Elevated Pre-injection Basal Luteinizing Hormone Concentrations are Common in Girls Treated for Central Precocious Puberty

Objective: A consensus on how to monitor girls with central precocious puberty (CPP) during gonadotropin-releasing hormone agonist (GnRHa) treatment is lacking. Increased, unstimulated basal luteinizing hormone (LH) concentrations have been suggested to indicate lack of suppression. The aim was to evaluate pre-injection basal LH concentrations during GnRHa (leuprorelin 3.75 mg) treatment every four weeks in girls with CPP. Methods: Medical records were reviewed for girls with CPP treated at a single center from 2014-2019. Clinical characteristics and laboratory findings during treatment were systematically recorded. Results: A total of 587 GnRHa pre-injection basal LH concentrations were analyzed in 74 girls. Basal LH was pubertal (≥0.3 IU/L) in 53.5% of blood samples and 87.8% of all girls had a pubertal basal LH concentration at least once. A GnRH test (n=29) was repeated in 23 girls due to suspicion of clinical progression, elevated basal LH or recordable estradiol concentrations. None had a stimulated LH >3.1 IU/L. The predictability of treatment suppression (specificity) of basal LH concentrations was 12.0% when compared to repeated GnRH stimulation tests. Despite shortening the GnRHa injection interval to three weeks, basal LH concentrations remained pubertal in 85.7% girls. A significant reduction in height standard deviation score (p<0.001) and bone age advance (p<0.001) was observed during treatment. Conclusion: Pre-injection basal LH remains at pubertal concentrations during treatment with leuprorelin 3.75 mg in girls with CPP. Clinical monitoring of pubertal progression is preferable to routine basal LH concentrations. Repeat GnRH stimulation testing should be regarded as the gold standard.

COVID-19 reopening causes high risk of irritant contact dermatitis in children.

INTRODUCTION: Childhood irritant contact dermatitis (ICD) is the most common cause for developing chronic hand eczema as an adult. The COVID-19 reopening in Denmark included regulations introducing frequent hand washing. The aim of the present study was to evaluate if frequent hand washing increases the incidence of ICD in children. METHODS: We conducted an observational study in Denmark during the reopening of schools and daycare facilities for children aged 0-12 years (April 22nd to May 1st 2020). A questionnaire was sent out to parents in four municipalities consisting of 20 questions about frequency of hand washing, use of hand sanitiser, symptoms of ICD, atopic dermatitis, allergy and predispositions. RESULTS: The study included 6,273 children. In children without any prior symptoms of dermatitis, 42.4% experienced ICD (dry, red and itchy skin) due to increased hand hygiene. Schoolchildren had a 1.5 times greater relative risk of developing ICD than preschool children. Frequency of hand washing was a strong risk factor, whereas this was not the case for alcohol-based hand sanitiser. Hand washing 7-10 times/day and >10 times/day increased the relative risk by 1.83 and 2.23 times, respectively. CONCLUSIONS: A higher frequency of hand washing during the COVID-19 reopening increased the incidence of ICD in children. Hand hygiene is essential in our fight against novel coronavirus, but prophylactic initiatives are important to reduce the possible long-term consequences of ICD in children. FUNDING: none TRIAL REGISTRATION: Clinicaltrials.gov (NCT04375410).

Combination treatment of nocturnal enuresis with desmopressin and indomethacin.

BACKGROUND: We investigated the effect of combining indomethacin and desmopressin in treating children with monosymptomatic nocturnal enuresis (MNE) and desmopressin-resistant nocturnal polyuria. METHODS: Twenty-three children with MNE, nocturnal polyuria, and partial or no response to desmopressin were recruited from incontinence clinics of our tertiary referral center. We used a randomized single-arm crossover placebo-controlled study design consisting of two 3-week treatment periods with a combination of desmopressin (0.4 mg) and indomethacin (50 mg) or desmopressin and placebo at bedtime. Home recordings at baseline and for the final 2 weeks of each treatment period were performed and included nocturnal urine output measurements. The number of dry nights achieved and reduction in the nocturnal urine output were the main effect parameters. Student's t test and Pearson's correlation coefficient were used for statistical analysis. RESULTS: The addition of indomethacin to desmopressin significantly reduced nocturnal urine output (from 324 ± 14 ml to 258 ± 13 ml, p < 0.001). This did not lead to more dry nights in all children, and we found no statistically significant reduction in enuresis frequency (from 68 % ± 0.1 to 56 % ± 0.1, p = 0.24). CONCLUSIONS: Addition of indomethacin to desmopressin can further reduce nocturnal urine output in children with MNE and desmopressin-resistant nocturnal polyuria. The combination treatment does not, however, improve outcome in terms of frequency of nights with enuresis. The dissociation of antidiuretic and antienuretic effect may reflect nocturnal bladder reservoir dysfunction in children who present with normal daytime bladder function.

Transcutaneous Electrical Nerve Stimulation Increases Rectal Activity in Children.

OBJECTIVES: Neurostimulation is increasingly used in treating bladder and bowel dysfunction, but its effect on rectal motility is obscure. The aim of the study was to evaluate the acute effect of transcutaneous electrical nerve stimulation (TENS) on rectal motility in children with overactive bladder (OAB). METHODS: In this double-blind placebo-controlled study in 20 children with OAB (mean age 8.6 ±â€Š1.8 years; 7 girls), 48-hour urodynamic monitoring including rectal manometry was performed. After 24-hours of baseline investigation without stimulation the children were randomised to either active TENS (n = 10) or placebo (n = 10). Surface electrodes were placed over the sacral bone. The exterior of active and placebo stimulators was identical. Starting in the morning, the children received either continuous TENS stimulation or placebo until bedtime. Rectal contractions were defined as pressure runs exceeding 5 cm H2O and lasting ≥3 minutes. RESULTS: At baseline there was no significant difference in proportion of time with rectal contractions in the 2 groups (TENS group median 31% [range 12%-66%] vs placebo group median 31% [range 10%-66%]; P = 0.75); however, on the day of stimulation there was more time with rectal contractions in the group receiving TENS (median 51% [range 25%-78%]) compared with placebo (median 32% [range 4%-68%]; P = 0.02). Also, there was an increase in time with rectal contractions in the TENS group (P = 0.007) but not in the placebo group (P = 0.39). The night after the TENS was disabled, rectal activity in both groups returned to baseline level. CONCLUSIONS: TENS acutely increases time with rectal contractions in children undergoing urodynamic investigation. The effect disappears when the stimulator is turned off.

Outcome of a standardized approach to childhood urinary symptoms-long-term follow-up of 720 patients.

AIMS: To investigate the relevance of enuresis subtyping for selection of treatment modality and for long-term outcome in a large consecutive patient cohort. MATERIALS AND METHODS: We included all patients referred for urinary incontinence during a 5-year period but excluding recurrent urinary tract infections (UTI). Type and severity of incontinence, prior history, results of examinations performed, number of visits, and effect of all treatments provided, were included in a clinical database. RESULTS: Seven hundred twenty children aged 4-16 years (mean 8.5 ± 2.2 years, 239 girls) were included in the analysis (42% with monosymptomatic (MNE), 55% with non-MNE, and 3% with isolated daytime incontinence). Initial evaluation revealed only few underlying causes (one neurological and eight anatomical). Investigations showed significant differences between MNE and non-MNE patients as both maximal voided volume and nocturnal urine volume was lower in non-MNE patients (P < 0.001). Follow-up for average 1,587 days (3.4 years) was performed in 660 (92%) patients. A higher number of visits and a longer treatment period were needed for non-MNE patients (on average 4.7 ± 2.8 visits) than MNE patients (3.1 ± 1.6 visits, P < 0.001). The most common treatment regimen that resulted in dryness in both MNE (40%) and non-MNE (36%) was the alarm system. Interestingly, of the 539 patients who initially were referred due to desmopressin resistance 177 (33%) of these were dry on desmopressin monotherapy. CONCLUSIONS: The study indicated that MNE and non-MNE are two distinct disease entities with different optimal treatments and showed that the latter patients are more difficult and time-consuming to manage.

Rectal motility in pediatric constipation.

OBJECTIVES: Constipation is a common disorder in children, but little is known about its etiology. Rectal impedance planimetry determines segmental rectal cross-sectional area (CSA) and pressure, allowing detailed description of rectal motility. The aim of the present study was to compare rectal motility in healthy and constipated children. METHODS: We analyzed data from 10 children (1 girl) with constipation according to the Rome III criteria, mean age 8.8 years (standard deviation ±â€Š1.2), and 10 healthy children (5 girls), mean age 9.9 years (standard deviation ±â€Š1.5). CSA was determined at 3 levels (4, 5.5, and 7 cm from the anal verge). The resting rectal motility was recorded for 30 minutes followed by a distension protocol to assess compliance. Runs of phasic rectal contractions were defined as changes of >10% from baseline CSA and lasting at least 2 minutes. Rectal dimensions were expressed as mean CSA. RESULTS: A low-amplitude contraction pattern (3%-5% of baseline CSA) with a frequency of 6 to 8/minute was present in all of the children. There was significantly more time with phasic rectal contractions in constipated children (median 38%, range [0-100]) compared with healthy children (median 8.8%, range [0-57]) (P < 0.05). The rectal CSA was higher in constipated children (median 1802 mm [range 1106-2948]) compared with healthy children (1375 mm [range 437-1861]) (P < 0.05), but compliance did not differ (constipated: median 38 mm/H2O [range 12-86] vs healthy 33 mm/H2O [range 10-63]) (P = 30). CONCLUSIONS: In children with constipation, we found phasic rectal contractions for a significantly longer period compared with healthy children, and their rectum is larger than normal.

Bladder and bowel dysfunction and the resolution of urinary incontinence with successful management of bowel symptoms in children.

AIM: To investigate the effect of treating defecation problems on urinary incontinence in children suffering from combined urinary bladder and bowel dysfunction (BBD). METHODS: We established a clinical database from medical records of all children referred to the urinary incontinence and gastroenterology outpatient clinics with BBD. The following variables were extracted: symptoms of constipation, faecal incontinence, urinary incontinence, age at onset of symptoms, treatment, including duration and response. All children went through the same treatment protocol. Faecal disorders were treated primarily and once relieved, the daytime incontinence was managed and followed by intervention for nocturnal enuresis. RESULTS: In total, 73 children were included in the study. The treatment regimen resulted in resolution of the defecation disorder in 96% of the patients. Of the children with daytime urinary incontinence, 68% had at least a 50% reduction in number of daytime incontinence episodes by successful relief of bowel dysfunction and 27% became completely continent during daytime. Only 17% of the children suffering from enuresis had a significant reduction in number of wet nights after relief of their faecal problem. CONCLUSION: The empirical treatment approach of managing bowel symptoms before intervening for bladder dysfunction in children with BBD is found to be appropriate.

Reduced anti-diuretic response to desmopressin during wet nights in patients with monosymptomatic nocturnal enuresis.

OBJECTIVE: To investigate why not all children with monosymptomatic nocturnal enuresis (MNE) treated with desmopressin give an adequate response. MATERIALS AND METHODS: We included 114 children with MNE aged 5-15 years (9.8 ± 0.2 years) who experienced at least 1 wet night and more than 2 dry nights during desmopressin treatment. The patients made home recordings for 2 weeks as baseline and for 2-4 weeks of desmopressin titration. Nocturnal urine production during wet and dry nights, and maximum voided volumes (MVVs) were documented in all patients. RESULTS: Sixty-four patients were desmopressin non-responders, 29 were either partial responders or responders, while 21 patients were full responders. Desmopressin reduced nocturnal urine production dramatically during dry nights compared with pre-treatment wet nights. Nocturnal urine production during desmopressin treatment was significantly greater during wet nights compared to dry nights (243 ± 9.32 vs 176 ± 5.31 ml, P < 0.001). There was a highly significant correlation between individual nocturnal urine output and MVV, and dry nights were characterized by nocturnal urine output/MVV ratios well below 1.0. CONCLUSION: The anti-enuretic response to desmopressin seems to be dependent upon the degree of reduction in nocturnal urine production. Research on desmopressin bioavailability in children is needed.

Tailoring treatment of monosymptomatic nocturnal enuresis: the role of maximum voided capacity.

PURPOSE: We evaluated bladder reservoir function in children with monosymptomatic nocturnal enuresis with and without response to desmopressin, and assessed the importance of first morning voiding when defining maximum voided volume. MATERIALS AND METHODS: A total of 238 patients 5 to 15 years old with monosymptomatic nocturnal enuresis completed 2 weeks of enuresis recordings and 4 days of frequency-volume charts. Of the patients 186 completed subsequent home recordings during titration with desmopressin. Maximum voided volumes with and without the first morning void were calculated. Desmopressin response was defined as greater than 50% reduction in wet nights. Maximum voided volume with and without first morning voiding was evaluated as a prognostic factor for desmopressin response. RESULTS: Mean ± SD maximum voided volume without first morning void was comparable between desmopressin responders and nonresponders (230.5 ± 69.3 ml and 219.0 ± 84.8 ml, respectively, p = 0.391). Inclusion of the first morning void demonstrated responders to have significantly larger values than nonresponders (mean ± SD 296.0 ± 94.0 ml vs 233.5 ± 90.0 ml, p <0.001). When first morning void was included, desmopressin response was seen in 40% of patients with voided volumes of 65% expected volume for age vs 10% of patients with volumes less than 65% expected volume for age. CONCLUSIONS: Maximum voided volume can be used as a predictor of desmopressin response only if first morning voids are taken into consideration. All patients with monosymptomatic nocturnal enuresis should receive clear instructions to include this measure when completing frequency-volume charts.

Timer watch assisted urotherapy in children: a randomized controlled trial.

PURPOSE: We evaluated the effect of timer watch treatment in addition to standard urotherapy in children with overactive bladder and daytime urinary incontinence. MATERIALS AND METHODS: A total of 60 children with daytime urge incontinence were included in the study. Following a 4-week run-in period of standard urotherapy children were randomized to 12 weeks of standard urotherapy with or without a timer watch. Incontinence episodes were registered and 48-hour bladder diaries were obtained before randomization, and at weeks 1, 11 and 12. Long-term response was evaluated at 7 months. RESULTS: Two children became continent during the run-in period. Before intervention children in the timer group were slightly more wet than children in the standard urotherapy group (median 7 [IQR 25% to 75% 6 to 7] vs 6 [3 to 7] wet days per week, p <0.05). Following 12 weeks of standard urotherapy children randomized to timer assisted urotherapy had significantly fewer wet days per week (median 2, IQR 25% to 75% 0 to 5) vs those undergoing standard urotherapy alone (5, 2.75 to 6.75, p <0.01). In the timer group 18 children (60%) achieved a greater than 50% decrease in incontinence episodes, compared to only 5 (18%) treated without timer assistance. Nine patients (30%) in the timer group and no child in the standard urotherapy group achieved complete daytime continence. The timer increased compliance with the timed voiding regimen. At 7 months of followup 60% of children in the timer group were still continent in the daytime. CONCLUSIONS: A programmable timer watch significantly improves the effect of standard urotherapy. When using the timer watch as a supplement to standard urotherapy 60% of the children obtained complete and sustainable daytime continence.

Excess diuresis and natriuresis during acute sleep deprivation in healthy adults.

The transition from wakefulness to sleep is associated with a pronounced decline in diuresis, a necessary physiological process that allows uninterrupted sleep. The aim of this study was to assess the effect of acute sleep deprivation (SD) on urine output and renal water, sodium, and solute handling in healthy young volunteers. Twenty young adults (10 male) were recruited for two 24-h studies under standardized dietary conditions. During one of the two admissions, subjects were deprived of sleep. Urine output, electrolyte excretions, and osmolar excretions were calculated. Activated renin, angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic peptide were measured in plasma, whereas prostaglandin E(2) and melatonin were measured in urine. SD markedly increased the diuresis and led to excess renal sodium excretion. The effect was more pronounced in men who shared significantly higher diuresis levels during SD compared with women. Renal water handling and arginine vasopressin levels remained unaltered during SD, but the circadian rhythm of the hormones of the renin-angiotensin-aldosterone system was significantly affected. Urinary melatonin and prostaglandin E(2) excretion levels were comparable between SD and baseline night. Hemodynamic changes were characterized by the attenuation of nocturnal blood pressure dipping and an increase in creatinine clearance. Acute deprivation of sleep induces natriuresis and osmotic diuresis, leading to excess nocturnal urine production, especially in men. Hemodynamic changes during SD may, through renal and hormonal processes, be responsible for these observations. Sleep architecture disturbances should be considered in clinical settings with nocturnal polyuria such as enuresis in children and nocturia in adults.

24-hour rectal manometry for overactive bladder.

PURPOSE: We describe prolonged rectal manometry used to characterize rectal motor activity patterns and possible rectum-bladder interaction during defecation and micturition in children with nonneuropathic overactive bladder. MATERIALS AND METHODS: We evaluated 10 children with a mean +/- SD age of 9.7 +/- 1.3 years with overactive bladder who underwent urodynamics and 24-hour rectal manometric recording. All records were analyzed visually. Rectal contractions were defined as pressure runs exceeding 5 cm H(2)O and lasting longer than 5 seconds. RESULTS: Three rectal motility patterns were noted in all children, including 1) slow tonic pressure waves with a frequency of 3 to 12 per hour, b) rectal motor complexes with a frequency of 3 to 10 per minute and c) single contractions 10 to 30 seconds in duration. The median nocturnal duration of rectal motor complexes was longer than that during the day (16.3 minutes, range 10.8 to 18.8 vs 11.0, range 8.9 to 12.6, p <0.05). As a percent of time, median total contraction time was greater at night than during the day (51.9%, range 42.6% to 56.9% vs 30.6%, range 19.4% to 49.3%, p <0.05). Characteristic rectal activity was seen during defecation and voiding but no bladder-rectum interaction was detected. CONCLUSIONS: We identified 3 rectal motility patterns in all children with overactive bladder. Like the upper gastrointestinal tract, the rectum shows some periodic motor activity, which is more frequent at night. No association was observed between bladder and rectal activity during micturition and defecation.

Transcutaneous electrical nerve stimulation for refractory daytime urinary urge incontinence.

PURPOSE: We studied the effect of transcutaneous electrical nerve stimulation in children with overactive bladder and treatment refractory daytime urinary incontinence. MATERIALS AND METHODS: We recruited 27 children 5 to 14 years old with daytime urge incontinence refractory to timer assisted standard urotherapy and anticholinergics who had normal urinalysis, and unremarkable urinary tract ultrasound and physical examination. Study exclusion criteria were bladder underactivity, lower urinary tract obstruction, ongoing defecation disorders, lower urinary tract surgery and previous transcutaneous electrical nerve stimulation. After a 2-week run-in of standard urotherapy the children underwent natural fill ambulatory urodynamics to confirm detrusor overactivity. Subsequently they were randomly allocated to 4 weeks of 2 hours of daily active or placebo S2-S3 transcutaneous electrical nerve stimulation. The severity of incontinence and urgency, and 48-hour bladder diaries were recorded before randomization and during intervention week 4. Children withdrew from anticholinergics throughout the study period. RESULTS: Two children were excluded from randomization due to urodynamic signs of lower urinary tract obstruction. After 4 weeks of intervention 8 children (61%) in the active group showed a significant decrease in incontinence severity but this occurred in only 2 (17%) in the sham treated group (p <0.05). The active group had a significantly greater decrease in daily incontinence episodes compared to the sham treated group (p <0.01). Transcutaneous electrical nerve stimulation did not alter maximal and average voided volumes. CONCLUSIONS: Sacral transcutaneous electrical nerve stimulation seems superior to placebo for refractory daytime incontinence in children with overactive bladder. This effect does not seem to be a consequence of improved bladder reservoir function.

Treatment outcome of day-time urinary incontinence in children.

OBJECTIVE: To analyse retrospectively the efficacy of day-time incontinence treatment in a secondary referral centre and consider characteristics of responders to the different therapeutic interventions. MATERIAL AND METHODS: All children treated for day-time urinary incontinence at the authors' clinics from 2000 to 2004 were included. Children with ongoing urinary tract infections were excluded. Before treatment, children filled out registrations of incontinence episodes and 48h frequency-volume charts. Faecal disorders were treated before urinary incontinence. All children were subjected to standard urotherapy and were secondarily recommended a timer-watch. If standard urotherapy had no effect, anticholinergics were added. RESULTS: The study included 240 children with day-time urinary incontinence. Of these, 45 had faecal problems and 17% obtained urinary continence when these were successfully treated. In total, 126 (55%) became dry on standard urotherapy. Of the 60 children who had a timer-watch in addition to standard urotherapy, 70% became dry. Of the 62 children who had anticholinergics in addition to standard urotherapy, 81% became continent. Fifteen (6%) did not achieve continence and another 11 patients were lost to follow-up. Children who became dry solely on standard urotherapy had a significantly lower voiding frequency (p<0.05), larger voided volumes as a percentage of those expected for age (p<0.01) and fewer incontinence episodes per week (p<0.05) than children needing anticholinergics. CONCLUSIONS: Most children achieve day-time continence solely on standard urotherapy. Children who need anticholinergics to achieve dryness seem to be those with more severe bladder reservoir function abnormalities and symptoms.

The impact of daytime diuresis on voiding frequency and incontinence classification in children.

PURPOSE: Daytime voiding frequency is an important criterion in the classification of childhood incontinence. The aim of this study was to assess the relative impact of diuresis and bladder capacity on voiding frequency. MATERIALS AND METHODS: We analyzed data from 570 children 4 to 15 years old (median age 8.3 +/- 2.0 years) treated for urinary incontinence at a secondary referral center, and 87 healthy controls. Based on frequency-volume charts, daytime voiding frequency, age adjusted maximum voided volume, daytime diuresis and fluid intake were calculated. Children were classified according to voiding frequency into 3 groups-decreased (fewer than 3 voids daily), normal (3 to 7) and increased voiding frequency (more than 7). RESULTS: A total of 219 children had monosymptomatic enuresis, while 351 children presented with daytime symptoms. In children with daytime symptoms we found a significant difference between voiding frequency groups regarding daytime diuresis (decreased voiding frequency 12.3 +/- 4.1 ml/kg, normal 18.7 +/- 6.0 ml/kg, increased 31.1 +/- 9.8 ml/kg, p <0.001). In contrast, maximum voided volume observed/expected bladder capacity for age did not differ significantly between normal and increased frequency groups (72% +/- 25% vs 74% +/- 23%), compared to patients with decreased voiding frequency (89% +/- 30%, p <0.01). Also, in healthy children we found a positive correlation between voiding frequency and daytime diuresis, whereas maximum voided volume observed/expected bladder capacity for age did not correlate with voiding frequency. Furthermore, we observed a significant positive correlation between fluid intake and diuresis (r = 0.53, p <0.001). CONCLUSIONS: In healthy controls and children with incontinence daytime voiding frequency depends mainly on diuresis, and seems less influenced by bladder capacity. Diuresis should be taken into consideration when evaluating voiding frequency from frequency-volume charts in children.

Transabdominal ultrasound of rectum as a diagnostic tool in childhood constipation.

PURPOSE: We tested whether transverse rectal diameter measured by ultrasound could identify rectal impaction, investigated whether transverse diameter is enlarged in constipated children compared to healthy children and evaluated transverse diameter during treatment of constipation. MATERIALS AND METHODS: A total of 51 children 4 to 12 years old were included in the study. Of the children 27 (mean age 7.0 +/- 1.8 years) had been diagnosed with chronic constipation by Rome III criteria and 24 (9.1 +/- 2.7 years) were healthy controls. All patients underwent a thorough medical history and physical examination, including digital rectal examination and measurement of rectal diameter by transabdominal ultrasound. Constipated children underwent repeat investigations after 4 weeks of laxative treatment. RESULTS: Average rectal diameter of children with negative digital rectal examination was 21 +/- 4.2 mm (mean +/- SD), leading to the approximation that a value greater than 29.4 mm (mean +/- 2 SD) indicates rectal impaction. All children with rectal impaction identified by digital examination had a rectal diameter larger than 29.4 mm. Moreover, constipated children had a significantly larger rectal diameter (42.1 +/- 15.4 mm) than healthy children (21.4 +/- 6.0 mm, p <0.001). After 4 weeks of laxative treatment constipated children had a significant reduction in rectal diameter (mean 26.9 +/- 5.6 mm, p <0.001). CONCLUSIONS: Transverse rectal diameter seems to be a valuable tool to identify rectal impaction and may replace digital rectal examination. Constipated children have a significantly larger rectal diameter compared to healthy children, and when constipation is treated the diameter is reduced significantly.

Combination of the enuresis alarm and desmopressin: second line treatment for nocturnal enuresis.

PURPOSE: We sought to evaluate the combination of the enuresis alarm and desmopressin in treating children with enuresis. MATERIALS AND METHODS: A retrospective analysis was performed on data from 423 children treated at our clinics with the enuresis alarm during the years 2000 to 2004. Frequency volume charts and desmopressin titration facilitated characterization of the participants using the current International Children's Continence Society standardization. Children were treated with the enuresis alarm as monotherapy before the addition of desmopressin, which commenced after 6 weeks in patients exhibiting inadequate response to alarm or after 2 weeks in patients experiencing multiple enuretic episodes per night or showing no indication of improvement. RESULTS: Of the initial population 315 children (74%) were treated only with alarm, of whom 290 became dry. A total of 108 children (26%) were treated with a combination of alarm and desmopressin, with 80 being cured. Children dry on alarm therapy were not different from those needing the addition of desmopressin in terms of demographics. Children dry on desmopressin plus alarm had higher average nocturnal urine production on wet nights (303 +/- 12 ml compared to 269 +/- 5 ml, p <0.001). Maximum voided volume before treatment corrected for age was not different between children dry on alarm and those dry on combination therapy (0.84 +/- 0.02 compared to 0.86 +/- 0.05, not significant). CONCLUSIONS: Children needing the addition of desmopressin have a higher nocturnal urine production on wet nights but do not seem to differ in terms of bladder reservoir function characteristics.

Bladder reservoir function in children with monosymptomatic nocturnal enuresis and healthy controls.

PURPOSE: We investigated bladder reservoir function in children with monosymptomatic nocturnal enuresis and in healthy controls. MATERIALS AND METHODS: A total of 18 children with monosymptomatic nocturnal enuresis and 119 controls who were 7 to 13 years old were recruited. Children completed frequency volume charts and measurements of nocturnal urine production. Mean diuresis in the period preceding each voiding was calculated. Those with enuresis were grouped according to bladder capacity and hospitalized for 4 nights, including a baseline night and 3 with an oral water load. Enuresis volumes and post-void residual volume were estimated, allowing the calculation of bladder volume at the time of enuresis. RESULTS: Nine children with monosymptomatic nocturnal enuresis were characterized as having normal bladder capacity and 9 had decreased bladder capacity. We found large intra-individual variability in daytime voided volume in all 3 groups of participants. Children with enuresis and small bladder capacity generally voided with volumes close to maximal voided volume. A total of 93 enuresis episodes were recorded. Large intra-individual variability was seen in bladder volume at enuresis and it was lower than maximal voided volume in more than 50% of episodes. Variability in bladder volume at enuresis was greatest in the patient group with decreased bladder capacity. We found a significant correlation between diuresis and bladder capacity in all groups during the day and night. CONCLUSIONS: There is a great intra-individual diurnal variability in voided volume in children with enuresis and in healthy children. Enuresis seems to occur at bladder volumes that are smaller and larger than the maximal voided volume obtained from voiding charts.

Urinary calcium excretion in healthy children and children with primary monosymptomatic nocturnal enuresis.

PURPOSE: We investigated the role of urinary Ca excretion in monosymptomatic nocturnal enuresis, and defined normality and intra-individual variability in Ca excretion in healthy children. MATERIALS AND METHODS: We included 46 Danish children with desmopressin resistant nocturnal enuresis and 96 healthy controls. We performed fractional urine collections at home during 2 days in controls or during hospitalization in children with enuresis. Urine volume, osmolality, and Ca and creatinine measurements were performed and Ca-to-creatinine ratios were calculated and compared between groups. Based on nocturnal urine output children with enuresis were characterized as having polyuria (nocturnal urine volume greater than 130% of expected bladder capacity) or not having polyuria. RESULTS: We did not find any differences in controls compared with children with enuresis who did not and did have nocturnal polyuria in daytime Ca excretion (mean +/- SE 0.121 +/- 0.012, 0.078 +/- 0.014 and 0.095 +/- 0.020 mg/mg creatinine), nighttime Ca excretion (0.115 +/- 0.011, 0.092 +/- 0.019 and 0.139 +/- 0.029 mg/mg creatinine) or 24-hour Ca excretion (0.118 +/- 0.011, 0.083 +/- 0.014 and 0.106 +/- 0.020 mg/mg creatinine, respectively). Urinary Ca excretion was not influenced by patient age, sex or body weight and, furthermore, we did not find evidence of diurnal variation. However, we observed considerable intra-individual variability in diurnal, nocturnal and total 24-hour urinary Ca-to-creatinine ratios. CONCLUSIONS: These observations contradict several previous reports and speculations on a role of Ca in the pathogenesis of nocturnal enuresis.