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Background: Obstructive sleep apnea syndrome (OSAS) is a chronic syndrome, affecting about 1%-5% of children. OSAS is characterized by increased resistance and collapse of the upper airways, with different degrees of severity requiring interventions ranging from lifestyle modifications to surgery. Sympathetic activity is increased in OSAS, and the reduction of disease symptoms, occurring after adenotonsillectomy, correlates with biomarkers indicating a reduced sympathetic response. The aim of this study is to explore the potential role of single nucleotide polymorphisms (SNPs) in the gene encoding β2-adrenergic receptors (ADRB2) as a biomarker for the early identification of pediatric OSAS patients at high risk of developing severe symptoms., Materials and Methods: In this exploratory genetic study, the frequencies of functional SNPs in ADRB2 within a cohort of pediatric patients were evaluated by using reverse transcription-polymerase chain reaction with TaqMan probes. The severity of OSAS was assayed by the apnea-hypopnea index (AHI)., Results: The rs1042713 SNP (GG genotype) in ADRB2 was more frequent in patients with severe OSAS compared to patients with mild/moderate OSAS., Conclusions: The availability of genetic biomarkers for the early identification of patients at high risk of severe OSAS will help clinicians start personalized treatments, thus reducing morbidity associated with OSAS., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Insubria Ethics Committee issued approval 14/2019. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ferrari et al.)

Background/objectives: Obstructive Sleep Apnoea Syndrome (OSA) in children disrupts normal breathing patterns and sleep architecture, potentially leading to severe consequences. Early identification and intervention are crucial to prevent these issues. This study explored the relationships between waiting times for polysomnography (PSG), clinical history, patient age at the time of PSG, and PSG outcomes in children., Methods: Two hundred and fourteen children were prospectively enrolled. Data were extracted from medical records regarding the patients' age at the time of a referral for PSG and their age at the time of its execution. Information on the waiting times for PSG, a diagnosis (primary snoring, mild, moderate, and severe OSA), and a history of snoring and apnoea were also collected. Additional data included medications, surgical interventions, passive smoke exposure, and allergies. The records also included the Paediatric Sleep Questionnaire (PSQ)., Results: The patient age at the time of a PSG prescription was lower for patients with a short history of sleep apnoeas (≤12 months; 4.6 (SD 2.6) years) compared to those with a long history (>12 months; 5.5 (SD 2.7) years; p = 0.027). The waiting time from prescription to PSG execution was shorter for patients with a short history of sleep apnoea (4.1 (SD 3.8) months) compared to those with a longer history (5.9 (SD 3.8) months; p = 0.001). A higher frequency of having an adenotonsillectomies before a PSG prescription was observed in the long-history group compared to the short-history group (13.3% vs. 6.9%). Conversely, a higher frequency of adenoidectomies before a PSG prescription was noted in the short-history group compared to the long-history group (9.7% vs. 1.3%)., Conclusions: This study found that younger children with a shorter history of OSA are diagnosed and evaluated earlier than older children with a longer history of the condition, suggesting that prolonged symptoms may delay a diagnosis. ENT surgeries also vary among patients, with less invasive procedures (adenoidectomy) being more common in younger children with shorter histories of OSA. The increasing awareness of OSA highlights the need for improved access to diagnostic and treatment resources.

(1) Background: Sleep-disordered breathing and asthma are often interrelated. Children and adults with asthma are more susceptible to sleep apnea. Inhaled corticosteroids effectively reduce inflammation and prevent structural changes in the airways. Objective: to explore the existing literature to determine whether inhaled corticosteroids play a role in sleep-disordered breathing in patients with asthma. (2) Methods: We conducted a thorough search of the PubMed, Scopus, and Web of Science databases for English-language articles published up to 12 May 2024. We utilized the ROBINS-E tool to assess the risk of bias. (4) Conclusions: 136 articles were discerned upon conducting the literature search. A total of 13 articles underwent exhaustive full-text scrutiny, resulting in 6 being considered non-relevant. The remaining seven articles, assessed for eligibility, were incorporated into the final analysis. Five studies were identified in adults and two in children. In adult patients, inhaled corticosteroids, especially at high doses, appear to increase the risk of sleep apnea in a dose-dependent manner. Moreover, the properties of inhaled corticosteroids, such as particle size, may impact the risk of developing sleep apnea. In children, the severity of asthma is a key factor affecting the prevalence of sleep apnea, whereas inhaled corticosteroids appear to be a less significant risk factor compared to adults. All of the studies reviewed were classified as having a high risk of bias or some concerns regarding bias. Each study revealed at least one type of bias that raised notable concerns. This research highlights a complex interaction between the use of inhaled corticosteroids, the severity of asthma, and the onset of sleep apnea. Additional research is necessary to investigate these relationships further.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20-40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Background: Nocturnal infant crying is often empirically treated with acid suppressants. The aim of this study was to evaluate the prevalence and characteristics of gastroesophageal reflux (GER) in infants with unexplained persistent crying., Methods: We enrolled all infants (0-12 months) referred for suspected GER disease who underwent esophageal impedance-pH monitoring (MII-pH) for unexplained persistent crying not improved by parental reassurance, dietary modification or alginate. Gastrointestinal malformation/surgery, neurological impairment and infections were exclusion criteria. Demographic and anthropometric parameters, GER symptoms and questionnaires (I-GERQ-R) and MII-pH data were recorded and analyzed. Normal MII-pH was defined when acid exposure was <3%, symptom index was <50% and symptom association probability was <95%. Acid exposure >5% and >10% was also considered. Statistical analysis was performed using Chi-Square and univariate and multivariable regression analysis., Results: We included 50 infants (median age 3.5 months) who fulfilled the study criteria: 30 (60%) had normal MII-pH. I-GERQ-R score was abnormal in 33 (66%) infants, and 21/33 (64%) had normal MII-pH ( p = 0.47). In the 26 (52%) infants with nocturnal crying, MII-pH was normal in 16 (54%) ( p = 0.82). Associated regurgitation (>3 or >10 episodes/die) did not predict abnormal MII-pH ( p = 0.74, p = 0.82, respectively). Univariate and multivariable regression analysis did not identify any clinical variable significantly associated with abnormal MII-pH., Conclusions: Infants with persistent unexplained and nocturnal crying should not be empirically treated with acid inhibitors.

(1) Background: Sleep-disordered breathing represents a growing public health concern, especially among children and adolescents. The main risk factors for pediatric sleep-disordered breathing in school-age children are tonsillar and adenoid hypertrophy. Adenoidectomy, often in combination with tonsillectomy, is the primary treatment modality for pediatric sleep-disordered breathing. This study aims to comprehensively investigate various risk and protective factors in children with sleep-disordered breathing undergoing adenotonsillar or adenoidal surgeries. We also aim to explore the differences in neuropsychological profiles. (2) Methods: This is an observational, retrospective cohort study. We collected information on adenoidectomy or adenotonsillectomy in children referred to our center. We reviewed the clinical history and preoperative visits and collected data through a telephone questionnaire. The Pediatric Sleep Questionnaire (PSQ) and the Pediatric Quality of Life Inventory (PedsQL) screen sleep-disordered breathing and quality of life, respectively. The data were statistically analyzed using SPSS version 22.0 for Windows (SPSS Inc., Chicago, IL, USA). (3) Results: The study involved 138 patients, but only 100 children participated. A higher percentage of patients with sleep-disordered breathing were observed to have mothers who smoked during pregnancy. A smaller proportion of patients with sleep-disordered breathing habitually used a pacifier. A rise in physical score was associated with a reduced PSQ at follow-up ( p = 0.051). An increase in the overall academic score was related to a decrease in the PSQ at follow-up ( p < 0.001). A more significant proportion of patients undergoing adenotonsillectomy were observed to have a history of prematurity and cesarean birth. (4) This comprehensive study delves into the intricate interplay of risk and protective factors impacting children with sleep-disordered breathing undergoing adenotonsillectomy and adenoidectomy.

Background: Brief Resolved Unexplained Events (BRUEs), formerly known as Apparent Life-Threatening Events (ALTEs), are concerning episodes of short duration (typically <1 min) characterized by a change in breathing, consciousness, muscle tone, and/or skin color. In some cases, SARS-CoV-2 infection has been associated with episodes of BRUEs in previously healthy children. This study aimed to compare the demographic, respiratory, perinatal, and infectious characteristics in children affected by BRUEs before the COVID-19 pandemic and after the spread of SARS-CoV-2., Methods: We conducted a retrospective observational study covering January 2018 to March 2020 (pre-COVID-19) and April 2023 (during the ongoing COVID-19 pandemic). Collected variables included clinical information during pregnancy and neonatal details of children with BRUEs., Results: The number of children in the pre-COVID-19 period was 186 (41%); after the emergence and spread of SARS-CoV-2 this number was 268 (59%). The risk of infection at birth for children developing BRUEs was higher during the pandemic. Children were less likely to have ongoing symptomatic infection during BRUEs during the pandemic (coefficient B = 0.783; p = 0.009). Respiratory symptoms during BRUEs were more frequent during the pandemic (coefficient B = 0.654; p = 0.052). Fever during BRUEs was less likely during the pandemic (coefficient B = -0.465, p = 0.046)., Conclusions: These findings could have significant clinical implications for managing children with BRUEs during the COVID-19 pandemic.

This review investigates the relationship between pediatric obstructive sleep apnea, often associated with adenotonsillar hypertrophy, and cardiovascular health, particularly pulmonary hypertension. We conducted a comprehensive literature search using electronic databases, including Medline Pub-Med, Scopus, and the Web of Science. The study analyzed a total of 230 articles and screened 48 articles, with 20 included in the final analysis, involving 2429 children. The PRISMA flowchart visually illustrates the selection process, and the ROBINS-E and -I tools help ensure the reliability and validity of the evidence produced by these studies. These studies explored various aspects, including the severity of obstructive sleep apnea, cardiac anomalies, cardiac stress markers, risk factors for pulmonary hypertension, and the impact of adenoidectomy and tonsillectomy on cardiac function. The research found that adenotonsillar hypertrophy and obstructive sleep apnea are significant risk factors for cardiovascular complications, especially pulmonary hypertension, in children. Adenoidectomy and tonsillectomy may provide effective treatments. Following adenoidectomy in relation to obstructive sleep apnea, there appears to be a reduction in mean pulmonary artery pressure during echocardiographic examination. However, the efficacy of these procedures can vary based on the severity of obstructive sleep apnea and individual cardiac conditions. The study also identified concerns regarding data bias. The authors emphasize the need for well-designed clinical studies, including both healthy patients with adenotonsillar hypertrophy and vulnerable children with genetic disorders, to ensure that clinical decisions are based on solid scientific evidence.

Obstructive sleep apnea (OSA) affects neurobehavioral, cognitive, and cardiovascular aspects, particularly in children, by obstructing the upper airways during sleep. While its impact in adult ocular health is recognized, there is ongoing debate about OSA's relevance in pediatrics. This review explores the relationship between OSA and ocular health in children, focusing on the effects and potential improvements through treatment. A systematic search found 287 articles through PubMeD/MEDLINE, Scopus, Web of Science, and ScienceDirect; 94.4% were excluded. After careful selection, six English articles were included, addressing the effects of OSA on children's eyes. Three studies examined choroidal alterations, three explored retinal and optic nerve changes, and two analyzed ocular changes following otorhinolaryngological intervention. The immediate correlation in children is inconclusive, but age may be a contributing factor. Pediatric OSA patients exhibit corneal anomalies and increased optic nerve thickness, possibly due to intermittent hypoxia. OSA influences retinal vascular density in children, with increased density after treatment and reduced choroidal thickness in cases of adenotonsillar hypertrophy. This review emphasized OSA's significant impact on children's ocular health, revealing alterations in the optic nerve, choroid, retina, and cornea. While the direct correlation with the optic nerve is not always evident, OSA raises intraocular pressure and induces structural changes. Treatment holds promise, highlighting the need for regular monitoring to promptly address childhood OSA.

Sleep-disordered breathing is a significant problem affecting the pediatric population. These conditions can affect sleep quality and children's overall health and well-being. Difficulties in social interaction, communication, and repetitive behavioral patterns characterize autism spectrum disorder. Sleep disturbances are common in children with ASD. This literature review aims to gather and analyze available studies on the relationship between SDB and children with autism spectrum disorder. We comprehensively searched the literature using major search engines (PubMed, Scopus, and Web of Science). After removing duplicates, we extracted a total of 96 records. We selected 19 studies for inclusion after a thorough title and abstract screening process. Seven articles were ultimately incorporated into this analysis. The research findings presented herein emphasize the substantial influence of sleep-disordered breathing on pediatric individuals diagnosed with autism spectrum disorder (ASD). These findings reveal a high incidence of SDB in children with ASD, emphasizing the importance of early diagnosis and specialized treatment. Obesity in this population further complicates matters, requiring focused weight management strategies. Surgical interventions, such as adenotonsillectomy, have shown promise in improving behavioral issues in children with ASD affected by OSA, regardless of their obesity status. However, more comprehensive studies are necessary to investigate the benefits of A&T treatment, specifically in children with ASD and OSA. The complex relationship between ASD, SDB, and other factors, such as joint hypermobility and muscle hypotonia, suggests a need for multidisciplinary treatment approaches. Physiotherapy can play a critical role in addressing these intricate health issues. Early sleep assessments and tailored weight management strategies are essential for timely diagnosis and intervention in children with ASD. Policy initiatives should support these efforts to enhance the overall well-being of this population. Further research is crucial to understand the complex causes of sleep disturbances in children with ASD and to develop effective interventions considering the multifaceted nature of these conditions.

Adenotonsillar hypertrophy has been well-acknowledged as the primary instigator of sleep-disordered breathing in the pediatric population. This condition spans a spectrum, from typical age-related growth that the immune system influences to persistent pathological hypertrophy. Reduction in air spaces, metabolic changes, neurobehavioral alterations, and chronic inflammation characterizes the latter form. As the go-to treatment, adenotonsillectomy has proven effective. However, it is not a guarantee for all patients, leaving us without reliable predictors of treatment success. Evidence suggests a connection between adenotonsillar hypertrophy and specific oral breathing patterns resulting from craniofacial development. This finding implies an intricate interdependence between the two, hinting at a self-sustaining vicious cycle that persists without proper intervention. The theories regarding the relationship between craniofacial conformation and sleep-disordered breathing have given rise to intriguing perspectives. In particular, the "gracilization theory" and the "gravitational hypothesis" have provided fascinating insights into the complex interaction between craniofacial conformation and SDB. Further investigation is crucial to unraveling the underlying pathophysiological mechanisms behind this relationship. It is also vital to explore the risk factors linked to adenotonsillectomy failure, study the long-term effects of adenotonsillar hypertrophy on craniofacial growth, and devise innovative diagnostic techniques to detect upper airway compromise early. Moreover, to assess their efficacy, we must delve into novel therapeutic approaches for cases that do not respond to traditional treatment, including positional therapy and orofacial myofunctional therapy. Though complex and unpredictable, these challenges promise to enhance our understanding and treatment of adenotonsillar hypertrophy and its related complications in children. By taking on this task, we can pave the way for more effective and targeted interventions, ultimately improving affected individuals' well-being and quality of life.

Background: Obstructive sleep apnea can have a negative impact on children's and adolescents' neurocognitive abilities and hinder their academic and adaptive progress in academic, social, and/or behavioral dimensions. In this retrospective cross-sectional study, we investigated the influence of body weight conditions and allergy status on long-term mental health, cognitive development, and quality of life in children and adolescents who snored., Methods: The study sample included 47 subjects (age range 4.1 to 15.3 years) who exhibited high levels of snoring and underwent home-based polysomnography between 2015 and 2019. Follow-up assessments (3 years on average between baseline and follow-up) entailed phone interviews with the subject's parents/caregivers who completed three validated questionnaires investigating sleep, quality of life, and parental ratings., Results: We found a correlation between age at diagnosis and being retrospectively overweight and high levels of snoring. In addition to a higher risk of developing emotional symptoms (8.2% increase in retrospective overweight status for each unit increase in the emotional score at follow-up) and oppositional behavior (9% increase in retrospective overweight status for each unit of oppositional T points at follow-up), we also noted reduced long-term social symptoms (11% decrease in retrospective overweight status for each unit increase in the social score at follow-up) and cognitive symptoms (10.6% decrease in retrospective overweight status for each unit increase in the cognitive score at follow-up), as well as a 6.1% increase in retrospective allergy status for each unit increase in academic performance at follow-up., Conclusions: Snoring can have negative impacts on mental health and cognitive development in the long term. Early detection and intervention for neuropsychological disorders is important in children and adolescents who score high on snoring. In the long term, the effects of snoring on neuropsychological disorders may vary based on previous body weight and allergy status.

Pediatric obstructive sleep apnea can negatively affect children's neurocognitive function and development, hindering academic and adaptive goals. Questionnaires are suitable for assessing neuropsychological symptoms in children with sleep-disordered breathing. The study aimed to evaluate the effectiveness of using the Oxygen Desaturation Index compared to the Obstructive Apnea-Hypopnea Index in predicting long-term consequences of sleep-disordered breathing in children. We conducted a retrospective analysis of respiratory polysomnography recordings from preschool and school-age children (mean age: 5.8 ± 2.8 years) and followed them up after an average of 3.1 ± 0.8 years from the home-based polysomnography. We administered three validated questionnaires to the parents/caregivers of the children by phone. Our results showed that children with an Oxygen Desaturation Index (ODI) greater than one event per hour exhibited symptoms in four domains (physical, school-related, Quality of Life [QoL], and attention deficit hyperactivity disorder [ADHD]) at follow-up, compared to only two symptoms (physical and school-related) found in children with an Obstructive Apnea-Hypopnea Index greater than one event per hour at the time of diagnosis. Our study also found a significant correlation between the minimum SpO 2 (%) recorded at diagnosis and several outcomes, including Pediatric Sleep Questionnaire (PSQ) scores, physical, social, and school-related outcomes, and ADHD index at follow-up. These results suggest that the Oxygen Desaturation Index could serve as a valuable predictor of long-term symptoms in children with sleep-disordered breathing, which could inform treatment decisions. Additionally, measuring minimum SpO 2 levels may help assess the risk of developing long-term symptoms and monitor treatment outcomes.

Since the beginning of 2020, a remarkably low incidence of respiratory virus hospitalizations has been reported worldwide. We prospectively evaluated 587 children, aged <12 years, admitted for respiratory tract infections from 1 September 2021 to 15 March 2022 in four Italian pediatric hospitals to assess the burden of respiratory viruses during the COVID-19 pandemic in Italy. At admission, a Clinical Respiratory Score was assigned and nasopharyngeal or nasal washing samples were collected and tested for respiratory viruses. Total admissions increased from the second half of October 2021 to the first half of December 2021 with a peak in early November 2021. The respiratory syncytial virus (RSV) incidence curve coincided with the total hospitalizations curve, occurred earlier than in the pre-pandemic years, and showed an opposite trend with respect to the incidence rate of SARS-CoV-2. Our results demonstrated an early peak in pediatric hospitalizations for RSV. SARS-CoV-2 may exhibit a competitive pressure on other respiratory viruses, most notably RSV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nenna, Matera, Licari, Manti, Di Bella, Pierangeli, Palamara, Nosetti, Leonardi, Marseglia, Midulla and ICHRIS Group.)

Study Objectives: Obstructive sleep apnea (OSA) in children is associated with acute metabolic, cardiovascular, and neurocognitive abnormalities. The long-term outcomes of childhood OSA into adulthood have not been established. We performed a 20-year follow-up of patients with polysomnography-documented OSA in childhood compared to a healthy control group to evaluate the long-term anthropometric, sleep, cognitive, and cardiovascular outcomes., Methods: Children diagnosed with severe OSA between ages 1 and 17 years (mean, 4.87 ± 2.77) were prospectively contacted by telephone as young adults after approximately 20 years. Data collected included reported anthropometric information, educational level, health history, and Berlin questionnaire scores., Results: Young adults with confirmed severe OSA in childhood had significantly higher adulthood body mass index ( P = .038), fewer academic degrees ( P < .001), and more snoring ( P = .045) compared to control patients. The apnea-hypopnea index during childhood trended toward predicting cardiovascular outcomes and the results of the Berlin questionnaire in adulthood., Conclusions: Adults with a history of severe childhood OSA have a high risk of snoring, elevated body mass index, and lower academic achievement in adulthood. Thus, children with severe OSA may be at increased risk of chronic diseases later in life. The intervening coronavirus disease 2019 (COVID-19) pandemic has introduced considerable additional neurobehavioral morbidity complicating the identification of the full long-term consequences of childhood OSA., Citation: Nosetti L, Zaffanello M, Katz ES, et al. Twenty-year follow-up of children with obstructive sleep apnea. J Clin Sleep Med. 2022;18(6):1573-1581., (© 2022 American Academy of Sleep Medicine.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nosetti, Agosti, Franchini, Milan, Piacentini and Zaffanello.)

Cow's milk allergy (CMA) and gastro-esophageal reflux disease (GERD) may manifest with similar symptoms in infants making the diagnosis challenging. While immediate reaction to cow's milk protein indicate CMA, regurgitation, vomiting, crying, fussiness, poor appetite, sleep disturbances have been reported in both CMA and GERD and in other conditions such as functional gastrointestinal disorders, eosinophilic esophagitis, anatomic abnormalities, metabolic and neurological diseases. Gastrointestinal manifestations of CMA are often non-IgE mediated and clinical response to cow's milk free diet is not a proof of immune system involvement. Neither for non-IgE CMA nor for GERD there is a specific symptom or diagnostic test. Oral food challenge, esophageal pH impedance and endoscopy are recommended investigations for a correct clinical classification but they are not always feasible in all infants. As a consequence of the diagnostic difficulty, both over- and under- diagnosis of CMA or GERD may occur. Quite frequently acid inhibitors are empirically started. The aim of this review is to critically update the current knowledge of both conditions during infancy. A practical stepwise approach is proposed to help health care providers to manage infants presenting with persistent regurgitation, vomiting, crying or distress and to solve the clinical dilemma between GERD or CMA.

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., Competing Interests: the authors declare that they have no conflict of interest.

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., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

The best hypothesis to explain Sudden Infant Death Syndrome (SIDS) pathogenesis is offered by the "triple risk model", which suggests that an interaction of different variables related to exogenous stressors and infant vulnerability may lead to the syndrome. Environmental factors are triggers that act during a particular sensible period, modulated by intrinsic genetic characteristics. Although literature data show that one of the major SIDS risk factors is smoking exposure, a specific involvement of molecular components has never been highlighted. Starting from these observations and considering the role of GSTT1 and GSTM1 genes functional polymorphisms in the detoxification process, we analyzed GSTM1 and GSTT1 null genotype frequencies in 47 SIDS exposed to tobacco smoke and 75 healthy individuals. A significant association (p < .0001) between the GSTM1 null genotype and SIDS exposed to smoke was found. On the contrary, no association between GSTT1 polymorphism and SIDS was determined. Results indicated the contribution of the GSTM1 -/- genotype resulting in null detoxification activity in SIDS cases, and led to a better comprehension of the triple risk model, highlighting smoking exposure as a real SIDS risk factor on a biochemical basis., (Copyright © 2018. Published by Elsevier B.V.)

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., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Five years after the first edition, we have revised and updated the guidelines, re-examining the queries and relative recommendations, expanding the issues addressed with the introduction of a new entity, recently proposed by the American Academy of Pediatrics: BRUE, an acronym for Brief Resolved Unexplained Events. In this manuscript we will use the term BRUE only to refer to mild, idiopathic cases rather than simply replace the acronym ALTE per se.In our guidelines the acronym ALTE is used for severe cases that are unexplainable after the first and second level examinations.Although the term ALTE can be used to describe the common symptoms at the onset, whenever the aetiology is ascertained, the final diagnosis may be better specified as seizures, gastroesophageal reflux, infection, arrhythmia, etc. Lastly, we have addressed the emerging problem of the so-called Sudden Unexpected Postnatal Collapse (SUPC), that might be considered as a severe ALTE occurring in the first week of life.

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., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

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.

Background: Past studies reported evidence of associations between air pollution and respiratory symptoms and morbidity for children. Few studies examined associations between air pollution and emergency room (ER) visits for wheezing, and even fewer for gastroenteric illness. We conducted a multicity analysis of the relationship between air pollution and ER visits for wheezing and gastroenteric disorder in children 0-2 years of age., Methods: We obtained ER visit records for wheezing and gastroenteric disorder from six Italian cities. A city-specific case-crossover analysis was applied to estimate effects of particulate matter (PM), nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide, adjusting for immediate and delayed effects of temperature. Lagged effects of air pollutants up to 6 prior days were examined. The city-specific results were combined using a random-effect meta-analysis., Results: CO and SO(2) were most strongly associated with wheezing, with a 2.7% increase [95% confidence interval (CI), 0.5-4.9] for a 1.04-microg/m(3) increase in 7-day average CO and a 3.4% (95% CI, 1.5-5.3) increase for an 8.0-microg/m(3) increase in SO(2). Positive associations were also found for PM with aerodynamic diameter < or = 10 microg and NO(2). We found a significant association between the 3-day moving average CO and gastroenteric disorders [3.8% increase (95% CI, 1.0-6.8)]. When data were stratified by season, the associations were stronger in summer for wheezing and in winter for gastroenteric disorders., Conclusion: Air pollution is associated with triggering of wheezing and gastroenteric disorders in children 0-2 years of age; more work is needed to understand the mechanisms to help prevent wheezing in children.