Enuresis and sleep disordered breathing: An old and new link

Abstract

The causes of nocturnal enuresis (NE) are likely multifactorial. It has been related to several (urological-nephrological-hormonal) reasons but clear and univocal pathogenesis remains mostly undetermined. Sleep disordered breathing (SDB) is a syndrome of upper airway dysfunction that occurs during sleep and is characterized by snoring and/or increased respiratory effort secondary to increased upper airway resistance and pharyngeal collapsibility. Adenotonsillar hypertrophy is the main cause of SDB in children. To date, several studies have associated childhood NE with coexistent SDB. Adenotonsillectomy was successful for both SDB and NE in about half of patients. Unfortunately, practical consensus guidelines for the management of primary NE do not mention, or marginally concern, SDB in these children, particularly in those who have treatment resistance and comorbidities. The concerns regard the concomitant presence of two relatively frequent sleep disorders, raising the question whether they are really coincidental problems of childhood.

Key Words: Children, Sleep disordered breathing, Enuresis

Core tip: Several studies have pointed out the high frequency of sleep disordered breathing (SDB) in children with nocturnal enuresis (NE), particularly refractory (medication resistant) or secondary. Practical consensus guidelines for NE, corroborated by recent investigation of the topics, need to be revisited considering the high recurrence of SDB in childhood NE and a high success rate of intervention for it.

INTRODUCTION

Nocturnal enuresis (NE) is a frequent problem in pediatrics. The age related prevalence is between 2%-15%[1,2]. NE is characterized by intermittent incontinence that occurs exclusively during sleep in children who are at least 5 years old[1,3]. There are two subtypes, monosymptomatic NE and nonmonosymptomatic NE, according to the absence or presence of lower urinary tract and bladder dysfunction[1]. Furthermore, primary NE (PNE) and secondary NE applies to children who have not achieved a previous dry period or who have had a previous dry period of almost 6 mo, respectively[3].

NE has been related to several (urological-nephrological-hormonal) conditions[4], but clear and univocal pathogenesis remains mostly undetermined[5].

Sleep disordered breathing (SDB) is a syndrome of upper airway dysfunction occurring during sleep and characterized by snoring and/or increased respiratory effort secondary to increased upper airway resistance and pharyngeal collapsibility. About 40 years ago, Guilleminault et al[6] included NE among various symptoms of adulthood SDB. The same authors observed that in completely toilet trained children, bedwetting reappeared contemporary to the development of obstructive sleep apnea syndrome (OSAS), similar to that seen in adults[6]. OSAS is characterized by witnessed apnea, unrefreshing sleep and excessive daytime sleepiness[7]. The prevalence of OSAS in childhood is approximately 0.7%-3%[8,9]. Adenotonsillar hypertrophy is the main cause of SDB in children[10].

To date, several studies have associated childhood NE with coexistent SDB[11,12]. In investigations for an association between asthma and SDB, enuretic children were 5.34 times more prone to have apnea reported by parents[13]. By using a subjective instrument, enuretic children showed a high comorbidity with other sleep disturbances, like SDB and parasomnias[14]. Moreover, among 87 patients with MNE, a family history of NE was diagnosed in 91% and constipation in 89%. Interestingly, mild/moderate apnea was found in 41% and severe sleep apnea in 7%[15]. NE and SDB[16,17] are urological and respiratory conditions, respectively associated with sleep. Increased brain natriuretic peptide (BNP) levels may account for the increased prevalence of enuresis in the context of SDB[18].

NE has been reported in 8%-47% of children with SDB, mainly attributable to adenotonsillar hypertrophy[18,19]. Complete resolution of NE has been reported in 31%-76% of OSAS children within months of adenotonsillectomy[20,21]. Adenotonsillectomy was successful in both NE and SDB in about half of patients[22]. Recently, Park et al[23] reported that there was a strong association between NE and obstructive SDB, and adenotonsillectomy markedly improved NE in the majority of children. Accordingly, plasma antidiuretic hormone and BNP normalized post intervention[24]. Moreover, resolution has been reported successfully after rapid maxillary expansion in 50% of patients after 1 mo of treatment[25], and after nasal budesonide in two patients[26].

The causes of NE are likely multifactorial[15]. Unfortunately, practical consensus guidelines for the management of PNE do not mention[27], or marginally concern, SDB in children with NE, particularly in those who have treatment resistance and comorbidities[28]. The concerns regard the concomitant presence of two relatively frequent sleep disorders, raising the question whether they are really incidental problems of childhood. Hormonal normalization after surgery highlights the suspicions that they might be linked. Furthermore, various studies reported a success rate of surgical intervention in several bedwetting patients. The question is whether spontaneous resolution of NE is concerned in some OSAS patients, when a not-early resolution is observed post treatment.

In children with NE, validated questionnaires are important tools to screen for SDB, although with weak predictive value[29,30]; urologist/general practitioner may detect the problem and refer the patients to otolaryngology or sleep medicine evaluation.

In conclusion, several studies have pointed out the high frequency of SDB in children with NE raising the questions whether: (1) children with NE without clinical evidence of SDB can be firstly treated with standard treatment for NE; (2) children with NE and clinical evidence of SDB need to be investigated and treated firstly for OSAS; (3) children with refractory (medication resistant) and secondary NE need to be investigated for underlying and subclinical sleep respiratory problems; and (4) polysomnography should be included for a more comprehensive evaluation of bedwetting children included in point 2 and 3.