ABSTRACT
PURPOSE: To outline the prevalence of vitamin D and vitamin B12 deficiencies in enuretic children. METHODS: An analytical descriptive study was conducted on enuretic children who were followed up at the outpatient clinic for nocturnal enuresis at the Children's Hospital, Cairo University. Sociodemographic and clinical data were recorded. The levels of vitamin D and vitamin B12 were assessed and correlated with the severity of enuresis. RESULTS: Two hundred and eighty-eight children were enrolled. Insufficiency of Vitamin D predominated (n = 139; 48.3%). Vitamin D deficiency was present in 31.3%, n = 90 and it was normal in 20.5%, n = 59). Vitamin B12 deficiency was observed in 25% of the studied children, n = 72). The one-sample Wilcoxon signed-rank test was significant for both vitamins (P value =0.001). Vitamin D showed a stronger inverse correlation with the number of enuresis episodes per day than vitamin B12 (-0.680 vs. -0.219 respectively). A cut-off of 13.7 ng/ml for vitamin D was detected, below which the child was predicted to have failed dry nights. Using multivariate logistic regression, higher vitamin D levels and behavioural treatment coexistence were significant protective factors for the absence of dry nights. CONCLUSION: Low levels of vitamin D and B12 were detected in children with primary nocturnal enuresis, which could be considered a burden on the clinical severity of enuresis.
What is already known on this topic?Children with Primary Nocturnal Enuresis may have vitamin D and vitamin B12 abnormalities as deficienciesWhat does this study add?Vitamin D insufficiency may be the most prevalent vitamin D abnormality in children with primary nocturnal enuresis. Vitamin D insufficiency may be more common in children with severe enuresis than vitamin B12 deficiency.How might this study affect research, practice, or policy?This study may invite further research to examine the possible use of vitamin D and vitamin B12 as potential adjuvant therapies for children with Primary Nocturnal Enuresis.
Subject(s)
Nocturnal Enuresis , Vitamin B 12 Deficiency , Vitamin B 12 , Vitamin D Deficiency , Vitamin D , Humans , Child , Male , Female , Nocturnal Enuresis/blood , Nocturnal Enuresis/epidemiology , Cross-Sectional Studies , Vitamin D/blood , Vitamin B 12/blood , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/blood , Vitamin B 12 Deficiency/epidemiology , Vitamin B 12 Deficiency/blood , Prevalence , Egypt/epidemiology , Child, Preschool , AdolescentABSTRACT
Background/aim: Nocturnal enuresis can be frustrating for children and their families as the child ages. Our aim is to evaluate urine aquaporin 2 (AQP-2) as a noninvasive biomarker of water balance in children with primary monosymptomatic nocturnal enuresis (PMNE). Material and methods: The study included 90 children; sixty-eight children suffering from PMNE aged (9.57 ± 2.16) years and 22 healthy children with good toilet control, matched sex and age. All enuretic children were subjected to complete history taking, clinical evaluation, and bed wetting diary. Serum arginine vasopressin (AVP) and urine AQP-2 were tested in the morning (at 9-11 am) and evening (at 9-11 pm). Blood urea, creatinine, Na, glucose, urine osmolality, Ca/Cr, Alb/Cr and specific gravity were tested simultaneously. Results: Serum AVP, urine AQP-2, and urine osmolality were statistically lower in patients than controls. Patients had a significantly lower level of night serum AVP concentrations, urine AQP-2, and urine osmolality than the corresponding morning level. Urine AQP-2 was significantly correlated with urine osmolality (p < 0.05). AQP-2 had a sensitivity of 90% and a specificity of 70%. However, no statistically significant correlation was found between serum AVP and urine AQP-2. Conclusion: Primary monosymptomatic nocturnal enuresis in children could be associated with reduction of urine excretion of AQP-2 at night. Urine AQP-2 is significantly correlated with urine osmolality. Therefore, it may be a noninvasive biomarker of hydration status in children with PMNE, with good sensitivity and specificity.
Subject(s)
Aquaporin 2 , Biomarkers , Circadian Rhythm , Nocturnal Enuresis , Humans , Child , Nocturnal Enuresis/urine , Nocturnal Enuresis/blood , Male , Female , Aquaporin 2/urine , Circadian Rhythm/physiology , Biomarkers/urine , Biomarkers/blood , Osmolar Concentration , Case-Control Studies , Arginine Vasopressin/blood , Arginine Vasopressin/urine , AdolescentABSTRACT
OBJECTIVE: To study the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of desmopressin (dDAVP) oral lyophilisate in children below the age of 8 years with special emphasis on age-related and size-related differences in bioavailability. DESIGN: Open label, non-randomised, interventional PK and PD trial. SETTING: Single-centre study. PATIENTS: Children (age: 6 months to 8 years) with nocturnal polyuria, including both children with uropathy or nephropathy (glomerular filtration rate >60 mL/min/1.73 m²) and children (age: 5-8 years) with severe monosymptomatic nocturnal enuresis, who were unresponsive to treatment with 400 µg of the dDAVP tablet for at least 1 month. INTERVENTIONS: After a water load, dDAVP was administered sublingually as a single dose of oral lyophilisate. Subsequently, blood and urine samples were collected until 7 hours post-administration. MAIN OUTCOME MEASURES: Non-compartmental analysis of PK parameters was performed based on dDAVP concentrations in both plasma and urine. To evaluate the effect of dDAVP lyophilisate (PD parameters), the urinary concentration capacity (urine osmolality (mOsm/kg)) and antidiuretic effect (diuresis rate (mL/kg/h)) were calculated. RESULTS: The PK data support the need for size-dependent dosing in children. Body weight was shown to be a significant covariate for apparent clearance (CL/F) and apparent volume of distribution (Vd/F). A double absorption peak of dDAVP lyophilisate in the first 2 hours post-administration was demonstrated. CONCLUSIONS: For the first time, a double absorption profile of dDAVP lyophilisate was found in children, questioning extrapolation of bioequivalence from adults towards children. Moreover, the need for size-adapted dosing regimens of dDAVP lyophilisate in young children is indicated. TRIAL REGISTRATION NUMBER: NTC02584231.
Subject(s)
Antidiuretic Agents/pharmacokinetics , Deamino Arginine Vasopressin/pharmacokinetics , Nocturnal Enuresis/drug therapy , Administration, Oral , Antidiuretic Agents/administration & dosage , Biological Availability , Child , Child, Preschool , Deamino Arginine Vasopressin/administration & dosage , Female , Humans , Infant , Male , Nocturnal Enuresis/blood , Tablets , Therapeutic EquivalencyABSTRACT
OBJECTIVES: Enuresis is one of the most frequently seen psycho-social problems in childhood, which causes anxiety and stress in the child, thus affecting his/her self-respect and quality of life. The aim of the study was to determine the role of bladder function or psychologic factors or both as factors causing enuresis. METHODS: This study on pediatric patients with primary enuresis included 30 patients with monosymptomatic nocturnal enuresis (MonoNE), 30 patients with polysymptomatic nocturnal enuresis (PolyNE), and 30 healthy controls, making a total of 90 subjects with an age range of 8-18. In all subjects, the levels of serum and urinary Brain-Derived Neurotrophic Factor (BDNF) were measured, in addition to urinary creatinine levels and calculated as BDNF/Cr ng/mg creatinine (BDNF/ Cr). RESULTS: The serum BDNF results of the PolyNE group (0.949±0.587) were significantly lower than those of the control group (1.158±0.587) (p=0.014). The urinary BDNF results of the PolyNE group (1.107±0.360) were significantly higher than those of both the MonoNE (0.657±0.272) and the control (0.670±0.271) groups (p<0.0001). The BDNF/Cr results of the PolyNE group (1.472±0.714) were significantly higher than those of the MonoNE group (0.956±1.017) and the control group (0.931±0.618) (p=0.044 and p=0.032, respectively). CONCLUSIONS: In addition to bladder-specific problems, it is possible for anxiety and psychological stress-induced problems to occur in PolyNE. Therefore, in addition to the increasing number of studies on the bladder in enuresis, further studies on the neurogenic and psychogenic aspects of enuresis should be carried out.
OBJETIVOS: La enuresis es uno de los problemas psicosociales más frecuentes en la infancia, que causa ansiedad y estrés a los niños, afectando a su autoestima y calidad de vida. El objetivo de este estudio es la determinación del papel de la función vesical, los factores psicológicos o ambos como factores causales de la enuresis.MÉTODOS: Este estudio en pacientes pediátricos con enuresis incluyó 30 pacientes con enuresis nocturna monosintomática (ENmono), 30 pacientes con enuresis nocturna polisintomática (ENpoli) y 30 controles sanos, sumando un total de 90 individuos con un rango de edad entre 8-18 años. En todos los casos se midieron los niveles séricos y urinarios de factor neurotrófico derivado del cerebro (FNDC), además de los niveles de creatinina urinaria y se hizo el cálculo de FNDC/Cr ng/mg creatinina. RESULTADOS: Los resultados de FNDC sérico en el grupo ENpoli (0,949±0,587) fueron significativamente menores que los del grupo control (1,158±0,587) (p=0,014). Los resultados de FNDC urinario en el grupo de ENpoli (1,107±0,360) fueron significativamente mayores que los de los grupos ENmono (0,657±0,272) y control (0,670±0,271) (p<0,0001). Los resultados de FNDC/Cr el grupo ENpoli (1,472±0,714) eran significativamente mayores que los de los grupos ENMono (0,956±1,017) y control (0,931±0,618) (p=0,044 y p=0,032, respectivamente). CONCLUSIONES: Además de problemas específicos vesicales, es posible que los problemas de ansiedad e inducidos por estrés psicológico ocurran en la ENPoli. Por lo tanto, además del creciente número de estudios sobre la vejiga en enuresis, es necesario desarrollar más estudios sobre los aspectos neurogénicos y psicogénicos de la enuresis.
Subject(s)
Anxiety , Brain-Derived Neurotrophic Factor , Nocturnal Enuresis , Stress, Psychological , Urinary Incontinence , Brain-Derived Neurotrophic Factor/blood , Brain-Derived Neurotrophic Factor/urine , Child , Female , Humans , Male , Nocturnal Enuresis/blood , Nocturnal Enuresis/psychology , Nocturnal Enuresis/urine , Quality of Life , Urinary BladderABSTRACT
OBJECTIVES: Enuresis is one of the most frequently seen psycho-social problems in childhood, which causes anxiety and stress in the child, thus affecting his/her self-respect and quality of life. The aim of the study was to determine the role of bladder function or psychologic factors or both as factors causing enuresis. METHODS: This study on pediatric patients with primary enuresis included 30 patients with monosymptomatic nocturnal enuresis (MonoNE), 30 patients with polysymptomatic nocturnal enuresis (PolyNE), and 30 healthy controls, making a total of 90 subjects with an age range of 8-18. In all subjects, the levels of serum and urinary Brain-Derived Neurotrophic Factor (BDNF) were measured, in addition to urinary creatinine levels and calculated as BDNF/Cr ng/mg creatinine (BDNF/ Cr). RESULTS: The serum BDNF results of the PolyNE group (0.949 ± 0.587) were significantly lower than those of the control group (1.158 ± 0.587) (p = 0.014). The urinary BDNF results of the PolyNE group (1.107 ± 0.360) were significantly higher than those of both the MonoNE (0.657 ± 0.272) and the control (0.670 ± 0.271) groups (p < 0.0001). The BDNF/Cr results of the PolyNE group (1.472 ± 0.714) were significantly higher than those of the MonoNE group (0.956 ± 1.017) and the control group (0.931 ± 0.618) (p = 0.044 and p = 0.032, respectively). CONCLUSIONS: In addition to bladder-specific problems, it is possible for anxiety and psychological stress-induced problems to occur in PolyNE. Therefore, in addition to the increasing number of studies on the bladder in enuresis, further studies on the neurogenic and psychogenic aspects of enuresis should be carried out
OBJETIVOS: La enuresis es uno de los problemas psicosociales más frecuentes en la infancia, que causa ansiedad y estrés a los niños, afectando a su autoestima y calidad de vida. El objetivo de este estudio es la determinación del papel de la función vesical, los factores psicológicos o ambos como factores causales de la enuresis. MÉTODOS: Este estudio en pacientes pediátricos con enuresis incluyó 30 pacientes con enuresis nocturna monosintomática (ENmono), 30 pacientes con enuresis nocturna polisintomática (ENpoli) y 30 controles sanos, sumando un total de 90 individuos con un rango de edad entre 8-18 años. En todos los casos se midieron los niveles séricos y urinarios de factor neurotrófico derivado del cerebro (FNDC), además de los niveles de creatinina urinaria y se hizo el cálculo de FNDC/Cr ng/mg creatinina. RESULTADOS: Los resultados de FNDC sérico en el grupo ENpoli (0,949 ± 0,587) fueron significativamente menores que los del grupo control (1,158 ± 0,587) (p = 0,014). Los resultados de FNDC urinario en el grupo de ENpoli (1,107 ± 0,360) fueron significativamente mayores que los de los grupos ENmono (0,657 ± 0,272) y control (0,670 ± 0,271) (p < 0,0001). Los resultados de FNDC/Cr el grupo ENpoli (1,472 ± 0,714) eran significativamente mayores que los de los grupos ENMono (0,956 ± 1,017) y control (0,931 ± 0,618) (p = 0,044 y p = 0,032, respectivamente). CONCLUSIONES: Además de problemas específicos vesicales, es posible que los problemas de ansiedad e inducidos por estrés psicológico ocurran en la ENPoli. Por lo tanto, además del creciente número de estudios sobre la vejiga en enuresis, es necesario desarrollar más estudios sobre los aspectos neurogénicos y psicogénicos de la enuresis
Subject(s)
Humans , Male , Female , Child , Anxiety , Brain-Derived Neurotrophic Factor/blood , Brain-Derived Neurotrophic Factor/urine , Nocturnal Enuresis/blood , Nocturnal Enuresis/psychology , Nocturnal Enuresis/urine , Stress, Psychological , Urinary Incontinence , Quality of Life , Urinary BladderABSTRACT
BACKGROUND: Nocturnal enuresis is defined as bed-wetting in children from the age of five years that occurs during sleep; if untreated, the condition can result in social and psychological problems both for the children and their parents. Nocturnal enuresis is a complicated disease that includes multiple pathogenetic factors. Nocturnal enuresis is divided into two subgroups: monosymptomatic and non-monosymptomatic. The role of some biomarkers in patients with monosymptomatic enuresis has been reported in a small number of the studies. OBJECTIVE: The aim of this research was to evaluate the serum levels of copeptin and corticotropin-releasing factor (CRF) in monosymptomatic and non-monosymptomatic nocturnal enuresis cases. Although these markers were previously examined in children with monosymptomatic enuresis, there is no study that has evaluated these markers in non-monosymptomatic children. STUDY DESIGN: One hundred nineteen children with nocturnal enuresis (5-16 years) and forty healthy children (5-17 years) were enrolled to the study. Of the nocturnal enuresis group, forty-nine were monosymptomatic and seventy were non-monosymptomatic. Copeptin and CRF were measured by a competitive inhibition method with enzyme-linked immunosorbent assay. RESULTS: The serum copeptin levels were significantly lower in children with monosymptomatic and non-monosymptomatic nocturnal enuresis than in the controls.(median, 34.7 [interquartile range (IQR): 34 pg/ml], 39.8 [IQR: 29 pg/ml] vs 52.1 [IQR: 14 pg/ml], respectively, P < 0.05). The serum CRF levels were significantly lower in children with monosymptomatic and non-monosymptomatic nocturnal enuresis than in the controls (median, 35.1 [IQR: 19 pg/ml], 34.05 [IQR: 24 pg/ml] vs 78.3 [IQR: 39 pg/ml], respectively, P < 0.05). There was no significant difference in copeptin and CRF levels between the children with monosymptomatic and non-monosymptomatic nocturnal enuresis. DISCUSSION: Copeptin is presumed to be a sensitive surrogate biomarker for arginine vasopressin release. To date, there are only two studies in the literature that assess the relationship between copeptin and monosymptomatic enuresis. The only study in the literature demonstrated significantly decreased levels of CRF in monosymptomatic enuretic children. It was demonstrated that the levels of copeptin and CRF differ in both children with monosymptomatic and non-monosymptomatic nocturnal enuresis from the control groups. It was also demonstrated that copeptin and CRF levels were not different between the children in monosymptomatic and non-monosymptomatic groups. CONCLUSION: Those changes in both copeptin and CRF which were shown in this study in monosymptomatic and non-monosymptomatic enuretic children may contribute to the pathogenesis of nocturnal enuresis. Further case-control studies can evaluate the copeptin and CRF levels before treatments in monosymptomatic and non-monosymptomatic patients to decide potential effectiveness of treatment.
Subject(s)
Corticotropin-Releasing Hormone/blood , Glycopeptides/blood , Nocturnal Enuresis/blood , Urination/physiology , Adolescent , Biomarkers/blood , Child , Child, Preschool , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Male , Nocturnal Enuresis/physiopathology , Prospective StudiesABSTRACT
PURPOSE: For a new formulation of a drug, only pharmacokinetic bioequivalence with the original formulation has to be demonstrated in healthy, young adults. However, "children are not small adults," and to guarantee a safe and effective treatment, age-adapted drug development is required. Desmopressin, a vasopressin analogue prescribed for nocturnal enuresis in children, was studied as an example formulation first developed in adults and then extrapolated to a pediatric indication. METHODS: Population pharmacokinetic and pharmacodynamic modeling was used to analyze previously published desmopressin data of 18 children suffering from nocturnal enuresis. The main objective was the comparison of the therapeutic equivalence of two desmopressin formulations: tablet and lyophilisate. The measurements for pharmacokinetics and pharmacodynamics were respectively plasma desmopressin concentration and urine osmolality and diuresis. RESULTS: The half maximal inhibitory concentration for inhibition of urine production was 0.7 pg/mL lower for the lyophilisate than for the tablet. The effect of formulation on the half maximal inhibitory concentration seems to suggest that the 120-µg lyophilisate has a more pronounced effect on the urine volume and osmolality than the 200-µg tablet, even when the same exposure is achieved. CONCLUSIONS: A new indirect response model for desmopressin was constructed and validated, using a previously built pharmacokinetic model and additional pharmacodynamic data. In order to draw solid conclusions regarding the efficacy and safety of desmopressin in children, pharmacokinetics and pharmacodynamics data should be analyzed together. This study adds proof to potential differences in pediatric and adult pharmacokinetic and pharmacodynamic properties of desmopressin and exemplifies the need for pediatric clinical trials, not only for every new drug but also for every new formulation.
Subject(s)
Antidiuretic Agents/administration & dosage , Deamino Arginine Vasopressin/administration & dosage , Drug Compounding , Models, Biological , Nocturnal Enuresis/drug therapy , Administration, Sublingual , Adolescent , Age Factors , Antidiuretic Agents/blood , Antidiuretic Agents/pharmacokinetics , Antidiuretic Agents/therapeutic use , Child , Cross-Over Studies , Deamino Arginine Vasopressin/blood , Deamino Arginine Vasopressin/pharmacokinetics , Deamino Arginine Vasopressin/therapeutic use , Female , Freeze Drying , Humans , Kidney Concentrating Ability/drug effects , Male , Needs Assessment , Nocturnal Enuresis/blood , Nocturnal Enuresis/urine , Osmolar Concentration , Pilot Projects , Tablets , UrinalysisABSTRACT
PURPOSE: Desmopressin is a synthetic V2 specific analogue of antidiuretic hormone (arginine vasopressin) that is widely used as first line treatment for monosymptomatic nocturnal enuresis. However, no biomarkers to predict desmopressin effectiveness have yet been established. Because arginine vasopressin is unstable, we prospectively measured the major urine concentration factor aquaporin 2 and serum copeptin (as a surrogate marker for vasopressin) in patients with monosymptomatic nocturnal enuresis, and evaluated whether they are useful for predicting desmopressin treatment outcome. MATERIALS AND METHODS: The study included 32 children 6 to 11 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria. Exclusion criteria were daytime urinary symptoms and underlying diseases causing nocturnal enuresis. Subjects were treated with 120 µg or 240 µg desmopressin oral disintegrating tablet and were divided into responders (at 120 or 240 µg) and nonresponders (at 240 µg). Day/night ratios of plasma copeptin and urinary aquaporin 2 were measured during desmopressin treatment. RESULTS: There was no significant difference in baseline day/night ratio of urinary aquaporin 2 between desmopressin responders and nonresponders. After 8 weeks of treatment there was a significant correlation between day/night ratio of aquaporin 2 and percentage of wet nights. In responders (but not nonresponders) there was a significant difference in the change in aquaporin 2 day/night ratio from before treatment to complete remission (p = 0.0004). For plasma copeptin the baseline day/night ratio for responders at 120 µg was significantly lower than in the 240 µg nonresponder group (p = 0.02). CONCLUSIONS: Urinary aquaporin 2 appears to be a biomarker of desmopressin treatment effectiveness during therapy, while plasma copeptin levels before treatment are predictive of desmopressin response.
Subject(s)
Antidiuretic Agents/therapeutic use , Aquaporin 2/urine , Deamino Arginine Vasopressin/therapeutic use , Glycopeptides/blood , Nocturnal Enuresis/drug therapy , Biomarkers, Pharmacological/blood , Biomarkers, Pharmacological/urine , Child , Female , Humans , Male , Nocturnal Enuresis/blood , Nocturnal Enuresis/urine , Predictive Value of Tests , Prospective Studies , Recurrence , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: Primary nocturnal enuresis is one of the sleep related phenomena characterized by disruption in the relationship between arousal and urination. Corticotropin-releasing factor (CRF) is a neurohormone released from the paraventricular nucleus of the hypothalamus into the median eminence to elicit release of adrenocorticotrophin from the anterior pituitary. It may act to modulate autonomic function and behavior in concert with the endocrine effects. Conflicting animal studies about the role of CRF in micturition, either facilitating or inhibiting, have been raised. It was suggested to be a novel target for treatment of urinary disorders based on the finding that manipulation of CRF in the pontine micturition circuit could affect urodynamic function. AIM: The aim was to throw light on the possible role of CRF in primary monosymptomatic nocturnal enuresis by assessing its serum level. SUBJECTS AND METHODS: Twenty-nine children aged 8-14 years complaining of primary monosymptomatic nocturnal enuresis and 16 age- and sex-matched healthy children with good toilet control day and night were recruited to the study. History taking, clinical examination, and assessment of serum CRF levels in the morning and evening (9 a.m. and 9 p.m.) were carried out for all patients and controls. RESULTS AND DISCUSSION: A positive family history of enuresis was detected in 82.8% of enuretic patients. Serum levels of CRF (both morning and evening) were significantly lower in patients than in controls. Several animal studies suggested that CRF in descending projections from Barrington's nucleus to the lumbosacral parasympathetic neurons is inhibitory to micturition, which supports our results and the assumption that reduction of the evening serum CRF level could have a role in the occurrence of primary monosymptomatic nocturnal enuresis. No significant difference was found between morning and evening CRF serum levels in either cases or controls, which negates our assumption of having a rhythmic pattern of release (figure). No correlations with age were found. According to their history, all our enuretic patients were deep sleepers. Deep sleep and difficult arousal were found to have a major role in primary monosymptomatic nocturnal enuresis. It was proposed that CRF function may allow arousal to occur before micturition to facilitate preparative behaviors. A lower CRF level may explain deep-sleep pattern in children with enuresis. CONCLUSION: CRF was deficient in our enuretic children, which may draw attention to the possible pathophysiological implications in primary nocturnal enuresis (either at the level of loss of inhibitory effect on micturition or lack of arousal in response to bladder distension). Further proof studies are recommended.
Subject(s)
Corticotropin-Releasing Hormone/blood , Nocturnal Enuresis/blood , Nocturnal Enuresis/physiopathology , Adolescent , Biomarkers/blood , Case-Control Studies , Child , Egypt , Female , Humans , Male , Nocturnal Enuresis/epidemiology , Predictive Value of Tests , Prognosis , Reference Values , Severity of Illness Index , UrodynamicsABSTRACT
BACKGROUND: Vitamin D has been recognized to contribute to various physiological processes. However, no study has investigated serum 25-hydroxyvitamin D [25(OH)D] concentrations in children with nocturnal enuresis (NE) in the English literature. OBJECTIVE: In the present study, serum 25(OH)D concentrations were measured in five- to seven-year-old children with NE and compared with those in non-enuretic children to investigate whether there was any relationship between 25(OH)D and NE as the first time in the literature. DESIGN: Two hundred forty-seven five- to seven-year-old children were recruited from Taizhou, Zhejiang Province, China. Serum 25(OH)D concentrations were measured, and the structured questionnaire was administered to the parents of all children. Low 25(OH)D was defined as serum 25(OH)D concentrations below 20 ng/ml. RESULTS: The prevalence of NE was 7.3% in the group of children with 25(OH)D concentrations that exceeded 20 ng/ml; this prevalence was much lower than the 17.5% observed in the group of children with 25(OH)D concentrations below 20 ng/ml (p<0.05). After adjusting for potential confounders, serum 25(OH)D (≥20 ng/ml) was significantly associated with NE and represented a protective factor against NE (ORâ=â0.31, 95%CIâ=â0.092, 1.0, P<0.05). A nonlinear relationship between 25(OH)D and NE was observed. The prevalence of NE decreased with increasing 25(OH)D concentrations above 19 ng/ml. Additionally, children exhibiting higher frequencies of bedwetting had lower 25(OH)D concentrations [5-7 times/week: 18.3±4.8; 2-4 times/week: 20.9±4.1; 0-1 times/week: 23.6±6.4 (ng/ml), P<0.05)]. CONCLUSIONS: Low 25(OH)D was associated with an increased risk of NE in children aged five to seven years.
Subject(s)
Nocturnal Enuresis/blood , Nocturnal Enuresis/epidemiology , Vitamin D/analogs & derivatives , Child , Child, Preschool , China , Female , Humans , Male , Prevalence , Risk Factors , Surveys and Questionnaires , Vitamin D/bloodABSTRACT
Desmopressin 120 µg oral lyophilisate and 200 µg tablet are considered bioequivalent, based on extrapolation of studies in a limited number of adults and on one dose-finding study of desmopressin oral lyophilisate in children. However, no comparative pharmacokinetic study in children was executed confirming this statement. No data are available on the influence of food intake on the bioavailability of desmopressin tablet in a pediatric setting, although studies in adults have documented that food intake results in a significantly lower desmopressin plasma concentration. In this study, we analyzed plasma concentrations of desmopressin oral lyophilisate and tablet with concomitant food intake. Twenty-three children with monosymptomatic nocturnal enuresis (mean age, 12.7 years) were recruited. Two tests were performed on two separate days in identical conditions with a standardized food and fluid intake. Desmopressin was administered as desmopressin tablet or desmopressin oral lyophilisate immediately after a meal. Desmopressin plasma concentration was measured at 1 h, 2 h, and 6 h postdosing. No significant difference in plasma concentration of 120 µg desmopressin oral lyophilisate and 200 µg tablet was demonstrated, even with concomitant food intake. A significant difference in variability was found, identifying a smaller variance for desmopressin oral lyophilisate plasma concentrations at all time points. This study demonstrates comparable plasma levels for desmopressin oral lyophilisate, despite the lower dose. The dosage for desmopressin oral lyophilisate is more predictable due to the significantly smaller variance. Therefore, desmopressin oral lyophilisate seems more suitable, especially in the younger age group for which time interval between dinner and drug administration is limited.
Subject(s)
Deamino Arginine Vasopressin/administration & dosage , Deamino Arginine Vasopressin/pharmacokinetics , Freeze Drying , Nocturnal Enuresis/blood , Nocturnal Enuresis/drug therapy , Administration, Oral , Adolescent , Biological Availability , Child , Cross-Over Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Food-Drug Interactions , Humans , Male , Metabolic Clearance Rate/physiology , Tablets , Therapeutic EquivalencySubject(s)
Biomarkers/blood , Glycopeptides/blood , Nocturnal Enuresis/blood , Female , Humans , MaleABSTRACT
OBJECTIVE: To investigate the relation between copeptin, arginine vasopressin (AVP), and nocturnal enuresis (NE). METHODS: Forty-four patients with NE and 44 healthy children aged between 6 and 14 years were enrolled. Patients with nonmonosymptomatic and secondary NE were excluded from the study. A small questionnaire, filled by parents, collected information about sociodemographic characteristics. Blood was obtained for plasma AVP and copeptin concentrations. RESULTS: Copeptin levels were significantly lower in patient group (3.74 ± 1.44 pg/mL) than the control group (16.57 ± 3.91 pg/mL), whereas AVP levels were not significantly different between groups. Copeptin levels were significantly lower in patients (3.17 ± 1.15 pg/mL) who had bed-wetting 2 or more nights a week, which is considered as severe bed-wetting, than the patients (4.95 ± 1.24 pg/mL) who had bed-wetting 1 night or less than 1 night a week. CONCLUSION: This study demonstrates the presence of decreased levels of copeptin in patients with NE compared with healthy patients. AVP levels were not different between groups. To our knowledge, this is the first report assessing the relationship between copeptin and NE.
Subject(s)
Biomarkers/blood , Glycopeptides/blood , Nocturnal Enuresis/blood , Adolescent , Arginine Vasopressin/blood , Case-Control Studies , Child , Female , Humans , Male , Prospective Studies , Surveys and QuestionnairesABSTRACT
OBJECTIVE: To investigate whether primary nocturnal enuresis (PNE) is related to a disturbance in anti-diuretic hormone (ADH) secretion pattern at night which may be genetically inherited. SUBJECTS AND METHODS: This study included 121 children aged 6-18 years with PNE and 45 matched healthy children as controls. Enuretic children were subjected to genetic evaluation and cytogenetic assessment (n = 99). Assay of ADH levels (9-11 am & 9-11 pm) was performed for cases (n = 99) and controls. RESULTS: There was a positive family history in 82.4% (autosomal dominant in 35.4% and autosomal recessive in 64.6%). ADH morning and evening values were reversed in cases vs controls with significant difference in morning level. Reversal of circadian rhythm was present in 71.7% of cases and normal rhythm in 28.3% of them. Morning and evening ADH levels revealed significant difference between patients with reversed rhythm and those with normal one, and with controls. Mode of inheritance had no influence on hormonal level. Chromosomal abnormality was detected in 3 cases with reversed ADH rhythm, involving chromosome 22 in two of them. CONCLUSION: PNE could be attributed in part to reversed ADH circadian rhythm which may be linked to chromosome 22.
Subject(s)
Chromosomes, Human, Pair 22 , Genetic Testing , Nocturnal Enuresis/blood , Nocturnal Enuresis/genetics , Vasopressins/genetics , Adolescent , Child , Circadian Rhythm/genetics , Family Health , Female , Genes, Dominant , Genes, Recessive , Humans , Karyotyping , Male , Nocturnal Enuresis/metabolism , Pedigree , Vasopressins/metabolismABSTRACT
PURPOSE: Decreased nocturnal antidiuretic hormone (ADH) excretion has been suggested to be a causative factor for PNE in children. We investigate the demographic characteristics and nocturnal ADH levels of children with PNE who attended a tertiary referral center and to determine their response to treatment with desamino-D-arginine vasopressin (DDAVP). METHODS: We performed a retrospective study in 90 PNE children aged 6-12 years. We recorded the gender, height, weight, number of children per family, and psychosocial problems and compared these findings with the corresponding data obtained from a national survey. We also measured the nocturnal ADH levels and evaluated the response rate to DDAVP. RESULTS: The number of PNE patients decreased with an increase in age. Enuresis was significantly associated with male gender (P = 0.044) and more number of children per family (P = 0.043). The rates of comorbidity with defecation problems, obesity, attention-deficit hyperactivity disorder (ADHD), and overweight were 36.7, 17.8, 12.2, and 10%, respectively. Although the prevalence of obesity and ADHD was higher among children with PNE, there was no significant difference between PNE patients and their prevalence in the community. The ADH levels at 2 a.m. and 8 a.m. were 0.87 ± 0.75 and 0.89 ± 0.76 pg/ml, respectively. In the 50 (55.5%) patients who received DDAVP treatment, the complete- and partial response rates were 86 and 14%, respectively. CONCLUSIONS: Our data confirmed that PNE was predominant in boys and larger family, and similar to the findings for disease prevalence, the number of children seeking treatment tended to decrease with increasing age. Low ADH levels were recognized as a possible cause of PNE, thereby explaining the good response to DDAVP treatment in Taiwanese children with PNE.
Subject(s)
Antidiuretic Agents/therapeutic use , Deamino Arginine Vasopressin/therapeutic use , Nocturnal Enuresis/blood , Nocturnal Enuresis/drug therapy , Vasopressins/blood , Age Factors , Child , Family Characteristics , Female , Humans , Male , Nocturnal Enuresis/epidemiology , Osmolar Concentration , Retrospective Studies , Sex Characteristics , Taiwan/epidemiology , Treatment OutcomeABSTRACT
OBJECTIVES: To determine the prevalence of primary nocturnal enuresis in children, to define the possible role of sleep-disordered breathing (SDB) related to adenotonsillar hypertrophy in enuresis, to explore the role of brain natriuretic peptide (BNP) levels in measuring the severity of SDB in enuretic children, and to evaluate the response to surgical interventions (adenotonsillectomy) in indicated enuretic patients. METHODS: Parental surveys of 5-10 year-old children were reviewed for SDB and enuresis. Children with SDB were clinically and radiologically examined. Plasma BNP levels were determined in 33 children with SDB and enuresis and in 30 otherwise healthy children of whom 15 had enuresis. RESULTS: A total of 15.3% of the studied children had primary nocturnal enuresis, and 47 children with enuresis (30.7%) had SDB. There was a downward trend of enuresis and SDB as age increased. There appeared to be an association between the frequency of enuresis, snoring and adenotonsillar enlargement. Plasma BNP concentrations were significantly higher among enuretic children. All enuretic children with SDB underwent surgical intervention (33 patients), and an improvement was observed in 29 children (87.8%). Among them, 15 were cured completely, and 12 made a significant improvement in the initial 3 months, but two made just a partial improvement over one year, and four did not show any improvement over one year follow up. All enuretic children with SDB who underwent surgery exhibited a significant reduction in daytime enuresis. CONCLUSIONS: The data suggests an association between nocturnal enuresis and adenotonsillar related SDB in children. Enuresis may add to the indications for surgical intervention in this group. Increased BNP levels may account for the increased prevalence of enuresis in context of SDB.
Subject(s)
Adenoids/pathology , Natriuretic Peptide, Brain/blood , Nocturnal Enuresis/etiology , Palatine Tonsil/pathology , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/surgery , Adenoidectomy , Adenoids/surgery , Child , Child, Preschool , Female , Humans , Hyperplasia , Logistic Models , Male , Nocturnal Enuresis/blood , Palatine Tonsil/surgery , Prospective Studies , Sleep Apnea Syndromes/pathology , Tonsillectomy , Treatment OutcomeABSTRACT
OBJECTIVE: To elucidate the background behind the attenuated circadian rhythm of vasoactive hormones in patients with nocturnal enuresis, we tested the hypothesis that enuretic children exhibit an abnormal neuroendocrine response to a baroreflex stimulus during daytime. DESIGN AND PATIENTS: In fifteen children and adolescents (aged 13.4 +/- 0.9 years) with severe nocturnal enuresis and 10 age- and sex-matched healthy controls, we performed a 'daytime supine posture' (DSP) study at 10:00 h. MEASUREMENTS: Blood was sampled for measurements of plasma vasopressin (P(AVP)), angiotensin II (P(ANGII)), atrial natriuretic peptide (P(ANP)) and serum aldosterone (S(ALDO)), and mean arterial blood pressure (MAP) and heart rate (HR) were measured during the study. RESULTS: In both controls and patients with enuresis, DSP at 10:00 h resulted in a marked fall in MAP and HR, a rise in pulse pressure (PP) and estimated plasma volume (PV) and a significant suppression of P(AVP), P(ANGII) and S(ALDO), whereas P(ANP) increased. There were no significant differences between groups in haemodynamic or neuroendocrine responses to DSP. CONCLUSIONS: The study showed that children with nocturnal enuresis exhibit a normal neuroendocrine response to supine posture during daytime indicating that baroregulatory mechanisms per se are not playing a significant pathogenic role. Interestingly, the normal neuroendocrine response to supine posture seems to undergo marked circadian changes, as supine posture at night-time is associated with increased levels of vasoactive hormones.
Subject(s)
Neurosecretory Systems/physiology , Nocturnal Enuresis/physiopathology , Supine Position/physiology , Adolescent , Angiotensin II/blood , Angiotensin II/metabolism , Blood Pressure/physiology , Body Fluids/metabolism , Body Fluids/physiology , Child , Circadian Rhythm , Female , Health , Heart Rate/physiology , Humans , Male , Neurosecretory Systems/metabolism , Nocturnal Enuresis/blood , Posture/physiology , Vasopressins/blood , Vasopressins/metabolismABSTRACT
AIMS: To identify the relationship between nocturnal AVP deficiency, nocturnal polyuria (NP), and low urinary osmolality in children suffering of primary monosymptomatic nocturnal enuresis (NE). PATIENTS AND METHODS: The study included 50 children (28 males and 22 females) with primary monosymptomatic NE and 30 non enuretic children of the same age group (controls). Night samples of blood and urine were obtained for AVP, blood osmolality, and urine osmolality. In addition, volume frequency charts, arousal threshold, and urodynamics were performed for these children. RESULTS: Twenty eight (56%) of the enuretic children were considered to have NP. Mean AVP level was 44.80 +/- 8.19 and 32.49 +/- 18.25 pg/ml while mean urine osmolality was 865.07 +/- 158.66 mOsm/kg and 700.06 +/- 84.42 mOsm/kg in controls and enuretic group respectively. These differences were highly significant. No significant difference was found between the controls and enuretics without NP. On the other hand, nocturnal AVP and urine osmolality were significantly lower in enuretics with NP when compared to both controls and enuretics without NP. Blood osmolality did not reach statistically significant difference between subgroups. Arousal threshold was significantly higher in enuretic children irrespective to NP. The timing for NE episodes were predominantly late in the night in NE children without NP while patients suffering of NE with NP typically experienced multiple incidents each night. CONCLUSION: We have shown that low nocturnal AVP and urine osmolality may play a role in the pathophysiology of enuretics with NP. This abnormality doesn't occur as an isolated disease as these children suffer from arousal defect as well.
Subject(s)
Circadian Rhythm , Neurophysins/blood , Nocturnal Enuresis/etiology , Polyuria/complications , Protein Precursors/blood , Vasopressins/blood , Adolescent , Case-Control Studies , Child , Diagnostic Techniques, Urological , Female , Humans , Male , Nocturnal Enuresis/blood , Nocturnal Enuresis/physiopathology , Nocturnal Enuresis/urine , Osmolar Concentration , Polyuria/blood , Polyuria/physiopathology , Polyuria/urine , Predictive Value of Tests , ROC Curve , Sensitivity and Specificity , Sleep Arousal Disorders/complications , UrodynamicsABSTRACT
INTRODUCTION: Habitual snoring and obstructive sleep apnea have been associated with bed-wetting in children, and effective obstructive sleep apnea treatment may improve enuresis. OBJECTIVES: The purpose of this work was to assess whether habitual snoring is associated with increased incidence of enuresis and whether severity of obstructive sleep apnea correlates with enuretic frequency and to evaluate brain natriuretic peptide levels. METHODS: Parental surveys of 5- to 7-year-old children were reviewed for habitual snoring and enuresis. Enuresis was also assessed in a cohort of 378 children with habitual snoring undergoing overnight polysomnographic evaluation, and brain natriuretic peptide plasma levels were determined in 20 children with obstructive sleep apnea, 20 with habitual snoring without obstructive sleep apnea, and 20 nonsnoring children, matched for enuresis. RESULTS: There were 17,646 surveys completed (50.6% boys; 18.3% black). A total of 1976 (11.2%) of these children were habitual snoring (53% boys; 25.2% black). A total of 531 habitual snoring children also had enuresis (26.9%), with a predominant representation of boys (472 boys [87.5%]). Among the 15670 nonsnoring children, enuresis was reported in 1821 children (11.6%), of whom 88.8% were boys. However, enuresis among 378 children with habitual snoring did not correlate with the magnitude of sleep respiratory disturbances. Indeed, enuresis was reported in 33 of 149 children with obstructive sleep apnea (obstructive apnea hypopnea index: >2 per hour of total sleep time; 53% boys) as compared with 36 habitual snoring children with enuresis (62% boys) and obstructive apnea hypopnea index <2 per hour of total sleep time. Brain natriuretic peptide levels were elevated among children with enuresis and were marginally increased among children with obstructive sleep apnea. CONCLUSIONS: Habitual snoring is associated with increased prevalence of enuresis, and brain natriuretic peptide levels are increased in enuretic children with further increases with obstructive sleep apnea. However, the prevalence of enuresis is not modified by severity of sleep disturbance. Even mild increases in sleep pressure because of habitual snoring may raise the arousal threshold and promote enuresis, particularly among prone children, that is, those with elevated brain natriuretic peptide levels.
Subject(s)
Circadian Rhythm , Natriuretic Peptide, Brain/blood , Nocturnal Enuresis/blood , Sleep Apnea, Obstructive/blood , Child , Child, Preschool , Female , Humans , Male , Nocturnal Enuresis/complications , Polysomnography , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Snoring/blood , Snoring/complicationsABSTRACT
PURPOSE: We correlated the circadian rhythm of plasma arginine vasopressin and urine output profile to desmopressin response, presence or absence of an enuretic episode, and age and gender in children with nocturnal enuresis. MATERIALS AND METHODS: We studied 125 children 6 to 17 years old (mean age 10.4 +/- 3 years) with monosymptomatic nocturnal enuresis. Circadian inpatient studies were performed with standardized fluid intake, 7 blood sampling times and 6 urine collection periods. Subsequently, nocturnal urine volume was measured at home by diaper weighing for 4 weeks in 78 patients (2 weeks without treatment followed by 2 weeks of dose titration from 20 to 40 mug desmopressin at bedtime). RESULTS: The circadian studies showed that all groups of patients had an attenuated arginine vasopressin rhythm, females generally had lower circadian plasma arginine vasopressin levels than males, desmopressin responders with enuresis during the study night had the largest nocturnal urine excretion rate and most pronounced arginine vasopressin deficiency, and nocturnal urine output was significantly greater during nights with enuresis than nights without. Part of this polyuria was caused by increased sodium excretion. The home recordings confirmed higher nocturnal urine volume on enuresis nights. CONCLUSIONS: In addition to providing further pathophysiological support for the role of a nocturnal arginine vasopressin deficiency behind nocturnal polyuria in a subset of patients with enuresis, the results emphasize the clinical value of estimating nocturnal urine production on wet nights before selecting a therapeutic modality.
