According to ICS Nocturnal Enuresis (NE) is defined as the complaint of involuntary voiding that occurs at night during the main sleep period. 
Enuresis in children without any other Lower Urinary Tract Symptoms (LUTS) and without a history of bladder dysfunction is defined as mono-symptomatic enuresis (MNE). Other children with enuresis and any other LUTS are said to experience non mono-symptomatic enuresis (NMNE)¹. 
NE is subdivided into primary and secondary forms: primary enuresis is the presence of enuresis in a child 5 years old who has never achieved a night-time dryness; secondary enuresis is the presence of enuresis in a child who has achieved an asymptomatic period (6 months) of consistent night-time dryness in the past. 
NE is almost twice as common in boys rather than girls. Approximately 15% of 5 years-children have NE, with most children (80%) diagnosed with primary enuresis. In 15% of cases it is resolved spontaneously, but it can persist until adulthood². The wide prevalence of NE speaks to the need for an improved understanding of this condition by patients, families, pediatricians, primary care doctors and urologists alike. 
NE has a multifactorial etiology (nocturnal polyuria, decreased bladder capacity, detrusor over activity or associated sleep arousal disturbances) and it may benefit from different treatment strategies. Since It is a disorder characterized by a deep impact on psychological, behavioral and social functioning of the child, it is reasonable to start with a behavioral approach (BA). This kind of approach seems to be very useful in the management of this condition because it improves the patient’s motivation and compliance to other types of therapy. 
The aim of our study is to give to pediatricians the tools for improving therapeutic strategies for individuals diagnosed with NE.

This is a original retrospective study group that included 151 children (99 boys and 52 girls, mean age 9±2,2 years) who experienced primary nocturnal enuresis and achieved complete resolution with different therapeutic approaches (behavioral approach, enuresis alarm or desmopressin), followed up between 2009 and 2019. Resolution was evaluated with a clinical or telephonic follow up, asking for a complete response to the treatment defined by full resolution of NE (using the International Children’s Continence Society criteria) and also asking which type of therapy was successful. 
To be eligible for inclusion, patients had to meet the ICS`s definition of NE. Exclusion criteria were secondary NE, history of urinary tract infections, patients with comorbidities and/or neuropsychiatric disorders. 
The most important diagnostic step in the evaluation of a patient with NE is a thorough medical history to assess the presence of LUTS. Out of 151 children, 55 had a clinical diagnosis of NMNE. For these patients it was first identified and treated the day time problem with frequency/volume charts. A general inspection with a neuro-urological examination, as well as a urine dipstick were performed on all patients to exclude anatomical abnormalities, urinary tract infections and glycosuria. Behavioural approach (BA) was the first line approach in all of the study groups: it consists of instructions for a proper hygiene in voiding (reduce fluid intake before 1 to 2 hours before bedtime and empty bladder immediate before sleeping), reinforcement of motivation and a dry/wet night calendar. Other therapeutic strategies were the addition of enuresis alarm (EA) or pharmacological treatment (desmopressin) in patients that did not responded to BA.

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100 out of 151(66,2%) children achieved a complete success receiving only BA therapy. The mean age of these patients was 8,8 ± 2,1 years old and 60 (60%) were male and 40 (40%) were female. The proportion of females who achieved success with BA was 77% (40/52) compared to 60% of males. The mean time of resolution was 8,1 ± 5,7 months. 
Out of 151 patients, 34 (22,5%) received BA and EA therapies, and the resolution therapy for all children was EA. The mean age of these patients was 9,7 ± 2,2 years old. Out of these 34, 27 (79,4%) were male and 7 (20,5%) were female. The mean time of resolution was 5,3 ± 4,9 months. 
10 out of 151 (6,6%) patients received all three treatments and 6 out of 10 (60%) resolved NE with EA, 3 of 10 (30%) with desmopressin and only 1 out of 10 (10%) with BA. The mean age of these 10 children was 9,8 ± 2,3 years old, 7 (70%) were male and 3 (30%) were female. The mean time of resolution was 13 ± 22 months. 
7 out of 151 (4,6%) patients received BA and desmopressin and in 5 out of 7 (71,4%) the resolution therapy was desmopressin. The mean age of this study group was 11,3 ± 2,2 years old with 5 (71%) males and 2 (29%) females. The mean time of resolution was 12,3 ± 11,4 months. 
Out of 52 girls who were included in the study, 41(79%) achieved complete success with BA; of 99 boys, 62 (63%) had a full resolution of NE with BA. The difference between female and male in the response to BA is significant (p value <0,05). 
There was a difference in mean age at diagnosis between patients who underwent a simple BA and patients who received more than one therapeutic approach: in the first group the mean age was 8,8 ± 2,1; in the second one the mean age was 9,4 ±  2,4. The difference in the mean age was not statistically significant (p value > 0,05).

Based on our experience, first line treatment is education for both patients and their families. It is of the utmost importance that physicians take extra-time to reassure and fully answer questions of the children and their parents with regular follow-up appointments. In fact, our research shows that BA alone was the best approach for 66,2% of the study group, especially in the female group. Girls are more likely to respond to simple BA than boys. 
The second best therapeutic approach was BA in addition with EA. Also in this case it is important that there is family compliance because there are a lot of practical problems with these devices including difficulties in set up and discontinuing the use due to failure of the alarm to wake the child, false alarms and skin irritation. 
Alarm device shows to be helpful to children who were resistant to simple BA and the combination therapy demonstrated to be resolutive in 5,3 months. 
For children with refractory NE to BA and EA, treatment with desmopressin could be effective especially when a nocturnal polyuria is suspected and there are family difficulties (low adherence to the other treatments). Even if we observed a difference in the mean age between the group who received a simple BA and the patients who received more therapeutic approaches, these difference were not statistically significant.

The treatment of NE remains a challenge for pediatricians and our results support the concept that a multidisciplinary and personalized approach is necessary for achieving success in the treatment of children with NE. NE is a disorder with emotional, relational and psychological consequences that often requires more medical care and time and long term BA can be a valid alternative to pharmacological therapy and EA, that still represent the two recommended treatments³.

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DiBianco John Michael, Morley Chad, Al-Omar Osama. Nocturnal enuresis: a topic review and institution experience. Avicenna J. Med. 2014 Oct-Dec; 4(4):77-86.
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