bluuebunny/crossref_metadata_2025_split huggingface dataset:
0789 Sleep Spindle Density is Associated with Core Symptom Severity in Autism Spectrum Disorder
Authors: Ishii Toru , Kawai Makoto , Chick Christina , Cotto Isabelle , Hallmayer Joachim , O'hara Ruth 
Published: May 2023

Abstract

Introduction
Converging evidence suggests that dysregulation of thalamocortical interactions, mediated by the thalamic reticular nucleus (TRN), contributes to the expression of autism spectrum disorder (ASD). Risk genes for ASD have been found to affect the TRN early in development. Two hallmarks of NREM sleep –slow oscillations (SO) and sleep spindles– reflect TRN function and distinct thalamic/thalamocortical circuits. While studies demonstrate disrupted sleep quality that correlates with symptoms in children with ASD, studies of spindles in ASD have produced inconsistent findings. It is yet unclear if and how spindle properties are associated with ASD symptoms. Herein, based on studies implicating TRN-mediated thalamocortical dysregulation in ASD, we hypothesized that 1) sleep spindles are reduced in ASD; 2) spindle abnormalities correlate with worse clinical symptoms and cognition.

Methods
Forty participants with ASD (32 males, age: 11.8 ± 3.2; range 6-15) and 46 typically developing (TD) controls (32 males, age: 11.2 ± 2.3; range 6-15) participated in the study. All participants underwent ambulatory overnight polysomnography (PSG) for sleep assessment after systematic desensitization. The Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) were used to assess core behavioral symptoms.

Results
Spindle density was significantly lower in ASD compared to TD participants (ASD: 2.5 ± 2.0; TD: 3.0 ± 2.1; d= 0.45, p=0.01). In the ASD group, less spindle density was associated with more severe behavioral symptoms, as measured by the total ADOS score (R2=0.15, p=0.01) and the three main subscales of the ADI-R (reciprocal social interaction: R2=0.22, p=0.002; communication and language: R2=0.19, p=0.003; and restricted and repetitive, stereotyped interests and behaviors: R2=0.14, p=0.01).

Conclusion
Alterations in the maturational trajectory of spindles are related to the core symptoms of ASD individuals. The results have the potential to identify novel biomarkers that index distinct aspects of ASD pathophysiology and point to multiple neural mechanisms underlying disease heterogeneity. The study may contribute to producing novel evidence to elucidate the bidirectional relationship between sleep and ASD.

Support (if any)
Simons Foundation Autism Research Initiative grant (177986).
0793 Effect of Sleeping Position on Obstructive sleep apnea in Children Undergoing Polysomnography
Authors: Rao Harish 
Published: May 2023

Abstract

Introduction
Obstructive sleep apnea (OSA) in children is characterized by partial or complete upper airway obstruction during sleep, associated with gas exchange abnormalities and disrupted sleep with well-recognized neurobehavioral, neurocognitive, cardiovascular consequences. Positional obstructive sleep apnea (POSA) is defined as a lower AHI (by 50%) in the non-supine position than in the supine position. POSA has been well described in adults, affecting about 55% of adults with OSA. This occurs because airway collapse is maximal in the supine position compared to lateral or prone positions in this subset of patients with significant reduction in airway dimension occurring antero-posteriorly compared to circumferential reduction in airway dimension. However, POSA has not been well studied in children.

Methods
In this single center retrospective study, data was collected from one hundred consecutive polysomnographic studies from children (6-18 years) with moderate and severe OSA. Mean age was 10.7 years with 50% males in our cohort. Regression analysis was performed to study the relationship of sleeping position with the following variables: Age, sex, BMI, neck circumference, AHI, and desaturation index (DI) in supine and non-supine positions.

Results
60% of the patients in our study had significantly lower (by 50%) AHI and DI in non-supine position. This effect was seen in both moderate and severe OSA, though the effect was higher with increasing AHI and BMI. The effect of sleeping position persisted even when corrected for time spent in each position.

Conclusion
Most of the children in our cohort showed significant reduction in OSA in non-supine sleeping position. Positional therapy (PT), being a low-cost and non-invasive intervention is a reasonable approach in patients who demonstrate differences in AHI, oxygenation, and ventilation. Identifying the OSA phenotype and the subset of OSA patients likely to benefit from non-supine position increases the success of PT. PT may be helpful in situations where adenotonsillectomy may not be indicated and CPAP may not be well tolerated, not desired by the patient, and/or not sufficient to improve OSA. We intend to perform further analysis to study the effect of position on gas exchange and identify the phenotype who may benefit from PT in a larger cohort.

Support (if any)
0796 Safety and efficacy of the combination of atomoxetine and oxybutynin for OSA treatment in children with Down Syndrome
Authors: Combs Daniel , Edgin Jamie , Hsu Chiu-Hsieh , Bottrill Kenneth , Van Vorce Hailey , Gerken Blake , Matloff Daniel , Rue Sicily La , Esparza Lucia , Parthasarathy Sairam 
Published: May 2023

Abstract

Introduction
Children with Down syndrome (DS) are at very high risk for obstructive sleep apnea (OSA), with a prevalence of OSA of 50-79%. Current OSA treatments for children with DS have limited effectiveness, as positive airway pressure therapy is poorly tolerated and adenotonsillectomy is not curative in most children with DS. The combination of atomoxetine and oxybutynin (ato-oxy) is a promising OSA treatment in adults. Ato-oxy has been shown to improve upper airway hypotonia, a key feature of OSA in children with DS, thus it may be particularly effective for OSA in children with DS.

Methods
We performed a randomized, double-blind, crossover pilot trial examining the short-term efficacy of ato-oxy in 15 children aged 6 to 17 years with DS and OSA. Participants received 4 weeks of low dose (0.5 mg/kg atomoxetine and 5 mg oxybutynin) as well as 4 weeks of high dose (1.2 mg/kg atomoxetine and 5 mg oxybutynin) in random order. Participants underwent polysomnography as well as parent-reported health-related quality of life assessment using the OSA-18 at baseline and at the end of each dosing period. The primary study endpoint was reduction in obstructive apnea-hypopnea index (oAHI) from baseline. Paired t-tests were used to compare baseline to low and high dose ato-oxy.

Results
15 participants qualified for randomization and 11 participants had complete data at all points. Baseline oAHI was 7.4 ± 3.7 (mean ± standard deviation), oAHI with low dose ato-oxy was 3.6 ± 3.3 (p=0.001 vs baseline) and oAHI with high dose ato-oxy was 3.9 ± 2.8 (p=0.003 vs baseline). There were no differences in sleep architecture or sleep efficiency between baseline and either dose of ato-oxy. OSA-18 total score was 51.5 ± 18.5 at baseline; improved to 44.6 ± 17.0 (p=0.09) at the end of 4-weeks of low dose ato-oxy; and improved to 45.5 ± 15.7 (p=0.37) at the end of high-dose ato-oxy therapy. The most common adverse effects were irritability and fatigue, and these were generally mild.

Conclusion
Ato-oxy is a promising treatment for OSA in children with DS.

Support (if any)
Funding provided by NIH (HL151254 and HD109777) as well as the Lumind-IDSC foundation.
0798 Frequency of Sleep Disordered Breathing and Comorbidities Among Pre-school Aged Children with Down Syndrome
Authors: Kolstad Tessa , Cho Yeilim , DelRosso Lourdes , Sobremonte-King Michelle 
Published: May 2023

Abstract

Introduction
Children with Down Syndrome (DS) are at high risk of sleep disordered breathing (SDB). The American Academy of Pediatrics recommends a polysomnogram (PSG) in children with DS prior to the age of 4. Data describing PSG parameters in this age group is limited. The purpose of this study is to examine the frequency of SDB, gas exchange abnormalities and comorbidities in this patient population.

Methods
This is a retrospective chart review of children ages 2-4 years with DS who underwent first PSG at Seattle Children’s Hospital from 2015-2021. Data collected included demographics, comorbidities and PSG parameters: obstructive apnea hypopnea index (oAHI), central apnea index (CAI), time spent with CO2 levels &gt; 50 mmHg, percentage of time spent with saturations &lt; 88% and saturation nadir. Data is presented by descriptive statistics and comparison by unpaired t test.

Results
A total of 154 children underwent PSG during the study period and 75 met the inclusion criteria. Mean age was 3.03 years (SD 0.805), 56% were male and 54.7% were caucasian. Comorbidities included (n, %): cardiac (43, 57.3%), dysphagia or aspiration (24, 32.0%), prematurity (17, 22.7%), pulmonary (16, 21.3%), immune dysfunction (2, 2.7%) and hypothyroidism (23, 30.7%). PSG parameter data collected included (mean, SD): obstructive AHI (7.9, 9.4) and central AHI (2.4, 2.4). 94.7% met criteria for pediatric OSA, 9.5% met criteria for central apnea, and 9.5% met criteria for hypoventilation. Only 1 child met criteria for hypoxemia. 60% had surgical intervention with 89% of these being adenotonsillectomy. There was no statistically significant difference in the frequency of OSA at different ages and no significant difference in OSA or CSA in children with or without hypothyroidism or dysphagia (p&gt;0.05).

Conclusion
Children with DS ages 2-4 years have high frequency of OSA. The most commonly encountered comorbidities were cardiac and dysphagia. Among those with OSA, more than half underwent surgical intervention, highlighting the importance of early diagnosis. Our previously published work showed that in infants with DS, dysphagia is correlated with severity of OSA. However, this was not shown in this abstract suggesting a potential larger contribution of other factors, such as adenotonsillar hypertrophy.

Support (if any)
0801 Predictive value of heart rate variability on BP outcomes in OSA status – a 10yr longitudinal study
Authors: Guo Wei 
Published: May 2023

Abstract

Introduction
The apnoea/hypopnoea index (AHI) is commonly used as the indicator of OSA severity, but it cannot fully describe the illness severity, comorbidities, or treatment response. Heart rate variability (HRV) is a non-invasive way of detecting cardiac autonomic nervous system activity variations. It adds a new dimension to help understand the interplay between cardiac and nervous systems involvement in OSA. Aims: To explore the associations of HRV with OSA status in subjects from a longitudinal study where measurements were performed at 4-yr and 10-yr follow-up visits.

Methods
The cohort was established in 2003 to examine the prevalence of OSA in primary school children. During the 4-yr follow-up, HRV data in the time domain and frequency domain for 243 subjects when they were 10-17 years old were collected. Participants were invited to return for the 10-yr follow-up visit to undergo anthropometric measurements, overnight sleep study, and 24-hour ambulatory blood pressure (ABP) monitoring.

Results
Two hundred forty-three participants returned for the 10-yr follow-up. Participants who completed the HRV measurements at the 4-yr follow-up were included in this preliminary analysis. There were 122 participants (48.4% with OSA). Participants with OSA (AHI &gt;=5 event/h) at the 10-yr follow-up had a higher high frequency (HF) norm, a kind of HRV parameter, at the 4-yr follow-up than those without OSA (40.5 ±22.1n.u.) vs (33.7 ±15.2n.u.) (P = 0.030).

Conclusion
HRV parameters combined with OAHI at 4yr likely partially explain SBP, and it can better predict SBP at 10yr than independent OAHI. HRV is prone to have an interaction effect, instead of a mediation effect, to help us predict SBP.

Support (if any)
0805 Targeting Sleep Disordered Breathing Screening During the SARS-CoV2 Pandemic: Parents or Providers?
Authors: Balog Matthew 
Published: May 2023

Abstract

Introduction
Sleep-disordered breathing (SDB) can significantly impact a child’s physical and psychological well-being. Primary care teams are strongly positioned to first note the signs of SBD and the American Academy of Pediatrics recommends routine screening for snoring at all well-child visits (WCV). However, the literature demonstrates low rates of application of this recommendation. This is likely multifactorial as noted by previous studies on the subject. This study aimed to assess if providing an electronic questionnaire to families ahead of the WCV would increase the snoring screening rate.

Methods
This quality improvement (QI) program consisted of a convenience sample (control n=504, program n=222) of 726 children, age 2-17 years presenting for their new or well-child-visit (WCV) over six weeks during the SARS-CoV2 pandemic. The Pediatric Sleep Questionnaire (PSQ) was delivered to parents via the electronic patient portal (EPP) 1-2 weeks before their child's appointment. The questionnaire was then auto imported into the physician's note at the time of the appointment.

Results
The QI program showed a lower overall SDB screening rate (16.7%) than the pre-program control (21%), however, 3 of 4 (75%) of the participating physicians saw an increase in SDB screening during the program. Statistical significance was seen in two physicians (X2 (1, N=262) = 27.150, p=.000, Phi = .332 and Fisher exact test p=.000, 2-tailed, Phi = .366.

Conclusion
The screening rate for snoring significantly increased among physicians when electronic questionnaires were provided to families prior to scheduled WCV. This is an early but promising pattern. The electronic patient portal can serve as an important asynchronous tool for providers to gather valuable information about the sleep quality of children in their practice, aligning with AAP goals and better supporting families.

Support (if any)
none
0811 Impact of Tonsillectomy and Adenoidectomy on Delta Power in Children with Obstructive Sleep Apnea
Authors: Naha Sowjanya , Kranthi Bhavana , Cohen David , Ner Zarah , Sahota Pradeep , Thakkar Mahesh 
Published: May 2023

Abstract

Introduction
Delta power is a known indicator of sleep drive and sleep pressure. Non-REM sleep delta power is increased in adults with sleep-disordered breathing, and lowered by treatment with continuous positive airway pressure (CPAP). Our purpose was to investigate the effect of tonsillectomy and adenoidectomy on delta power in children with sleep apnea. Here we report results from the pilot study phase of this project.

Methods
A retrospective study was performed using consecutive children between the age of 5 and 15 years presenting to our Sleep Disorders Clinic between October 2019 and October 2022 who underwent tonsillectomy and adenoidectomy for obstructive sleep apnea and for whom polysomnographic data was available from before and after the procedure. Spectral power density analysis was performed using polysomnography data to determine delta power.

Results
A total of 41 children were screened of whom appropriate polysomnography studies were available for 10 children. The mean delta power prior to surgery was 2687.8±1081, while the mean delta power after surgery was 1737.9±522.9. Paired t-test was performed and showed a significant and large (~65%) reduction in delta power (Cohen’s D 0.91; p=0.018).

Conclusion
Results of the pilot study showed a large and statistically significant reduction in delta power after tonsillectomy and adenoidectomy. This finding is consistent with the expected improvement in sleep pressure with correction of sleep apnea. Delta power represents a potent new metric to measure the biological efficacy and impact of surgery in children with sleep apnea.

Support (if any)
None
0813 Increasing accessibility of assessment of obstructive sleep apnea syndrome in youth with Down syndrome
Authors: Xanthopoulos Melissa , Arputhan Ahtish , Stefanovski Darko , Cielo Christopher , Kelly Andrea , Walega Rachel , Tapia Ignacio 
Published: May 2023

Abstract

Introduction
Because of the high risk for obstructive sleep apnea syndrome (OSAS) in youth with Down syndrome (DS), in-lab polysomnogram (PSG) is recommended by age 4-years and if symptom screening warrants. Unfortunately, screening for “traditional” OSAS symptoms has been considered unreliable DS. Further, while in-lab polysomnography (PSG) is the gold standard in assessment of OSAS, undergoing in-lab PSG is time and cost intensive and often stressful for youth with DS and their families. This study examined the relationship of sleep disturbance questionnaires with in-lab PSG and home sleep apnea testing (HSAT) in youth with DS.

Methods
As part of a larger study comparing PSG to HSAT in individuals with DS aged 6-25y, caregivers completed the parent-proxy Pediatric Promis Sleep Disturbance Measure (PPSDM) and Modified Epworth Sleepiness Scale (ESS). The relationships of the PPSDM and ESS and sleep study variables (total sleep time, oxygen desaturation nadir (SpO2 nadir), wake after sleep onset (WASO), sleep efficiency, obstructive hypopnea index (OAHI), and arousal index) were examined using Spearman correlation.

Results
Caregiver-completed questionnaires were available for 38 individuals with DS (18 males; mean age of 15.0±4.7, 84% White; 95% Non-Hispanic). PSG OAHI median [IQR] was 12.9[5.5-22.8] events per hour, SpO2 nadir 86.5[81-89] %, PPSDM 25[20-33], ESS 2.5[1-8]. The PPSDM was negatively correlated with PSG SpO2 nadir (r=-0.437; p=0.006) but with no additional HSAT or PSG variables. ESS was positively correlated with the obstructive apnea hypopnea index (OAHI) on both PSG (r=0.340, p=0.03) and HSAT (r=0.372; p=0.02) and negatively correlated with HSAT WASO (r=-0.369; p=0.02).

Conclusion
Given the limited availability of sleep specialists and labs equipped to complete PSG in individuals who may require increased attention, overnight pulse oximetry overnight coupled with ESS and caregiver completed sleep disturbance questionnaires may provide an initial, noninvasive, cost-effective method to screen for OSAS in individuals with DS. Considering that ESS correlated with OAHI, this questionnaire could be used to decide repeat PSG in youth with DS.

Support (if any)
This study was support by NICHHD grant R21HD101003 (PIs: Kelly and Tapia).
0815 Utilization of Telemedicine visits in a Pediatric Sleep Center and the Effect on PAP Adherence Rates
Authors: Scribner April , Spray Beverly , Willis Denise , Pruss Kristi , Jambhekar Supriya 
Published: May 2023

Abstract

Introduction
Although positive airway pressure (PAP) is an effective treatment for OSA, adherence is often suboptimal. Consistent follow up is needed to address barriers to adherence; however, in-person clinic attendance in our center has been low and was further reduced during the COVID-19 pandemic. Suboptimal adherence may result in cessation of reimbursement by insurance, leaving OSA untreated. Untreated OSA in children can lead to behavior and learning problems, impaired growth and cardiovascular complications. Due to the decrease in show rates, in-home telemedicine visits were offered in lieu of in-person visits.

Methods
A retrospective chart review was performed for children with OSA seen in the pediatric sleep clinic from March 2020 and October 2022. Subjects were excluded from analysis if they did not transition to telemedicine. Telemedicine visits were conducted in the same manner as in-person visits. PAP usage after telemedicine was compared to in-person visits. Adherence was reported as percent of total usage and percent of usage greater than four hours (U&gt;4h) per night.

Results
Three hundred nineteen charts were reviewed of whom the majority were male (69.9%). The median age (interquartile range) at PAP initiation was 12 years (7-15). Seventy eight subjects were included in the analysis. Mean U&gt;4h and total usage decreased when subjects transitioned from in-person to telemedicine visits (4.18% ± 26.7, p=0.17 (3.08% ± 22.5, p=0.23), respectively. These differences were not significant. 36 subjects (46%) had &lt; ± 5% change in total adherence, 23 (29%) had &gt; 5% increase in total adherence, and 19 (24%) had &gt; 5% decrease. When comparing change in U&gt;4h, 29 (37%) subjects had &lt; ± 5% change in adherence, 22 (28%) had &gt; 5% decrease, and 27 (35%) had &gt; 5% increase in adherence.

Conclusion
There were no statistically significant differences in adherence rates between telemedicine and in-person visits. Adherence improved in some children on transition from in-person to telemedicine visits. Utilization of in-home telemedicine visits may be a useful alternative for some children treated with PAP. Further studies are needed to determine which specific patient populations may benefit most from in-home telemedicine visits.

Support (if any)
0816 Actigraphy-Measured Sleep Timing and Risk of Breast Cancer in the UK Biobank
Authors: Freeman Joshua , Saint-Maurice Pedro , Watts Eleanor , Moore Steve , Shams-White Marissa , Wolff-Hughes Dana , Hong Hyokyoung , Loftfield Erikka , Matthews Charles 
Published: May 2023

Abstract

Introduction
Shift work leading to circadian disruption is associated with increased breast cancer risk, but it remains unclear whether typical sleep timing variation in the general population that may cause less extreme disruption is also associated with increased risk. Prior studies relied on sleep timing assessed using self-report, but research using actigraphy is limited. Our goal was to characterize the association between sleep timing and breast cancer risk using actigraphy-based measures.

Methods
Our sample included 43,109 women without a history of breast cancer in the UK Biobank cohort who wore Axivity-AX3 accelerometers over 7 days. We estimated sleep midpoints, the median of sleep onset and waking. Social jetlag was estimated as the absolute difference in average weekend and weekday sleep midpoints. We used multivariable Cox models to estimate hazards ratios (HRs) and 95% confidence intervals (CI), adjusting for age, body mass index, participant characteristics, socioeconomic status, physical activity, menopause, parity, and oral contraceptive use. We conducted a sensitivity analysis excluding shift workers to control for potential strong confounding from shift work.

Results
Over 6.2 years of follow-up, there were 683 incident breast cancer cases. Earlier and later sleep midpoints were not associated with breast cancer (Early, &lt; 4:00AM HR:1.08 [95%CI: 0.89-1.32]; Later, ≥5:00AM HR:1.24 [0.86-1.81]; vs. Reference 4:00-4:59 AM). Per-hour increases in social jetlag were suggestively associated with greater breast cancer risk (HR:1.09 [0.96-1.24]), but significantly higher risk was only noted at the highest levels of social jetlag comparing ≥2 hours to &lt; 1 hour (HR:1.58 [1.13-2.20]). Results were unchanged when excluding shift workers.

Conclusion
Higher levels of social jetlag among UK women appeared to be associated with elevated breast cancer risk, possibly due to circadian disruption. While our results suggest that minimizing variation between weekday and weekend sleep timing may be related to lower breast cancer risk, replication of our findings in future studies using actigraphy-based measures and larger case numbers is needed.

Support (if any)
Supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health.