights a week	The mean number of wet nights a week in the desmopressin group was 1.76 to 2.68	Participants in the alarm group experienced 0.64 fewer wet nights a week (1.77 fewer to 0.49 more) compared with the desmopressin group.	‐	285 (4 RCTs)	⊕⊕⊝⊝ LOW^{a, b}	‐
Proportion of children achieving 14 consecutive dry nights by the end of treatment	398 per 1000	446 per 1000 (370 to 541)	RR 1.12 (0.93 to 1.36)	1168 (12 RCTs)	⊕⊕⊝⊝ LOW^{c, d}	48 more childrenper 1000 achieving 14 dry nights with alarm (from 28 fewer to 143 more)
Proportion of children dry at follow‐up (maintaining 14 consecutive dry nights post‐treatment)	254 per 1000	315 per 1000 (234 to 468)	RR 1.30 (0.92 to 1.84)	565 (5 RCTs)	⊕⊕⊕⊝ MODERATE^a	76 more childrenper 1000 maintaining 14 dry nights post‐treatment with alarm (from 20 fewer to 214 more)
Proportion of children with adverse events	212 per 1000	81 per 1000 (42 to 150)	RR 0.38 (0.20 to 0.71)	565 (5 RCTs)	⊕⊕⊕⊝ MODERATE^a	131 fewer childrenper 1000 experiencing adverse events with alarm (from 169 fewer to 61 fewer)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Alarm versus miscellaneous treatments for nocturnal enuresis in children
Patient or population: children with nocturnal enuresis Setting: outpatient Intervention: alarm Comparison: miscellaneous treatments
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with miscellaneous treatment	Risk with alarm	Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
Mean number of wet nights a week ‐ alarm versus cognitive behavioural therapy	The mean number of wet nights a week in the cognitive behavioural therapy group was 1.03	Participants in the alarm group experienced 0.20 more wet nights per week (2.65 fewer to 3.05 more)	‐	33 (1 RCT)	⊕⊝⊝⊝ VERY LOW^{a, b}	An additional study, comparing alarms to shaming, could not be incorporated into analyses due to missing standard deviations. The mean number of wet nights was similar to the observed data
Proportion of children achieving 14 consecutive dry nights by the end of treatment ‐ alarm versus cognitive behavioural therapy	750 per 1000	630 per 1000 (413 to 968)	RR 0.84 (0.55 to 1.29)	39 (1 RCT)	⊕⊝⊝⊝ VERY LOW^{a, b}	120 fewer children per 1000 achieving 14 dry nights with alarm (from 218 more to 337 fewer)
Proportion of children dry at follow‐up (maintaining 14 consecutive dry nights post‐treatment) ‐ alarm versus cognitive behavioural therapy	833 per 1000	400per 1000 (208 to 767)	RR 0.48 (0.25 to 0.92)	33 (1 RCT)	⊕⊝⊝⊝ VERY LOW^{a, b}	‐
Proportion of children achieving 14 consecutive dry nights by the end of treatment ‐ alarm versus psychotherapy	129 per 1000	457 per 1000 (177 to 1000)	RR 3.62 (1.38 to 9.50)	116 (2 RCTs)	⊕⊝⊝⊝ VERY LOW^{a, c}	328 morechildren per 1000 achieving 14 dry nights with alarm (from 48 more to 1000 more)
Proportion of children achieving 14 consecutive dry nights by the end of treatment ‐ alarm versus hypnotherapy	146 per 1000	438per 1000 (206 to 932)	RR 3.00 (1.41 to 6.39)	96 (1 RCT)	⊕⊝⊝⊝ VERY LOW^{b, d}	292 morechildrenper 1000 achieving 14 dry nights with alarm, (from 60 more to 786 more)
Proportion of children dry at follow‐up (maintaining 14 consecutive dry nights post‐treatment) ‐ alarm versus hypnotherapy	104 per 1000	313per 1000 (123 to 792)	RR 3.00 (1.18 to 7.60)	96 (1 RCT)	⊕⊝⊝⊝ VERY LOW^{b, d}	‐
Proportion of children achieving 14 consecutive dry nights by the end of treatment ‐ alarm versus restricted diet	13 per 1000	307per 1000 (43 to 1000)	RR 23.00 (3.19 to 165.98)	150 (1 RCT)	⊕⊝⊝⊝ VERY LOW^{d, e}	293 morechildren per 1000 achieving 14 dry nights with alarm (from 29 more 1000 more)
Proportion of children adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Date	Event	Description
12 March 2021	Amended	Republished to fix a technical issue with the PRISMA diagram
22 April 2020	New search has been performed	For this fifth update, published in 2020, we made the following changes:  1. We updated the search to June 2018 and included 19 new trials (Ahmed 2013; Bak 2007; Bryant 2003; Caldwell 2015; Evans 2011; Fagundes 2017; Hoseinzadeh 1997; Kwak 2010#; Ma 2007; Naitoh 2005; Onol 2015; Ozden 2008; Seabrook 2005; Shakiba 2001; Titawee 2000; Tuncel 2014; Tuygun 2007; Van Hoeck 2008; Vogt 2010). 2. We have substantially updated the methodology in the review to include risks of bias and implemented the GRADE approach to assess the quality of the body of evidence. We have also developed 'Summary of findings' tables.
22 April 2020	New citation required but conclusions have not changed	This version has not changed previous findings and remains in agreement with other systematic reviews. However, due to the low‐quality evidence of most of the included studies and the adoption of GRADE, we are uncertain of the conclusions that we drew in the previous review. Our conclusion for this update is therefore that response rates with alarm therapy compared to rewards, waking and drugs are similar at the end of treatment, but fewer children relapse with alarm therapy after stopping treatment. Alarms combined with desmopressin or overlearning have an additive effect.
20 August 2008	Amended	Converted to new review format.
28 February 2007	New search has been performed	Third (minor) update (Issue 3 2007). One new trial comparing desmopressin and alarms (Ng 2005) was added. The review conclusion that children are less likely to relapse after alarm treatment than after desmopressin was not altered.
22 February 2005	New citation required and conclusions have changed	Substantive amendment. Second update Issue 2 2005. Three new trials (Gibb 2004, Nawaz 2002 and Tobias 2001) were added. There was some evidence that dry bed training may reduce the relapse rate.
26 February 2003	New citation required and conclusions have changed	Substantive amendment. First update Issue 2 2003. Twelve trials which were previously included only in a sensitivity analysis and 20 new trials were added. Two previously included trials were excluded. Compared to the previous version, there was more evidence that alarms were better than no treatment, desmopressin or tricyclics. Overlearning may reduce the relapse rate.

Outcome	Alarm + overlearning + bladder training	No treatment	Result
Mean number of wet nights a week at the end of treatment	not reported
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	4/13	11/11	Favoursalarm + overlearning + bladder training RR 0.34 (95% CI 0.16 to 0.72) (Houts 1986)
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	5/13	11/11	RR 0.41 (95% CI 0.21 to 0.79) (Houts 1986)
Proportion of children with adverse events	not reported

Outcome	Alarm + bladder training	No treatment	Result
Mean number of wet nights a week at the end of treatment	n = 22	n = 21	Favours alarm + bladder training MD −3.96 (95% CI −5.01 to −2.90) Bennett 1985; Nawaz 2002
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	9/35	31/32	Favours alarm + bladder training RR 0.33 (95% CI 0.12 to 0.94) (Bennett 1985; Houts 1986; Nawaz 2002)
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	11/25	22/23	Favours alarm + bladder training RR 0.47 (95% CI 0.30 to 0.73) (Houts 1986; Nawaz 2002)
Proportion of children with adverse events	not reported

Ahmed 2013	Wet nights on treatment = mean (SD) wet nights at end of treatment: A (n = 45): 2.06 (1.31). B (n = 46): 1.76 (1.59). C (n = 45): 1.00 (1.13) Mean (SD) wet nights at end of follow‐up: A (n = 45): 3.04 (1.24). B (n = 46): 4.45 (1.20). C (n = 45): 2.97 (1.19) Number not achieving 14 consecutive dry nights (failure of therapy) A 39/45. B 34/46. C 27/45 Complete response (no wet nights) at end of treatment: A 6/45. B 12/46. C 18/45 Nonresponse (defined as < 50% reduction in the number of wet nights) at end of treatment: A 13/45. B 10/46. C 4/45 Number failing to achieve 14 consecutive dry nights or relapsing at follow‐up: A = 39/45. B = 42/46. C = 33/45 Adverse events: ‘No adverse events were seen during the study period’
Azrin 1974	Fewer wet nights in first 2 weeks with A+C vs B+D (median 1 vs 5 in second week, P < 0.005). More children achieving 6 dry nights in A+C
Azrin 1978	Per cent wet nights during first 2 weeks: A 15%; B 76% (P < 0.00001) No. of children swapping to other group after 2 weeks of treatment: A 0/27; B 23/27
Bak 2007	Wet nights on treatment = mean wet nights at end of treatment: A 4.8 ± 6.5 B 2.9 ± 4.1. C 1.9 ± 2.5 Number not achieving 14 consecutive dry nights (failure of therapy) A: 23; B: 25; C: 22 Complete response: A 30%. B 27%. C 35% Number failed or relapsed after end of treatment = number not achieving 14 dry nights or relapsing at follow‐up: Failed or relapsed: A 30; B: 26; C:25. Relapse: A = 67% x 10 = 6.7. B = 11% x 9 = 1. C = 22% x 12 = 2.5
Baker 1969	Mean number of wet nights a week in last 3 weeks of treatment: A: 1.8; B: 3.1; C: 5.9 (no SDs) Minor behavioural adverse events, self‐limiting
Bennett 1985	Mean dry nights in last 2 weeks of 12 weeks follow‐up: A, 12 (SD 3.9); B, 7.5 (5.2); C, 11.2 (3.6); D, 3.7 (3.0) Number achieving 14 dry nights: A, 4/9; B, 2/12; C, 5/10; D, 0/9 Mean dry nights a fortnight at follow‐up: A, 12.3 (3.1); B, 7.1 (5.8); C, 9.3 (5.3). (D treated after 12 weeks)
Bollard 1981a	Experiment 1 Mean number of wet nights at end of 20 weeks: A: 0.8, B: 2.2, C: 4.6 2 treatment groups did not differ significantly in number of wet beds at end of 20 weeks or number of days taken to reach dryness criterion Number achieving 14 consecutive dry nights: A: 12, B: 9, C: 0 Number relapsing at 12 month follow‐up: A: 4, B: 5
Bollard 1981b	Experiment 2 Comparing DBT vs alarm ‐ DBT significantly more effective in terms of number of wet nights and days to dryness Mean number of wet nights a week at end of week 20: ‐ (including dropouts) A: 0, B: 0, C: 0, D: 3.8 (n = 20), E: 0.6, F: 4.4 ‐ (excluding dropouts) A: 0, B: 0, C: 0, D: 1.3 (n = 8), E: 0.6, F: 4.4 Number achieving 14 consecutive dry nights: A:20, B:20, C: 20, D: 5, E: 16, F: 2 (P < 0.05) Number relapsing: A: 5, B: 6, C: 4, D: 2, E: 6, F: 2 NS (i.e. number failing or relapsing: A: 5/20, B: 6/20, C: 4/20, D: 17/20, E: 10/20, F: 20/20)
Bollard 1982a	Mean number of wet nights during 20‐week treatment period: A: 27, B: 13, C: 24, D: 23, E: 14, F: 10, G: 21, H: 11 Number of cases becoming dry: A: 31, B: 12, C: 11, D: 10, E: 12, F: 12, G: 11, H: 20 Significant difference in response rate of group with waking schedule versus those without (Chi² = 13.04, df = 3, P < 0.01)
Bradbury 1995	Mean dry nights a week: A: n = 33, mean = 6.1, 95% CI 5.6 to 6.7; B: 27, 4.8, 4.0 to 5.6 Number not achieving 14 dry nights: A: 6/33, B: 11/27 Number failing or relapsing: A: 10/33, B: 14/27 Side effects: none reported Subgroup analysis in more severe group: A still better than B
Bryant 2003	Wet nights per 28 nights: At 16 weeks: A: 12, B: 16, C: 17 At 26 weeks: A: 9, B: 16, C: 10 At 52 weeks: A: 9, B: 4, C: 8
Butler 1988	Mean number of dry nights in last 4 weeks A: 20.76, B: 23.79, F (1.46) = 1.77 Number of children achieving 14 dry nights: A: 20/28 (71%), B: 25/35 (71%); no significant difference Mothers in dropout group significantly more angry with bedwetting than other groups
Butler 1990a	Experiment 1 Mean number of wet nights in 16 weeks: A: 18.9, B: 15.3 Number (%) children achieving 14 consecutive dry nights: A: 14 (70), B: 14 (70) Mean number of wet nights until achievement of 14 consecutive dry nights A: 54.8, B: 35.3 (t = 2.8, df = 26, P < 0.01) Number (%) children relapsing A: 4/14 (29) B: 3/14 (21) Most children preferred body‐worn alarm to pad and bell
Butler 1990b	Experiment 2 Mean number of wet nights in 16 weeks A: 28.7, B: 25.0 Number (%) attaining 14 consecutive dry nights A: 14 (58), B: 20 (83) Mean number of wet nights to achievement of 14 consecutive dry nights A: 53.7, B: 40.7 Number (%) children relapsing: A: 7 (50), B: 9 (45)
Caceres 1982	Not cured on original treatment: A: 0/7, B: 5/7
Caldwell 2015	Number not achieving response (50% or more reduction in wetting): A: 46/176, B: 59/177 Relapse (within 6 months): A: 62/176, B: 51/177 Participants with adverse events: A: 24/176, B: 18/177 Sleep disturbance: A: 14/176, B: 17/177 Frightened by the alarm: A: 2/176, B: 4/177 Alarm triggering sleepwalking/nightmares: A: 1/176, B: 1/177 Children satisfied with treatment: A: 90% (158/176?), B: 86% (152/177?)
Danquah 1975	Mean number wet nights a week at end of treatment: A: 5.6, B: 4.00, C: 3.2 Mean number wet nights a week at follow‐up: A: 5.61, B: 3.42, C: 1.49 Recipients of traditional shaming seemed depressed and showed evidence of loss of self‐esteem and isolating themselves from friends Drug treatment was said to cause drowsiness at first. Parents not disturbed by alarm because they slept outside
Elinder 1985	Number not cured: A: 0/36, B: 0/17 Adverse events: mentioned technical problems (same numbers in each group)
Evans 2011	Mean wet nights at end of treatment: A: 4.28, B: 5.0 Number not achieving 14 consecutive dry nights at end of treatment: A: 131/192, B: 37/59 Mean wet nights at end of follow‐up: A: 2.1. B: 1.5 Number not achieving 14 dry nights or relapsing at follow‐up: A: 156/192 (81.2%), B: 46/59 (78%) Adverse events: A: 30% (4 severe dysuria, urgency, appendicitis, rash, 3 headaches), B: 14% (1 severe anxiety) Other: compliance, mean sleep duration
Fagundes 2017	"Response to treatment was classified using the ICCS 2014 criteria for initial success." Number not achieving 14 dry nights at end of treatment: A: 20/30, B: 14/20, C: 14/24 Adverse events: not reported
Faraj 1999	Dry nights at 3 months: A: 85%, B: 90% Dry nights at six months: A: 78%, B: 94% Number not achieving 14 dry nights at 3 months: A: 12/39, B: 6/37 Adverse events: not mentioned
Fielding 1980	Mean number of wet nights in third month of alarm: A: 6.2, B: 2.3 Number not achieving 14 dry nights at end of treatment: A: 5/16, B: 3/17 Number (%) relapsing after 3 months: A: 3 (28), B: 4 (29) After 6 months: A: 3 (28), B: 5 (36) After 12 months: A: 4 (36), B: 8 (57) Number not achieving 14 dry nights or relapsing after 12 months: A: 9/16, B: 11/17 Adverse events: not mentioned
Finley 1973	Mean wet episodes during 6th week: A: 0.2, B: 0.6, C: 8 Number not achieving 7 dry nights: A: 1/10, B: 2/10, C: 10/10 Number dry at 6 weeks: A: 9/10, B: 8/10, C: 0/10 Number failing or relapsing after 'cure': A: 5/10, B: 3/10, C 10/10
Finley 1977	Number not achieving 14 dry nights: A: 3/10, B: 6/10 Relapse rate: A: 3/7, B: 1/4 Failed or relapsed: A: 6/10, B: 7/10
Fournier 1987	Mean number of wet nights a week: A: 1.9, B: 2.5, C: 5, D: 3.3, E: 1 No results for F, G or H 4 boys dropped out because of side effects or non‐compliance, 1 girl with UTI Adverse events: 4 boys dropped out because of side effects or non‐compliance, but adverse events by individual interventions not specifically mentioned
Geffken 1986a	Mean (SD) number of wet nights a week: A: 1.7 (1.2), C: 2.5 (0.9) Significant interaction between maximal functional bladder capacity and treatment: F (1, 33) = 4.90, P = 0.03 Number of children achieving 14 dry nights at end of treatment: A: 9, C: 9 Number of children relapsing during follow‐up: A: 4, C: 4
Geffken 1986b	Mean (SD) number of wet nights a week: B: 2.3 (1.0), D: 1.6 (1.1) Significant interaction between maximal functional bladder capacity and treatment: F (1, 33) = 4.90, P = 0.03 Number of children achieving 14 dry nights at end of treatment: B: 10, D: 9 Number of children relapsing during follow‐up: B: 6, D: 3
Gibb 2004	Cure = 28 dry nights, relapse = 2 wet nights in 2 weeks Wet nights during treatment (number, mean (SD)): A: 101, 1.8 (1.13), B: 106, 2.4 (1.53) Cure during treatment: A: 52/101, B: 51/106 P = 0.63 (failed: A: 49/101, B: 55/106) Relapse after treatment stopped: A: 7, B: 3 Failed or relapsed: A: 56/101, B: 58/106 Adverse events: A: 1 (headache), B: 1 (nose bleed) Other: compliance same in both groups Cure in daytime wetting: A: 6/11, B: 3/8
Hojsgaard 1979	Cured: A: 20/32, B: 17/30 Improved: A: 5/32, B: 6/30
Hoseinzadeh 1997	"1st 45 days the drug was much more effective but after 90 days there was no obvious difference between them, in case of recurrence 45 days after stopping treatments there was no difference between 2 groups.”
Houts 1986	A: cured 9, failed 4, dropout 2; B: cured 13, dropout 2; C: cured 9, failed 3, dropout 3; D: none cured (11/11 failed) Relapse at end of study after retreatment if necessary: A: 1, B: 6, C: 3 i.e. failed or relapsed: A 5/13, B: 6/13, C: 6/12
Jehu 1977	Mean number of wet nights a week 12: A: 0.3, B: 5.3 Achieved 14 dry nights: A: 18/19, B: 0/20 1 had absconded (counted as failure) 3 children had relapsed at 6 months and another at 8 months (needed repeat treatment)
Kennedy 1968	Number not achieving 14 dry nights: A: 0/5, B: 0/5, C: 0/3, D: 4/5
Kolvin 1972	Mean number of wet night in final month (% improvement): A: 9.3 (64), B: 9.1 (62), C: 11.0 (53) At follow‐up mean number of wet nights a month (% improvement): A: 13.4 (43), B: 9.3 (64), C: 11.3 (54)
Kwak 2010#	Mean % decrease in wet nights at end of treatment (3 months): A: 69.5% decrease from 23.1 = 7.0, B: 78.4% decrease from 21.7 = 4.7 Number failing to achieve 14 consecutive dry nights at end of treatment: A 34/54, B 25/50 Mean wet nights at follow‐up: Unable to calculate as cross‐over Number failing to achieve 14 consecutive dry nights or relapsing after cure: A: 34 + 10/54, B: 25 + 3/50 Adverse events: Abdominal pain, voiding difficulty (n = 1, desmopressin group)
Leebeek 2001	Wet nights (number of participants, mean): After 3 weeks: A: 47, 2.93, B: 46, 3.86 (P = 0.014) After 6 weeks: A: 44, 2.18, B: 42, 3.57 (not significant) After 9 weeks: A: 43, 2.77, B: 39, 2.21 (not significant) Number cured (90% or greater reduction in wet nights a week compared to baseline): 2 weeks after end of treatment: A: 15/47, B: 18/46 6 months after end of treatment: A: 17/47, B: 17/46 i.e. failed at six months: A: 30/47, B: 29/46 Wet nights at 6 months (number of participants, mean): A:41, 2.72, B:37, 1.90 Adverse events: none in either group
Longstaffe 2000	Number not achieving 14 dry nights after 6 months: A: 26/61, B: 31/60, C: 38/61 All children improved psychologically, e.g. behaviour and self‐concept, regardless of outcome or treatment assignment Adverse events: not mentioned
Lovibond 1964a	Experiment 1 Number not achieving 14 dry nights: A: 0/12, B: 1/12, C: 1/12 Number failing or relapsing after trial: A: 5/12, B: 6/12, C: 5/12 Adverse events: B: corrosive skin burns (3); discontinued due to fear of shocks (2)
Lovibond 1964b	Experiment 2 Number not achieving 14 dry nights: A1: 0/5, A2: 0/5, B1: 0/5, B2: 0/5 Number failing or relapsing after 24 months: A1: 3/5, A2: 3/5, B1: 3/5, B2: 2/5
Lovibond 1964c	Experiment 3 Number not achieving 14 dry nights: A: 0/12, B: 2/12 Number failing or relapsing: A: 5/12, B: 6/12

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Mean number of wet nights a week	4	127	Mean Difference (IV, Random, 95% CI)	‐2.68 [‐4.59, ‐0.78]
1.1.1 alarm vs control	4	100	Mean Difference (IV, Random, 95% CI)	‐3.42 [‐4.98, ‐1.87]
1.1.2 delayed alarm vs control	1	27	Mean Difference (IV, Random, 95% CI)	0.13 [‐1.37, 1.63]
1.2 Numbers achieving 14 dry nights	18	827	Risk Ratio (M‐H, Random, 95% CI)	7.23 [1.40, 37.33]
1.2.1 alarm vs no treatment	16	650	Risk Ratio (M‐H, Random, 95% CI)	8.63 [5.23, 14.26]
1.2.2 delayed alarm vs no treatment	2	47	Risk Ratio (M‐H, Random, 95% CI)	2.98 [0.60, 14.93]
1.2.3 intermittent alarm vs control	1	15	Risk Ratio (M‐H, Random, 95% CI)	9.27 [0.64, 134.31]
1.2.4 electric shock alarm vs control	2	115	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.92, 1.10]
1.3 Numbers achieving 14 dry nights post‐treatment	10	366	Risk Ratio (M‐H, Fixed, 95% CI)	9.67 [4.74, 19.76]
1.3.1 alarm vs control	10	331	Risk Ratio (M‐H, Fixed, 95% CI)	10.43 [4.82, 22.56]
1.3.2 intermittent alarm vs control	1	15	Risk Ratio (M‐H, Fixed, 95% CI)	8.18 [0.56, 119.85]
1.3.3 delayed alarm vs control	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	2.86 [0.16, 52.42]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Numbers achieving 14 dry nights	2	181	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [1.16, 2.17]
2.1.1 alarm vs placebo	2	143	Risk Ratio (M‐H, Fixed, 95% CI)	1.53 [1.08, 2.18]
2.1.2 twin‐signal alarm vs placebo	1	21	Risk Ratio (M‐H, Fixed, 95% CI)	1.47 [0.62, 3.45]
2.1.3 intermittent alarm vs placebo	1	17	Risk Ratio (M‐H, Fixed, 95% CI)	2.29 [0.77, 6.80]
2.2 Mean number of wet nights a week	1	47	Mean Difference (IV, Fixed, 95% CI)	‐0.96 [‐2.32, 0.41]
2.2.1 alarm vs placebo	1	23	Mean Difference (IV, Fixed, 95% CI)	‐1.32 [‐3.32, 0.68]
2.2.2 twin‐signal alarm vs placebo	1	24	Mean Difference (IV, Fixed, 95% CI)	‐0.64 [‐2.51, 1.23]
2.3 Numbers achieving 14 dry nights: subgroup analysis	2	181	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [1.16, 2.17]
2.3.1 Monosymptomatic nocturnal enuresis	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	1.52 [1.03, 2.24]
2.3.2 Non‐monosymptomatic nocturnal enuresis	1	59	Risk Ratio (M‐H, Fixed, 95% CI)	1.72 [1.02, 2.91]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Mean number of wet nights a week	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.1.1 immediate alarm vs delayed alarm	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.1.2 alarm vs twin‐signal alarm	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.2 Numbers achieving 14 dry nights at the end of treatment	11		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.2.1 bell and pad alarm vs body alarm	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.67, 1.50]
3.2.2 alarm vs intermittent alarm	3	86	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.82, 1.36]
3.2.3 immediate alarm vs delayed alarm	2	62	Risk Ratio (M‐H, Fixed, 95% CI)	1.88 [0.97, 3.63]
3.2.4 alarm vs twin‐signal alarm	3	78	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.79, 1.13]
3.2.5 bell and pad alarm vs electric shock alarm	1	24	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.79, 1.27]
3.2.6 loud alarm vs quiet alarm	2	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.89, 1.99]
3.2.7 body‐worn audio alarm vs body‐worn vibrating alarm	1	47	Risk Ratio (M‐H, Fixed, 95% CI)	0.68 [0.45, 1.01]
3.2.8 Code‐word alarm vs standard alarm	1	353	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.97, 1.27]
3.3 Numbers achieving 14 dry nights post‐treatment	8		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.3.1 bell and pad alarm vs body alarm	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.50, 1.64]
3.3.2 alarm vs intermittent alarm	2	59	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.37, 1.35]
3.3.3 immediate alarm vs delayed alarm	1	26	Risk Ratio (M‐H, Fixed, 95% CI)	3.00 [0.74, 12.21]
3.3.4 alarm vs twin‐signal alarm	2	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.56, 1.53]
3.3.5 bell and pad alarm vs electric shock alarm	1	24	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.56, 2.45]
3.3.6 loud alarm vs quiet alarm	2	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.47, 1.71]
3.3.7 code‐word alarm vs standard alarm	1	353	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.79, 1.05]
3.4 Numbers with adverse events	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Outcome	Alarm + desmopressin	Alarm + imipramine	Result
Mean number of wet nights per week at the end of treatment	2.5 (n = 35)	2.15 (n = 33)	No SDs reported (Naitoh 2005)
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	26/33	26/37	RR 1.12 (95% CI 0.85 to 1.48) (Naitoh 2005)
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	not reported
Proportion of children with adverse events	not reported

Outcome	Alarm + imipramine	Placebo	Result
Mean number of wet nights a week at the end of treatment	1 (n = 8)	5 (n = 8)	No SDs reported (Fournier 1987)
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	not reported
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment
Proportion of children with adverse events

Outcome	Alarm + imipramine	Random waking	Result
Mean number of wet nights per week at the end of treatment	1 (n = 8)	3.3 (n = 8)	No SDs reported (Fournier 1987)
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	not reported
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment
Proportion of children with adverse events

Outcome	Alarm + nortriptyline	Alarm + placebo	Result
Mean number of wet nights a week at the end of treatment	not reported
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	6/15	9/15	RR 0.67 (95% CI 0.32 to 1.40) (Scholander 1968)
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	6/15	9/15	RR 0.67 (95% CI 0.32 to 1.40) (Scholander 1968)
Proportion of children with adverse events	not reported

Outcome	Alarm + behavioural therapy	Desmopressin	Result
Mean number of wet nights a week at the end of treatment	Not reported
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	13/52	24/46	Favours alarm + behavioural therapy RR 0.48 (95% CI 0.28 to 0.83) (Ma 2007)
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	15/52	33/36	Favours alarm + behavioural therapy RR 0.40 (95% CI 0.25 to 0.64) (Ma 2007)
Proportion of children with adverse events	not reported

Outcome	Alarm + behavioural therapy + desmopressin	Desmopressin	Result
Mean number of wet nights a week at the end of treatment	not reported
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	6/40	24/46	Favours alarm+ behavioural therapy + desmopressin RR 0.29 (95% CI 0.13 to 0.63) (Ma 2007)
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	8/40	33/46	Favours alarm+ behavioural therapy + desmopressin RR 0.28 (95% CI 0.15 to 0.53) (Ma 2007)
Proportion of children with adverse events	not reported

Outcome	Alarm + behavioural therapy	Fluid restriction & lifting + behavioural therapy	Result
Mean number of wet nights a week at the end of treatment	not reported
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	11/40	34/40	Favours alarm + behavioural therapy RR 0.32 (95% CI 0.19 to 0.54) (Titawee 2000)
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	19/40	39/40	Favours alarm + behavioural therapy RR 0.49 (95% CI 0.35 to 0.68) (Titawee 2000)
Proportion of children with adverse events	not reported

Outcome	Alarm + dry bed training	No treatment	Result
Mean number of wet nights a week at the end of treatment	0 (n = 60)	4.4 (n = 20)	No SDs (Bollard 1981b)
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	0/60	18/20	Favours alarm + dry bed training RR 0.01 ( 95% CI 0.00 to 0.15) (Bollard 1981b)
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	15/60	20/20	Favours alarm + dry bed training RR 0.26 (95 CI 0.17 to 0.40) (Bollard 1981b)
Proportion of children with adverse events	not reported

Outcome	Alarm + dry bed training	Dry bed training (no alarm)	Result
Mean number of wet nights a week at the end of treatment	0 (n = 60)	3.8 (n = 20)	No SDs (Bollard 1981b)
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	0/60	15/20	Favours alarm + dry bed training RR 0.01 (95% CI 0.00 to 0.18) (Bollard 1981b
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	15/60	17/20	Favours alarm + dry bed training RR 0.29 (95% CI 0.18 to 0.47) (Bollard 1981b
Proportion of children with adverse events	not reported

Outcome	Alarm + immediate reward	Alarm + delayed alarm	Result
Mean number of wet nights a week at the end of treatment	not reported
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	1/38	6/39	RR 0.17 (95% CI 0.02 to 1.35) (Van Londen 1993)
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	1/38	21/39	Favours alarm + immediate reward RR 0.05 (95% CI 0.01 to 0.35) (Van Londen 1993)
Proportion of children with adverse events	not reported

PERMALINK

Alarm interventions for nocturnal enuresis in children

Patrina HY Caldwell

Miriam Codarini

Fiona Stewart

Deirdre Hahn

Premala Sureshkumar

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Prevalences and causes

Description of the intervention

Enuresis alarms

Overlearning

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Main outcomes for 'Summary of findings' tables

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

1.

Included studies

Design

Sample size

Setting

Participants

Duration

Interventions

1. Studies investigating combination therapies.

Types of outcomes

Excluded studies

Ongoing studies

Risk of bias in included studies

2.

3.

Allocation

Random sequence generation

Allocation concealment

Blinding

Incomplete outcome data

Follow‐up after cessation of treatment

Selective reporting

Baseline wetting

Exclusion of organic causes or daytime wetting

Reporting of adverse events

Statistical reporting

Outcome	Alarm + pretreatment A	Alarm + pretreatment B	Result
Mean number of wet nights a week at the end of treatment	not reported
Proportion of children failing to achieve 14 consecutive dry nights by the end of treatment	12/29 (bladder training and placebo)	14/30 (placebo)	RR 0.89 (95% CI 0.50, 1.58)
	12/29 (bladder training and placebo)	14/30 (bladder training and oxybutynin)	RR 0.89 (95% CI 0.50, 1.58)
	24/30 (oxybutynin and bladder training)	14/30 (placebo)	RR 1.00 (95% CI 0.58 to 1.72)
Proportion of children failing to achieve 14 consecutive dry nights or relapsing after stopping treatment	10/29 (bladder training and placebo)	9/30 (placebo)	RR 1.15 (95%% CI 0.55 to 2.41)
	10/29 (bladder training and placebo)	14/30 (bladder training and oxybutynin)	RR 0.74 (95% CI 0.39 to 1.39)
	14/30 (oxybutynin and bladder training)	9/30 (placebo)	RR 1.56 (95% CI 0.80 to 3.03)
Proportion of children with adverse events	not reported

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Mean number of wet nights a week	3	95	Mean Difference (IV, Random, 95% CI)	‐0.81 [‐2.01, 0.38]
4.1.1 alarm vs waking	1	22	Mean Difference (IV, Random, 95% CI)	‐0.33 [‐2.26, 1.60]
4.1.2 twin‐signal alarm vs waking	1	23	Mean Difference (IV, Random, 95% CI)	0.35 [‐1.44, 2.14]
4.1.3 alarm vs bladder training	1	21	Mean Difference (IV, Random, 95% CI)	‐2.75 [‐4.70, ‐0.80]
4.1.4 alarm vs star chart + rewards	1	29	Mean Difference (IV, Random, 95% CI)	‐0.70 [‐2.05, 0.65]
4.2 Numbers achieving 14 dry nights	6	179	Risk Ratio (M‐H, Random, 95% CI)	1.77 [0.98, 3.19]
4.2.1 alarm vs waking	2	32	Risk Ratio (M‐H, Random, 95% CI)	1.45 [0.19, 10.84]
4.2.2 twin‐signal alarm vs waking	2	33	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.71, 1.40]
4.2.3 alarm vs bladder training	1	21	Risk Ratio (M‐H, Random, 95% CI)	2.67 [0.62, 11.49]
4.2.4 alarm vs dry‐bed training (no alarm)	2	54	Risk Ratio (M‐H, Random, 95% CI)	3.13 [1.66, 5.87]
4.2.5 alarm vs star chart + rewards	1	39	Risk Ratio (M‐H, Random, 95% CI)	2.11 [0.99, 4.47]
4.3 Mean number of wet nights a week at follow‐up	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
4.4 Numbers achieving 14 dry nights post‐treatment	3	89	Risk Ratio (M‐H, Fixed, 95% CI)	1.39 [0.81, 2.41]
4.4.1 alarm vs waking	1	10	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.18, 2.42]
4.4.2 twin‐signal alarm vs waking	1	10	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.22, 4.56]
4.4.3 alarm vs dry‐bed training (no alarm)	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	3.33 [1.08, 10.34]
4.4.4 alarm vs star chart + rewards	1	29	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.39, 2.22]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Mean number of wet nights per week	4	285	Mean Difference (IV, Random, 95% CI)	‐0.64 [‐1.77, 0.49]
5.1.1 Monosymptomatic nocturnal enuresis	1	84	Mean Difference (IV, Random, 95% CI)	‐1.83 [‐2.82, ‐0.84]
5.1.2 Non‐monosymptomatic nocturnal enuresis	3	201	Mean Difference (IV, Random, 95% CI)	‐0.20 [‐1.16, 0.77]
5.2 Mean number of wet nights a week at follow‐up	3	195	Mean Difference (IV, Fixed, 95% CI)	‐1.47 [‐1.90, ‐1.04]
5.3 Numbers achieving 14 dry nights	12	1168	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.93, 1.36]
5.3.1 Monosymptomatic nocturnal enuresis	8	854	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.97, 1.47]
5.3.2 Non‐monosymptomatic nocturnal enuresis	4	314	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.54, 1.47]
5.4 Numbers achieving 14 dry nights post‐treatment	5	565	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.92, 1.84]
5.5 Numbers with adverse events	5	565	Risk Ratio (M‐H, Fixed, 95% CI)	0.38 [0.20, 0.71]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Mean number of wet nights a week	1	29	Mean Difference (IV, Fixed, 95% CI)	‐1.13 [‐2.74, 0.48]
6.1.1 alarm v imipramine	1	15	Mean Difference (IV, Fixed, 95% CI)	‐0.65 [‐2.70, 1.40]
6.1.2 alarm vs clomipramine	1	14	Mean Difference (IV, Fixed, 95% CI)	‐1.90 [‐4.50, 0.70]
6.2 Numbers achieving 14 dry nights	3	208	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [1.33, 3.17]
6.3 Numbers achieving 14 dry nights post‐treatment	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Mean number of wet nights a week	1	33	Mean Difference (IV, Fixed, 95% CI)	0.20 [‐2.65, 3.05]
7.1.1 alarm vs cognitive behavioural therapy	1	33	Mean Difference (IV, Fixed, 95% CI)	0.20 [‐2.65, 3.05]
7.2 Numbers achieving 14 dry nights	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
7.2.1 alarm vs cognitive behavioural therapy	1	39	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.55, 1.29]
7.2.2 alarm vs psychotherapy	2	116	Risk Ratio (M‐H, Fixed, 95% CI)	3.62 [1.38, 9.50]
7.2.3 alarm vs hypnotherapy	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	3.00 [1.41, 6.39]
7.2.4 alarm vs restricted diet	1	150	Risk Ratio (M‐H, Fixed, 95% CI)	23.00 [3.19, 165.98]
7.3 Number achieving 14 dry nights post‐treatment	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.3.1 alarm vs cognitive behavioural therapy	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.3.2 alarm vs hypnotherapy	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
8.1 Mean number of wet nights a week	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
8.1.1 alarm + bladder training vs bladder training	1	22	Mean Difference (IV, Random, 95% CI)	‐2.35 [‐4.20, ‐0.50]
8.1.2 alarm + desmopressin vs desmopressin	2	156	Mean Difference (IV, Random, 95% CI)	‐0.88 [‐1.38, ‐0.38]
8.2 Mean number of wet nights a week: alarm + desmopressin v desmopressin subgroup analysis	2	156	Mean Difference (IV, Random, 95% CI)	‐0.88 [‐1.38, ‐0.38]
8.2.1 Monosymptomatic nocturnal enuresis	1	91	Mean Difference (IV, Random, 95% CI)	‐0.76 [‐1.33, ‐0.19]
8.2.2 Non‐monosymptomatic nocturnal enuresis	1	65	Mean Difference (IV, Random, 95% CI)	‐1.30 [‐2.35, ‐0.25]
8.3 Numbers achieving 14 dry nights	7		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
8.3.1 alarm + bladder training vs bladder training	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	3.00 [0.73, 12.27]
8.3.2 alarm + dry‐bed training vs dry‐bed training	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	3.79 [1.85, 7.77]
8.3.3 alarm + desmopressin vs desmopressin	5	359	Risk Ratio (M‐H, Fixed, 95% CI)	1.32 [1.08, 1.62]
8.4 Numbers achieving 14 dry nights: alarm + desmopressin v desmopressin subgroup analysis	5	359	Risk Ratio (M‐H, Fixed, 95% CI)	1.32 [1.08, 1.62]
8.4.1 Monosymptomatic nocturnal enuresis	3	221	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [1.02, 1.64]
8.4.2 Non‐monosymptomatic enuresis	2	138	Risk Ratio (M‐H, Fixed, 95% CI)	1.38 [0.94, 2.02]
8.5 Mean number of wet nights a week at follow‐up	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
8.5.1 alarm + bladder training vs bladder training	1	22	Mean Difference (IV, Random, 95% CI)	‐1.10 [‐3.42, 1.22]
8.5.2 alarm + desmopressin vs desmopressin	2	149	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐1.86, ‐0.94]
8.6 Number achieving 14 dry nights post‐treatment	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
8.6.1 alarm + dry‐bed training vs dry bed training	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	0.56 [0.15, 2.12]
8.6.2 alarm + desmopressin vs desmopressin	2	161	Risk Ratio (M‐H, Fixed, 95% CI)	2.33 [1.26, 4.29]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
9.1 Mean number of wet nights a week	10		Mean Difference (IV, Random, 95% CI)	Subtotals only
9.1.1 alarm + bladder training vs alarm	3	59	Mean Difference (IV, Random, 95% CI)	0.13 [‐0.92, 1.17]
9.1.2 alarm + dry bed training vs alarm	1	24	Mean Difference (IV, Random, 95% CI)	‐2.42 [‐4.13, ‐0.71]
9.1.3 alarm + desmopressin vs alarm	6	528	Mean Difference (IV, Random, 95% CI)	‐0.80 [‐1.33, ‐0.26]
9.2 Numbers achieving 14 dry nights	21		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
9.2.1 alarm + overlearning vs alarm	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.65, 1.63]
9.2.2 alarm + overlearning vs intermittent alarm	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.27 [0.73, 2.23]
9.2.3 alarm + bladder training + over‐learning vs alarm	1	25	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.57, 1.50]
9.2.4 alarm + bladder training vs alarm	5	117	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.82, 1.43]
9.2.5 alarm + dry‐bed training vs alarm	2	104	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [1.11, 1.81]
9.2.6 alarm + desmopressin vs alarm	9	770	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [1.02, 1.41]
9.2.7 alarm + imipramine vs alarm	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.31, 1.63]
9.2.8 alarm + methedrine vs alarm	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	1.60 [0.95, 2.68]
9.2.9 alarm + nortriptyline vs alarm + placebo	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	1.50 [0.71, 3.16]
9.2.10 alarm + immediate reward for correct behaviour vs alarm	1	74	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [1.09, 1.66]
9.2.11 alarm + immediate reward for correct behaviour vs alarm + delayed reward if dry in morning	1	77	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [1.00, 1.33]
9.2.12 alarm + delayed reward if dry in morning vs alarm	1	75	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.92, 1.49]
9.2.13 alarm + pretreatment (placebo) vs alarm	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.47, 1.03]
9.2.14 alarm + pretreatment (bladder training + placebo) vs alarm	1	59	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.53, 1.10]
9.2.15 alarm + pretreatment (oxybutynin) vs alarm	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.51, 1.07]
9.2.16 alarm + pretreatment (bladder training + oxybutynin) vs alarm	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.47, 1.03]
9.3 Mean number of wet nights a week at follow‐up	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
9.3.1 alarm + bladder training vs alarm	1	19	Mean Difference (IV, Random, 95% CI)	1.50 [‐0.43, 3.43]
9.3.2 alarm + desmopressin vs alarm	3	196	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.33, 0.29]
9.4 Number achieving 14 dry nights post‐treatment	14		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
9.4.1 alarm + overlearning vs alarm	2	144	Risk Ratio (M‐H, Fixed, 95% CI)	1.48 [1.16, 1.89]
9.4.2 alarm + overlearning vs intermittent alarm	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.80 [0.77, 4.23]
9.4.3 alarm + bladder training + over‐learning vs alarm	1	25	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.60, 2.50]
9.4.4 alarm + bladder training vs alarm	2	58	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.65, 2.04]
9.4.5 alarm + dry‐bed training vs alarm	2	104	Risk Ratio (M‐H, Fixed, 95% CI)	1.74 [1.12, 2.70]
9.4.6 alarm + desmopressin vs alarm	6	589	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.88, 1.33]
9.4.7 alarm + imipramine vs alarm	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.41 [0.14, 1.16]
9.4.8 alarm + immediate reward for correct behaviour vs alarm	1	74	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.74, 1.31]
9.4.9 alarm + immediate reward for correct behaviour vs alarm + delayed reward if dry in morning	1	77	Risk Ratio (M‐H, Fixed, 95% CI)	2.11 [1.50, 2.97]
9.4.10 alarm + delayed reward if dry in morning vs alarm	1	75	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.43, 0.95]
9.4.11 alarm + pretreatment (placebo) vs alarm	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.77, 1.58]
9.4.12 alarm + pretreatment (bladder training + placebo) vs alarm	1	59	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.71, 1.51]
9.4.13 alarm + pretreatment (oxybutynin) vs alarm	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.59, 1.35]
9.4.14 alarm + pretreatment (bladder training + oxybutynin) vs alarm	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.55, 1.30]

*Study characteristics*
Methods	Design: RCT Systematic baseline measure of wetting: yes Organic causes excluded: yes Daytime wetting specifically excluded: yes
Participants	Setting: participants were consecutively enrolled from those referred to urology and paediatric clinics at hospitals in Saudi Arabia Number of participants (boys/girls): 136 (A 32/13; B 30/16; C 33/12) Number of dropouts: 21 (A 9, B 4, C 8) Inclusion criteria: 6 to 14 years of age, having wetting episodes at least twice a week over 3 consecutive months, and whose parents agreed to allocation of treatment. Exclusion criteria: identifiable LUTS other than NE and those with other disorders, such as diabetes; abnormal urine analysis results; renal, urological, cardiovascular, or neurological diseases; or previously treated with an enuresis alarm or desmopressin Mean (SD) age: A 8.21 (2.05); B 7.97 (2.10); C 8.01 (1.96) Baseline wetting: mean (SD) number wet nights a week: A 4.56 (1.71); B 5.04 (1.58); C 4.73 (1.66)
Interventions	A (n = 45): alarm only. Children were instructed to test the alarm before sleep, with the sound (or vibration) in mind, and the families were instructed to awake the child immediately after onset of the alarm and to send him to the bathroom to finish voiding B (n = 46): desmopressin only. An oral lyophilizate form of desmopressin (melt formulation) was used. The participants were advised to place the tablet under the tongue and to allow it to dissolve completely without water. They started on 120 µg 1 hour before bedtime. If no considerable response was achieved after 2 weeks (> 1 wet night/week), the doses were increased to 240 µg C (n = 45): alarm + desmopressin All participants (groups A, B, C) were advised to urinate just before going to bed and to restrict their fluid intake (not to drink more than sufficient to satisfy thirst) from 1 hour before bedtime. They were also instructed to avoid drinking liquids with a diuretic effect at night, to keep regular sleep hours, and to keep a record of nightwetting episodes. In addition, the children used a star chart for recording the number of dry and wet nights and compliance with treatment Duration of treatment: 12 weeks Duration of follow‐up: 12 weeks after end of treatment Dosage of desmopressin: 120 µg, increasing to 240 µg if clinically necessary
Outcomes	Wet nights on treatment = mean (SD) wet nights at end of treatment Mean (SD) wet nights at end of follow‐up Number not achieving 14 consecutive dry nights (failure of therapy) Complete response (no wet nights) at end of treatment Non‐response (defined as < 50% reduction in the number of wet nights) at end of treatment Number failing to achieve 14 consecutive dry nights or relapsing at follow‐up Adverse events
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly divided into 3 groups through a computer randomisation programme
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not possible to blind participants
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not possible
Incomplete outcome data (attrition bias) All outcomes	Low risk	No differential attrition, ITT analysis carried out Quote: "Counting defaulters due to noncompliance issues as a form of failure"
Selective reporting (reporting bias)	Low risk	Outcomes reported in full
Other bias	Unclear risk	Not stated

*Study characteristics*
Methods	Design: RCT Systematic baseline measure of wetting: yes Organic causes excluded: yes Daytime wetting: not mentioned
Participants	Setting: respondents to a newspaper advertisement for enuretics Number of children (boys): 26 (19) Exclusion criteria: medical causes Ages: 3+, mean 8 years Baseline wetting: 7 days/week.
Interventions	Experiment 1 A (n = 7): DBT with alarm that woke parent and child B (n = 7): standard (child‐only) alarm for first 2 weeks, then DBT with alarm that woke parent and child Experiment 2 C (n = 6): DBT with alarm that woke only parent D (n = 6): standard (child‐only) alarm for first 2 weeks, then DBT with alarm that woke only parent
Outcomes	Median wet nights in first 2 weeks Numbers achieving 6 dry nights
Notes	Pairs matched for age, sex and frequency of wetting No useable data
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Each pair was randomly assigned by a coin flip
Allocation concealment (selection bias)	Low risk	Investigators did not know the upcoming assignments
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Blinding not possible
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Blinding not possible
Incomplete outcome data (attrition bias) All outcomes	High risk	2 children remained dry in the first 2 weeks of treatment for more than 6 nights in the standard urine alarm group. Possibly dropped out and not included in the analysis. Dropout < 10%
Selective reporting (reporting bias)	Unclear risk	Not stated
Other bias	Unclear risk	Pairs matched for age, sex and frequency of wetting at randomisation

*Study characteristics*
Methods	Design: RCT (details not given) Systematic baseline measure of wetting: yes Organic causes excluded: yes Daytime wetting excluded: yes
Participants	Setting: respondents to a newspaper advertisement for enuretics Number of children (boys): 55 (41) Number of dropouts: 4 Inclusion criteria: age at least 3 years; no daytime wetting; wetting at least 4 times a week; able to understand instructions Age: mean 7.1 years (range 3 to 14) (20 < 6 years) Baseline wetting: 91% of nights
Interventions	A (n = 28): intensive DBT plus rehearsing during the day with increased fluid intake, stream interruption exercises, retention control training, repeated awakening, rewards for dry nights or compliance but no alarm B (n = 27): alarm (pad and buzzer) Duration of trial: 2 weeks, after which parents could swap to other arm
Outcomes	% wet nights during first 2 weeks Number of children swapping to other group after 2 weeks of treatment
Notes	Comparability of groups at baseline not reported No follow‐up possible after 2 weeks No SDs Very young children (20 < 6 years) included Reasons for children not swapping groups after 2 weeks treatment: A: 27/28 were dry most nights; 1/28 dropped out after first night B: 3/27 were dry most nights; 1/27 thought DBT inconvenient
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomly assigned but method not given
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Blinding not possible
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Blinding not possible
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	2 weeks treatment results presented for 54 children. 1 dropped out after 1 night of treatment.
Selective reporting (reporting bias)	High risk	Comparability of groups at baseline not reported Systematic baseline measure of wetting: mentioned Organic causes excluded: mentioned Daytime wetting excluded: mentioned
Other bias	Unclear risk	Not stated