Development and validation of the PROMIS Pediatric Sleep Disturbance and Sleep-Related Impairment item banks.

Study Objectives: To develop and evaluate the measurement properties of child-report and parent-proxy versions of the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Sleep Disturbance and Sleep-Related Impairment item banks. Methods: A national sample of 1104 children (8-17 years old) and 1477 parents of children 5-17 years old was recruited from an internet panel to evaluate the psychometric properties of 43 sleep health items. A convenience sample of children and parents recruited from a pediatric sleep clinic was obtained to provide evidence of the measures' validity; polysomnography data were collected from a subgroup of these children. Results: Factor analyses suggested two dimensions: sleep disturbance and daytime sleep-related impairment. The final item banks included 15 items for Sleep Disturbance and 13 for Sleep-Related Impairment. Items were calibrated using the graded response model from item-response theory. Of the 28 items, 16 are included in the parallel PROMIS adult sleep health measures. Reliability of the measures exceeded 0.90. Validity was supported by correlations with existing measures of pediatric sleep health and higher sleep disturbance and sleep-related impairment scores for children with sleep problems and those with chronic and neurodevelopmental disorders. The sleep health measures were not correlated with results from polysomnography. Conclusions: The PROMIS Pediatric Sleep Disturbance and Sleep-Related Impairment item banks provide subjective assessments of child's difficulty falling and staying asleep as well as daytime sleepiness and its impact on functioning. They may prove useful in the future for clinical research and practice. Future research should evaluate their responsiveness to clinical change in diverse patient populations.

Financial Analysis of an Intensive Pediatric Continuous Positive Airway Pressure Program.

Study Objectives: Continuous positive airway pressure (CPAP) is effective in treating obstructive sleep apnea in children, but adherence to therapy is low. Our center created an intensive program that aimed to improve adherence. Our objective was to estimate the program's efficacy, cost, revenue and break-even point in a generalizable manner relative to a standard approach. Methods: The intensive program included device consignment, behavioral psychology counseling, and follow-up telephone calls. Economic modeling considered the costs, revenue and break-even point. Costs were derived from national salary reports and the Pediatric Health Information System. The 2015 Medicare reimbursement schedule provided revenue estimates. Results: Prior to the intensive CPAP program, only 67.6% of 244 patients initially prescribed CPAP appeared for follow-up visits and only 38.1% had titration polysomnograms. In contrast, 81.4% of 275 patients in the intensive program appeared for follow-up visits (p < .001) and 83.6% had titration polysomnograms (p < .001). Medicare reimbursement levels would be insufficient to cover the estimated costs of the intensive program; break-even points would need to be 1.29-2.08 times higher to cover the costs. Conclusions: An intensive CPAP program leads to substantially higher follow-up and CPAP titration rates, but costs are higher. While affordable at our institution due to the local payer mix and revenue, Medicare reimbursement levels would not cover estimated costs. This study highlights the need for enhanced funding for pediatric CPAP programs, due to the special needs of this population and the long-term health risks of suboptimally treated obstructive sleep apnea.

Upper Airway Vibration Perception in School-Aged Children with Obstructive Sleep Apnea.

STUDY OBJECTIVES: Children with the obstructive sleep apnea (OSA) have impaired upper airway two-point discrimination compared to controls. In addition, blunted vibration threshold detection (VT) in the palate has been recognized in adults with OSA, but has not been studied in children. Both findings are indicative of a defect in the afferent limb of the upper airway dilator reflex that could prevent upper airway dilation secondary to airway loading, resulting in airway collapse. We hypothesized that children with OSA have impaired palate VT compared to controls, and that this improves after OSA treatment. METHODS: Case-control study. Children with OSA and healthy non-snoring controls underwent polysomnography and palate VT measurements. Children with OSA were retested after adenotonsillectomy. RESULTS: 29 children with OSA (median [interquartile range] age = 9.5 [7.5-12.6] years, obstructive apnea-hypopnea index [OAHI] = 11.3 [5.7-19.5] events/h, BMI z = 1.8 [1.3-2.1]) and 32 controls (age = 11.2 [9.3-13.5] years, P = 0.1; OAHI = 0.5 [0.1-0.7] events/h, P < 0.001; BMI z = 1 [0.3-1.7], P = 0.004) were tested. OSA palate VT (1.0 [0.8-1.5] vibration units) was similar to that of controls (1 [0.8-1.3], P = 0.37). 20 children with OSA were retested 4.4 (3.2-7.1) months after treatment. OAHI decreased from 13.1 (5.8-19) to 0.6 (0.2-2.5) events per hour (P < 0.001) postoperatively, but palate VT did not change (before = 1 [0.7-1.5], after = 1.2 [0.8-1.4], P = 0.37). CONCLUSIONS: Children with OSA and controls have similar palate VT. Unlike in adults, palate VT does not seem to be affected by childhood OSA.

Validation of Actigraphy in Middle Childhood.

STUDY OBJECTIVES: Few studies have examined the validity of actigraphy in school-aged children. The objective of this study was to examine the validity of a commonly used actigraph compared to polysomnography (PSG) in a sample of children age 5 to 12 y born prematurely, sleeping in their natural home environment. METHODS: 148 children born preterm (85 boys and 63 girls), ages 5-12 y (mean = 9.3 y, standard deviation = 2.0) wore the Philips Respironics Actiwatch-2 for 1 night concurrently with comprehensive, ambulatory PSG in the child's home. Sleep outcome variables were sleep onset latency, total sleep time (TST), and sleep efficiency. Epoch-by-epoch comparisons were used to determine sensitivity, specificity, and accuracy. Secondary analyses examined differences between children with no sleep issues, obstructive sleep apnea syndrome, and periodic limb movements in sleep (PLMS). RESULTS: Actigraphy significantly underestimated TST (30 min) and sleep efficiency (5%). Actigraphy underestimated or overestimated sleep onset latency by at least 10 min for a third of the children. Sensitivity and accuracy were good at 0.88 and 0.84, respectively, whereas specificity was lower at 0.46. Differences between actigraphy and PSG for TST and sleep efficiency were greatest for children with PLMS. CONCLUSIONS: This study adds to the small existing literature demonstrating the validity of actigraphy in middle childhood. Although actigraphy shows good sensitivity (ability to detect sleep), specificity (ability to detect wake) is poor in this age group. Further, the results highlight the importance of considering whether a child has PLMS when interpreting actigraphic data, as well as the difficulties in accurately capturing sleep onset latency with actigraphy.

Evolution of Obstructive Sleep Apnea in Infants with Cleft Palate and Micrognathia.

STUDY OBJECTIVES: Children with craniofacial anomalies are a heterogeneous group at high risk for obstructive sleep apnea (OSA). However, the prevalence and structural predictors of OSA in this population are unknown. We hypothesized that infants with micrognathia would have more significant OSA than those with isolated cleft palate ± cleft lip (ICP), and those with ICP would have more significant OSA than controls. We postulated that OSA severity would correlate with reduced mandibular size, neurodevelopmental scores, and growth. METHODS: Prospective cohort study. 15 infants with ICP, 19 with micrognathia, and 9 controls were recruited for polysomnograms, neurodevelopmental testing, cephalometrics (ICP and micrognathia groups) at baseline and a follow-up at 6 mo. RESULTS: Baseline apnea-hypopnea index (AHI) [median (range)] of the micrognathia group [20.1 events/h (0.8, 54.7)] was greater than ICP [3.2 (0.3, 30.7)] or controls [3.1 (0.5, 23.3)] (p = 0.001). Polysomnographic findings were similar between ICP and controls. Controls had a greater AHI than previously reported in the literature. Cephalometric measures of both midface hypoplasia and micrognathia correlated with OSA severity. Neurodevelopment was similar among groups. OSA improved with growth in participants with ICP and postoperatively in infants with micrognathia. CONCLUSIONS: Micrognathia, but not ICP, was associated with more significant OSA compared to controls. Both midface and mandibular hypoplasia contribute to OSA in these populations. OSA improved after surgical correction in most infants with micrognathia, and improved without intervention before palate repair in infants with ICP.

Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome.

STUDY OBJECTIVES: Children with obstructive sleep apnea syndrome (OSAS) often experience periods of hypercapnia during sleep, a potent stimulator of cerebral blood flow (CBF). Considering this hypercapnia exposure during sleep, it is possible that children with OSAS have abnormal CBF responses to hypercapnia even during wakefulness. Therefore, we hypothesized that children with OSAS have blunted CBF response to hypercapnia during wakefulness, compared to snorers and controls. METHODS: CBF changes during hypercapnic ventilatory response (HCVR) were tested in children with OSAS, snorers, and healthy controls using diffuse correlation spectroscopy (DCS). Peak CBF changes with respect to pre-hypercapnic baseline were measured for each group. The study was conducted at an academic pediatric sleep center. RESULTS: Twelve children with OSAS (aged 10.1 ± 2.5 [mean ± standard deviation] y, obstructive apnea hypopnea index [AHI] = 9.4 [5.1-15.4] [median, interquartile range] events/hour), eight snorers (11 ± 3 y, 0.5 [0-1.3] events/hour), and 10 controls (11.4 ± 2.6 y, 0.3 [0.2-0.4] events/hour) were studied. The fractional CBF change during hypercapnia, normalized to the change in end-tidal carbon dioxide, was significantly higher in controls (9 ± 1.8 %/mmHg) compared to OSAS (7.1 ± 1.5, P = 0.023) and snorers (6.7 ± 1.9, P = 0.025). CONCLUSIONS: Children with OSAS and snorers have blunted CBF response to hypercapnia during wakefulness compared to controls. Noninvasive DCS blood flow measurements of hypercapnic reactivity offer insights into physiopathology of OSAS in children, which could lead to further understanding about the central nervous system complications of OSAS.

Perinatal Risk Factors Associated with the Obstructive Sleep Apnea Syndrome in School-Aged Children Born Preterm.

STUDY OBJECTIVES: The obstructive sleep apnea syndrome (OSAS) is more prevalent in ex-preterm children compared to the general pediatric population. However, it is unknown whether OSAS in ex-preterm children is associated with specific perinatal risk factors. This multicenter cohort study aimed to determine perinatal factors associated with OSAS at school age. METHODS: 197 ex-preterm (500-1,250 g) children aged 5-12 y who participated as neonates in a double-blind, randomized clinical trial of caffeine versus placebo (Caffeine for Apnea of Prematurity) underwent comprehensive ambulatory polysomnography. A negative binomial regression model was used to identify perinatal risk factors associated with OSAS. RESULTS: 19 children had OSAS (9.6%). Chorioamnionitis and multiple gestation were positively associated with OSAS with P values of 0.014 and 0.03, respectively. Maternal white race (P = 0.047) and maternal age (P = 0.002) were negatively associated with OSAS. Other risk factors, such as birth weight, Apgar score at 5 min, antenatal corticosteroids, delivery route, and sex were not significant. CONCLUSIONS: OSAS is very frequent, and is associated with chorioamnionitis and multiple gestation in ex-preterm children. Those born to older white mothers appear to be protected. We speculate that the former may be due to systemic inflammation and the latter to a higher socio-economic status. COMMENTARY: A commentary on this article appears in this issue on page 721.

Airway Resistance in Children with Obstructive Sleep Apnea Syndrome.

STUDY OBJECTIVES: Enlarged tonsils and adenoids, the main cause of obstructive sleep apnea syndrome (OSAS) in children, results in upper airway (UA) loading. This contributes to the imbalance between structural and neuromotor factors ultimately leading to UA collapse during sleep. However, it is unknown whether this UA loading can cause elevated airway resistance (AR) during wakefulness. We hypothesized that children with OSAS have elevated AR compared to controls and that this improves after OSAS treatment. METHODS: Case control study performed at an academic hospital. Children with OSAS and nonsnoring healthy controls underwent baseline polysomnography and spirometry, and AR measurement by body plethysmography while breathing via an orofacial mask. Children with OSAS repeated the previously mentioned tests after adenotonsillectomy. RESULTS: 31 OSAS participants (mean age ± SD = 9.7 ± 3.0 y, obstructive apnea-hypopnea index (OAHI) median [range] = 14.9 [2-58.7] events/h, body mass index [BMI] z = 1.5 ± 1) and 31 controls (age = 10.5 ± 2.5 y, P = 0.24; OAHI = 0.4 [0-1.4], P < 0.001; BMI z = 0.9 ± 1, P = 0.01) were tested. OSAS AR at baseline was 3.9 [1.5-10.3] cmH2O/L/sec and controls 2.8 [1.4 - 6.2] (P = 0.027). Both groups had similar spirometry results. 20 patients with OSAS were tested 6.4 ± 6.6 mo after adenotonsillectomy. OAHI decreased from 15.2 [2.1-58.7] to 0.5 [0 - 5.1] events/h postoperatively (P < 0.001), and AR decreased from 4.3 [1.5 - 10.3] to 2.8 [1.7 - 4.7] cmH2O/L/sec (P = 0.009). CONCLUSIONS: Children with OSAS have elevated AR that decreases after treatment. This is likely because of upper airway loading secondary to adenotonsillar hypertrophy and may contribute to the increased frequency of respiratory diseases in untreated children with OSAS.

Mandibular distraction osteogenesis for the treatment of neonatal tongue-based airway obstruction.

Early postnatal tracheostomy for airway compromise is associated with high morbidity and cost. In certain patients with tongue-base airway obstruction (TBAO), mandibular distraction osteogenesis may be preferred. We present a comprehensive analysis of surgical, airway, and cephalometric outcomes in a large series of neonatal patients with TBAO. A retrospective review was performed of patients with laryngoscopically proven TBAO who underwent mandibular distraction osteogenesis before 1 year of age at our institution. Demographic, operative, postoperative, polysomnographic, and radiographic data were analyzed with the appropriate statistical test. Between 2010 and 2013, 28 patients younger than 1 year underwent mandibular distraction for TBAO. Distraction was performed for documented TBAO and failure to thrive at an average age of 58 days (range, 11-312) days with distractor removal after an average of 90 days. Preoperative polysomnograms were obtained on 20 patients with an average apnea-hypopnea index of 39.3 ± 22.0/h; the apnea-hypopnea index on postoperative polysomnograms obtained after distraction completion was significantly reduced in all 14 patients in whom it was measured (mean, 3.0 ± 1.5/h; P < 0.0001). Twenty patients transitioned to oral feeding, and cephalometric and airway diameters were improved (P < 0.0001). Distraction was successful in all but 4 patients including all patients with GILLS scores of 2 or less and 66% of patients with GILLS scores of 3 or greater. Neonatal mandibular distraction is a powerful tool to treat critical obstructive apnea in patients with TBAO. Appropriate patient selection remains a challenge; however, mandibular distraction represents a compelling treatment modality.

Neurobehavioral functioning in adolescents with and without obesity and obstructive sleep apnea.

STUDY OBJECTIVES: Children and adults with obstructive sleep apnea syndrome (OSAS) exhibit neurobehavioral abnormalities, but few studies have evaluated the transitional stage of adolescence. Obesity is also associated with neurobehavioral abnormalities, and many patients with OSAS are obese. However, the confounding effect of obesity on neurobehavioral abnormalities in adolescents with OSAS has not been evaluated. We hypothesized that obese adolescents with OSAS would exhibit more neurobehavioral abnormalities than obese and lean adolescents without OSAS. DESIGN: Cross-sectional, case control. SETTING: Sleep Center and community. PARTICIPANTS: Obese adolescents with OSAS compared to (1) nonsnoring, obese controls without OSAS, and (2) nonobese, nonsnoring controls. INTERVENTIONS: Neurobehavioral evaluation. MEASUREMENTS AND RESULTS: Obese adolescents with OSAS had significantly worse executive function and attention compared to both obese (P < 0.001) and lean (P < 0.001) controls, and more depression (P = 0.004) and externalizing symptoms than lean controls (P = 0.008). A higher percentage of participants in the OSAS group scored in the clinically abnormal range on executive functioning, attention, sleepiness, and behavioral functioning than lean controls. Mediation analyses indicated that level of sleep apnea significantly mediated the effect of body mass on executive functioning, attention, and behavior. CONCLUSIONS: Obese adolescents with OSAS show impaired executive and behavioral function compared to obese and lean controls, and are more likely to score in the clinically abnormal range on measures of neurobehavioral functioning. These results are especially concerning given that the frontal lobe is still developing during this critical age period. We speculate that untreated OSAS during adolescence may lead to significant neurobehavioral deficits in adulthood.

Prevalence of periodic limb movements during sleep in normal children.

STUDY OBJECTIVES: Although the American Academy of Sleep Medicine (AASM) mandates that periodic limb movements during sleep (PLMS) be scored on every polysomnogram, and considers a periodic limb movement index (PLMI) > 5/h abnormal in children, there is a lack of community-derived data regarding the prevalence of PLMS in children, and no data to support this cutoff value. Therefore, the aim of this study was to determine the prevalence of PLMS in a sample of normal children. DESIGN: Retrospective study. PARTICIPANTS: 195 healthy, non-snoring children aged 5-17 years, recruited from the community, who underwent polysomnography for research purposes. METHODS: PLMS were scored using the AASM 2007 criteria. MEASUREMENTS AND RESULTS: The group age (median [IQR]) was 12.9 [10-15] years, and 58% were male. Sleep architecture was normal, and the obstructive apnea hypopnea index was 0.1 [0-0.3]/h. The median PLMI was 0/h, ranging from 0 to 35.5/h. Fifteen (7.7%) subjects had a PLMI > 5/h, and only 3 (1.5%) met the adult pathologic criterion of more than 15/h. Use of the 95th percentile PLMI cutoff of 7.2/h produced little difference in categorization between groups. Children with a PLMI > 5/h had a higher arousal index than those with a lower PLMI (11.6 [8.8-14.6] vs 8.1 [6.1-9.9]/h, respectively, P = 0.003). CONCLUSIONS: This study provides normative data to the field and supports the clinical periodic limb movement index cutoff of > 5/h based on both prevalence and the correlate of increased sleep fragmentation. Periodic limb movements during sleep are infrequent in normal children recruited from the community. CITATION: Marcus CL, Traylor J, Gallagher PR, Brooks LJ, Huang J, Koren D, Katz L, Mason TB, Tapia IE. Prevalence of periodic limb movements during sleep in normal children.

Investigating reasons for CPAP adherence in adolescents: a qualitative approach.

STUDY OBJECTIVES: Adolescents with obstructive sleep apnea syndrome (OSAS) represent an important but understudied subgroup of long-term continuous positive airway pressure (CPAP) users. The purpose of this qualitative study was to identify factors related to adherence from the perspective of adolescents and their caregivers. METHODS: Individual open-ended, semi-structured interviews were conducted with adolescents (n = 21) and caregivers (n = 20). Objective adherence data from the adolescents' CPAP machines during the previous month was obtained. Adolescents with different adherence levels and their caregivers were asked their views on CPAP. Using a modified grounded theory approach, we identified themes and developed theories that explained the adolescents' adherence patterns. RESULTS: Adolescent participants (n = 21) were aged 12-18 years, predominantly male (n = 15), African American (n = 16), users of CPAP for at least one month. Caregivers were mainly mothers (n = 17). Seven adolescents had high use (mean use 381 ± 80 min per night), 7 had low use (mean use 30 ± 24 min per night), and 7 had no use during the month prior to being interviewed. Degree of structure in the home, social reactions, mode of communication among family members, and perception of benefits were issues that played a role in CPAP adherence. CONCLUSIONS: Understanding the adolescent and family experience of using CPAP may be key to increasing adolescent CPAP adherence. As a result of our findings, we speculate that health education, peer support groups, and developmentally appropriate individualized support strategies may be important in promoting adherence. Future studies should examine these theories of CPAP adherence.

The significance of ASDA arousals in children.

Sleep disorders are common in children. The sleep disturbances associated with these disease processes may impact neurodevelopment and result in daytime behavioral and cognitive changes. Currently, there are no precise methods to accurately assess sleep disruption in the pediatric age group. There is evidence that American Sleep Disorders Association (ASDA) arousals are insufficient markers of sleep disruption in children. Other techniques that have been used to assess sleep disruption include unconventional means of evaluating the electroencephalogram (EEG) during sleep and evaluating subcortical or autonomic activation. The aim of this review is to discuss the application of conventional and unconventional markers of sleep disruption in children.

Acoustic arousal responses in children with obstructive sleep apnea.

Our objectives were to study the arousal responses to nonrespiratory (acoustic) stimuli in children with obstructive sleep apnea syndrome (OSAS). The acoustic arousal response was studied in children with OSAS due to adenotonsillar hypertrophy compared to normal, age-matched children. Acoustic stimuli were delivered incrementally from 30-100 dB during stage 2, slow wave sleep, and rapid eye movement (REM) sleep. The percentage of children who aroused in response to acoustic stimuli, and the arousal threshold (i.e., sound level at which arousal occurred), were compared between groups and sleep stages. The percentage of children who aroused was similar between children with OSAS and controls. The percentage of children who aroused was lower during slow wave sleep than REM sleep and stage 2 in both OSAS and controls. There were no statistically significant differences in acoustic arousal threshold between OSAS and control children. There was no difference in arousal response to moderate acoustic stimulation between children with OSAS and controls. These results contrast with previous data showing blunted arousal responses to hypercapnia and upper airway loading during sleep in children with OSAS, suggesting that children with OSAS have an arousal deficit specific to respiratory stimuli. However, further studies evaluating arousal to both respiratory and nonrespiratory stimuli in the same subjects are needed.

Late-onset hypoventilation without PHOX2B mutation or hypothalamic abnormalities.

Most children with idiopathic central hypoventilation have symptoms at birth or shortly thereafter and have mutations of the PHOX2B gene. Those whose symptoms appear later usually have obesity and hypothalamic abnormalities. We describe a case of a boy who presented at 5 years of age with severe idiopathic central hypoventilation, but no obesity or hypothalamic abnormalities, and who tested negative for mutation of the PHOX2B gene. This case illustrates the heterogeneity of childhood idiopathic central hypoventilation syndromes and indicates the multifactorial etiology of these syndromes.

Night-to-night variability of polysomnography in children with suspected obstructive sleep apnea.

OBJECTIVES: To determine whether a single polysomnographic night was a valid measure of obstructive sleep apnea syndrome (OSAS) in children with symptoms of sleep-disordered breathing. STUDY DESIGN: The night-to-night variability of respiratory and sleep parameters was measured prospectively in 30 snoring children aged 1.6 to 11.3 years (mean +/- SD, 4.1 +/- 2) by using 2 nocturnal polysomnograms performed 7 to 27 days apart (14 +/- 5 days). RESULTS: The mean of the respiratory variables including apnea index, apnea/hypopnea index, arterial oxygen saturation, and end-tidal partial pressure of carbon dioxide were not significantly different from night to night. Among the sleep parameters, there was no significant night-to-night difference in sleep efficiency, arousal index, percent rapid eye movement, or percent of slow wave sleep. Only the percentage of stage 2 was significantly different between the nights. The polysomnographic clinical diagnosis remained the same on both nights for all children, although the disease severity differed slightly in 2 patients. CONCLUSIONS: There is little clinically significant night-to-night variability in pediatric polysomnography, and no first-night effect. These data suggest that a single polysomnographic night is an adequate measure of the OSAS in children with symptoms of sleep-disordered breathing.

Body position and obstructive sleep apnea in children.

STUDY OBJECTIVES: In adults, sleep apnea is worse when the patient is in the supine position. However, the relationship between sleep position and obstructive apnea in children is unknown. The objective of this study was to evaluate the relationship between obstructive apnea and body position during sleep in children. DESIGN: Retrospective analysis of the relationship between body position and obstructive apnea in obese and non-obese children. SETTING: Tertiary care pediatric sleep center. PATIENTS: Otherwise healthy children, aged 1-10 years, undergoing polysomnography for suspected obstructive sleep apnea syndrome. Obese and non-obese children were evaluated separately. INTERVENTIONS: Retrospective review of the relationship between sleep position and obstructive apnea during polysomnography. MEASUREMENTS AND RESULTS: Eighty polysomnograms from 56 non-obese and 24 obese children were analyzed. Body position was determined by a sensor during polysomnography, and confirmed by review of videotapes. Children had a lower obstructive apnea hypopnea index when supine vs. prone, and shorter apneas when supine then when on their side. There was no difference in apnea duration between the supine and prone positions. Obese and non-obese children showed similar positional changes. CONCLUSIONS: Children with obstructive sleep apnea, in contrast to adults, breathe best when in the supine position.