Polysomnographic Characteristics of Sleep Architecture in Children With Obstructive Sleep Apnea.

BACKGROUND: The conventional measure of sleep fragmentation is via polysomnographic evaluation of sleep architecture. Adults with OSA have disruption in their sleep cycles and spend less time in deep sleep stages. However, there is no available evidence to suggest that this is also true for children and published results have been inconclusive. OBJECTIVE: To determine polysomnographic characteristics of sleep architecture in children with OSA and investigate effects relative to OSA severity. METHODS: Overnight polysomnograms (PSG) of children referred for suspected OSA were reviewed. Subjects were classified by apnea hypopnea index (AHI). PSG parameters of sleep architecture were recorded and analyzed according to OSA severity. RESULTS: Two hundred and eleven children were studied (median age of 7.0 years, range 4-10 years) Stage N1 sleep was longer while stage N2 sleep and REM sleep was reduced in the OSA group when compared to those without OSA (6.10 vs 2.9, P < .001; 42.0 vs 49.7, P < .001; 14.0 vs 15.9, P = .05). The arousal index was also higher in the OSA group (12.9 vs 8.2, P < .001). There was a reduction in sleep efficiency and total sleep time and an increase in wake after sleep onset noted in the OSA group (83.90 vs 89.40, P = .003; 368.50 vs 387.25, P = .001; 40.1 ± 35.59 vs 28.66 ± 24.14, P = .007; 29.00 vs 20.50; P = .011). No significant difference was found in N3 sleep stage (33.60 vs 30.60, P = .14). CONCLUSION: We found evidence that children with OSA have a disturbance in their sleep architecture. The changes indicate greater sleep fragmentation and more time spent in lighter stages of sleep. Future research is needed and should focus on more effective methods to measure alterations in sleep architecture.

Impact of 8-hour time-limited eating on sleep in adolescents with obesity.

STUDY OBJECTIVES: The relationship between time-limited eating (TLE) and sleep quality is a topic of growing interest in the field of chronobiology. Data in adult cohorts shows that TLE may improve sleep quality, but this has not been evaluated in adolescents. The aim of this secondary analysis was to (1) examine the impact of 8-hour TLE on sleep parameters in youth with obesity and (2) explore if there was any association between sleep patterns and glycemic profiles. METHODS: Adolescents with obesity were randomized into one of three groups: 8-hour TLE (participants self-selected their eating window) + real-time continuous glucose monitor, 8-hour TLE + blinded continuous glucose monitor, or a prolonged eating window. In the primary analysis, it was found that participants in the real-time continuous glucose monitor group + 8-hour TLE group did not access their continuous glucose monitor data and thus for this analysis the two TLE groups were combined and only completers who had available Pittsburgh Sleep Quality Index (PSQI) data at all three time points were included. Participants completed the PSQI at baseline, week 4, and week 12. Mixed-effects generalized linear regression models were utilized to examine the change in PSQI score and assess association between glycemic variability and PSQI total score overtime by intervention arm. RESULTS: The median PSQI total score for the TLE groups (n = 27) was 6 at week 0 (interquartile range = 5 to 10) and 5 at week 12 (interquartile range = 2 to 7). There was no significant difference in the change in total PSQI score or sleep latency between TLE and control over the study period (P > .05). There was no association between PSQI score and change in weight or glycemic profile between groups (all P values > 0.05). CONCLUSIONS: These results suggest that in adolescents with obesity, an 8-hour TLE approach did not negatively impact sleep quality or efficiency when compared to a prolonged eating window. The potential effects of TLE on sleep should be further investigated in larger randomized trials. CITATION: Jayakumr A, Gillett ES, Wee CP, Kim A, Vidmar AP. Impact of 8-hour time-limited eating on sleep in adolescents with obesity. J Clin Sleep Med. 2023;19(11):1941-1949.

Sleep Consequences of Prader-Willi Syndrome.

PURPOSE OF REVIEW: This paper reviews how sleep is impacted in patients with Prader-Willi syndrome (PWS), focusing on sleep-related breathing disturbances and excessive daytime sleepiness (EDS). RECENT FINDINGS: Hypothalamic dysfunction may underlie several aspects of the PWS phenotype. Central sleep apnea (CSA) can persist beyond infancy. Nocturnal hypoventilation is common and may occur without central or obstructive sleep apnea (OSA). Adenotonsillectomy, a mainstay of OSA treatment, may cause velopharyngeal insufficiency. Growth hormone (GH) is considered safe, but close surveillance for OSA remains important. Cardiac autonomic dysfunction occurs during slow wave sleep and may increase the risk of cardiovascular events. EDS and narcolepsy are also common. Modafinil and pitolisant are treatment options currently being studied. Sleep disorders are prevalent in individuals with PWS. Sleep-related breathing disorders present as CSA in infancy and later in life as OSA and hypoventilation. GH therapy has improved the clinical outcomes of patients with PWS, but close surveillance and treatment for OSA is recommended. EDS can persist even after sleep-related breathing disorders are treated, and some individuals may even develop narcolepsy. Early recognition and treatment of sleep-related disorders may prevent morbidity and result in improved survival of patients with PWS.

Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea.

STUDY OBJECTIVES: Pulmonary hypertension (PH) is a rare yet serious complication of obstructive sleep apnea (OSA). Echocardiographic screening for PH is recommended in children with severe OSA, but the health care burden of universal screening is high. We sought to determine the prevalence of PH on echocardiogram among children with severe OSA and identify variables associated with a positive PH screen. METHODS: Retrospective study of 318 children with severe OSA (obstructive apnea-hypopnea index ≥ 10 events/h) and echocardiogram within 1 year of polysomnogram. PH-positive echocardiogram was defined by peak tricuspid regurgitation velocity ≥ 2.5 m/s and/or 2 or more right-heart abnormalities suggestive of elevated pulmonary artery pressure. Patient characteristics and polysomnogram data were compared to identify factors associated with PH. RESULTS: Twenty-six children (8.2%; 95% confidence interval [CI] 5.4-11.8%) had echocardiographic evidence of PH. There was no difference in age, sex, body mass index, obstructive apnea-hypopnea index, or oxygenation indices between patients with and without PH. Sleep-related hypoventilation (end-tidal CO2 > 50 mmHg for > 25% of total sleep time) was present in 25% of children with PH compared with 6.3% of children without PH (adjusted prevalence ratio = 2.73; 95% CI 1.18-6.35). Forty-six percent of children (12/26) with PH had Down syndrome vs 14% (41/292) without PH (adjusted prevalence ratio = 3.11; 95% CI 1.46-6.65). CONCLUSIONS: There was a relatively high prevalence of PH on echocardiogram in our cohort of children with severe OSA. The findings of increased PH prevalence among children with sleep-related hypoventilation or Down syndrome may help inform the development of targeted screening recommendations for specific pediatric OSA populations. CITATION: Maloney MA, Davidson Ward SL, Su JA, et al. Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea. J Clin Sleep Med. 2022;18(6):1629-1637.

Sleep positions in children with Down syndrome and obstructive sleep apnea.

OBJECTIVES: To assess sleep positions in children with both Down syndrome (DS) and obstructive sleep apnea (OSA) and determine if there is a preferred sleep position by severity of apnea. METHODS: A single-center retrospective review of patients with both DS and OSA was performed. Caregivers reported sleep position utilized greater than 50% of observed sleep time. Accuracy of this report was confirmed through review of hypnograms from polysomnography studies. RESULTS: Eighty-two patients met inclusion criteria. Median body mass index (BMI) was 26.6 and 56% of patients had a prior tonsillectomy and/or adenoidectomy. The mean obstructive AHI (OAHI) was 25.33 with 90.4% having severe OSA, 9.6% having moderate OSA, and no patients having mild OSA. Reported sleep positions were skewed towards lateral/decubitus (82.9%) compared to prone (11.0%) and supine (6.1%). This was consistent with hypnogram data where 71% of total sleep time in lateral/decubitus positions compared to prone (13%) and supine (6%). The median changes in sleep position per patient was 5 (IQR: 3-6). Lower BMI (p < 0.001, 95% CI: 0.32-1.13) and tonsillectomy (p < 0.001, 95% CI: 7.7-18.19) were associated with lower OAHI. Sleep position was not associated with age (p = 0.19), sex (p = 0.66), race (p = 0.10), ethnicity (p = 0.68) nor history of tonsillectomy (p = 0.34). Preferred sleep position was not correlated with OAHI (p = 0.78, r = 0.03) or OSA severity (p = 0.72, r = 0.03). CONCLUSIONS: This study highlights the possibility that children with DS may have preferential sleep positions that cater to optimized airflow in the context of OSA although further prospective study is needed.

Disorders of Sleep and Ventilatory Control in Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is an imprinted genetic disorder conferred by loss of paternal gene expression from chromosome 15q11.2-q13. Individuals with PWS have impairments in ventilatory control and are predisposed toward sleep disordered breathing due to a combination of characteristic craniofacial features, obesity, hypotonia, and hypothalamic dysfunction. Children with PWS progress from failure to thrive during infancy to hyperphagia and morbid obesity during later childhood and onward. Similarly, the phenotype of sleep disordered breathing in PWS patients also evolves over time from predominantly central sleep apnea in infants to obstructive sleep apnea (OSA) in older children. Behavioral difficulties are common and may make establishing effective therapy with continuous positive airway pressure (CPAP) more challenging when OSA persists after adenotonsillectomy. Excessive daytime sleepiness (EDS) is also common in patients with PWS and may continue after OSA is effectively treated. We describe here the characteristic ventilatory control deficits, sleep disordered breathing, and excessive daytime sleepiness seen in individuals with PWS. We review respiratory issues that may contribute to sudden death events in PWS patients during sleep and wakefulness. We also discuss therapeutic options for treating sleep disordered breathing including adenotonsillectomy, weight loss, and CPAP. Lastly, we discuss the benefits and safety considerations related to growth hormone therapy.

Spindle checkpoint proteins and chromosome-microtubule attachment in budding yeast.

Accurate chromosome segregation depends on precise regulation of mitosis by the spindle checkpoint. This checkpoint monitors the status of kinetochore-microtubule attachment and delays the metaphase to anaphase transition until all kinetochores have formed stable bipolar connections to the mitotic spindle. Components of the spindle checkpoint include the mitotic arrest defective (MAD) genes MAD1-3, and the budding uninhibited by benzimidazole (BUB) genes BUB1 and BUB3. In animal cells, all known spindle checkpoint proteins are recruited to kinetochores during normal mitoses. In contrast, we show that whereas Saccharomyces cerevisiae Bub1p and Bub3p are bound to kinetochores early in mitosis as part of the normal cell cycle, Mad1p and Mad2p are kinetochore bound only in the presence of spindle damage or kinetochore lesions that interfere with chromosome-microtubule attachment. Moreover, although Mad1p and Mad2p perform essential mitotic functions during every division cycle in mammalian cells, they are required in budding yeast only when mitosis goes awry. We propose that differences in the behavior of spindle checkpoint proteins in animal cells and budding yeast result primarily from evolutionary divergence in spindle assembly pathways.