Investigators will study the efficacy and safety of mirabegron25 in treatment of primary nocturnal enuresis in comparison to oral desmopressin 120 mcg and behavioral therapy

No doubt that nocturnal enuresis is one of the commonest types of urinary incontinence which affect children and always run in family . Nocturnal enuresis occurs at the age of 5 years with leakage of urine involuntarily during sleep for two times or more per week in three consecutive months not due to congenital or acquired cause. Nocturnal enuresis can be categorized into primary or secondary depending on occurrence of bed dryness for more than six months or not .

Nocturnal enuresis affects 15% to 20 % of children at five years old mainly due to delay of bladder development and function more in male children with presence of family history in half of cases but 15% of children with enuresis recover spontaneously every year .

limitation of fluid intake, urotherapy and bedwetting alarms are non-pharmacological treatments of nocturnal enuresis while the mostly used drugs for treatment of NE are tricyclic antidepressants(Imipramine®) an arginine vasopressin analog (Desmopressin®) and anticholinergic drugs . Enuresis alarms have pitfalls which disgust a lot of patients as skin irritation, sleep disturbances of other family members and failure to wake the child so that about 30% of patients stop its usage .

Desmopressin is approved as a first-line drug therapy for nocturnal enuresis , but a lot of series declared that monotherapy with desmopressin has little efficacy in treating patients which have bladder storage dysfunction furthermore, high recurrence rate after treatment cessation .

The International Children's Continence Society (ICCS) recommended combination therapy for treatment of primary nocturnal enuresis after failure of first line therapy with desmopressin or enuresis alarms . As regard anticholinergic drugs, oxybutynin was firstly prescribed then tolterodine with less side effects and lately solifenacin . Cognitive impairment as a neurological side effect was authenticated for oxybutynin and other side effects (e.g. headache, dry mouth, behavior change, flushed cheeks, constipation, and blurred vision) were unbearable to many children and impulsed them to stop treatment early .

Mirabegron, a b3-adrenoceptor (b3-AR) agonist was the answer to the question about a drug that can relax detrusor muscle and increasing bladder capacity without the limitations of anti-cholinergic drugs. Mirabegron is the first b3-AR agonist to be prescribed clinically for OAB symptoms in adults and showed promising outcomes . while it is not licensed to be used in children with overactive bladder, some early reports declared its efficacy and tolerability in children .

So investigators will study the efficacy and safety of mirabegron in treatment of primary nocturnal enuresis

Inclusion Criteria:

• primary nocturnal enuresis,
• negligible daytime wetting,
• wet at least 4 times over 4 weeks
• normal clinical examination with no neurological or urological cause for the enuresis

Exclusion Criteria:

• secondary enuresis, polysymptomatic
• neurologic bladder, neurological disorders,
• urinary incontinence disorders
• previous anti NE drugs.