Enuresis: Clinical Guidelines

List of Abbreviations

ICCS (International Children's Continence Society)

ADH – antidiuretic hormone

OAB – overactive bladder

LUTD – lower urinary tract dysfunction

IDB – idiopathic bladder dysfunction

NGB – neurogenic bladder

EDBC – expected bladder capacity

ADHD – attention deficit hyperactivity disorder

TCAs – tricyclic antidepressants

Terms and Definitions

Detrusor overactivity — involuntary contractions of the detrusor during filling cystometry [1].

Overactive bladder (OAB) — a clinical syndrome characterized by pollakiuria (increased urinary frequency), urgency, accompanied by urinary incontinence (or without it) in combination with nocturia (one or more micturitions between sleep onset and final awakening) [2].

Dysuria — burning or discomfort during urination.

Dysfunctional voiding — a voiding disorder caused by discoordination of contractions of the detrusor, internal urethral sphincter, and pelvic floor muscles without signs of organic central nervous system lesions at various levels [2].

Bladder capacity (cystometric capacity) — the volume of the bladder at the end of the filling phase when the patient is allowed to void. Cystometric capacity is the sum of the voided and residual volume [2].

Urinary retention — the sensation of inability to void despite persistent effort in the presence of a fully filled bladder [1].

Urgent urinary incontinence — periodic uncontrolled urine leakage accompanied by a sudden desire to urinate [2].

Urinary incontinence — involuntary leakage of urine; it can be continuous or intermittent. The term urinary incontinence includes: urgent incontinence, stress incontinence, paradoxical ischuria, reflex form, combined form.

Nighttime urine output, nocturnal diuresis — Nighttime urine output does not include the urine produced during the last urination before sleep, but includes the urine produced during the first morning urination [1].

Nochurnal polyuria — nocturnal diuresis exceeding 130% of the EBCC for age.

Urinary leakage (dribbling) — involuntary loss (with or without urgency) of a small volume of urine contained in the bladder, followed by complete bladder emptying.

Expected bladder capacity (EBCC). This concept is used as a standard for comparison. EBC is determined by the formula: 30 × (age in years + 1) in ml. The EBC formula is applicable for children from 4 to 12 years old, since by 12 years of age it reaches the level of 390 ml [1].

Polyuria — excessive urine output leading to profuse and frequent urination. Polyuria is defined as a urine output volume of >40 ml/kg of body weight over 24 hours or >2.8 l of urine in a child or adolescent with a body weight of >70 kg [1].

Intermittent flow — several discrete spurts of urination with stopping and starting [1].

Increase or decrease in urinary frequency. Increased daytime urinary frequency is recognized when the number of urinations is 8 or more per day, and decreased daytime urinary frequency is recognized when the number of urinations is 3 or less per day [1].

Urinary urgency — the occurrence of sudden, strong, and difficult-to-control urges to urinate (imperative urges), often followed by uncontrolled urine leakage [2].

Functional bladder capacity — the amount of urine a child can hold in the bladder until an intolerable desire to urinate appears. For children under 12 years old, it is calculated by the formula: [30 + (age in years • 30)] ml [159, 160].

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Enuresis — episodes of periodic urinary incontinence during nighttime sleep in children older than 5 years. Enuresis is diagnosed if urinary incontinence occurs regularly at least three times a month in children under 7 years old and at least once a month at 7 years and older. Daytime urinary incontinence is not included in the definition of enuresis.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Diuresis regulation occurs due to the coordinated work of the autonomic, peripheral, and central nervous systems, which control and modulate the activity of the smooth and striated muscles of the bladder and urethra.

Enuresis is a polyetiological disease with several possible pathogenetic variants. The etiology and pathogenesis of enuresis in children are closely interrelated; often the etiological factor is also considered as a link in pathogenesis. A detailed understanding of pathogenesis is necessary to form an idea of the mechanisms of enuresis development, which subsequently justifies the choice of diagnostic methods and a multidisciplinary approach to patient management and treatment.

The main pathogenetic factors influencing the development of enuresis include the following:

1. Polyuria [6, 7, 8].

Polyuria may be caused either by excessive water intake by the child in the evening [7] or by a decreased nighttime plasma level of antidiuretic hormone (ADH) – vasopressin, the secretion of which normally increases at this time of night [9-12, 13]. However, polyuria is only one of the pathogenetic factors, as it is not observed in all children with enuresis. On the other hand, some children with nocturnal polyuria wake up to urinate at night while remaining dry [14].

Currently, an independent etiological role of idiopathic reduction in nighttime ADH production in patients with enuresis is being discussed [10-12], with particular attention given to alterations in the circadian rhythm of ADH secretion [13].

In enuresis occurring secondary to comorbid conditions, polyuria may result from various disorders such as kidney diseases, endocrine disorders (diabetes mellitus and diabetes insipidus, sickle cell anemia [1, 4, 12, 94, 95], etc.). However, nocturnal polyuria is most often explained by a simpler cause – increased fluid intake by the child in the evening due to habits or specific dietary patterns [180].

2. Detrusor overactivity [3, 4, 5].

The association between nocturnal enuresis and daytime urgency or imperative urinary incontinence, reduced voided volume, and cystometric findings indicates the involvement of nocturnal detrusor overactivity in the pathogenesis. However, it is noted that detrusor overactivity is not present in all cases of enuresis [15, 16, 17].

3. Arousal difficulties [17-22].

It was previously believed that excessively deep sleep in a child with enuresis causes difficulty waking up when experiencing the urge to urinate. However, recent studies have shown that children with enuresis may have light sleep associated with frequent cortical neuronal discharges and detrusor activity, yet they wake up worse than healthy peers. It has been hypothesized that prolonged excessive stimulation by signals from an overactive detrusor suppresses the transition from light sleep to arousal [23]. A limitation of this study was that the groups of studied children with enuresis included patients with ADHD. At the same time, other studies have demonstrated the presence of at least three different polysomnographic sleep patterns associated with a high arousal threshold in children with enuresis [24, 25].

Arousal difficulties are associated with impaired functioning of central micturition control mechanisms, which are represented by a hierarchically organized interaction of the prefrontal cortex, hypothalamus, cerebellum, brainstem neuronal network, and spinal and autonomic structures.

From modern neurobiological perspectives, central neural control of nighttime urination plays a leading role in regulating arousal processes in response to bladder filling, detrusor contraction, or polyuria. It represents a hierarchical system in which spinal control mechanisms are regulated by complex switching mechanisms in the brainstem that initiate reflex micturition [28]. The micturition-switching function is performed by a network of neurons located in several brainstem areas [29]. The control of voluntary micturition, in turn, is modulated by input signals from the prefrontal frontal cortex [28, 30]. The involvement of the hypothalamus, limbic system, and cerebellum in the regulation of micturition has also been proven [31-36]. The integration of brainstem centers with the hypothalamus and limbic system indicates the influence of emotional states and hormonal status on micturition. The cerebellum participates in adapting somatovisceral reactions (in this case, referring to the urinary bladder and urethra) to changing internal and external environmental conditions [30].

Researchers pay special attention to the locus coeruleus as one of the brainstem micturition control centers, pointing to the pivotal role of its pathology in the realization of all three aforementioned pathogenetic factors of enuresis [4, 37].

Etiological factors predisposing to the development of enuresis include: functional and organic neurological disorders, genetic predisposition, psychiatric illnesses, neural tube closure defects, small bladder capacity, urogenital system malformations, bladder dysfunction, urinary tract infections, chronic constipation, chronic kidney disease, endocrinopathies (diabetes mellitus and diabetes insipidus), obstructive sleep apnea, and obesity.

1. Genetic predisposition.

Congenital forms of enuresis are characterized by a genetic predisposition [38]. If one of the parents had enuresis for a prolonged period in childhood, the probability of enuresis in the child is 50%; if both parents had enuresis, the probability in their children is about 75% [39]. In most cases, enuresis is inherited in an autosomal dominant manner. For example, the autosomal dominant form of primary monosymptomatic nocturnal enuresis, with a penetrance of over 90% in Danish families, is linked to a locus on chromosome 13q13-q14.3 (MIM%600631) [40]. Genetic loci associated with enuresis have also been identified on chromosomes 12q13-q21 (MIM600808), 13q22.3, 22q11, and 6q16.2 [41, 42].

2. Functional CNS disorders.

Delay in CNS maturation accompanied by neuropsychiatric disorders and "soft neurological signs" is one of the leading etiological factors of enuresis [44-49]. Neuroelectrophysiological studies conducted in patients with enuresis confirm the immaturity of bioelectrical activity [50-52]. Indeed, speech disorders, motor skill deficits, attention-deficit/hyperactivity disorder, and reduced certain cognitive functions are more frequently recorded in the group of children with congenital enuresis compared to healthy children [46, 53-56, 57].

According to modern concepts, the causes of brain maturation delay (and, consequently, the emergence of non-organic functional neuropsychiatric disorders) include genetic predetermination, abnormal pregnancy and childbirth, prematurity, perinatal encephalopathy, malnutrition, and other factors [57-62].

The presence of mild functional neuropsychiatric disorders in a child with primary enuresis indicates a common etiopathogenesis of neurofunctional brain immaturity/insufficiency and enuresis. This allows such cases to be classified into a distinct form of enuresis (neurofunctional), requiring specific therapeutic approaches.

3. Organic CNS lesions.

Organic lesions of the brain and spinal cord (cerebral palsy, neurodegenerative diseases including demyelinating conditions, neurometabolic disorders, tumors, etc.) can cause the development of enuresis [58, 63].

Severe intellectual disability also predisposes to the development of the condition [43]. In this case, the prognosis of enuresis depends on the course of the underlying disease.

Manifestations of spinal dysraphism can cause enuresis: simple non-fusion of the vertebral arches in the lower spine (spina bifida), tethered cord syndrome, myelomeningocele, anorectal malformations (occult dysraphism), etc. [1, 65, 66]. In relation to enuresis, Russian and some foreign literature also use the term myelodysplasia [67]. Non-fusion of the sacral vertebral arches was diagnosed significantly more often in children with congenital enuresis, suggesting that this type of dysplasia may serve as a marker of underdevelopment of the spinal-peripheral structures regulating micturition, which play a pathogenetic role in the development of enuresis [68].

In spinal dysraphism, enuresis may be combined with daytime voiding and defecation disorders.

4. Psychiatric disorders.

Various psychiatric disorders can lead to the secondary development of enuresis [69]. Primarily, this concerns stress, neurotic reactions [43, 69, 70], pathohistorical/pathocholeric behavioral reactions such as oppositional defiant behavior, and psychosis in schizophrenia [43, 70].

5. Decreased bladder capacity.

Reduced bladder capacity may also be a factor predisposing to the development of enuresis [71-75]. Clinically, this reduction in bladder capacity manifests as frequent urination, constipation, and cystitis [76]. However, the reduced bladder volume in patients with enuresis is functional rather than anatomical [77, 78]. These studies showed that daytime bladder volume in patients with enuresis did not differ from that of healthy children, whereas the maximum nighttime volume was significantly smaller.

6. Bladder dysfunction.

Lower urinary tract dysfunction (LUTD) or bladder dysfunction, according to the International Children's Continence Society (ICCS), encompasses the following spectrum of symptom complexes: overactive bladder, urinary retention, underactive bladder, infrequent voiding, daytime-only urinary frequency, vaginal reflux, bladder neck dysfunction, giggle incontinence, neurogenic bladder, and idiopathic non-neurogenic bladder [79].

LUTD occurs in 17–22% of children of various ages [80–82].

Detrusor overactivity may be caused by LUTD.

In turn, LUTD may be part of another condition—bladder and bowel dysfunction (BBD). BBD includes the symptoms of LUTD and defecation problems, which primarily manifest as constipation and/or encopresis [83]. The causes of LUTD are not fully understood; the development of LUTD may be associated with vesicoureteral reflux, urinary tract infections, and emotional-behavioral disorders [79, 84].

Neurogenic bladder (NB), which falls under LUTD, is a collective term including various conditions ranging from areflexic non-contractile bladder to detrusor overactivity [84–90].

NB is a dysfunctional disorder identified in a wide range of neurological diseases: spinal dysraphism (most commonly), sacral agenesis, tethered cord syndrome or malformations associated with imperforate anus, cloacal malformations, spinal cord injuries, central nervous system anomalies including cerebral palsy, and learning disabilities such as attention deficit hyperactivity disorder (ADHD) or attention deficit disorder. These diseases are heterogeneous, which determines the heterogeneous mechanisms of NB formation.

In the case of idiopathic non-neurogenic bladder (INNB), neurological pathology as the primary cause is not obvious, although recent studies demonstrate the presence of primary changes in the CNS and autonomic nervous system in INNB [91–93]. Given the above, it remains debatable to what extent NB, INNB, and LUTD as a whole can be considered as an independent etiological factor in relation to enuresis. Perhaps it is more appropriate to consider these conditions as an important symptom complex of enuresis.

7. Urinary tract infections.

Previous urinary tract infections can be an etiological factor in the development of enuresis, as can parasitic infections (enterobiasis, trichomoniasis) [1]. Lower urinary tract infections can cause and be a consequence of LUTD, leading to the emergence of a combined LUTD + enuresis symptom complex [79].

The effect of chronic kidney pathology [1] and metabolic nephropathies [55] on the onset of enuresis has been proven. The development of enuresis in kidney pathology is caused by the onset of polyuria.

8. Endocrine diseases.

Another source of polyuria causing enuresis is endocrinopathies: diabetes mellitus and diabetes insipidus [1, 4, 94].

9. Other conditions.

Currently, an association with enuresis has been proven for chronic constipation, obstructive sleep apnea, and obesity, although the pathogenesis is not yet fully understood [67, 95, 98, 99].

Chronic constipation has long been distinguished as an independent etiological factor of enuresis, including outside the BBD symptom complex [67, 95]. Possible mechanisms of enuresis in chronic constipation are: mechanical pressure on the bladder and pathological changes in neighboring pelvic organs due to a phenomenon known as pelvic organ "cross-sensitization" [95–97].

In obstructive sleep apnea, enuresis may be caused, firstly, by constant arousal stimuli from blocked airways, which causes paradoxically high arousal thresholds, and secondly, by negative intrathoracic pressure, which causes polyuria through increased secretion of atrial natriuretic peptide [98, 99].

In sickle cell anemia, possible mechanisms of enuresis are hyposthenuria leading to nocturnal polyuria, decreased bladder capacity or nocturnal bladder overactivity, elevated arousal thresholds, and sleep-disordered breathing [100].

Knowledge of etiological factors is essential for an effective diagnostic search in primary and secondary enuresis in children.

The concepts of the etiology and pathogenesis of enuresis in children presented in this section also formed the basis of the combined classification of enuresis based on the etiopathogenetic principle, proposed by the expert working group.

1.3 Epidemiology of the Disease or Condition

The prevalence of enuresis is 5 to 10% at age 7, about 5% at age 10, and 1–2% at age over 15 [101–104]. Boys are affected about twice as often as girls [100, 104]. During each year after the age of 5, approximately 15% of children suffering from the simple primary form of enuresis recover spontaneously [106, 107]; however, the longer enuresis persists, the lower the chance of spontaneous remission [103, 106].

1.4 Features of Coding the Disease or Condition

N31.9 – Neuromuscular dysfunction of urinary bladder, unspecified

N39 – Other disorders of urinary system

N39.3 – Stress incontinence

N39.4 – Other specified urinary incontinence

N39.8 – Other specified disorders of urinary system

N39.9 – Disorder of urinary system, unspecified

R32 – Unspecified urinary incontinence

F98.0 – Nonorganic enuresis

G96.8 – Other specified disorders of central nervous system

However, this coding system does not cover the entire spectrum of enuresis forms according to its most commonly used classifications [161].

1.5 Classification of the disease or condition

Currently, there is no unified classification that would take into account all disciplinary approaches based on etiopathogenetic concepts of enuresis from modern neurobiological perspectives. Given this, the expert development group of these clinical guidelines proposes an expanded classification of enuresis based on the etiopathogenetic principle as a working option.

1.5.1. Classification of enuresis based on the presence of a dry interval (recommended for use at the initial stage of the diagnostic search for the etiological factor of enuresis):

- congenital enuresis: there is no dry interval (nocturnal enuresis has been observed always – from birth to the present), or the patient remained "dry" for less than six months; it can be either primary or secondary.

- acquired enuresis: enuresis occurred at least 6 months after a dry interval; it is more often secondary.

This option is a revision of the classification used by the ICCS, according to which primary enuresis includes conditions without a dry interval (or with an interval of less than 6 months), and secondary enuresis includes conditions with a dry interval of more than 6 months [1], which generally does not correspond to the etiopathogenetic principle of "secondariness" adopted in medicine. Thus, truly secondary enuresis due to congenital diseases (cerebral palsy) or malformations (urogenital or myelomeningocele) is conditionally "primary" according to the ICCS classification due to the absence of a dry interval.

1.5.2. Expanded combined classification of enuresis based on the etiopathogenetic principle (recommended for primary use in the diagnostic process, proposed by the expert group of authors of these clinical guidelines).

This classification reflects not only etiopathogenetic differences in a hierarchical order, but also clinical differences between forms.

1.6 Clinical presentation of the disease or condition

Enuresis symptoms may manifest as nocturnal urinary incontinence in the absence of other manifestations. However, most often, enuresis symptoms are accompanied by manifestations of disorders that are the root cause of this condition: for example, daytime urinary incontinence, symptoms of bladder dysfunction, constipation, ADHD, symptoms of urinary tract diseases, etc.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Enuresis is a multidisciplinary problem. The scope of diagnostics in enuresis is determined by its form in accordance with the classification.

The criteria for establishing the diagnosis of "enuresis" are the presence of episodes of involuntary nocturnal urination in children aged 5 years and older [162].

Examination of the child involves establishing the form of enuresis, which subsequently determines the necessary therapeutic and diagnostic measures.

Thus, at the first stage of diagnostics, it is important to verify the isolated (simple) neurofunctional and habitual (polydipsic) forms of enuresis.

The second stage of diagnostic measures is carried out if it was not possible to confirm the isolated neurofunctional and habitual polydipsic forms of enuresis.

First stage of diagnostics

(specialists performing diagnostics: pediatrician, pediatric urologist-andrologist/urologist, neurologist).

The purpose of the first stage of diagnostics is to verify the isolated (simple) neurofunctional and habitual polydipsic forms of enuresis, or to determine the priority direction of specialized examination to verify other forms of enuresis.

The algorithm for referring children with enuresis to the specialized examination stage to specialists based on the results of primary diagnostics, if the isolated (simple) neurofunctional or habitual polydipsic forms of enuresis have not been verified, is presented in Appendix B1.

2.1 Complaints and Anamnesis

In addition to the specific complaint of nocturnal urinary incontinence, the patient or caregiver may present with complaints characteristic of the underlying disease against the background of which enuresis developed.

A detailed history taking is very important, as it allows suspecting a particular form of enuresis already at the history-taking stage. The patient or their legal representative must answer the following questions:

1. Questions clarifying the main characteristics of enuresis: frequency of enuresis, regularity of enuresis (stable or undulating course), approximate amount of urine excreted during enuresis, whether the child wakes up after urination. If the course is irregular: with what events or diseases are exacerbations associated? Depth of sleep, difficulty waking up at night. Approximate volume of fluid drunk in the evening, when the last fluid intake before falling asleep occurs.

2. Question: was there a lucid (dry) interval, if so - when did enuresis appear? If there was a lucid interval: what event or disease is it temporarily associated with?

3. Questions regarding concomitant voiding disorders: is there daytime urinary incontinence during wakefulness, frequency of daytime voluntary urinations, imperative urges to urinate, difficulties with voluntary urination. Are there encopresis, chronic constipation?

4. Questions regarding concomitant neuropsychiatric disorders: tics, headaches, increased fatigue, hyperactive behavior, impulsivity and inattention, speech development, learning difficulties, coordination, difficulty falling asleep, behavioral disorders.

5. Questions regarding the presence of urogenital and anorectal malformations, current and past urinary tract infections, chronic kidney diseases, diabetes mellitus, diabetes insipidus, anemia, sleep-related breathing disorders, adenoid hypertrophy.

6. Was there a history of an unfavorable course of pregnancy (hypoxia, other disorders), labor pathology (hypoxic-ischemic CNS damage and others), birth injury, cerebrovascular accident in the postnatal period, developmental delays, sleep disorders, tics, stuttering, timing of the formation of toilet training for urination and defecation, cleanliness skills.

7. Family history: presence of enuresis in childhood and currently in close relatives, urinary system malformations, endocrinological diseases in close relatives.

Comment: the sequence of history-taking items must be followed. If primary diagnostics is carried out by a specialized specialist (neurologist, urologist, nephrologist, psychiatrist), they may additionally conduct a detailed history-taking within their field of expertise.

2.2 Physical Examination

During the physical examination of the child, it is necessary to pay attention to the following symptoms, which also make it possible to suspect a concomitant disease that is the cause of enuresis:

- delay in physical and neuropsychic development. For this purpose, an assessment of weight and height indicators (Measurement of body weight, Measurement of height) and Initial and follow-up consultation (examination) of a pediatrician and/or Initial and follow-up consultation (examination) of a neurologist are carried out, within the framework of which the specialist conducts an initial assessment of the patient's neuropsychic development (level of intellectual development, motor skills (walking), general behavior of the child);

- presence of hyperpigmentation, dimples, subcutaneous lipomas, hypertrichosis in the lumbosacral spine, as well as asymmetry of the gluteal folds or buttocks, which indicates spinal dysmorphism and malformations;

- malformations of external genitalia, phimosis, balanoposthitis, labial synechiae and vulvovaginitis in girls, skin maceration of the perineum from daytime urinary incontinence), signs of fecal incontinence;

- fullness of the sigmoid colon with fecal masses upon abdominal palpation [163];

- assessment of nasal breathing (adenoid hypertrophy). The sequence of examination procedures is determined by the specialist themselves. If primary diagnostics is carried out by a specialized specialist (neurologist, pediatric urologist-andrologist/urologist, nephrologist, psychiatrist), they may additionally perform extra examination procedures within their specialization.

2.3 Laboratory Diagnostics

• All children with enuresis, in order to exclude infectious and inflammatory diseases of the urinary tract and kidneys and to identify signs of diabetic ketoacidosis, "water intoxication", are recommended to undergo a general (clinical) urinalysis with determination of urine specific gravity, leukocyte and erythrocyte counts, as well as determination of protein, glucose, urine pH, and detection of ketone bodies in the urine [1, 2, 47, 67, 163].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

Comment: The urine sample obtained during the first morning urination is examined.

2.4 Instrumental Diagnostics

At the primary diagnostics stage, instrumental diagnostics is not performed.

2.5 Other Procedures

Comment: The diary is kept by parents or guardians. A sample diary and the procedure for filling it out are presented in Appendix B. It is important to fill out the diary in the specified order according to the example given in Appendix B. It is permissible for parents to keep the diary on any paper medium in the order provided by the official form.

• Children with enuresis and symptoms of obstructive sleep apnea with suspected adenoid hypertrophy based on history taking and physical examination are recommended to undergo an initial otorhinolaryngologist consultation (examination) for diagnostic purposes [1, 67].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

• For children with enuresis and suspected chronic constipation based on medical history and physical examination, an initial recommended diagnostic evaluation includes a primary appointment (examination, consultation) with a gastroenterologist [1, 67].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

Stage Two (Specialized) of Enuresis Diagnosis.

Below is the diagnostic algorithm for enuresis in patients whose isolated (simple) neurofunctional or habitual polydipsic forms of enuresis were not confirmed at the first stage.

The second (specialized) diagnostic stage involves identifying comorbid conditions that may act as etiological factors for enuresis.

The specialized diagnostic stage is performed by the following specialists (as clinically indicated): a neurologist, pediatric urologist-andrologist/urologist, nephrologist, psychiatrist, pediatric endocrinologist, pediatrician, etc., to clarify the form of enuresis (excluding the isolated (simple) neurofunctional and habitual polydipsic forms of enuresis, for which the primary stage is sufficient).

2.5.1. History and Anamnesis.

See Section 1.6 "Clinical Presentation" and Section 2.1 "History and Anamnesis".

During the neurological examination, in addition to Section 2.1:

1. Details of the course of pregnancy and childbirth are clarified to identify etiological factors of neurological pathology.

2. Aspects of postnatal development, examination data, and treatment history reflecting the formation and development of neurological pathology and enuresis are specified.

3. Aspects of behavior, learning, and social adaptation necessary to assess neuropsychological development and parent-child relationships are clarified.

4. The child's attitude toward enuresis is clarified.

5. Family psychoneurological history is specified.

During the urological examination, in addition to Section 2.1:

1. Details of the course of pregnancy and childbirth are clarified to identify etiological factors of urological pathology, including bladder dysfunction.

2. Aspects of postnatal development, examination data, and treatment history reflecting the formation and development of urological pathology, including bladder dysfunction and enuresis, are specified.

3. Details of fluid intake regimen, frequency, and pattern of voluntary and involuntary daytime urination are clarified.

4. The child's attitude toward enuresis is clarified.

5. Family nephrourological history is specified.

During the psychiatric examination, in addition to Section 2.1:

1. Details of the course of pregnancy and childbirth are clarified to identify etiological factors of psychiatric pathology.

2. Aspects of postnatal development, examination data, and treatment history reflecting the formation and development of psychiatric pathology and enuresis are specified.

3. The causal relationship between the onset of behavioral disorders and enuresis is clarified.

4. Aspects of behavior, learning, and social adaptation necessary to assess neuropsychological development and parent-child relationships are clarified.

5. The child's attitude toward enuresis is clarified.

6. Family psychoneurological history is specified.

During the nephrological examination, in addition to Section 2.1:

1. Details of the course of pregnancy and childbirth are clarified to identify etiological factors of nephrourological pathology.

2. Aspects of postnatal development, examination data, and treatment history reflecting the formation and development of nephrourological pathology are specified.

3. Family nephrourological history is specified.

During the endocrinological examination, in addition to Section 2.1:

1. Details of the course of pregnancy and childbirth are clarified to identify etiological factors of endocrine pathology.

2. Aspects of postnatal development, examination data, and treatment history reflecting the formation and development of endocrine pathology are specified.

3. Family endocrinological history is specified.

2.5.2. Physical Examination.

See Section 1.6 "Clinical Presentation" and Section 2.2 "Physical Examination".

In addition to Section 2.2, depending on the clinical focus, procedures are performed to assess neuropsychological, urogenital, nephrological, and endocrinological status.

2.5.3. Laboratory diagnostic tests

Comments: further evaluation should be carried out in accordance with the clinical situation and relevant guidelines.

2.5.4 Instrumental diagnostic tests

Comment: in addition to diagnosing structural anomalies of the urinary system, ultrasound can be used to determine bladder capacity, post-void residual volume, and bladder wall thickness.

Comment: Uroflowmetry (Measurement of urine flow rate (uroflowmetry)) is a test that determines the flow rate of urine expelled through the urethra. Values are measured in milliliters per second. Uroflowmetry is a non-invasive method used to assess bladder emptying function. It can provide information on peak flow rate, voided volume, and residual urine volume.

At least two bladder filling cycles are required when performing uroflowmetry.

Urodynamic studies are performed only in children with enuresis accompanied by daytime urinary incontinence, urinary tract infections (including history), symptoms indicating structural kidney anomalies, and in cases of enuresis refractory to therapy [164, 165, 166].

Comment: To differentiate from epilepsy, overnight video-EEG monitoring should be performed. In other cases, the choice between awake EEG and sleep EEG is made based on neurological indications.

2.5.5. Other diagnostic tests

During neurological, urological, nephrological, endocrinological, and psychiatric evaluations, it is recommended to order additional investigations (such as keeping detailed fluid intake and voiding diaries, consultation/examination by a medical psychologist or psychiatrist, cystography, laboratory hormone assays, and others depending on the suspected etiology of enuresis) to confirm the presence of underlying or comorbid conditions causing enuresis, including those listed in the "Classification" and "Etiopathogenesis" sections.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

These clinical guidelines prioritize the treatment of congenital and acquired neurofunctional forms and the habitual polydipsic form of enuresis.

In acquired secondary enuresis, when established primary diseases/conditions causing the disorder are present, the primary focus is the treatment or elimination of the etiological factors causing enuresis, the management of which is discussed in the relevant clinical guidelines. However, some treatment methods presented in these clinical guidelines are also applicable to these forms as adjunctive therapy

Given the high proportion of spontaneous remissions, in some cases supported by family history, the questions of the appropriate age to initiate therapy and its overall necessity for prognostically favorable forms are relevant. This primarily concerns neurofunctional forms, especially isolated neurofunctional enuresis, which have a better prognosis and a high rate of spontaneous remissions.

It is recommended to initiate treatment for isolated and combined neurofunctional forms starting from the age of 7 due to the high risk of psychological and social complications for the child starting from school age. In individual cases for these forms, treatment may be initiated at an earlier age if signs of social maladjustment or psychological problems significant to the child are already documented.

For other forms of enuresis, it is recommended to initiate treatment as soon as the diagnosis is established.

3.1. Non-pharmacological non-device-based treatment

Comment: The main provisions of the educational program «Education and recommendations for parents and caregivers of a child with enuresis» are given in Appendix A3.3.

• Parents and other individuals involved in the care and upbringing of a child with enuresis (neurofunctional forms and habitual polydipsic form) are recommended to undergo training in «Motivational Therapy» with the aim of enhancing the child's cortical control over urination and facilitating waking up when the bladder is full [1, 109, 111-113; 170].

GOR BLOE 2Grade of Recommendation – B (Level of Evidence – 2).

Comments: Motivational therapy is a type of psychotherapy and is conducted by a clinical psychologist or psychotherapist with the parents, who subsequently apply it at home.

The main provisions of motivational therapy are presented in Appendix A3.4.

• Children with neurofunctional forms are recommended the method of «Alarm Therapy» («Enuresis Alarm Therapy») with the aim of developing the skill of waking up when the bladder is full [1, 2, 108, 109, 114].

GGR BLEL 1Grade of Recommendation – B (Level of Evidence – 1).

Comment: Indications for the use of «Alarm Therapy» are:

- age 6 years and older or established motivation to get rid of enuresis in a child aged 5 years;

- established motivation in the child and parents to get rid of enuresis and readiness to implement alarm therapy (see below);

- lack of efficacy from enuresis education and recommendations and/or motivational therapy for at least 3 months and/or other types of treatment [1, 108, 115, 116].

It must be remembered that the alarm therapy method carries high risks of adverse reactions. Contraindications for its use are: enuresis frequency less than 2 times a week or a fluctuating course with periodic lucid intervals; regularity of more than 1 enuresis episode per night; sleep disorders (difficulty falling asleep, restless sleep); attention deficit hyperactivity disorder [1, 2, 108].

Instructions on the methodology and use of the «alarm» are provided by a physician. At the same time, parents should not expect an instantaneous positive effect. They must be prepared for long-term treatment that requires effort and resources from the family and the child. The medical professional should contact the family 1-3 weeks after the start of therapy to monitor the treatment process. If no positive effect is observed after 6 weeks, therapy should be discontinued. If progress is observed (the child wakes up to the alarm sound, the alarm goes off later, fewer alarms per night, fewer «wet» nights), therapy should be continued until 14 consecutive dry nights are achieved.

The probability of complete recovery with a sustained effect ranges from 50 to 70% and depends on compliance with all the above-mentioned conditions for prescribing therapy [117, 118]. The efficacy of therapy largely depends on the correct application of the methodology and the presence of motivation in the child and parents to get rid of enuresis.

Requirements for performing the methodology are set out in Appendix A3.5.

• Children with a neurofunctional form of enuresis, in case of ineffectiveness of the above conservative treatment methods, with the aim of increasing bladder capacity, reducing nocturnal urine volume, and enhancing cortical control over urination, are recommended urotherapy – a complex of methods aimed at forming the correct stereotype of a controlled act of urination [2].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

Comments: the methodology consists of asking the child to hold urine during urination successively for longer intervals in order to increase bladder volume.

• In neurotic forms of enuresis and those associated with pathohistorical/pathochacterological reactions, all children are recommended cognitive behavioral therapy (CBT) with the aim of eliminating psychogenic causative factors triggering enuresis [171].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

Comments: the plan and content of psychotherapy are determined depending on the psychiatric nosology and the emotional-volitional characteristics of the patient after psychiatric/psychological diagnosis, as well as based on the patient's cognitive characteristics and age. For preschool children and those with cognitive deficits, behavioral techniques (including relaxation techniques), play therapy, and fairy-tale therapy are the leading methods; cognitive techniques are included in psychotherapy at an older age.

Cognitive behavioral therapy should include training in self-control skills: developing sensitivity to physiological sensations (bladder pressure), practicing self-control in various situations, self-observation exercises, and self-reinforcement. The cognitive block of therapy is aimed at working with irrational beliefs, rational analysis of nocturnal enuresis, and additional work with comorbid psychiatric problems.

Therapy is carried out by a medical psychologist/psychotherapist competent in the field of pediatric cognitive behavioral therapy.

The duration of therapy depends on the complexity of the psychiatric pathology and the emotional-volitional characteristics of the child, averaging from 10 to 30 consultations.

3.2. Pharmacological treatment

Alarm therapy and drug therapy are alternative options for initiating treatment, the choice of which in each individual case is made by the physician in accordance with the indications and advantages of each type of therapy.

3.2.1. Therapy with vasopressin group drugs and their analogues.

The main mechanism of action of antidiuretic hormone (ADH) (vasopressin group drugs and their analogues) in enuresis is a decrease in the volume of nocturnal urine production. These drugs are most effective in enuresis accompanied by nocturnal polyuria. During treatment, a complete effect is achieved in 1/3 of patients, a partial effect in 1/3, and no effect is noted in the remaining patients [108, 123]. Compared to alarm therapy, treatment with vasopressin group drugs and their analogues is associated with a higher relapse rate [119].

They act faster than alarm therapy, the course of treatment is shorter, and medical supervision is less stringent.

• In neurofunctional forms of enuresis, drug therapy with a vasopressin group drug and its analogue, desmopressin**, is recommended with the aim of reducing nocturnal urine production [1, 2, 172].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

Comment: Indications for prescribing desmopressin** (approved for use in children from 5 years of age) are:

- frequency of enuresis predominantly less than 2 times a week;

- the need to achieve a rapid effect from treatment (for example, in the case of an overnight trip or staying at a sports camp, or a stressful situation caused by the fact of enuresis);

- nocturnal polyuria with normal daytime urination volume.

The drug is prescribed if the urine specific gravity in Zimnitsky's test is 1010-1012; if bladder capacity is increased according to the voiding diary and ultrasound.

Therapy principles include fluid restriction starting 1 hour before and ending 8 hours after administration; desmopressin** (approved for children from 5 years of age) is prescribed orally 60 minutes before bedtime. The starting dose is 0.2 mg (conventional tablets) or 120 mcg (orally disintegrating tablets). If necessary, the dose can be increased to 0.4 mg (conventional tablets) or 240 mcg (orally disintegrating tablets) after seven days [1, 108]. Tablets can be crushed and mixed with a small amount of soft food (e.g., applesauce, yogurt) or chewed. The dose is adjusted to achieve the best effect; with correct dosing and drug efficacy, enuresis decreases immediately [1, 108]. Greater treatment efficacy and adherence are demonstrated with sublingual forms compared to conventional tablets [124, 125]

The effect of desmopressin** should be evaluated within 1–2 weeks [108]. Treatment should be continued for 3 months if there are signs of a positive effect (e.g., a decrease in the number of wet spots on the bedding, a decrease in the number of nocturnal enuresis episodes, a decrease in the number of wet nights) [123].

The decision to continue therapy after 3 months and the dosing schedule are made based on the analysis of efficacy from the previous treatment course. There are no guidelines limiting the duration of therapy in cases of its partial efficacy [108]. If a full or partial effect is achieved with desmopressin**, the physician, family, and child can decide whether desmopressin** should be taken every evening or only on special occasions situationally (e.g., during sleepovers away from home).

Short courses are acceptable if the goal of therapy is to prevent enuresis during a trip with an overnight stay away from home or in other situations.

Before short-term administration of desmopressin**, a "test dose" should be performed at least six weeks prior to the event (trip, etc.) to correctly select the dose and ensure its efficacy.

During long-term daily administration of desmopressin**, a 1-week treatment break should be taken every three months to decide on the necessity of continuing treatment [108, 123].

When discontinuing scheduled administration of desmopressin**, a gradual dose reduction is necessary (e.g., switching to a daily intake of half the effective dose for 2 weeks and then discontinuing). Abrupt cessation of treatment or increasing the interval between doses should not be done [1, 119]. Relapse rates with desmopressin** are: 27.5% with gradual tapering and 41.1% with abrupt discontinuation [126].

If desmopressin** is ineffective after 2 weeks of treatment, the drug should be discontinued.

In case of relapse, repeated courses are recommended, but no earlier than 3 months after the end of the previous course.

3.2.2. Antidepressant therapy (non-selective monoamine reuptake inhibitors).

Therapy with non-selective monoamine reuptake inhibitors (NSMRIs) – tricyclic antidepressants (TCAs) – is indicated for children with neurofunctional forms of enuresis. The primary mechanism of action of non-selective monoamine reuptake inhibitors (TCAs) is the blockade of norepinephrine, dopamine, and serotonin reuptake by synaptic alpha-receptors into neurons, which prolongs their effects. Additionally, TCAs (non-selective monoamine reuptake inhibitors) exert anticholinergic or antispasmodic effects on the urinary bladder and other organs and possess local anesthetic properties [127]. Imipramine**, a drug from the non-selective monoamine reuptake inhibitors group, also affects sleep, making it lighter [128]. Presumably, the leading mechanism of action of imipramine** is its effect on sleep and central noradrenergic effects [127, 129, 130, 131].

In general, the tolerability of TCAs (non-selective monoamine reuptake inhibitors) in the treatment of enuresis is satisfactory. Only in isolated observations (1 case during enuresis treatment and several cases when using the drugs for other pathologies) was a cardiotoxic effect of the drug noted. Otherwise, in none of the 37 studies described by researchers were serious side effects observed from TCA (non-selective monoamine reuptake inhibitors) intake [1, 108, 132]. Only manifestations such as dizziness, headache, mood changes, gastrointestinal discomfort, and neutropenia were recorded [127].

To date, two TCAs (non-selective monoamine reuptake inhibitors) with confirmed efficacy in enuresis are registered in the Russian Federation: Imipramine** and Amitriptyline**. Imipramine** is the drug of choice as it has a lower sedative effect [133] and a larger volume of evidence-based research on enuresis treatment [127]. However, comparative studies on the efficacy of Imipramine** and Amitriptyline** are practically absent, with only one study with limited data showing greater efficacy of imipramine** [127, 134].

Complete cessation of enuresis after TCA (non-selective monoamine reuptake inhibitor) treatment is observed in 30–50% of children [135, 136]. After treatment discontinuation, the probability of relapse is high (more than 90% of cases) [127]. However, in some patients after relapse, enuresis symptoms become less frequent than before therapy initiation. In case of relapse, repeated courses of TCAs (non-selective monoamine reuptake inhibitors) should be considered, but no earlier than 3 months after the end of the previous treatment. Re-administration of the drugs can lead to a more pronounced and lasting therapeutic effect.

Comment: the drug is prescribed after meals 1 hour before nighttime sleep. Recommended doses are: for children 6–8 years old (body weight 20–25 kg) – 25 mg/day; 9–12 years old (body weight 25–35 kg) – 25–50 mg/day; older than 12 years (body weight over 35 kg) – 50–75 mg/day. Therapy should be initiated at the minimum recommended dose, and in the absence of effect after 1–2 weeks, the dose should be doubled [127]. The duration of the treatment course is 2–3 months [127]. Discontinuation of imipramine** therapy should be carried out gradually by halving the dose over 1–2 weeks to reduce the risk of adverse effects upon terminating therapy [129]. Before prescribing the drug and during treatment, the presence of contraindications and side effects according to the drug's instructions for use must be considered. If the child has a history of unexplained syncope or tachycardia, or a family history of sudden cardiac death, the drug should not be prescribed without a preliminary electrocardiographic examination (electrocardiogram recording). Do not use in case of QT interval prolongation according to ECG data [108].

Comment: The drug is prescribed after meals 1 hour before nighttime sleep. Recommended dose: 12.5–25 mg at bedtime (the dose should not exceed 2.5 mg/kg of body weight). Therapy should be initiated at the minimum recommended dose, and in the absence of effect after 2 weeks, the dose should be doubled [127]. The duration of the treatment course is 2–3 months [127]. Before prescribing the drug and during treatment, the presence of contraindications and side effects according to the drug's instructions for use must be considered.

3.2.3 Therapy with drugs for frequent urination and urinary incontinence (Anticholinergic drugs).

The drugs exhibit anticholinergic activity by blocking M-cholinergic receptors, thereby eliminating spasms and reducing the tone of the smooth muscles of the urinary tract and bladder. As a result, in patients with neurogenic or idiopathic bladder dysfunction, particularly with overactive bladder, bladder capacity increases, while detrusor relaxation and contraction frequency decrease. The patient is able to suppress urges, and the frequency of urination (involuntary and voluntary) decreases [108, 138, 139, 140]. Therefore, agents for the treatment of frequent urination and urinary incontinence (anticholinergic drugs [ACDs]) are most indicated for the neurovesical form of enuresis, which presents with daytime urinary incontinence and/or other symptoms of overactive bladder caused by detrusor overactivity or low bladder capacity [1, 108, 141]. Since detrusor overactivity is also hypothesized to participate in the pathogenesis of other neurofunctional forms not clinically accompanied by symptoms of overactive bladder or idiopathic bladder dysfunction, the prescription of agents for frequent urination and urinary incontinence (ACDs) is recommended for other neurofunctional forms as well, but only in cases where other pharmacotherapy is ineffective [108], Algorithms for the Diagnosis and Treatment of Children with Urination Disorders of Non-Organic Genesis (Without Spinal Cord and Spinal Malformations and Injuries): A Methodological Guide for Physicians. Pharmstandard, Moscow, 2020, 30].

Agents for the treatment of frequent urination and urinary incontinence (ACDs) are highly effective as part of combination pharmacotherapy for acquired enuresis [1, 108, 139, 142, 143], whereas data on their efficacy as monotherapy are contradictory [144-147].

An important condition for the use of agents for the treatment of frequent urination and urinary incontinence (ACDs) in enuresis is the absence of post-void residual urine and chronic constipation [108, 141]. If enuresis recurs after the initial therapeutic effect, constipation should be ruled out. Temporarily stopping anticholinergic drugs for a couple of weeks until constipation is resolved often leads to dry mouth upon resuming the medication.

Comment: Oxybutynin is currently the only drug in the group of agents for the treatment of frequent urination and urinary incontinence (ACDs) approved for the treatment of enuresis in children. It is currently the drug of choice, prescribed for children starting from 5 years of age.

The drug is taken twice a day: in the morning and 1 hour before bedtime, at an initial dose of 2.5 mg twice a day. Subsequently, a gradual increase in dosage to 5 mg twice a day is possible if the expected effect is absent. Treatment efficacy is evaluated and dosages are reviewed 1 to 2 months after initiating therapy. Before prescribing the drug and during treatment, it is necessary to consider the contraindications and side effects indicated in.

Comment: #Tolterodine is prescribed to patients in the absence of constipation and post-void residual urine.

The drug is taken twice a day: in the morning and 1 hour before bedtime at a dose of 2 mg. [108].

Comment: if residual urine is detected during the bladder ultrasound, ACDs are discontinued.

3.2.4. Therapy with nootropic agents (Other psychostimulants and nootropics).

Therapy with nootropic agents (other psychostimulants and nootropics) is indicated as part of combination pharmacotherapy for neurofunctional forms of enuresis, particularly combined and mixed neurofunctional forms. The effects of nootropic agents (other psychostimulants and nootropics) consist of the activation and optimization of neuronal activity and interneuronal interaction, which can be especially beneficial in the presence of coexisting mild neurological symptoms alongside enuresis. Through the action of nootropic agents, cortical control of urination is enhanced in enuresis, and the frequency of involuntary nocturnal urination episodes is reduced.

Nicotinoyl gamma-aminobutyric acid additionally improves the adaptive functions of the bladder: it reduces detrusor hypoxia. Traditionally, therapy with nootropic agents has been actively used in domestic pediatric psychoneurology. However, these drugs are inferior in efficacy regarding enuresis symptoms compared to other medications. In the treatment of enuresis, this group of drugs is mainly used in combination with other medications. To date, among the available nootropic agents, only two have indications for the treatment of enuresis and other urination disorders: hopantenic acid and nicotinoyl gamma-aminobutyric acid.

Considering the main mechanisms of action, hopantenic acid is preferred for the combined neurofunctional and transitory forms of enuresis, while nicotinoyl gamma-aminobutyric acid is preferred for the neurovesical form.

Greater efficacy of nootropic therapy (other psychostimulants and nootropics) in enuresis combined with deep sleep has been observed when the final dose of the drug is taken 1 hour before sleep, as the activating potential of nootropic agents facilitates awakening in patients with deep sleep. However, this administration regimen for nootropic agents can only be applied if there are no difficulties falling asleep and deep sleep is present.

• For children with neurofunctional forms of enuresis, it is recommended to prescribe hopantenic acid as part of combination pharmacotherapy to stimulate the neuronal processes underlying the central control of urination [149-151].

Level of Evidence CGrade of Recommendation 4Level of Evidence – C (Grade of Recommendation – 4).

Comment: The recommended daily dose is 30–50 mg/kg of body weight. The frequency of administration is twice a day. The course duration is 2 months. The drug is indicated for children starting from 3 years of age.

• For children with neurofunctional forms of enuresis, it is recommended to prescribe nicotinoyl gamma-aminobutyric acid as part of combination pharmacotherapy to stimulate the neuronal processes underlying the central control of urination and to improve the adaptive functions of the bladder detrusor [173].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

Comment: Recommended doses according to the instructions: for children aged 3 to 10 years – 20 mg 2–3 times a day; for children aged 11–15 years – 50 mg twice a day; for children older than 15 years – 50 mg 3 times a day.

The duration of the treatment course is 1.5–2 months [173, 152].

3.2.3. Therapy with centrally acting sympathomimetics.

Another medication that can be used as alternative pharmacotherapy is #atomoxetine, a centrally acting sympathomimetic. A randomized placebo-controlled study showed that the efficacy of #atomoxetine in patients with enuresis is comparable to that of desmopressin** and imipramine** [153]. #Atomoxetine is a presynaptic norepinephrine transporter inhibitor. Its main indication in pediatrics is the treatment of ADHD. Because ADHD frequently accompanies enuresis, #atomoxetine should be considered in the pharmacotherapeutic management of such cases, which is supported by its efficacy demonstrated in a study involving a group of children with ADHD and enuresis [154]. However, due to the limited number of studies, #atomoxetine should be considered as an alternative treatment method when other medications are ineffective, primarily in cases where enuresis is combined with ADHD.

Comment: The recommended dose of #Atomoxetine — 0.5 mg/kg per day for the first 3 days, 1.0 mg/kg per day for the next 3 days, and 1.2 mg/kg per day for all subsequent days (the recommended maintenance dose according to the product labeling). Dosage escalation up to 1.5 mg/kg is permissible in the absence of a therapeutic effect [153]). #Atomoxetine — should be administered twice daily: in the morning and early evening (5:00–6:00 PM). The duration of the treatment course is 3 months.

3.2.5. Combined drug therapy.

In the drug treatment of enuresis, combined pharmacotherapy is preferred, as it achieves simultaneous impact on several key links of the pathogenesis.

Combined drug therapy is in most cases more effective compared to monotherapy (Table 2).

Table 2. Comparison of the efficacy of combined versus mono-pharmacotherapy of enuresis in children according to studies.

Comment: the optimal regimen is one in which treatment starts with a single drug followed by evaluation of efficacy and adverse reactions 2-4 weeks after the start of therapy, and subsequently adding a second medicinal product. It is necessary to adhere to the indications/contraindications for each medicinal product.

3.3. Management in the absence of response to ongoing pharmacotherapy.

In the absence of a response to initial pharmacotherapy for neurofunctional forms of enuresis, one of three alternative treatment scenarios should be considered:

1) alarm therapy as a standalone option or in combination with pharmacotherapy;

2) a course of treatment with another pharmacotherapeutic method as monotherapy or as part of another combination therapy;

3) repeating the course of treatment that the patient previously received [1, 108].

In the absence of a response to initial alarm therapy, selective use of pharmacotherapy in accordance with indications is possible.

• In the absence of an effect within 3-6 months of treating neurofunctional forms with various therapy options, it is recommended not to give up on repeated attempts after 6-12 months, as during this period the body's readiness to perceive therapy, including motivational therapy, may change, and pathogenetic mechanisms may also change [170].

GCR CLOE 5Grade of Recommendations – C (Level of Evidence – 5).

3.4. Non-pharmacological device-based treatment and physiotherapy

Non-drug hardware treatments using physical factors and physiotherapy can be used as an adjunct to basic therapy, which includes: educational/motivational programs, alarm therapy, and/or pharmacotherapy. At the same time, hardware methods of treatment using physical factors should not be combined simultaneously, except for those cases specifically highlighted in these Clinical Guidelines.

Comment: In studies conducted on the efficacy of basic therapy with Oxybutynin in children with enuresis with the simultaneous prescription of various physiotherapeutic rehabilitation methods (TCMT, TES, TCMT + TES), the combination of TCMT + TES demonstrated the best results. The combination of TCMT + TES in conjunction with pharmacotherapy covers various links of the pathogenesis in enuresis and increases the adaptive reserves of the child's body [174]. In the conducted study, the use of this combination of physiotherapeutic treatment and pharmacotherapy made it possible to achieve efficacy in 81% of patients.

The course of physical therapy consists of 10 sessions [174].

Comment: FBC therapy is based on the principles of biofeedback (BFB) in electromyography (EMG) mode, which allows for the restoration of the central mechanisms regulating urination and defecation, normalization of detrusor-sphincter relationships, and improvement of blood circulation in the pelvic organs.

EMG-based FBC therapy is a set of perineal muscle exercises aimed at tightening and relaxing the pelvic floor muscles with simultaneous relaxation of antagonist muscles. EMG-based FBC therapy sessions with a standard intensity type without prior electrical stimulation are conducted in the form of an interactive dynamic game under the control of a hardware-computer complex. The duration of treatment is usually 10 sessions [176].

• For children with neurogenic bladder and other neurofunctional forms of enuresis, it is recommended to selectively prescribe medical physical education (Physiotherapy exercises for diseases of the kidneys and urinary tract) to strengthen the pelvic floor and anterior abdominal wall muscles in case of urination disorders in children, including those associated with defecation disorders [2, 178].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comments: the exercise routine must be performed by the patient every day for 6 months, despite the absence of "wet" nights.

A number of methods have been patented to reduce the frequency of enuresis episodes and improve them through therapeutic gymnastics [149, 181].

• For children with the neurogenic bladder form of enuresis, it is recommended to selectively prescribe medical massage, abdominal massage (medical massage of the anterior abdominal wall), lumbosacral massage, and gluteal massage (massage of the hip joint and gluteal region) to improve blood circulation and lymph drainage in the pelvis, achieving a positive effect on metabolic processes and the motility of the distal urinary tract [178, 179].

GCR CLOE 5Grade of Recommendations – C (Level of Evidence – 5).

• For children with the neurogenic bladder form of enuresis, it is recommended to selectively prescribe vibromassage using EPS system devices (elastic pseudo-fluidized beds) (vibrational exposure) to inhibit pathological contraction of the bladder [178, 179].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comments: This technique makes it possible to use a wider range of mechanical vibration frequencies and a thermal component. Extracorporeal magnetic innervation (EMI) therapy is applied to the anorectal region, which inhibits bladder contraction via the detrusor-stabilizing reflex system. This technique is relevant for children with overactive bladder.

3.5. Treatment of significant comorbid conditions and underlying diseases/conditions causing acquired/secondary enuresis.

In cases where enuresis is combined with significant comorbid conditions that play a role in the pathogenesis of enuresis (bladder dysfunction, chronic constipation, obstructive sleep apnea, ADHD, etc.), or when it is secondary to primary diseases (myelomeningocele, tumors, other organic CNS diseases, urinary tract infections, urogenital malformations, chronic kidney disease, stress, psychiatric disorders, endocrine diseases, sickle cell anemia, etc.), the priority is treatment and, whenever possible, elimination of the conditions that initiate or significantly affect enuresis (presented in the relevant clinical guidelines). The treatment methods listed above may be used as adjunctive therapy provided there are no contraindications.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Medical rehabilitation and sanatorium-resort treatment can be carried out, first of all, for non-progressive chronic and acute neuroorganic forms as part of the rehabilitation of the primary diseases that caused enuresis. They can also be carried out for the transitory neurofunctional form and for all congenital primary forms resistant to basic treatment. In this case, the rehabilitation methods described in Section 3.4 may be used.

5. Prevention and Dispensary Observation

5.1. Prevention.

Not performed

5.2. Dispensary follow-up

5.2.1. General principles for the management of children with enuresis.

At the diagnostic stage of enuresis, the organization of interdisciplinary interaction between specialists (pediatrician, neurologist, psychiatrist, urologist/pediatric urologist-andrologist, nephrologist, endocrinologist/pediatric endocrinologist) is of paramount importance. Subsequently, depending on the established etiological factor and identified comorbid conditions, the patient with enuresis is managed by the relevant specialists.

If a child is cured, dispensary follow-up (dispanserization) is not required.

5.2.1. Lifestyle recommendations.

Comments: For other forms of enuresis, recommendations corresponding to the diseases/conditions that play a primary or significant pathogenetic role regarding enuresis are relevant.

6. Organization of Medical Care

Children with enuresis may receive any type, setting, and form of medical care provided for by the legislation of the Russian Federation, as clinically indicated.

Patients with enuresis receive primary health care predominantly in outpatient settings.

The main condition for providing care to a patient with enuresis must be ensuring continuous monitoring, receiving treatment, and referral for specialized examination when necessary.

The child is monitored by a pediatrician/general practitioner (family doctor) and/or neurologist and/or psychiatrist and/or pediatric urologist-andrologist and/or nephrologist and/or pediatric endocrinologist, with the involvement of doctors of other specialties when necessary.

Indications for scheduled or emergency hospitalization are determined based on comorbidity and/or diseases primary to enuresis: urinary tract infections, urethral and urogenital malformations, chronic kidney disease, manifestations of spinal dysraphism, neurodegenerative diseases and CNS tumors, psychiatric disorders, obstructive sleep apnea.

Organization of dietary nutrition for patients during inpatient treatment in medical organizations is carried out in accordance with Appendix 3 of the Order of the Russian Ministry of Health No. 1008n dated September 23, 2020, "On approval of the procedure for providing patients with therapeutic nutrition"

7. Additional Information

7.1 Prognosis

During each year after the age of 5, approximately 15% of children suffering from simple primary enuresis recover spontaneously [106, 107]; however, the longer enuresis persists, the lower the chances of spontaneous remission [103, 106].

7.2 Complications

The main complications of neurofunctional forms of enuresis include psychological problems (self-esteem), stress, and social maladaptation [1, 2, 43, 47, 108].

Criteria for Evaluating the Quality of Medical Care

Table 1 – Criteria for assessing the quality of medical care.

References

Appendix A1. Working Group Composition

1. Baranov A.A. – Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences; Honorary President of the Union of Pediatricians of Russia, Advisor to the Head of the Research Institute of Pediatrics and Child Health of the National Medical Research Center of Surgery named after Acad. B.V. Petrovsky, Professor at the Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University), Chief freelance pediatric specialist of the Russian Ministry of Health

2. Batysheva T.T. – Professor, Doctor of Medical Sciences, President of the Association of Pediatric Rehabilitologists of Russia, Director of the Scientific and Practical Center for Children's Psychoneurology of the Moscow Healthcare Department, Head of the Department of Pediatric Neurology, Physical and Rehabilitation Medicine, Additional Professional Education Faculty, RUDN University, Chief freelance pediatric rehabilitologist of the Russian Ministry of Health, Honored Doctor of Russia

3. Burkin A.G. – Pediatric Urologist-Andrologist, Candidate of Medical Sciences, Head of the Department of Pediatric Urology and Andrology, Z.A. Bashlyaeva City Children's Clinical Hospital of the Moscow Healthcare Department

4. Bykova O.V. – Doctor of Medical Sciences, Head of the Research Department, Scientific and Practical Center for Children's Psychoneurology of the Moscow Healthcare Department, Professor at the Department of Pediatric Neurology, Physical and Rehabilitation Medicine, Additional Professional Education Faculty, RUDN University, Moscow

5. Vishnyova E.A. – Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Deputy Head for Scientific Work at the Research Institute of Pediatrics and Child Health, National Medical Research Center of Surgery named after Acad. B.V. Petrovsky of the Ministry of Science and Higher Education of Russia, Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University), Member of the Union of Pediatricians of Russia

6. Vrublevskaya E.N. – Doctor of Medical Sciences, Head of the Surgical Department, V.F. Voyno-Yasenetsky Scientific and Practical Center for Specialized Medical Care for Children of the Moscow Healthcare Department, Associate Professor at the Department of Pediatric Surgery named after Academician Yu.F. Isakov, Pirogov Russian National Research Medical University of the Russian Ministry of Health

7. Vrublevsky S.G. – Doctor of Medical Sciences, Professor, Professor at the Department of Pediatric Surgery named after Academician Yu.F. Isakov, Pirogov Russian National Research Medical University (Pirogov University), Chief freelance pediatric urologist-andrologist of the Moscow Healthcare Department, Deputy Chief Medical Officer for Surgery, V.F. Voyno-Yasenetsky Scientific and Practical Center for Specialized Medical Care for Children of the Moscow Healthcare Department

8. Guseva N.B. – Doctor of Medical Sciences, Professor at the G.N. Speransky Department of Pediatrics, Russian Medical Academy of Continuous Professional Education, urologist of the highest qualification category, Head of the Moscow City Center for Urology, Andrology and Pelvic Organ Pathology of the Moscow Healthcare Department, Chief Researcher at the Department of Pediatric Surgery, Research Institute of Clinical Surgery, Pirogov Russian National Research Medical University (Pirogov University)

9. Zakharova I.N. – Doctor of Medical Sciences, Professor, Head of the Academician G.N. Speransky Department of Pediatrics, Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health, Honorary Professor at the National Medical Research Center for Children's Health of the Russian Ministry of Health, President of the Vitamin D Research Physicians Association, Full Member of ESPGHAN, EAACI, ERS

10. Zhamynchiev E.K. – Candidate of Medical Sciences, Pediatric Urologist-Andrologist at the Research Institute of Pediatrics and Child Health, National Medical Research Center of Surgery named after Acad. B.V. Petrovsky, Member of the Union of Pediatricians of Russia

11. Zokirov N.Z. – Doctor of Medical Sciences, Head of the Department, Academy of Postgraduate Education of the Federal Scientific and Clinical Center of the Federal Medical-Biological Agency, Federal Scientific and Clinical Center of Children and Adolescents of the Federal Medical-Biological Agency, Member of the Union of Pediatricians of Russia

12. Ivardava M.I. – Candidate of Medical Sciences, Head of the General Pediatrics Department, Pediatrician, Head of the Department for the Development of Scientific Approaches to the Management of Children with Motor Disorders, Research Institute of Pediatrics and Child Health, National Medical Research Center of Surgery named after Acad. B.V. Petrovsky, Member of the Union of Pediatricians of Russia

13. Karkashadze G.A. – Candidate of Medical Sciences, Head of the Department of Brain Development in Ontogeny, Cognitive Function Formation and Neurobiology, Neurologist at the Research Institute of Pediatrics and Child Health, National Medical Research Center of Surgery named after Acad. B.V. Petrovsky, Member of the Union of Pediatricians of Russia

14. Klimov Yu.A. – Candidate of Medical Sciences, Deputy Director for Medical Work, Scientific and Practical Center for Children's Psychoneurology of the Moscow Healthcare Department; Head of the Department of Neurology and Neurosurgery, Russian State Social University

15. Korochkin M.V. – Head of the Short-Term Inpatient Surgery Unit, pediatric surgeon of the highest qualification category, urologist-andrologist, holder of the "Moscow Doctor" status, Morozov Children's City Clinical Hospital of the Moscow Healthcare Department.

16. Korsunsky A.A. – Doctor of Medical Sciences, Professor, Head of the Department of Pediatrics and Pediatric Infectious Diseases, Pediatric Faculty, I.M. Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University)

17. Krapivkin A.I. – Doctor of Medical Sciences, Director of the Solntsevo Children's Scientific and Practical Medical Center (V.F. Voyno-Yasenetsky Scientific and Practical Center for Specialized Medical Care for Children of the Moscow Healthcare Department), Professor at the Department of Hospital Pediatrics named after Academician V.A. Tabolin, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University)

18. Kolodyazhnaya A.V. – Psychiatrist, Sevastopol

19. Margieva T.V. – Candidate of Medical Sciences, Chief Specialist of the Methodological Center for Specialist Accreditation, I.M. Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University), Nephrologist, Member of the Union of Pediatricians of Russia

20. Morozov S.L. – Candidate of Medical Sciences, Nephrologist, Research Institute of Pediatrics and Children's Surgery named after Academician Yu.E. Veltischev, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Member of the Pediatric Nephrologists Creative Association, Russian Dialysis Society (RDS), European Society for Paediatric Nephrology (ESPN), International Pediatric Nephrology Association (IPNA).

21. Moiseev A.B. – Doctor of Medical Sciences, Associate Professor, Head of the Department of Propaedeutics of Children's Diseases, Pediatric Faculty, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University)

22. Namazova-Baranova L.S. – Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, President of the Union of Pediatricians of Russia; Past President of EPA/UNEPSA; Head of the Research Institute of Pediatrics and Child Health, National Medical Research Center of Surgery named after Acad. B.V. Petrovsky, Head of the Department of Faculty Pediatrics, Pediatric Faculty, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University), Chief freelance pediatric specialist in preventive medicine of the Russian Ministry of Health

23. Nikitin S.S. – MD, Head of the Center for Pediatric Urology-Andrology and Nephrology at the State Budgetary Healthcare Institution of the Republic of Karelia "I.N. Grigovich Children's Republican Hospital", pediatric urologist-andrologist, pediatric surgeon, Professor at the Department of Pediatrics and Pediatric Surgery, Petrozavodsk State University. (Petrozavodsk)

24. Privalova T.E. – PhD, Associate Professor, Head of Studies at the Department of Faculty Pediatrics, Pediatric Faculty, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health, Leading Research Fellow at the Department of Social Pediatrics and Organization of Multidisciplinary Care for Children, Head of Department – Pediatrician at the Research Institute of Pediatrics and Child Health, National Medical Research Center No. 2 of the Petrovsky National Research Centre of Surgery, member of the Union of Pediatrists of Russia

25. Platonova M.M. – PhD, Researcher at the Research Institute of Pediatrics and Child Health, National Medical Research Center No. 2 of the Petrovsky National Research Centre of Surgery, pulmonologist

26. Prikhodina L.S. – MD, Nephrologist, Head of the Professor M.S. Ignatova Department of Hereditary and Acquired Kidney Diseases at the Research Institute of Pediatrics and Pediatric Surgery named after Academician Yu.E. Veltischev of the Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Professor at the G.N. Speransky Department of Pediatrics, Russian Medical Academy of Continuing Professional Education of the Ministry of Health of the Russian Federation, member of the NGO "Creative Association of Pediatric Nephrologists", Russian Dialysis Society (RDS), European Society for Paediatric Nephrology (ESPN), International Pediatric Nephrology Association (IPNA).

27. Tikhonov S.V. – PhD (Biology), Scientific Secretary, Research and Practical Center for Pediatric Psychoneurology of the Moscow Healthcare Department, Associate Professor at the Department of Neurology, Physical and Rehabilitation Medicine, Faculty of Continuous Medical Education, Medical Institute of RUDN University, Moscow

28. Turov F.O. – PhD, Leading Research Fellow, Pediatric Urologist-Andrologist at the Scientific and Practical Center for Specialized Medical Care for Children of the Moscow Healthcare Department, member of the Russian Society of Urology, member of the American Urological Association, member of the Union of Pediatrists of Russia

29. Ustinova N.V. – MD, Psychiatrist, Healthcare Administrator, Head of the Department of Social Pediatrics and Organization of Multidisciplinary Care for Children, Research Institute of Pediatrics and Child Health, National Medical Research Center No. 2 of the Petrovsky National Research Centre of Surgery, G.E. Sukhareva Scientific and Practical Center for Mental Health of Children and Adolescents of the Moscow Healthcare Department.

30. Khan M.A. – MD, Professor, Head of the Center for Medical Rehabilitation at the N.F. Filatov City Children's Clinical Hospital of the Moscow Healthcare Department, Head of the Department of Medical Rehabilitation of Children and Adolescents at the Moscow Scientific and Practical Center for Medical Rehabilitation, Restorative and Sports Medicine of the Moscow Healthcare Department, Professor at the Department of Physical and Rehabilitation Medicine with a Course of Clinical Psychology and Pedagogy, Central State Medical Academy of the Presidential Administration of the Russian Federation, Professor at the Department of Medical Rehabilitation and Physiotherapy, Faculty of Advanced Medical Training, Moscow Regional Research Clinical Institute named after M.F. Vladimirsky

31. Shmyrov O.S. – PhD, Head of the Department of Pediatric Urology and Andrology, pediatric surgeon, pediatric urologist-andrologist at the Morozov City Children's Clinical Hospital of the Moscow Healthcare Department

32. Yatsyk S.P. – MD, Corresponding Member of the Russian Academy of Sciences, Professor at the Department of Pediatric Surgery, Russian Medical Academy of Continuing Professional Education of the Ministry of Health of the Russian Federation

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Pediatricians;

2. Neurologists;

3. Pediatric urologists-andrologists;

4. Urologists;

5. Child psychiatrists;

6. Psychiatrists;

7. Nephrologists;

8. Endocrinologists;

9. General practitioners (family physicians);

10. Medical psychologists;

11. Medical students;

12. Residents and interns.

Methods used for evidence collection/selection: electronic database search.

Description of methods used for assessing the quality and strength of evidence: the evidence base for the recommendations includes publications from the Cochrane Library, EMBASE, MEDLINE, and PubMed databases. Search depth: 5 years.

Methods used to assess the quality and strength of evidence:

• expert consensus;

• assessment of significance in accordance with the rating scheme.

Methods used for evidence analysis:

• reviews of published meta-analyses;

• systematic reviews with evidence tables.

Description of methods used for evidence analysis

When selecting publications as potential sources of evidence, the methodology used in each study is examined to ensure its validity. The result of this examination affects the level of evidence assigned to the publication, which in turn affects the strength of the recommendations.

To minimize potential bias, each study was evaluated independently. Any discrepancies in evaluations were discussed by the full panel of authors. If a consensus could not be reached, an independent expert was involved.

Evidence tables: compiled by the authors of the clinical guidelines.

Methods used to formulate the recommendations: expert consensus.

Good Practice Points (GPPs)

Recommended good clinical practice is based on the clinical experience of the authors of these guidelines.

Economic analysis

Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.

Recommendation validation method

• External expert review.

• Internal expert review.

Description of the recommendation validation method

The draft of these recommendations was reviewed by independent experts who were primarily asked to comment on how comprehensible the interpretation of the evidence underlying the recommendations is.

Feedback was obtained from primary care physicians regarding the readability of these guidelines and their assessment of the importance of the proposed recommendations as a tool for daily practice.

All comments received from the experts were thoroughly systematized and discussed by the members of the working group (authors of the recommendations). Each item was discussed individually.

Consultation and peer review

The draft recommendations were reviewed by independent experts who were primarily asked to comment on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.

Working Group

For the final revision and quality control, the recommendations were re-evaluated by the members of the working group, who concluded that all comments and feedback from the experts had been taken into account and the risk of bias in the development of the recommendations was minimized.

Table 1. Scale for assessing levels of reliable evidence (LRE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing the levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading levels of recommendation certainty (LRC) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Appendix A3.1 Reference materials, including compliance of indications and contraindications, routes of administration and doses of medicinal products, instructions for use of the medicinal product

Care delivery pathways:

1. Order of the Ministry of Health and Social Development of the Russian Federation No. 366n dated April 16, 2012 "On Approval of the Procedure for Providing Pediatric Care"

Other documents:

1. Order of the Ministry of Health of the Russian Federation No. 1094n dated November 24, 2021 "On approval of the Procedure for prescribing medicinal products, forms of prescription blanks for medicinal products, the Procedure for issuing these blanks, their accounting and storage, forms of prescription blanks containing prescriptions for narcotic drugs or psychotropic substances, the Procedure for their manufacture, distribution, registration, accounting and storage, as well as the Rules for issuing prescription blanks, including in the form of electronic documents"

2. International Statistical Classification of Diseases and Related Health Problems (ICD-10);

3. Order of the Ministry of Health of the Russian Federation No. 205n dated May 2, 2023 (as amended on December 4, 2023), "On Approval of the Nomenclature of Positions of Medical Workers and Pharmaceutical Workers".

4. Order of the Ministry of Health of the Russian Federation No. 541n dated July 23, 2010. "Unified Qualification Handbook of Positions of Managers, Specialists, and Employees, Section: Qualification Characteristics of Positions of Healthcare Workers."

5. Federal Law No. 489-FZ dated December 25, 2018, "On Amendments to Article 40 of the Federal Law 'On Compulsory Medical Insurance in the Russian Federation' and the Federal Law 'On the Fundamentals of Public Health Protection in the Russian Federation' regarding Clinical Guidelines".

6. Order of the Ministry of Health of the Russian Federation No. 103n dated February 28, 2019, "On Approval of the Procedure and Timeframes for the Development and Revision of Clinical Guidelines, Their Template Form, and Requirements for Their Structure, Composition, and Scientific Validity of Information Included in Clinical Guidelines".

7. Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017 "On approval of the nomenclature of medical services".

8. Order of the Russian Ministry of Health No. 1008n dated September 23, 2020, "On approval of the procedure for providing patients with therapeutic nutrition"

Symbols and abbreviations:

** – a medicinal product included in the Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019 (as amended on June 9, 2023)

# – The use of a medicinal product in accordance with indications (characteristics) not specified in the instructions for its use (off-label) is carried out by the decision of the medical commission subject to a signed informed voluntary consent (in accordance with Federal Law No. 323-FZ dated November 21, 2011, as amended).

Appendix A3.2 Examples of diagnoses

• Enuresis, combined neurofunctional form. Tics. Attention deficit hyperactivity disorder.

• Enuresis associated with meningomyelocele.

Appendix A3.3 Main provisions of the educational program "Training and recommendations for parents and caregivers of a child with enuresis"

1. Parents and caregivers of the child should be instructed that:

A) Enuresis is a common phenomenon; it occurs at least once a week in approximately 15% of five-year-old children; in most children, enuresis resolves spontaneously.

B) Neither the child nor the caregivers are to blame for the onset of enuresis; children should not be punished for nocturnal enuresis.

C) Regular use of diapers and pull-ups may reduce the motivation to get up at night and is generally not recommended (exceptions may be made when the child is sleeping away from home).

D) The consequences of nocturnal enuresis can be reduced by:

- using bed protection aids and washable/disposable products

- using room deodorants

- washing the child thoroughly before dressing

- using emollients to prevent chafing.

E) Children suffering from enuresis should avoid consuming high-sugar and caffeinated beverages, especially in the evening hours.

F) Restricting fluid intake in the evening may be useful for some children, but should only be continued if it is successful.

G) It is necessary to ensure that the bed is not cold

2. The child and parents should be instructed that

E) It is necessary to develop a habit of regular urination approximately 4-7 times a day (the younger the child, the more frequent), including immediately before bedtime

Z) It is necessary to drink an adequate amount of water, especially in the morning and afternoon. Consuming a larger amount. Simply restricting fluid intake in the evening without a compensatory increase earlier in the day may prevent the child from meeting their daily fluid needs and generally does not lead to success. Fluid during the day in the morning and afternoon reduces the need for it during the evening.

I) It is necessary to adopt a correct posture for urination, with good thigh support.

Appendix A3.4. Main provisions of the «Motivational therapy» method

Motivational therapy is conducted by a clinical psychologist or psychotherapist with parents who must apply the received recommendations at home. The consultation consists of explaining the principles of positive reinforcement of behavior, explaining the need to eliminate accusations and other manifestations of disapproval for episodes of nocturnal enuresis, developing a system for recording "dry" and "wet" nights (a diary of dry and wet nights kept by the child or the child together with a parent), selecting proper motivation for the child, and modifying it correctly during therapy.

Initially, compliant behavior should be rewarded (e.g., using the toilet before bedtime) rather than dryness. For longer adherence to compliant behavior and, ultimately, longer dry periods, larger rewards agreed upon in advance are given (e.g., a sticker on the calendar for each dry night, a book for seven consecutive dry nights). The observation period continues until a result of 14 consecutive "dry" nights is achieved. At the final stage of therapy, upon achieving a positive result, it is permissible to increase fluid intake in the evening, if a restriction on the amount drunk was introduced, to consolidate the effect of therapy.

The average duration of therapy is 1–3 months. One training consultation with a specialist and the parents is required; if difficulties arise in establishing a motivation system, an additional consultation is needed shortly after (1–2 weeks), followed by a follow-up at 1.5 months for the specialist to assess dynamics. A prerequisite for therapy is the parents' readiness to cooperate and consistently follow recommendations; at the first consultation, parents must be warned about the necessity of following instructions over a long period to achieve a positive outcome. Those who have agreed to take on a certain amount of responsibility for their treatment can be motivated by tracking their progress.

Appendix A3.5. Basic rules of enuresis alarm therapy.

An enuresis alarm (bell and pad) is a device that emits a strong

arousal signal, usually acoustic, to the child and family members at the moment urine activates a detector placed in the bed or the child's clothing. Treatment efficacy also depends on selecting the appropriate type tailored to the child for individual ease of use.

The following practical recommendations must be followed during alarm therapy:

- The device should be selected based on individual ease of use and demonstrated in detail to both the child and the parents.

- The alarm must be used consistently, every single night without interruption.

- Within 1–2 minutes, the child should mentally rehearse in detail the sequence of events that occur when the alarm sounds (or vibrates) during sleep. The sequence is as follows:

1. The child turns off the alarm, gets out of bed, and finishes urinating in the toilet (only the child should turn off the alarm). For alarm therapy to succeed, it is crucial that the child wakes up completely and is aware of what is happening. However, at the beginning of alarm therapy, caregivers may need to wake the child up when the alarm sounds.

2. The child returns to the bedroom.

3. The child changes bed linen (under a caregiver's supervision) and clothing. A change of bed linen and clothing should be kept near the bed.

4. The child wipes the sensor with a damp cloth and then a dry one (or replaces the sensor if it is disposable).

5. The child turns off the alarm and goes back to sleep.

- A diary must be kept recording wet and dry nights. Positive reinforcement should be provided for successfully completing the sequence of actions described above, waking up and getting out of bed to use the bathroom, as well as for dry nights. Penalties (e.g., loss of rewards) for enuresis episodes are ineffective.

- Parents must be prepared to wake the child immediately as soon as the alarm sounds, because very often during the first weeks of treatment, the child does not wake up to the alarm on their own. This requires the caregiver to be prepared for close monitoring over a long period, as the course of treatment can last from 3 to 6 months.

The healthcare professional should contact the family after 1–3 weeks of starting therapy to provide support and resolve technical issues.

If no positive effect is observed after 6 weeks, therapy should be discontinued. If progress is observed during this time (wet areas decrease, the child wakes up to the alarm, the alarm goes off later at night, fewer alarms per night, fewer wet nights), therapy should be continued until 14 consecutive dry nights are achieved.

Therapy efficacy largely depends on the motivation of the child and parents to overcome enuresis.

Appendix B. Physician Action Algorithms

Appendix B1. Algorithm for referring children with enuresis for specialized examination by relevant specialists based on initial diagnostics results

Appendix C. Patient Information

Voiding diary.

VOIDING DIARY

EXAMPLE OF A VOIDING DIARY

Enuresis refers to episodes of intermittent urinary incontinence during nighttime sleep in children older than 5 years.

The diagnosis of enuresis is established if urinary incontinence occurs regularly at least three times a month in children under 7 years of age and at least once a month at age 7 and older.

Daytime urinary incontinence is not included in the definition of enuresis.

Enuresis can be caused by various factors.

To determine the cause, the child undergoes examination in accordance with the presenting manifestations.

Treatment depends on the cause of enuresis. In many situations, non-pharmacological methods are sufficient.

In each specific case, the required scope of treatment is determined by the physician.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Not used