Publications by authors named "Marco Zaffanello"

100 Publications

Case Report: Long-Term Tolvaptan Treatment in a Child With SIADH and Suprasellar Arachnoid Cyst.

Front Pediatr 2021 16;9:684131. Epub 2021 Jul 16.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Endocrinology Division, University of Verona, Verona, Italy.

Suprasellar arachnoid cysts represent a rare occurrence in the pediatric population and usually cause symptoms related to mass effect and can occasionally cause endocrine dysfunctions. The association between SAC and the syndrome of inappropriate antidiuretic hormone (SIADH) in the pediatric population has rarely been described previously. In most cases, SIADH is temporary and resolves by treating the underlying cause. The first-line treatment consists of fluid restriction in asymptomatic children. Oral urea and demeclocycline are other effective treatment options. Vaptans are a new class of medication for the management of SIADH. These agents are a nonpeptide vasopressin V2 receptor antagonist that selectively antagonizes the antidiuretic effect of AVP, resulting in excretion of diluted urine or "aquaresis." Their efficacy has been shown in adult patients with euvolemic or hypervolemic hyponatremia. However, evidence is lacking in pediatric patients with SIADH. We report the case of a 9-year-old female child with a SAC, who underwent endoscopic fenestration at the age of 2 years. After surgery she developed chronic hyponatremia due to SIADH. Hyponatremia was refractory to treatment with fluid restriction, oral sodium, and urea. In order to normalize serum sodium levels, tolvaptan treatment was started on a compassionate-use basis; 24-48 h later serum sodium levels returned to normal. To date, tolvaptan has been used regularly for 6 years with no side effects occurring during the treatment period. This is the first case of a child with chronic SIADH secondary to SAC successfully treated with tolvaptan. Further studies are needed to demonstrate its usefulness on a broader case series.
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http://dx.doi.org/10.3389/fped.2021.684131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322605PMC
July 2021

Thrombotic risk in children with COVID-19 infection: A systematic review of the literature.

Thromb Res 2021 09 16;205:92-98. Epub 2021 Jul 16.

Department of Hematology and Transfusion Medicine, Carlo Poma Hospital, Mantova, Italy. Electronic address:

Objective: Coagulation and inflammatory parameters are mildly altered in children with SARS-CoV-2 (COVID-19) infection, and laboratory evidence of a proinflammatory and procoagulant state has been noted in multisystem inflammatory syndrome in children (MIS-C). It is not clear whether this pediatric condition is related to thrombotic events. With this study we reviewed the literature for thrombotic complications in children with COVID-19 infection and MIS-C.

Data Sources: We searched the Medline PubMed Advanced Search Builder, Scopus, Web Of Science, and Google Scholar electronic databases (until 1 January 2021) using the medical subject headings (MeSH) terms and text words (their combinations and truncated synonyms): (THROMBOSIS OR THROMBOPHILIA) AND (CHILD OR CHILDREN OR INFANT) AND (COVID-19 OR SARS-CoV-2).

Study Eligibility Criteria: Inclusion criteria were children with COVID-19 or SARS-COV-2 infection. The search was limited to articles published in English. Exclusion criteria were: reviews of published studies, studies published only as abstracts, letters or conference proceedings, discussion papers, animal studies, or editorials.

Results: After screening for duplicates, the initial search yielded 86 records: 12 were case reports involving 19 children; comorbidities were absent or mild in 73.7%. The most common site of thrombosis the lung (21%); the most often used drug was heparin (42%). Two studies were an international survey (n = 337 patients) and a large multicenter study (n = 186 patients with MIS-C). The risk of ischemic stroke in SARS-CoV-2 infection (0.82%) and deep venous thrombosis in MIS-C (4.3%) was lower in children than in adults.

Conclusions: Thrombodic or thromboembolic events are rare in pediatric patients with COVID-19 infection and MIS-C. Nonetheless, as in adults, a high index of suspicion should be maintained in children with COVID-19 infection or MIS-C, particularly in those with comorbidities predisposing to thrombotic events.
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http://dx.doi.org/10.1016/j.thromres.2021.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284063PMC
September 2021

Bleeding Disorders in Primary Fibrinolysis.

Int J Mol Sci 2021 Jun 29;22(13). Epub 2021 Jun 29.

Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico and University of Milan, 20122 Milan, Italy.

Fibrinolysis is a complex enzymatic process aimed at dissolving blood clots to prevent vascular occlusions. The fibrinolytic system is composed of a number of cofactors that, by regulating fibrin degradation, maintain the hemostatic balance. A dysregulation of fibrinolysis is associated with various pathological processes that result, depending on the type of abnormality, in prothrombotic or hemorrhagic states. This narrative review is focused on the congenital and acquired disorders of primary fibrinolysis in both adults and children characterized by a hyperfibrinolytic state with a bleeding phenotype.
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http://dx.doi.org/10.3390/ijms22137027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268566PMC
June 2021

Convalescent Plasma for Pregnant Women with COVID-19: A Systematic Literature Review.

Viruses 2021 06 22;13(7). Epub 2021 Jun 22.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, I-37126 Verona, Italy.

The treatment of COVID-19 is particularly critical in pregnant women, considering the potential teratogenic effects of antiviral agents and the immune-depression related with pregnancy. The aim of this review is to systematically examine the current evidence on the clinical use of convalescent plasma during pregnancy. The electronic databases Medline PubMed Advanced Search Builder, Scopus, Web Of Science and Google Scholar were searched (until 1 January 2021). Inclusion criteria were pregnant women with COVID-19 (or SARS-CoV-2 infection), in whom convalescent plasma (or hyperimmune plasma) was used as treatment. We searched clinical trial registries (censored 5 January 2021) for eligible studies under way. After elimination of duplications, the initial search yielded 79 potentially relevant records, of which 67 were subsequently excluded. The 12 remaining records were case reports involving 12 pregnancies. Six of the mothers were reported to be well, two were reported to have preeclampsia, and in one case each the maternal outcome was described as survival, clinical improvement, discharged with oxygen and rehabilitation. With regard to the neonates, two were declared to be well, four had transient morbidity, two were critically ill and one died; normal ongoing pregnancies, but no post-delivery information, were reported for the remaining three cases. Clinical trials under way or planned to investigate the use of convalescent plasma for COVID-19 during pregnancy are lacking. This is the first systematic review of the literature regarding the treatment of COVID-19 in pregnancy. The published literature data seem to indicate that convalescent plasma administered to pregnant women with severe COVID-19 provides benefits for both the mother and the fetus. The quality of the available studies is, however, very limited since they are all case reports and thus suffer from relevant reporting bias.
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http://dx.doi.org/10.3390/v13071194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310344PMC
June 2021

Long-Term Pulmonary Damage From SARS-CoV-2 in an Infant With Brief Unexplained Resolved Events: A Case Report.

Front Med (Lausanne) 2021 11;8:646837. Epub 2021 Jun 11.

Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona, Verona, Italy.

A brief unexplained resolved event (BRUE) is an event observed in a child under 1 year of age in which the observer witnesses a sudden, brief but resolved episode of change in skin color, lack of breathing, weakness or poor responsiveness. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-2019 (COVID-19). We report the case of a previously healthy, full-term infant infected with SARS-CoV-2 when he was 8 months old. Previous to this event, both his grandfather and great-uncle had died of severe pneumonia and his mother had developed respiratory symptoms and fever. Over the following month he was seen five times in the emergency room and was hospitalized twice for recurrent BRUE. At the first hospital admission, after the second emergency room visit, he twice tested positive for COVID-19 after nasopharyngeal swab tests. During his second hospital admission, after the fifth emergency room visit, chest computed tomography revealed typical SARS-CoV-2 pneumonia. During a follow-up examination 6 months later, mild respiratory distress required administration of inhaled oxygen (0.5 L/min) and chest computed tomography disclosed a slight improvement in pulmonary involvement. The clinical manifestation of pulmonary complications from COVID-19 infection was unusual. This is the first report of an infant at high-risk for BRUE, which was the only manifestation of long-term lung involvement due to SARS-CoV-2 pneumonia.
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http://dx.doi.org/10.3389/fmed.2021.646837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225923PMC
June 2021

The Three Pillars of COVID-19 Convalescent Plasma Therapy.

Life (Basel) 2021 Apr 18;11(4). Epub 2021 Apr 18.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, I-37126 Verona, Italy.

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world in the last year causing the coronavirus disease 2019 (COVID-19), which still is a severe threat for public health. The therapeutic management of COVID-19 is challenging as, up until now, no specific and efficient pharmacological therapy has been validated. Translating the experience from previous viral epidemics, passive immunotherapy by means of plasma from individuals recovered from COVID-19 has been intensively investigated since the beginning of the pandemic. In this narrative review, we critically analyze the three factors, named "pillars", that play a key role in determining the clinical effectiveness of this biologic therapy: the convalescent plasma, the disease (COVID-19), and the patients.
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http://dx.doi.org/10.3390/life11040354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073137PMC
April 2021

Personal and Environmental Risk Factors at Birth and Hospital Admission: Direct and Vitamin D-Mediated Effects on Bronchiolitis Hospitalization in Italian Children.

Int J Environ Res Public Health 2021 01 17;18(2). Epub 2021 Jan 17.

Institute for Biomedical Research and Innovation, National Research Council, 90146 Palermo, Italy.

Seasonal variations in UV-B radiation may influence vitamin D status, and this, in turn, may influence the risk of bronchiolitis hospitalization. The aim of this study was using a causal inference approach to investigate, simultaneously, the interrelationships between personal and environmental risk factors at birth/hospital admission (RFBH), serum vitamin D levels and bronchiolitis hospitalization. A total of 63 children (<2 years old) hospitalized for bronchiolitis (34 RSV-positive) and 63 controls were consecutively enrolled (2014-2016). Vitamin D levels and some RFBH (birth season, birth weight, gestational age, gender, age, weight, hospitalization season) were recorded. The discovered RFBH effects on the risk ok bronchiolitis hospitalization were decomposed into direct and vitamin-D mediated ones through Mediation Analysis. Winter-spring season (vs. summer-autumn) was significantly associated with lower vitamin D levels (mean difference -11.14 nmol/L). Increasing serum vitamin D levels were significantly associated with a lower risk of bronchiolitis hospitalization (OR = 0.84 for a 10-nmol/L increase). Winter-spring season and gestational age (one-week increase) were significantly and directly associated with bronchiolitis hospitalization (OR = 6.37 and OR = 0.78 respectively), while vitamin D-mediated effects were negligible (1.21 and 1.02 respectively). Using a comprehensive causal approach may enhance the understanding of the complex interrelationships among RFBH, vitamin D and bronchiolitis hospitalization.
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http://dx.doi.org/10.3390/ijerph18020747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829957PMC
January 2021

The use of convalescent plasma for pediatric patients with SARS-CoV-2: A systematic literature review.

Transfus Apher Sci 2021 Apr 23;60(2):103043. Epub 2020 Dec 23.

Department of Hematology and Transfusion Medicine, Carlo Poma Hospital, ASST, 46100 Mantova, Italy. Electronic address:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19), a severe illness leading to pneumonia, multiorgan failure, and death. With this study, we performed a systematic review of the literature and ongoing clinical trials on convalescent plasma therapy in pediatric patients with COVID-19. The electronic databases Medline PubMed, Scopus, and Web Of Science were searched. Also, clinical trials registries were searched for potentially eligible studies. A total of 90 records were retrieved after duplicate removal. Eight studies were case reports of children treated with convalescent plasma therapy (14 children, age range, 9 weeks to 18 years); 5 children had a chronic disease. During the hospital stay, 5 received drugs (e.g., remdesivir) in addition to convalescent plasma therapy. No convalescent plasma therapy-related adverse events were reported in 5 studies and 3 made no mention of adverse events. Seven studies concluded that convalescent plasma therapy is or could be a useful therapeutic option; one study made no claims. Only 3 of the 13 retrieved trials underway were planned exclusively for children. This is the first systematic review of the literature regarding convalescent plasma therapy for COVID-19 in children. We found insufficient clinical information on the safety and efficacy of convalescent plasma therapy in children. Nevertheless, the positive outcomes of the few case reports published to date suggest that convalescent plasma therapy may be of potential benefit. Further research with well-designed and powered clinical trials is needed.
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http://dx.doi.org/10.1016/j.transci.2020.103043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834628PMC
April 2021

Electronic nose in discrimination of children with uncontrolled asthma.

J Breath Res 2020 07 21;14(4):046003. Epub 2020 Jul 21.

Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, Verona, Italy.

Measuring biomarkers (e.g. volatile organic compounds [VOCs]) in exhaled breath is an attractive approach to monitor airway inflammation in asthma and other lung diseases. Olfactive technology by electronic nose (e-Nose) has been applied to identify VOCs in exhaled breath. We compared e-Nose respiratory patterns in a pediatric cohort with asthma classificate children with different asthma control. This cross-sectional study involved 38 children: 28 with asthma and 10 healthy controls . The asthmatic patients were categorized as having controlled (AC), partially controlled (APC) or uncontrolled asthma (ANC) based on level of asthma symptom control according to Global Initiative for Asthma (GINA). Clinical exams, exhaled breath collection for generating e-Nose VOC profiles, and spirometry were performed. Exhaled breath samples were obtained using a commercial electronic nose (Cyranose 320; Smith Detections, Pasadena, CA, USA). The discriminative ability of breathprints were investigated by principal component analysis and penalized logistic regression. The e-Nose was able to discriminate between the CON (controls) + AC and the ANC + APC group with an area under the curve [AUC] of 0.85 (95% confidence interval [CI] 0.72 to 0.98) and a cross-validated AUC of 0.80 (95% CI 0.70 to 0.85). Sensitivity and specificity calculated using the Youden index were 0.79 and 0.84, respectively. Exhaled biomarker patterns were easy to obtain with the device and were able to differentiate children with uncontrolled symptomatic asthma from asymptomatic controls.
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http://dx.doi.org/10.1088/1752-7163/ab9ab0DOI Listing
July 2020

Prolonged slow expiration technique: has new chest physiotherapy a role in the treatment of bronchiolitis?

Minerva Pediatr (Torino) 2021 02 2;73(1):91-93. Epub 2020 Jun 2.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Clinic of Pediatric, University of Verona, Verona, Italy.

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http://dx.doi.org/10.23736/S0026-4946.20.05550-4DOI Listing
February 2021

Age and Upper Airway Obstruction: A Challenge to the Clinical Approach in Pediatric Patients.

Int J Environ Res Public Health 2020 05 18;17(10). Epub 2020 May 18.

Division of Neonatology and Neonatal Intensive Care Unit, "F. Del Ponte" Hospital, 21100 Varese, Italy.

Upper airway abnormalities increase the risk of pediatric morbidity in infants. A multidisciplinary approach to obstructive sleep apnea syndrome (OSAS) poses challenges to clinical practice. The incidence and causes of OSA are poorly studied in children under 2 years of age. To fill this gap, we performed this retrospective observational study to determine the causes of obstructive sleep apnea (OSA) in children admitted to our hospital between January 2016 and February 2018, after a brief unexplained event (BRUE) or for OSA. We reviewed the medical charts of 82 patients (39 males; BRUE n = 48; OSAS n = 34) and divided them into two age groups: < 1 year old (1-12 months; n = 59) and >1 year old (>12-24 months; n = 23). Assessment included nap polysomnography, multichannel intraluminal impedance-pH, and nasopharyngoscopy. Sleep disordered breathing was comparable between the two groups. Omega-shaped epiglottis, laryngomalacia, and nasal septum deviation were more frequent in the younger group, and nasal congestion in older group. Tonsillar and adenoidal hypertrophy was more frequent in the older group, while laryngomalacia and gastroesophageal reflux was more frequent in the younger group. Tonsil and adenoid size were associated with grade of apnea-hypopnea index severity in the older group, and laryngomalacia and gastroesophageal reflux in the younger group. The main causes of respiratory sleep disorders differ in children before or after age 1 year. Our findings have potential clinical utility for assessing the pathophysiology of obstructive sleep disordered breathing in patients less than 2 years old.
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http://dx.doi.org/10.3390/ijerph17103531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277641PMC
May 2020

The kidney in COVID-19: protagonist or figurant?

Panminerva Med 2020 May 20. Epub 2020 May 20.

Neonatal Intensive Care Unit, AOU Cagliari, Cagliari, Italy.

The etiology of injury in COVID-19 patients is diverse and multifactorial. Autopsy and biopsy studies reveal, alongside podocyte and tubular cell anomalies, the presence of virion within the cells. Evidence suggests that, in addition to the direct cytopathic effect of SARS- CoV2 on the glomeruli and renal tubules, there is also the indirect effect of cell-mediated immunity, the cytokines storm and the cross-talk between organs with possible systemic effects of the disease. These mechanisms are interconnected and have profound therapeutic implications involving extracorporeal removal of inflammatory cytokines. Dialysis patients, and children, in particular, should be classified as "at high risk" of contracting the disease. Infections are one of the most frequent causes of death in children with chronic renal failure who undergo dialysis. The reasons for this particular susceptibility are to be found in the compromised immune system, secondary to chronic malnutrition, immunosuppressive therapy, and uremia, frequent contact with healthcare personnel and other patients attending the dialysis unit and in need of the presence of other family members during treatment.
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http://dx.doi.org/10.23736/S0031-0808.20.03965-8DOI Listing
May 2020

Growth hormone retesting during puberty: a cohort study.

Eur J Endocrinol 2020 Jun;182(6):559-567

Pediatric Division, Department of Pediatrics, University Hospital of Verona, Verona, Italy.

Objectives: To report the frequency and characteristics of growth hormone (GH) deficiency (GHD) in adolescents who had normalized GH secretion at mid-puberty and to identify possible factors predictive for GH sufficiency at puberty.

Design: Clinical analysis of children affected by GHD at five time points: diagnosis; first year of therapy; intermediate stage of puberty; retesting and end of growth phase.

Methods: The study population was 80 children with idiopathic GHD and treated with GH for at least 2 years. Treatment was discontinued at the intermediate stage of puberty. Retesting with an arginine test was performed 12 weeks later. If GH peak at retesting was ≥8 μg/L, the therapy was definitively discontinued, otherwise it was restarted and continued until achievement of near-final height.

Results: GH therapy was discontinued in 44 children (55%), and restarted in 36 (45%). No evidence of differences in definitive height and in the delta height between the genetic target and the definitive height was found between the two groups. The only predictive factor for GHD at mid-puberty was the insulin growth factor-1 (IGF-1) level at 1 year of GH treatment.

Conclusions: GH secretion should be retested at mid-puberty. Retesting at puberty may reduce potential side effects and minimize costs, without impairing growth potential and final height.
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http://dx.doi.org/10.1530/EJE-19-0646DOI Listing
June 2020

Beyond the growth delay in children with sleep-related breathing disorders: a systematic review.

Panminerva Med 2020 09 23;62(3):164-175. Epub 2020 Apr 23.

National Research Council of Italy, Institute for Research and Biomedical Innovation, Palermo, Italy.

Introduction: The availability of high-quality studies on the association between sleep-disordered breathing in children and delayed growth associated with the hormonal profile recorded before surgery and at follow-up is limited.

Evidence Acquisition: Medline PubMed, Scopus and WebOfScience databases were searched for relevant publications published between January 2008 to January 2020 and a total of 261 potentially eligible studies were identified.

Evidence Synthesis: Following review 19 papers were eligible for inclusion: seven reported a significant postsurgical increase in growth regardless of initial weight status, type of surgery, type of study design, and length of follow-up period. The only high-quality study was a randomized controlled trial that found an increased risk of obstructive sleep apnea syndrome relapse in overweight children. Twelve studies reported the significant increase in growth parameters showing that IGF-1, IGFBP-3, and ghrelin may boost growth after surgery.

Conclusions: The current systematic review demonstrates a scarcity of high-quality studies on growth delay in children with sleep-disordered breathing. Significant catch-up growth after surgery in the short term and changes in IGF-1, IGFBP-3, ghrelin, and leptin levels has been reported in most published studies.
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http://dx.doi.org/10.23736/S0031-0808.20.03904-XDOI Listing
September 2020

The cardiovascular risk in paediatrics: the paradigm of the obstructive sleep apnoea syndrome.

Blood Transfus 2020 05 17;18(3):217-225. Epub 2020 Mar 17.

National Research Council of Italy, Institute for Research and Biomedical Innovation, Palermo, Italy.

Background: Obstructive sleep apnoea syndrome (OSAS) describes a spectrum of abnormal breathing patterns during sleep characterised by snoring, increased upper airway resistance and pharyngeal collapsibility, with alteration of normal oxygenation and ventilation. Intermittent desaturations during sleep have multi-organ implications. Adults with OSAS have an increased risk of developing a dysfunctional endothelium that is characterised by greater adherence of inflammatory mediators to endothelial cells and hypercoagulability. There is increasing evidence to show that risk factors for comorbid cardiovascular disease (CVD) can develop during childhood and adolescence and are likely to continue over time. Risk factors for CVD include both modifiable factors and factors that cannot be changed.

Materials And Methods: Using the MEDLINE electronic database, we reviewed the scientific literature for published studies evaluating the association between sleep-disordered breathing and cardiovascular damage in children.

Results: In this review, we show the role of blood markers in demonstrating the inflammation caused by intermitted oxygen desaturations during sleep in both healthy and obese children. Several instrumental techniques, in addition to serum biomarkers, can be used to assess vascular endothelial damage and its deterioration in the form of a pre-atherosclerotic condition. The confirmation of their role as markers of inflammation and vascular damage is supported by normalisation after resolution or improvement of the sleep-disordered breathing with surgery.

Discussion: Great attention should be given to this condition in infants and children as it will significantly affect their present and future well-being as they grow into adulthood. Healthcare professionals, especially paediatricians, should be trained to recognise the signs and symptoms of the disease in order to send children forward for specialist care in centres dealing with sleep-disordered breathing.
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http://dx.doi.org/10.2450/2020.0283-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250680PMC
May 2020

Application of latent class analysis in assessing the awareness, attitude, practice and satisfaction of paediatricians on sleep disorder management in children in Italy.

PLoS One 2020 3;15(2):e0228377. Epub 2020 Feb 3.

Bambino Gesù Paediatric Hospital IRCCS, Roma, Italy.

Aim: To identify subgroups regarding paediatricians' awareness, attitude, practice and satisfaction about management of Sleep-Disordered Breathing (SDB) in Italy using Latent Class Analysis (LCA).

Methods: A cross-sectional study was conducted on a large sample of Italian paediatricians. Using a self-administered questionnaire, the study collected information on 420 Paediatric Hospital Paediatricians (PHPs) and 594 Family Care Paediatricians (FCPs). LCA was used to discover underlying response patterns, thus allowing identification of respondent groups with similar awareness, attitude, practice and satisfaction. A logistic regression model was used to investigate which independent variables influenced latent class membership. Analyses were performed using R 3.5.2 software. A p-value<0.05 was considered statistically significant.

Results: Two classes were identified: Class 1 (n = 368, 36.29%) "Untrained and poorly satisfied" and Class 2 (n = 646, 63.71%) "Trained and satisfied." Involving paediatric pneumologists or otorhinolaryngologists in clinical practice was associated with an increased probability of Class 2 membership (OR = 5.88, 95%CI [2.94-13.19]; OR = 15.95, 95% CI [10.92-23.81] respectively). Examining more than 20 children with SDB during the last month decreased the probability of Class 2 membership (OR = 0.29, 95% CI [0.14-0.61]). FCPs showed a higher probability of Class 2 membership than PHPs (OR = 4.64, 95% CI [3.31-6.55]).

Conclusions: These findings suggest that the LCA approach can provide important information on how education and training could be tailored for different subgroups of paediatricians. In Italy standardized educational interventions improving paediatricians' screening of SDB are needed in order to guarantee efficient management of children with SDB and reduce the burden of disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228377PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996829PMC
April 2020

Popularity of sleep disordered breathing in childhood: an analysis of worldwide search using Google Trends.

Transl Pediatr 2019 Dec;8(5):383-390

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.

Background: Sleep-disordered breathing (SDB) is a general term encompassing a variety of breathing problems occurring during the sleep and characterized by frequently reported signs such as sleep apneas and snoring. Published studies on this topic are increasing over time, as demonstrated by the number of papers available on on-line databases.

Methods: Google Trends is a freely accessible and reliable online portal, which allows to explore internet search data. Due to the focus on of childhood SDB in published research, and because of its impact on health and wellbeing, this original study aims at investigating the worldwide popularity of most common sleep signs (apnea and snoring) from January 1st, 2004 to present time.

Results: The trend of interest for 'sleep', 'sleep apneas' and 'snoring' limited to pediatric age was lower than its overall popularity in the general population, thus reflecting a lower interest of these symptoms in children than in adults. Unlike an increasing trend of ongoing research, the popularity of pediatric sleep apnea and snoring was found to be relatively low around the world, and remained fairly stable over time.

Conclusions: This is a matter for concern, since the low popularity of SDB in children is counterbalanced by a need for reinforcing educational programs aimed at increasing widespread awareness, diagnosis and management of this condition.
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http://dx.doi.org/10.21037/tp.2019.03.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970122PMC
December 2019

Nasal cytology in children with primary snoring and obstructive sleep apnoea syndrome.

Int J Pediatr Otorhinolaryngol 2019 Jul 17;122:133-137. Epub 2019 Apr 17.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy. Electronic address:

Objective: Rhinitis is an acute or chronic inflammatory condition due to several causes (i.e. infections, allergens). There are controversial results that point out the role of nasal inflammation in primary snoring and obstructive sleep apnoea syndrome (OSAS).

Methods: The aim of the present investigation is to study the nasal cytology in 58 children aged from 1 to 15 affected by sleep disordered breathing.

Results: Inflammation of the nasal mucous was found in 88% of children. The most frequent problems were infectious rhinitis (36%), followed by non-allergic rhinitis (28%) and allergic rhinitis (21%). Infectious rhinitis was found in 31% of children with primary snoring and 41% with OSAS. Allergic rhinitis was found in 35% of children with primary snoring, and 6% with OSAS. Non-allergic rhinitis was found in 19% of children with primary snoring, and 34% with OSAS. Bacteria was found in 59% of children with OSAS and 46% in children with primary snoring.

Conclusion: the most prevalent forms of rhinitis in primary snoring were the allergic rhinitis, and in OSAS group were the non-allergic rhinitis. Bacteria were equally distributed in primary snoring and OSAS children. The nasal cytology provided interesting information that can be used to plan possible treatment strategies.
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http://dx.doi.org/10.1016/j.ijporl.2019.04.015DOI Listing
July 2019

Sleep-disordered breathing in paediatric setting: existing and upcoming of the genetic disorders.

Ann Transl Med 2018 Sep;6(17):343

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.

Childhood obstructive sleep apnea syndrome (OSAS) is characterized by anatomical and functional upper airway abnormalities as pathophysiological determinants, and clinical symptoms are frequently clear. OSAS is widely described in rare genetic disorders, such as achondroplasia, Down syndrome, Prader-Willi syndrome, Pierre Robin sequence, and mucopolysaccharidosis. Craniofacial and upper airway involvement is frequently morbid conditions. In children with genetic diseases, the clinical symptoms of OSAS are often slight or absent, and related morbidities are usually more severe and can be observed at any age. The present review is aimed to updating the discoveries regarding OSAS on Achondroplasia, Down syndrome, Prader-Willi syndrome, Pierre Robin sequence, Sickle cell disease, or encountered in our clinical practice (Ehlers-Danlos syndrome, Ellis-van Creveld syndrome, Noonan syndrome). Two additional groups of genetic disorders will be focused (mucopolysaccharidoses and osteogenesis imperfecta). The flowing items are covered for each disease: (I) what is the pathophysiology of OSAS? (II) What is the incidence/prevalence of OSAS? (III) What result from the management and prognosis? (IV) What are the recommendations? Considering the worries of OSAS, such as inattention and behavioural problems, daytime sleepiness, failure to thrive, cardiological and metabolic complications, the benefit of a widespread screening and the treatment in children with genetic diseases is undoubtful. The goals of the further efforts can be the inclusion of various genetic diseases into guidelines for the screening of OSAS, updating the shreds of evidence based on the research progression.
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http://dx.doi.org/10.21037/atm.2018.07.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174189PMC
September 2018

Metabolomics: a challenge for detecting and monitoring inborn errors of metabolism.

Ann Transl Med 2018 Sep;6(17):338

Department of Surgical Sciences, Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, University of Cagliari, Cagliari, Italy.

Timely newborn screening and genetic profiling are crucial in early recognition and treatment of inborn errors of metabolism (IEMs). A proposed nosology of IEMs has inserted 1,015 well-characterized IEMs causing alterations in specific metabolic pathways. With the increasing expansion of metabolomics in clinical biochemistry and laboratory medicine communities, several research groups have focused their interest on the analysis of metabolites and their interconnections in IEMs. Metabolomics has the potential to extend metabolic information, thus allowing to achieve an accurate diagnosis for the individual patient and to discover novel IEMs. Structural and functional information on 247 metabolites associated with 147 IEMs and 202 metabolic pathways involved in various IEMs have been reported in the human metabolome data base (HMDB). For each metabolic gene, a new computational approach can be developed for predicting a set of metabolites, whose concentration is predicted to change after gene knockout in urine, blood and other biological fluids. Both targeted and untargeted mass spectrometry (MS)-based metabolomic approaches have been used to expand the range of disease-associate metabolites. The quantitative targeted approach, in conjunction with chemometrics, can be considered a basic tool for validating known diagnostic biomarkers in various metabolic disorders. The untargeted approach broadens the identification of new biomarkers in known IEMs and allows pathways analysis. Urine is an ideal biological fluid for metabolomics in neonatology; however, the lack of standardization of preanalytical phase may generate potential interferences in metabolomic studies. The integration of genomic and metabolomic data represents the current challenge for improving diagnosis and prognostication of IEMs. The goals consist in identifying both metabolically active loci and genes relevant to a disease phenotype, which means deriving disease-specific biological insights.
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http://dx.doi.org/10.21037/atm.2018.09.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174193PMC
September 2018

Increased parental perception of sleep disordered breathing in a cohort of infants with ALTE/BRUE events.

Minerva Pediatr 2018 Oct 4. Epub 2018 Oct 4.

Department of Pediatrics, University of Insubria, Varese, Italy.

Background: An apparent life-threatening event (ALTE) describes an acute, unexpected change in an infant's breathing, aspect, or behavior frightening to the parent or caretaker. According to the new recent terminology, clinicians should use the term Brief Resolved Unexplained Event (BRUE) to describe an event occurring in an infant <1 year of age when the observer reports a sudden, brief, and now resolved episode. The aims of the present study in infants were: to investigate sleep disturbances in both ALTE event and after their classification according the new BRUE criteria.

Methods: We enrolled (from April to May 2016) 32 consecutive infants referred to our ambulatory for sleep disorders for follow-up after an ALTE episode and 32 pair healthy controls. We administered to parents the adapted questionnaire "Sleep Disturbance Scale for Children - SDSC".

Results: Among enrolled infants with ALTE, there were 26 infants in line with the new BRUE definition, of which 10 at low risk and 16 at the high-risk event.

Conclusions: BRUE had more referred-by-parents' sleep symptoms than controls. In particular, sleep disordered breathing wa prevalent in both, requiring a longer follow-up for this disturbance.
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http://dx.doi.org/10.23736/S0026-4946.18.05276-3DOI Listing
October 2018

Feasibility of structured light plethysmography for the evaluation of lung function in preschool children with asthma.

Allergy Asthma Proc 2018 Jul;39(4):e38-e42

Background: Structured light plethysmography (SLP) is a new noninvasive technology to capture the movement of the thoracic and abdominal wall, and to assess some parameters indicative for lung function.

Objective: The purpose of the study was to evaluate the feasibility of SLP in children with asthma.

Methods: A total of 52 patients were enrolled: 25 with asthma exacerbation (group 1), 13 with well-controlled asthma (group 2), and 14 healthy controls (group 3). Every patient underwent SLP evaluation and a lung function test.

Results: SLP evaluations showed that the ratio of inspiratory flow at 50% of tidal volume (Vt) to expiratory flow at 50% of Vt, in which Vt is taken to be the exhaled chest wall movement, and flow is taken to be the time derivative of the chest wall movement (IE50) value increased in group 1 compared with groups 2 and 3, with statistical significance (p = 0.018); the data were consistent with the spirometry parameter. A correlation between the IE50 and forced expiratory volume in the first second of expiration was highlighted (r = -0.35, p = 0.019).

Conclusion: SLP assessed airway obstruction, and its use in clinical practice could be applied in preschool children in future studies.
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http://dx.doi.org/10.2500/aap.2018.39.4143DOI Listing
July 2018

Measuring Airway Inflammation in Asthmatic Children.

Front Pediatr 2018 6;6:196. Epub 2018 Jul 6.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.

Asthma is the most common chronic respiratory disease in children characterized by airways inflammation, bronchial hyperresponsiveness, recurrent reversible airways obstruction, and respiratory symptoms. The diagnosis of the disease is based on clinical history, airways obstruction at spirometry, and bronchial reversibility. Asthma treatment is aimed to disease control, through the use of controller treatment and monitoring lung function. However, lung function and symptoms not always reflect the underlying airways inflammation and response to the therapy. Objective parameters of asthma inflammation could be important for the clinician in the management of patients with asthma. In the last years, some studies were focused on biomarkers to identify phenotype, inflammation, and pathobiological pathways to help the clinician in the diagnosis and in personalizing the management. Accordingly, clinically feasible tests are represented by the collection of exhaled breath condensate (EBC) and measurement of exhaled nitric oxide (FeNO). Other-methods such as the evaluation of volatile organic compound (VOCs), that reflect airways inflammation and treatment efficacy, are currently used for research purposes For some of these methods, The lack of standardization in pre-collection, collection, post-collection of samples, and interpretation of the results may a problem in clinical practice. Improved these limitations, several biomarkers will be useful to distinguish patients with a different disease condition to personalize the treatment.
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http://dx.doi.org/10.3389/fped.2018.00196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043865PMC
July 2018

Sleep-Disordered Breathing in Children with Rare Skeletal Disorders: A Survey of Clinical Records.

Med Princ Pract 2018 21;27(5):451-458. Epub 2018 Jun 21.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.

Objective: Craniofacial disharmony in skeletal diseases is strongly associated with sleep-disordered breathing. This study was aimed at studying the sleep respiratory patterns in young children with rare skeletal disorders.

Design: This retrospective study included children with achondroplasia (ACH), osteogenesis imperfecta (OI) and Ellis van Creveld Syndrome. Our subjects underwent an in-laboratory overnight respiratory polygraph between January 2012 and April 2016. All medical records were reviewed and brain Magnetic Resonance Imaging was conducted on patients with ACH, nasopharynx, oropharynx and laryngopharynx spaces.

Patients: Twenty-four children were enrolled, 13 with ACH, 2 with spondyloepiphyseal dysplasia, 1 with odontochondrodysplasia, 6 with OI and 2 with Ellis van Creveld Syndrome.

Results: Children with ACH, who had adenotonsillectomy, showed fewer sleep respiratory involvement than untreated children. Among 13 patients with ACH, brain magnetic resonance imaging was available in 10 subjects and significant negative correlation was found between sleep respiratory patterns, nasopharynx and oropharynx space (p < 0.05). In 2 patients with spondyloepiphyseal dysplasia, mild-to-moderate sleep respiratory involvement was found. Both subjects had a history of adenotonsillectomy. Mild sleep respiratory involvement was also observed in 4 out of 6 patients with OI. One patient with Ellis van Creveld syndrome had mild sleep respiratory disturbance.

Conclusions: Sleep respiratory disturbances were detected in children with ACH, and with less severity also in OI and Ellis van Creveld syndrome. Adenotonsillectomy was successful in ACH in reducing symptoms. In light of our findings, multicenter studies are needed to obtain further information on these rare skeletal diseases.
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http://dx.doi.org/10.1159/000491391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244108PMC
April 2019

Chiari 1 Malformation in a Child with Febrile Seizures, Parasomnias, and Sleep Apnea Syndrome.

Case Rep Pediatr 2017 17;2017:8189790. Epub 2017 Dec 17.

Pediatric Division, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.

Introduction: The type I is the most common Chiari malformation in children. In this condition, the lower part of the cerebellum, but not the brain stem, extends into the foramen magnum at the base of the skull leading to disturbances in cerebrospinal fluid circulation and to direct compression of nervous tissue.

Case Report: We describe a 4-year-old Caucasian female child with febrile seizures, headache, parasomnias, and a delay of speech. The child underwent a magnetic resonance imaging to investigate these neurological signs, disclosing a Chiari malformation type 1. The polysomnography showed a mild-moderate sleep-disordered breathing, increased number of central sleep apneas, and generalized spike waves at sleep onset.

Conclusions: Seizures have been seldom described in CM1 patients. The main reasons for performing MRI in this case were frequent seizures, a delay of speech, and headache, leading to an unexpected diagnosis of CM1. Polysomnography detected a discrete SDB.
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http://dx.doi.org/10.1155/2017/8189790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748138PMC
December 2017

Sleep-Disordered Breathing in Children with Recurrent Wheeze/Asthma: A Single Centre Study.

Children (Basel) 2017 Nov 14;4(11). Epub 2017 Nov 14.

Department of Surgery, Dentistry, Paediatrics and Gynaecology, Pediatric Division, University of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy.

The relationship between asthma and sleep-disordered breathing is bidirectional due to common risk factors that promote airway inflammation. Obstructive sleep-disordered breathing and recurrent wheeze/asthma are conditions that involve the upper and the lower respiratory system, respectively. The aim of the present study was to investigate the sleep disordered breathing in children with recurrent wheeze/asthma. This was a retrospective study concerning children older than 2 years who underwent-between January 2014 and November 2016-an in-laboratory overnight polygraphic study. We match the children between those who do or do not have recurrent wheeze/asthma disease. We examined the clinical records of 137 children. We excluded eight patients because of neurological and genetic conditions. Children with recurrent wheeze/asthma ( = 28) were younger ( = 0.002) and leaner ( = 0.013) compared to non-affected children ( = 98). Children with wheeze/asthma and unaffected ones had a similar obstructive apnea-hypopnea index ( = 0.733) and oxygen desaturation index ( = 0.535). The logistic regression analysis, in which the condition of wheeze/asthma (yes/no) was a dependent variable, while demographic (age, sex, body mass index (BMI) -score) and polygraphic results during sleep (obstructive apnea-hypopnea index, central apnea index, peripheral oxygen saturation (SpO₂), and snoring) were covariates, showed that children with wheeze/asthma had higher central apnea index (Exp(B) = 2.212; Wald 6.845; = 0.009). In conclusion, children with recurrent wheeze/asthma showed an increased number of central sleep apneas than unaffected children. This finding may suggest a dysfunction of the breathing control in the central nervous system during sleep. Systemic or central inflammation could be the cause.
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http://dx.doi.org/10.3390/children4110097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704131PMC
November 2017

Ambulatory clinical parameters and sleep respiratory events in a group of obese children unselected for respiratory problems.

World J Pediatr 2017 Dec 12;13(6):577-583. Epub 2017 Jul 12.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Division, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy.

Background: Obstructive sleep apnea in children is frequently due to tonsil and adenoid hypertrophy. This study aimed to investigate the relationship between ambulatory clinical parameters and sleep respiratory events in obese children.

Methods: We carried out a prospective respiratory sleep study between 2013 and 2015. Nails obstruction, tonsils enlargement and palate position were subjectively measured. Italian attention deficit hyperactivity disorder (ADHD) rating scale for parents was also performed. The polygraph study was performed using a portable ambulatory device.

Results: Forty-four obese children were consecutively recruited into this study. Mild sleep respiratory disturbance was showed in 31.8 % of patients; 18.2% previously had an adeno (tonsillectomy). In 50% of these obese children, both apnea-hypopnea index and oxygen desaturation index showed polygraph abnormal results. ADHD rating scale for parents scores were positive in 9.1% of patients.

Conclusions: We found a high rate of mild sleep respiratory disturbance and ADHD-like symptoms referred by parents. The respiratory disturbance was not totally cured by surgery. Finally, otorhinolaryngology variables were not able to explain mild sleep respiratory disturbance.
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http://dx.doi.org/10.1007/s12519-017-0054-1DOI Listing
December 2017

Indoor/outdoor not-voluptuary-habit pollution and sleep-disordered breathing in children: a systematic review.

Transl Pediatr 2017 Apr;6(2):104-110

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Division, University of Verona, Verona, Italy.

Background: Exposure to environmental pollutants is advocated to be a major risk factor, with increased morbidity and mortality in humans due to acute and chronic airway inflammation. The aim of the present review is to show the literature research regarding the link between the sleep-disordered breathing and exposure to indoor/outdoor pollution in children. We hypothesized that environmental air pollution can play a role in childhood sleep-disordered breathing.

Methods: We conducted an electronic search in Medline (with PubMed interface), Scopus and the ISI Web of Science using the keywords "sleep" or "sleep apnea" or "sleep disordered breathing" and "pollution" and "children" in "Title/Abstract/Keywords", with language restriction (non-English paper) and no date limitation to present. The tobacco smoke pollution is well established linking and is not considered for the present subject. We examined the strength of the evidence according to the Oxford Centre for Evidence-Based Medicine [2011] and the Centre for Evidence-Based Medicine [2009].

Results: A total of 105 articles were identified, but 97 of these had to be excluded after an accurate reading of the title, abstract or full text. In the end, eight studies were selected for our analysis for a total of a total of 5,826 children. The results suggest an involvement (grade C) of environmental (not from voluptuary habits) pollution in the worsening of sleep-disordered breathing in children.

Conclusions: To date, some studies reported significant differences between areas with higher and lower pollutants and the interventions on indoor pollution reduced sleep-disordered breathing in children. Therefore, although the relevance of the argument is high, the number of studies and the interest in the subject seems at this time quite limited.
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http://dx.doi.org/10.21037/tp.2017.03.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413472PMC
April 2017

Evaluation of the central sleep apnea in asymptomatic children with Chiari 1 malformation: an open question.

Childs Nerv Syst 2017 May 5;33(5):829-832. Epub 2017 Apr 5.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Division, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.

Introduction: Type I is the most common Chiari malformation in children. In this condition, the lower part of the cerebellum, but not the brain stem, extends into the foramen magnum at the base of the skull leading to intermittent brain hypertension. In symptomatic children, central sleep apneas are shown in polysomnography evaluation. A central apnea index of 1/h or more is considered abnormal, but >5/h is clearly considered pathological. Therefore, central sleep apnea evaluation in pediatric age may show great age-related variability.

Method And Subjects: We present three patients who were assessed by polysomnography with two different scores for central sleep apneas published in the literature: the method by Scholle (2011) and the American Academy of Sleep Medicine scoring system (2012).

Conclusions: We speculated that the Scholle scoring system can be more helpful in assessing children with asymptomatic Chiari 1 malformation for a closer follow-up. More studies are needed.
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http://dx.doi.org/10.1007/s00381-017-3399-9DOI Listing
May 2017

Obstructive sleep-disordered breathing, enuresis and combined disorders in children: chance or related association?

Swiss Med Wkly 2017 3;147:w14400. Epub 2017 Feb 3.

Department of Paediatrics, University of Insubria, Varese, Italy.

Nocturnal enuresis is usually diagnosed and treated by a primary paediatrician or family practitioner; if there is any doubt, the children may be referred to a paediatric urologist. Obstructive sleep-disordered breathing is a complex, multifactorial disorder. Adenotonsillar hypertrophy is considered an important factor associated with obstructive sleep apnoea syndrome. Enuresis and obstructive sleep-disordered breathing are both frequent problems of sleep in childhood. We conducted an electronic search in Medline, Scopus and the ISI Web of Science to look for published material and identify a putative link between nocturnal enuresis and obstructive sleep-disordered breathing. A total number of 98 documents were found, but 24 of these had to be excluded after an attentive reading of the title, abstract or full text because the information therein was not suitable for the aims of our search. Studies have found that children with obstructive sleep apnoea syndrome frequently also have nocturnal enuresis. Both disorders have an underlying sleep disturbance characterised by an altered arousal response and sleep fragmentation. The pathophysiology of enuretic events is seemingly linked to nocturnal obstructive events, causing increased intra-abdominal pressure and altered systemic blood pressure that induces natriuresis and polyuria by altering levels of antidiuretic hormone, and atrial and brain natriuretic peptides. We found 17 studies regarding the urological outcome of treatment for obstructive sleep-disordered breathing in children with enuresis. Although a vast amount of information is now available regarding the relationship between nocturnal enuresis and obstructive sleep-disordered breathing, many of the published studies were uncontrolled, retrospective or prospective cohort studies (grade C recommendation). Resolution of enuresis after medical or surgical treatment for obstructive sleep-disordered breathing has been emphasised. Consequently, symptoms such as snoring, sleep apnoeas and restless sleep should be sought for all children with enuresis. Confirmed obstructive sleep-disordered breathing should be treated promptly; subsequently, the persistence of enuresis requires treatment following the standard protocol.
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http://dx.doi.org/10.4414/smw.2017.14400DOI Listing
October 2017
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