Host-microbiome associations in saliva predict COVID-19 severity.

Established evidence indicates that oral microbiota plays a crucial role in modulating host immune responses to viral infection. Following severe acute respiratory syndrome coronavirus 2, there are coordinated microbiome and inflammatory responses within the mucosal and systemic compartments that are unknown. The specific roles the oral microbiota and inflammatory cytokines play in the pathogenesis of coronavirus disease 2019 (COVID-19) are yet to be explored. Here, we evaluated the relationships between the salivary microbiome and host parameters in different groups of COVID-19 severity based on their oxygen requirement. Saliva and blood samples (n = 80) were collected from COVID-19 and from noninfected individuals. We characterized the oral microbiomes using 16S ribosomal RNA gene sequencing and evaluated saliva and serum cytokines and chemokines using multiplex analysis. Alpha diversity of the salivary microbial community was negatively associated with COVID-19 severity, while diversity increased with health. Integrated cytokine evaluations of saliva and serum showed that the oral host response was distinct from the systemic response. The hierarchical classification of COVID-19 status and respiratory severity using multiple modalities separately (i.e. microbiome, salivary cytokines, and systemic cytokines) and simultaneously (i.e. multimodal perturbation analyses) revealed that the microbiome perturbation analysis was the most informative for predicting COVID-19 status and severity, followed by the multimodal. Our findings suggest that oral microbiome and salivary cytokines may be predictive of COVID-19 status and severity, whereas atypical local mucosal immune suppression and systemic hyperinflammation provide new cues to understand the pathogenesis in immunologically compromised populations.

Expanding the phenotype of PPP1R21-related neurodevelopmental disorder.

PPP1R21 encodes for a conserved protein that is involved in endosomal maturation. Biallelic pathogenic variants in PPP1R21 have been associated with a syndromic neurodevelopmental disorder from studying 13 affected individuals. In this report, we present 11 additional individuals from nine unrelated families and their clinical, radiological, and molecular findings. We identified eight different variants in PPP1R21, of which six were novel variants. Global developmental delay and hypotonia are neurological features that were observed in all individuals. There is also a similar pattern of dysmorphic features with coarse faces as a gestalt observed in several individuals. Common findings in 75% of individuals with available brain imaging include delays in myelination, wavy outline of the bodies of the lateral ventricles, and slight prominence of the bodies of the lateral ventricles. PPP1R21-related neurodevelopmental disorder is associated with a consistent phenotype and should be considered in highly consanguineous individuals presenting with developmental delay/intellectual disability along with coarse facial features.

The relationship between sleep and salivary and serum inflammatory biomarkers in adolescents.

Objectives: Poor sleep behavior can trigger an inflammatory response and contribute to the development of inflammatory diseases. Cytokines can act as indicators of inflammation and may precede the onset of inflammatory diseases. This study aimed to determine the association between sleep timing parameters (bedtime, sleep duration, sleep debt, and social jetlag) and the levels of nine serum and salivary inflammatory and metabolic biomarkers. Methods: Data were collected from 352 adolescents aged 16-19 years enrolled in Kuwait's public high schools. The levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), adiponectin, leptin, and insulin were measured from saliva and serum samples. We conducted mixed-effect multiple linear regression modeling to account for the school variable as a random effect to assess the relationship between the sleep variables and salivary and serum biomarkers. Mediation analysis was conducted to check if BMI was a mediator between bedtime and the biomarkers. Results: There was a statistically significant elevation in serum IL-6 level associated with later bedtime (0.05 pg./mL, p = 0.01). Adolescents with severe sleep debt of ≥2 h had an increase in salivary IL-6 biomarker levels (0.38 pg./mL, p = 0.01) compared to those who had sleep debt of <1 h. Adolescents with sleep debt of ≥2 h had significantly higher levels of serum CRP (0.61 µg/mL, p = 0.02) than those without sleep debt. Additionally, we found that the inflammatory biomarkers (CRP, IL-6, IL-8, IL-10, VEGF, and MCP-1) and metabolic biomarkers (adiponectin, leptin, and insulin) had more statistically significant associations with the bedtime variables than with sleep duration variables. CRP, IL-6, and IL-8 were associated with sleep debt, and IL-6, VEGF, adiponectin, and leptin levels were associated with social jetlag. BMIz was a full mediator in the relationship between late bedtime and increased serum levels of CRP, IL-6, and insulin. Conclusion: Adolescents who go to bed at or later than midnight had dysregulated levels of salivary and serum inflammatory biomarkers, suggesting that disrupted circadian rhythm can trigger higher levels of systemic inflammation and potentially exacerbate chronic inflammation and the risk of metabolic diseases.

Host-Microbiome Associations in Saliva Predict COVID-19 Severity.

Established evidence indicates that oral microbiota plays a crucial role in modulating host immune responses to viral infection. Following Severe Acute Respiratory Syndrome Coronavirus 2 - SARS-CoV-2 - there are coordinated microbiome and inflammatory responses within the mucosal and systemic compartments that are unknown. The specific roles that the oral microbiota and inflammatory cytokines play in the pathogenesis of COVID-19 are yet to be explored. We evaluated the relationships between the salivary microbiome and host parameters in different groups of COVID-19 severity based on their Oxygen requirement. Saliva and blood samples (n = 80) were collected from COVID-19 and from non-infected individuals. We characterized the oral microbiomes using 16S ribosomal RNA gene sequencing and evaluated saliva and serum cytokines using Luminex multiplex analysis. Alpha diversity of the salivary microbial community was negatively associated with COVID-19 severity. Integrated cytokine evaluations of saliva and serum showed that the oral host response was distinct from the systemic response. The hierarchical classification of COVID-19 status and respiratory severity using multiple modalities separately (i.e., microbiome, salivary cytokines, and systemic cytokines) and simultaneously (i.e., multi-modal perturbation analyses) revealed that the microbiome perturbation analysis was the most informative for predicting COVID-19 status and severity, followed by the multi-modal. Our findings suggest that oral microbiome and salivary cytokines may be predictive of COVID-19 status and severity, whereas atypical local mucosal immune suppression and systemic hyperinflammation provide new cues to understand the pathogenesis in immunologically naïve populations.

Salivary Biomarkers as Predictors of Obesity and Intermediate Hyperglycemia in Adolescents.

Introduction: Childhood obesity presents a major risk for metabolic diseases in adulthood. Noninvasive methods are needed for predicting the course of obesity in children and its complications. Using blood for longitudinal analyses of biomarkers to predict disease in children is not a convenient method. Saliva presents a noninvasive platform to detect inflammatory changes in biomarkers as possible predictive measures of future pathological events. Objectives: The aim of this study was to evaluate the relationship between specific salivary biomarkers, obesity, and intermediate hyperglycemia in children. We also investigated the longitudinal association between the salivary biomarkers and change in Body Mass Index-for-age percentile scores (BMIz). Methods: Data on 353 adolescents were collected from the individuals recruited for seven years in an ongoing Kuwait Healthy Life Study cohort. BMIz was measured at 10, 12, and 17 years of age. Interleukin (IL)-6, IL-8, IL-10, Leptin, C-Reactive Protein (CRP), Insulin, Vascular Endothelial Growth Factor (VEGF), and Monocyte Chemoattractant Protein-1 (MCP-1) were measured in saliva and serum. Additionally, fasting blood plasma glucose levels were recorded. Multilevel longitudinal regression modeling, mediation analyses, and logistic regression were used to determine the predictive value of salivary biomarkers in obesity and hyperglycemia. Results: Longitudinal analyses showed that with each one-unit increase of salivary CRP and insulin, there was a 3.5 kg/m2 and 3.2 kg/m2 increase in BMIz, respectively. Comparable to serum CRP and insulin, higher salivary CRP and insulin OR 4.94 [95%CI: 1.66,14., OR 2.64 [95%CI: 1.09, 6.38], respectively) were predictive of hyperglycemia and obesity (OR 4.53 [95%CI: 2.40,8.50], OR 3.29 [95%CI: 1.82,5.97], respectively). Insulin was a strong mediator in the relationship between obesity and hyperglycemia. Conclusion: Our findings demonstrated that salivary CRP and insulin were associated with hyperglycemia, obesity, and possibly diabetes in adolescents. Salivary biomarkers are a noninvasive approach with significant value for disease risk assessment and prevention.

Incidence of SARS-CoV-2 reinfection in a paediatric cohort in Kuwait.

OBJECTIVE: Subsequent protection from SARS-CoV-2 infection in paediatrics is not well reported in the literature. We aimed to describe the clinical characteristics and dynamics of SARS-CoV-2 PCR repositivity in children. DESIGN: This is a population-level retrospective cohort study. SETTING: Patients were identified through multiple national-level electronic COVID-19 databases that cover all primary, secondary and tertiary centres in Kuwait. PARTICIPANTS: The study included children 12 years and younger between 28 February 2020 and 6 March 2021. SARS-CoV-2 reinfection was defined as having two or more positive SARS-CoV-2 PCR tests done on a respiratory sample, at least 45 days apart. Clinical data were obtained from the Pediatric COVID-19 Registry in Kuwait. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary measure is to estimate SARS-CoV-2 PCR repositivity rate. The secondary objective was to establish average duration between first and subsequent SARS-CoV-2 infection. Descriptive statistics were used to present clinical data for each infection episode. Also, incidence-sensitivity analysis was performed to evaluate 60-day and 90-day PCR repositivity intervals. RESULTS: Thirty paediatric patients with COVID-19 had SARS-CoV-2 reinfection at an incidence of 1.02 (95% CI 0.71 to 1.45) infection per 100 000 person-days and a median time to reinfection of 83 (IQR 62-128.75) days. The incidence of reinfection decreased to 0.78 (95% CI 0.52 to 1.17) and 0.47 (95% CI 0.28 to 0.79) per person-day when the minimum interval between PCR repositivity was increased to 60 and 90 days, respectively. The mean age of reinfected subjects was 8.5 (IQR 3.7-10.3) years and the majority (70%) were girls. Most children (55.2%) had asymptomatic reinfection. Fever was the most common presentation in symptomatic patients. One immunocompromised experienced two reinfection episodes. CONCLUSION: SARS-CoV-2 reinfection is uncommon in children. Previous confirmed COVID-19 in children seems to result in a milder reinfection.

Whole-Cell and Acellular Pertussis Vaccine: Reflections on Efficacy.

Pertussis is a common respiratory infection caused by the bacterium Bordetella pertussis. Although most cases occur in developing countries, it is considered endemic globally. The World Health Organization estimates there are 20-40 million cases of pertussis annually. Pertussis vaccines played a pivotal role in reducing the burden of pertussis disease as well as infant morbidity and mortality. Although the two forms of pertussis vaccine are effective, each has its advantages and drawbacks. This review aims to review the current knowledge on pertussis vaccines, emphasizing vaccine effectiveness in different populations within a community. Clinical trials have shown favorable vaccine efficacy with acellular pertussis (aP)vaccine. However, observational and population-level studies showed that introducing at least a single dose of whole-cell pertussis (wP) vaccine within the routine immunization schedule is associated with better disease protection and a longer duration of immunity. On the other hand, wP vaccine is more reactogenic and associated with higher adverse events. Therefore, the selection of vaccine should be weighed against the effectiveness, reactogenicity, and cost-effectiveness. Due to its safety profile, aP vaccine can be offered to wider population groups. Booster adolescent and pregnant immunization programs have been implemented globally to control outbreaks and protect vulnerable infants. Due to the variable effectiveness performance of both vaccines, different countries adopted distinctive immunization programs. Determining the right vaccination approach depends on financial consideration, immunization program infrastructure, adverse event monitoring, and pertussis surveillance in the community.

Association between Frequency of Toothbrushing and Metabolic Syndrome among Adolescents: A 5-Year Follow-Up Study.

This study longitudinally examines the relationship between the frequency of toothbrushing and the development of selected components of metabolic syndrome (MetS), along with the potential role of salivary biomarkers in this relationship. In 2014, 6317 12-year-old children underwent health examinations (T1), of which, 348 children participated in the second stage of data collection in 2019 (T2). The association between the change in the metabolic status during the 5-year follow-up examination (between T1 and T2) and frequency of toothbrushing was assessed using multinomial logistic regression analyses. At T2, healthy adolescents had significantly higher odds of toothbrushing twice or more daily compared with adolescents with components of MetS (OR = 1.99, 95% CI 1.15-3.45). Adolescents who were healthy at T1 but developed components of MetS at T2, had significantly higher frequencies of dining-out compared with adolescents with components of MetS at both T1 and T2 (OR = 0.09, 95% CI 0.02 to 0.49). Adolescents who were 'healthy' at both T1 and T2 had significantly (p < 0.05) lower levels of C-reactive protein (T2), insulin (T1 and T2), interleukin-6 (T1) and adiponectin (T1) compared with adolescents who had components of MetS. Toothbrushing and frequency of dining-out were associated with the presence of MetS components.

Mediation effect of C-reactive protein in the relationship between abdominal obesity and intermediate hyperglycemia in Kuwaiti adolescents.

Aim: This study aimed to investigate the mediating effect of C-reactive protein (CRP) on obesity and hyperglycemia. Materials & methods: Fasting blood glucose, high-sensitivity CRP (hs-CRP) levels and waist circumference (WC) were measured on 353 participants. Multilevel regression modeling and mediation analyses were used to investigate the link between abdominal obesity, hs-CRP and hyperglycemia. Results: Elevation in hs-CRP was predictive of hyperglycemia in nonobese individuals (OR = 1.3, p = 0.03). With every 1-mg/l increase in hs-CRP, there was a 1-cm increase in WC (B = 0.87, p = 0.001). hs-CRP was a full mediator in the relationship between WC and hyperglycemia. Conclusion: hs-CRP predicts hyperglycemia development in nonobese individuals and the effect of increased WC on hyperglycemia was fully mediated by hs-CRP.

School start time change and motor vehicle crashes in adolescent drivers.

STUDY OBJECTIVES: The aim of this study was to examine the association between a 50-minute delay (7:20 am to 8:10 am) in high school start times in Fairfax County (FC) Virginia and changes in rates of adolescent motor vehicle crashes. Crash rates in FC were also compared to those in the rest of the state during the same time period. METHODS: Virginia Department of Motor Vehicles crash data in drivers age 16 to 18 years old between September and June of each year in FC versus the rest of the state were compared in the combined 2-year periods preceding (2013-2014 and 2014-2015; T1) and following (2015-2016 and 2016-2017; T2) school start time change in the fall of 2015. RESULTS: The crash rate per 1000 in 16- to 18-year-old licensed drivers in FC during T1 was significantly higher compared to T2, 31.63 versus 29.59 accidents per 1,000 (95% confidence interval, 1.0-1.14, odds ratio 1.07, P = .03). In contrast, adolescent crash rates in the rest of Virginia were not statistically significantly different at T1 versus T2. With regard to subtypes of crashes, there was a trend toward significance in distraction-related crashes per 1,000 in FC at T1 compared to T2 at 7.01 versus 6.13 (95% confidence interval, 0.99-1.31, odds ratio 1.14, P = .05), but were not significantly different in the remainder of the state. CONCLUSIONS: The results of this study suggest that school start time delay is associated with decreased adolescent motor vehicle crash risk, with significant implications for public health and safety.

Diagnosis, management and pathophysiology of central sleep apnea in children.

Central sleep apnea (CSA) is thought to occur in about 1-5% of healthy children. CSA occurs more commonly in children with underlying disease and the presence of CSA may influence the course of their disease. CSA can be classified based on the presence or absence of hypercapnia as well as the underlying condition it is associated with. The management of CSA needs to be tailored to the patient and may include medication, non-invasive ventilation, and surgical intervention. Screening children at high risk will allow for earlier diagnosis and timely therapeutic interventions for this population. The review will highlight the pathophysiology, prevalence and diagnosis of CSA in children. An algorithm for the management of CSA in healthy children and children with underlying co-morbidities will be outlined.

Nocturnal REM Sleep Without Atonia Is a Diagnostic Biomarker of Pediatric Narcolepsy.

STUDY OBJECTIVES: Compare nocturnal REM sleep without atonia (nRWA) and REM sleep behavior disorder (RBD) between pediatric patients with and without narcolepsy and determine if the nRWA index is a valid diagnostic biomarker for narcolepsy. METHODS: Retrospective cohort study of children ages 6 to 18 years who completed a nocturnal polysomnogram (PSG) and Multiple Sleep Latency Test (MSLT). Our study sample included 11 patients with narcolepsy type 1 (NT1), 6 with narcolepsy type 2 (NT2), 12 with idiopathic hypersomnia (IH), and 11 with subjective hypersomnia (sHS). We compared group nRWA indices (epochs of RWA/total stage R sleep epochs) from the nocturnal PSGs and analyzed nRWA index receiver operating curve (ROC) statistics for narcolepsy diagnosis. RESULTS: The median nRWA index of patients with NT1 was 15 to 30 times higher compared to sHS and IH (Ps < .005) but similar to that of the NT2 group (P = .46). RBD was present in 25% of patients with narcolepsy (NT1 and NT2). In comparing those with and without narcolepsy, the nRWA index area under the curve was 0.87 (0.6), 95% confidence interval (CI) = 0.75 to 0.99, P < .001. The threshold of having ≥ 1% of stage R sleep epochs with nRWA yielded a sensitivity of 88.2%, 95% CI = 63.6-98.5 and specificity of 60.9%, 95% CI = 38.5 to 80.3 for diagnosis of narcolepsy. In contrast, a threshold of ≥ 8% yielded a specificity of 95.7%, 95% CI = 78.1 to 99.9 and sensitivity of 52.9%, 95% CI = 27.8 to 77. CONCLUSIONS: The nRWA index is a very good diagnostic biomarker of pediatric narcolepsy. Depending on the clinical cutoffs utilized, this biomarker can identify more children/adolescents with narcolepsy using just the PSG or reduce false-positive diagnostic results.

Prevalence of obstructive sleep apnea among obese toddlers and preschool children.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder estimated at 1-5% in the school-aged children. With the obesity prevalence reaching staggering rates globally, OSA in obese adolescents is estimated to be 4-5-folds higher than their lean peers. There is a paucity of data regarding obesity-related OSA in children 6 years and less. This is particularly relevant as OSA is associated with neurocognitive deficits. The aim of this study is to evaluate the prevalence of OSA among obese toddlers and preschool children and further to determine what other factors may be associated with the presence of OSA. METHODS: A retrospective study involving children ≤6 years, identified from two Canadian pediatric tertiary care centers who had an in-lab polysomnography (PSG). Obesity was defined by a BMI of > 95th percentile for age and gender or a z-score of > 2. OSA was diagnosed if the obstructive apnea-hypopnea index (OAHI) was greater than 2 events per hour. RESULTS: There were 60 participants included; the mean age was 4.4 years (standard deviation [SD] ± 1.7), mean BMI z-score was 3.0 (SD ± 1.2). Of these, 22/60 (36.6%) had OSA. Compared with the non-OSA group, the OSA group had a higher Epworth sleepiness score (p = 0.03) and were more likely to snore (p = 0.01). CONCLUSION: Young obese children should be assessed for OSA. A history of snoring and daytime sleepiness may be useful indicators to facilitate triage for a PSG, especially in resource-limited settings.

Utility of Neck, Height, and Tonsillar Size to Screen for Obstructive Sleep Apnea among Obese Youth.

Objectives To determine whether neck:height ratio combined with adenoid and tonsillar size is a good predictive tool for obstructive sleep apnea in obese youth. Study Design Cross-sectional study. Setting Sleep clinics at the Hospital for Sick Children, Toronto, Canada. Subjects and Methods Consented obese individuals aged 8 to 18 years were recruited between 2013 and 2015. Anthropometric measures were obtained by a trained research coordinator in a standardized manner. Otolaryngologists evaluated adenoid and tonsil sizes. Obstructive sleep apnea was diagnosed with an overnight polysomnogram as an obstructive apnea-hypopnea index ≥2. Multivariable logistic regressions investigated the relationship between potential predictors and obstructive sleep apnea. The C-statistic measured the predictive ability. Results Of the 53 subjects (median age, 13 years; 55% males), 28 (53%) were diagnosed with obstructive sleep apnea, with a median index of 10.6 per hour. In a logistic regression controlling for adenoid size, enlarged tonsils were significantly associated with the presence of obstructive sleep apnea ( P < .01). Adding neck:height ratio into the model improved the model predictive ability (C-index increased from 0.73 to 0.84). Controlling for tonsil and adenoid sizes, an increase in neck:height ratio was significantly associated with the presence of obstructive sleep apnea ( P = .01). Conclusion Our study suggests that neck:height ratio combined with tonsillar hypertrophy may have a strong predictive ability for obstructive sleep apnea and may be useful in an ambulatory setting to screen obese youth at high risk. These findings should be confirmed in a larger study.

Resolution of Periodic Breathing in a Child with Idiopathic Pulmonary Arterial Hypertension.

Central sleep apnea (CSA) and periodic breathing are unusual findings described in pediatric patients with congestive heart failure. However, CSA has not been reported in children with pulmonary hypertension. We hereby report on a 10-year-old girl with idiopathic pulmonary arterial hypertension who had frequent central events in a periodic breathing fashion seen in her polysomnography, which was normalized following medical treatment leading to improvement of the pulmonary pressures.

Intelligent volume-assured pressured support (iVAPS) for the treatment of congenital central hypoventilation syndrome.

PURPOSE: Congenital central hypoventilation syndrome (CCHS) is characterized by ventilatory insensitivity to hypercapnia and hypoxemia during sleep and/or wakefulness. Management of CCHS includes a long-term ventilation. However, ventilation can be challenging given differences in the control of breathing during different sleep stages. Intelligent volume-assured pressure support (iVAPS) is a mode of Bi-level positive airway pressure (BPAP) ventilation in which the pressure support is modulated to ensure a constant alveolar ventilation. The aim of this study was to determine if BPAP with iVAPS mode is more effective at controlling hypercapnia than BPAP with spontaneous/timed (S/T) mode. METHODS: A retrospective chart review of CCHS patients who underwent both a titration polysomnogram (PSG) with standard BPAP S/T mode and a consecutive follow-up study with BPAP iVAPS mode at The Hospital for Sick Children, Toronto, Canada, between January 1, 2013 and September 30, 2015 were included. Comparisons were made between S/T mode and iVAPS mode. RESULTS: Eight (four males) children with CCHS were included. The median (IQR) age at the time of PSG using Bi-level ventilation with S/T mode for study participants was 10.0 (IQR 8.4, 11.6) years followed by PSGs with iVAPS mode, median age 10.6 (IQR 9.1, 12.5) years. The non-rapid eye movement (NREM) peak transcutaneous CO2 (tcCO2) median (IQR) for iVAPS was 43.0 (40.0-46.0-) mmHg versus 46.5 (45.0-48.0) mmHg for S/T mode, (p value <0.05). CONCLUSION: iVAPS was associated with a reduction in the maximum tcCO2 during NREM sleep as compared to traditional S/T mode. Prospective, longitudinal studies are needed to evaluate the benefits of BPAP therapy iVAPS mode for the treatment of pediatric CCHS.

Longitudinal evaluation of sleep disordered breathing in infants with Prader-Willi syndrome.

OBJECTIVE: To evaluate the course of sleep disordered breathing (SDB) in infants with Prader-Willi syndrome (PWS). DESIGN: Retrospective longitudinal observational study. SETTING: Sleep laboratory at The Hospital for Sick Children, Toronto, Canada. PATIENTS: Infants with PWS. MAIN OUTCOME MEASURES: The natural history of SDB in infants with PWS within 2 years from baseline assessment. RESULTS: We identified 28 (12 male) infants with PWS who had a baseline polysomnography (PSG) at a median age (interquartile (IQR)) of 0.9 (0.5, 1.1) years. The median central apnoea index (CAI) at baseline was 6.6 events/hour (IQR 2.6, 12.1). Of these, 15/28 (53%) infants with PWS were diagnosed with significant central sleep apnoea (CSA) (CAI≥5 events/hour). Median age (IQR) at follow-up PSG was 2.1 (1.5, 2.6) years. The median CAI improved from 6.6 to 2.3 events/hour (p<0.0001). Only four infants with PWS had persistent CSA at the time of the follow-up PSG. Furthermore, three infants with PWS were diagnosed with mild-to-moderate obstructive sleep apnoea (OSA) that has improved at follow-up studies whereas two patients with PWS with no evidence of OSA at baseline were diagnosed with severe OSA on the follow-up PSG requiring adenotonsillectomy. The overall median obstructive apnoea-hypopnoea index was similar between baseline and follow-up studies (0.6 and 0.8, respectively, p=0.91). CONCLUSIONS: CSA is prevalent in infants with PWS but usually improves with age. However, these patients continue to require ongoing PSG surveillance because some infants will have persistent CSA and others are at risk of developing OSA.