Sleep Disturbance in Children with Fetal Alcohol Spectrum Disorder and the Relationship to the Neurodevelopmental Profile.

OBJECTIVE: Sleep disturbance is an important feature of fetal alcohol spectrum disorder (FASD). We sought to describe sleep patterns in school-aged children with FASD, in comparison with a typically developing community group, and investigate the relationship between sleep and neurodevelopmental profiles. METHOD: The FASD cohort (N = 36) was recruited from a tertiary Australian FASD diagnostic center, and the typically developing group (N = 36) was previously recruited as a control cohort for a separate study. Sleep disturbance was assessed with the caregiver-completed Sleep Disturbance Scale for Children (SDSC) questionnaire. Neurodevelopmental assessment results for the 10 domains impaired in FASD were used for correlations with sleep disturbance. RESULTS: In the FASD group, 80% of children scored above the SDSC cutoff, compared with 22% of the control group (p < 0.001). Statistically significant group differences were seen for all 6 subscales of the SDSC (p < 0.05). The most frequently affected domains in the FASD group related to difficulties with initiating and maintaining sleep (58%), sleep-wake transition disorders (44%), and disorders of arousal (42%). A statistically significant relationship was not found between sleep and the severity of neurodevelopmental impairment or impairment of a particular domain, acknowledging the limitations of our small sample size. Half of the FASD sample (52%) were taking a pharmaceutical agent to support sleep, which was not associated with lower SDSC scores. CONCLUSION: In this small study, sleep disturbances were frequently reported by carers of children with FASD, independent of the severity of their neurodevelopmental impairments. Persistent sleep disturbance despite the use of sleep medications highlights the need for prospective studies exploring sleep interventions in this population. Integration of behavioral sleep medicine into management is recommended for all children with FASD.

Preterm infants experience a nadir in cerebral oxygenation during sleep three months after hospital discharge.

AIM: Preterm infants are at increased risk of Sudden Infant Death Syndrome (SIDS) and frequently experience short central apnoeas which can occur in isolation or a repetitive pattern (periodic breathing). We investigated the relationship between central apnoeas experienced before and over the 6 months after hospital discharge and cerebral oxygenation. METHODS: Preterm infants born between 28 and 32 weeks gestational age (GA) were studied during supine daytime sleep at 32-36 weeks post menstrual age (PMA) (n = 40), 36-40 weeks PMA (n = 27), 3-months corrected age (CA) (n = 20) and 6-months CA (n = 26). Cerebral tissue oxygenation (TOI), peripheral oxygenation (SpO2) and heart rate were recorded continuously. The percentage total sleep time (%TST) spent having central apnoeas at each study and cerebral fractional oxygen extraction (SpO2-TOI/SpO2) were calculated. RESULTS: %TST spent with central apnoeas decreased with increasing age in both active sleep (AS) and quiet sleep (QS). TOI tended to be lower and cerebral fractional oxygen extraction higher at 3 months compared to the other studies and this reached statistical significance compared to 32-36 weeks in QS. CONCLUSION: The nadir in cerebral tissue oxygenation at 3 months of age coincides with the peak risk period for SIDS and this may contribute to increased risk in these infants.

Follow-up of children with Down syndrome and sleep disordered breathing and the effects of treatment on actigraphically recorded sleep, quality of life, behaviour, and daytime functioning.

Children with Down syndrome are at increased risk of obstructive sleep disordered breathing, which has deleterious effects on daytime functioning. We aimed to examine the effects of treatment of sleep disordered breathing on sleep quality and daytime functioning in children with Down syndrome, and hypothesised that these would be improved. Thirty-four children completed a baseline study and a follow-up 2 years later. Measures at both time points included 7 days of actigraphy and parents completed a number of questionnaires assessing sleep, behaviour, daytime functioning, and quality of life. All children had overnight polysomnography at baseline; 15 children (44%) were treated. At baseline the treated group had more severe sleep disordered breathing compared with the untreated group: obstructive apneoa-hypopnoea index 29.3 ± 38.2 events/h versus 3.3 ± 5.2 events/h (p < 0.01). Actigraphy showed no significant differences in total sleep time, sleep efficiency, sleep schedules from baseline to follow up in either group. The sleep disturbance (p < 0.01) and total problems (p < 0.05) scales on the OSA-18 and the sleep disordered breathing subscale on the Paediatric Sleep Problem Survey Instrument (p < 0.01) improved in the treated children. There were no changes in any measure in the untreated children. Treatment of sleep disordered breathing improves symptoms, sleep disturbance and quality of life in children with Down syndrome, but has no demonstrable impact on actigraphic sleep measures or daytime behaviour or function. In contrast, children who were not treated, despite having less severe disease at baseline, had increased sleep disruption and no change in quality of life.

Sleep spindles are reduced in children with Down syndrome and sleep-disordered breathing.

BACKGROUND: Children with Down syndrome (DS) are at increased risk of sleep-disordered breathing (SDB). We investigated sleep spindle activity, as a marker of sleep quality, and its relationship with daytime functioning in children with DS compared to typically developing (TD) children. METHODS: Children with DS and SDB (n = 44) and TD children matched for age, sex and SDB severity underwent overnight polysomnography. Fast or Slow sleep spindles were identified manually during N2/N3 sleep. Spindle activity was characterized as spindle number, density (number of spindles/h) and intensity (density × average duration) on central (C) and frontal (F) electrodes. Parents completed the Child Behavior Check List and OSA-18 questionnaires. RESULTS: In children with DS, spindle activity was lower compared to TD children for F Slow and F Slow&Fast spindles combined (p < 0.001 for all). Furthermore, there were no correlations between spindle activity and CBCL subscales; however, spindle activity for C Fast and C Slow&Fast was negatively correlated with OSA-18 emotional symptoms and caregiver concerns and C Fast activity was also negatively correlated with daytime function and total problems. CONCLUSIONS: Reduced spindle activity in children with DS may underpin the increased sleep disruption and negative effects of SDB on quality of life and behavior. IMPACT: Children with Down syndrome (DS) are at increased risk of sleep-disordered breathing (SDB), which is associated with sleep disruption affecting daytime functioning. Sleep spindles are a sensitive marker of sleep quality. We identified for the first time that children with DS had reduced sleep spindle activity compared to typically developing children matched for SDB severity. The reduced spindle activity likely underpins the more disrupted sleep and may be associated with reduced daytime functioning and quality of life and may also be an early biomarker for an increased risk of developing dementia later in life in children with DS.

Autonomic cardiovascular control is altered by intermittent hypoxia in preterm infants.

AIM: Preterm infants frequently experience short apnoeas and periodic breathing. Animal studies have shown that repetitive hypoxia associated with periodic breathing can alter autonomic control. We aimed to elucidate if apnoea and periodic breathing were associated with changes in autonomic control assessed using heart rate variability, thus exacerbating the consequences of respiratory disturbance. METHODS: Forty very preterm infants (15 M/25 F) were studied at 34.3 weeks post-menstrual age with daytime polysomnography. Total power, low frequency (LF, sympathetic+parasympathetic activity) high frequency (HF, parasympathetic activity) and LF/HF (sympathovagal balance) were calculated. RESULTS: Infants were divided into those with above and below the median total sleep time spent with respiratory events: Active sleep (AS) 13%, Quiet sleep (QS) 10%. In AS, including respiratory events, Total power (p < 0.05) and HF power (p < 0.05) were higher in the above median group. During AS excluding respiratory events, Total power (p < 0.05) and HF power (p = 0.061) were higher and LF power (p < 0.01) and LF/HF (p < 0.05) were lower in the above median group. There were no differences in HRV parameters in QS. CONCLUSION: This study provides new evidence that short apnoeas, particularly periodic breathing, which is currently not detected or treated in the neonatal unit can affect autonomic cardiovascular control.

Developmental consequences of short apneas and periodic breathing in preterm infants.

OBJECTIVE: We investigated the relationship between respiratory events experienced before and after hospital discharge and developmental outcomes at 6 months corrected age (CA). STUDY DESIGN: Preterm infants born between 28-32 weeks gestational age (GA) were studied at 32-36 weeks postmenstrual age (PMA), 36-40 weeks PMA, 3- and 6-months CA. Percentage total sleep time (%TST) with respiratory events (isolated apneas, sequential apneas and periodic breathing (PB)) at each study was calculated. Stepwise multiple linear regressions determined significant predictors of developmental outcomes at 6 months. RESULT: %TST with respiratory events at term were significant predictors of language (R2 = 0.165, ß = -0.416) and motor (R2 = 0.180, ß = -0.485) composite scores of the Bayley Scales of Infant Development at 6 months, independent of GA, birth weight and sex. CONCLUSIONS: In clinically stable very preterm infants at term equivalent age, time spent having respiratory events, was related to a reduction in language and motor outcomes at 6 months.

Cortical grey matter changes, behavior and cognition in children with sleep disordered breathing.

This paper investigated cortical thickness and volumetric changes in children to better understand the impact of obstructive sleep disordered breathing (SDB) on the neurodevelopment of specific regions of the brain. We also aimed to investigate how these changes were related to the behavioral and cognitive deficits observed in the condition. Neuroimaging, behavioral, and sleep data were obtained from 30 children (15 non-snoring controls, 15 referred for assessment of SDB) aged 7 to 17 years. Gyral-based regions of interest were identified using the Desikan-Killiany atlas. Student's t-tests were used to compare regions of interest between the controls and SDB groups. We found that the cortical thickness was significantly greater in the right caudal anterior cingulate and right cuneus regions and there were volumetric increases in the left caudal middle frontal, bilateral rostral anterior cingulate, left, right, and bilateral caudate brain regions in children with SDB compared with controls. Neither cortical thickness nor volumetric changes were associated with behavioral or cognitive measures. The findings of this study indicate disruptions to neural developmental processes occurring in structural regions of the brain; however, these changes appear unrelated to behavioural or cognitive outcomes.

Periodic breathing in clinically stable very preterm infants.

OBJECTIVE: We aimed to investigate the frequency and severity of periodic breathing (PB) in clinically stable very preterm infants and identify infant and maternal factors associated with increased time spent and severity of PB in these infants. METHOD: Thirty-eight infants (28-32 weeks gestational age) who were ≥3 days off noninvasive respiratory support, were studied for 2-3 h with a daytime sleep study at 31-36 weeks postmenstrual age. Percent total sleep time spent in PB (%TSTPB) and time spent with SpO2 <90%, <80%, and cerebral oxygenation <55% during PB were calculated. Infant and maternal characteristics were correlated with %TSTPB and hypoxia during PB. RESULTS: The majority of infants (92%) had at least one episode of PB and infants spent a median 9.1 [interquartile range: 1.2, 15.5] %TSTPB. 80%, 37%, and 37% of infants experienced SpO2 <90%, <80% and cerebral oxygenation <55%, respectively, during PB. Shorter duration of respiratory support, multigravida, multiparity, and maternal vitamin D deficiency were associated with higher %TSTPB. Multigravida, shorter duration on respiratory support, apnea of prematurity, and resuscitation at birth were associated with hypoxia during PB. CONCLUSIONS: The majority of very preterm infants exhibited PB when they were off respiratory support and considered clinically stable. The time spent in PB was very variable between infants and was associated with significant hypoxia in some infants. Fewer days spent on respiratory support was associated with both increased frequency and severity of PB. However, the potential contribution of PB to neurocognitive outcomes remains uncertain and warrants further investigations.

Duration and Consequences of Periodic Breathing in Infants Born Preterm Before and After Hospital Discharge.

OBJECTIVE: To investigate the amount of time spent in periodic breathing and its consequences in infants born preterm before and after hospital discharge. METHODS: Infants born preterm between 28-32 weeks of gestational age were studied during daytime sleep in the supine position at 32-36 weeks of postmenstrual age (PMA), 36-40 weeks of PMA, and 3 months and 6 months of corrected age. The percentage of total sleep time spent in periodic breathing (% total sleep time periodic breathing) was calculated and infants were grouped into below and above the median (8.5% total sleep time periodic breathing) at 32-36 weeks and compared with 36-40 weeks, 3 and 6 months. RESULTS: Percent total sleep time periodic breathing was not different between 32-36 weeks of PMA (8.5%; 1.5, 15.0) (median, IQR) and 36-40 weeks of PMA (6.6%; 0.9, 15.1) but decreased at 3 (0.4%; 0.0, 2.0) and 6 months of corrected age 0% (0.0, 1.1). Infants who spent above the median % total sleep time periodic breathing at 32-36 weeks of PMA spent more % total sleep time periodic breathing at 36-40 weeks of PMA (18.1%; 7.7, 23.9 vs 2.1%; 0.6, 6.4) and 6 months of corrected age 0.9% (0.0, 3.3) vs 0.0% (0.0, 0.0). CONCLUSIONS: Percentage sleep time spent in periodic breathing did not decrease as infants born preterm approached term corrected age, when they were to be discharged home. High amounts of periodic breathing at 32-36 weeks of PMA was associated with high amounts of periodic breathing at term corrected age (36-40 weeks of PMA), and persistence of periodic breathing at 6 months of corrected age.

Effects of Treatment of Sleep Disordered Breathing on Sleep Macro- and Micro-Architecture in Children with Down Syndrome.

Background: Children with Down syndrome (DS) are at increased risk of obstructive sleep disordered breathing (SDB), which is associated with intermittent hypoxia and sleep disruption affecting daytime functioning. We aimed to examine the effects of treatment of SDB on sleep quality and daytime functioning in children with DS. Methods: Children with DS and SDB (n = 24) completed a baseline and follow-up overnight polysomnographic (PSG) study 22 ± 7 months (mean ± SD) later. Sleep micro-architecture was assessed using EEG spectral analysis, and parents completed a number of questionnaires assessing sleep, behavior, daytime functioning, and quality of life (QOL). Results: A total of nine children (38%) were treated. At baseline, the treated group had more severe SDB compared to the untreated group. SDB severity was significantly improved from 40.3 ± 46.9 events/h to 17.9 ± 26.9 events/h (p < 0.01) at follow up in children who were treated. There were no significant differences in sleep macro-architecture parameters from baseline to follow up in either the treated or untreated group. Sleep micro-architecture was not different between studies in the treated group, however this tended to improve in the untreated group, particularly in REM sleep. Daytime functioning and behavior were not different between the studies in either group, however, QOL improved after treatment. Conclusions: Our study identified that treatment of SDB improves severity of the disease as defined by PSG, and this was associated with parental reports of improved QOL, despite treatment having no demonstrable impacts on sleep quality, behavior, or daytime functioning.

Cost and economic determinants of paediatric tonsillectomy.

Objective Hospital utilisation research is important in pursuing cost-saving healthcare models. Tonsillectomy is one of the most common paediatric surgeries and the most frequent reason for paediatric hospital readmission. This study aimed to report the government-funded costs of paediatric tonsillectomy in the state of Victoria, Australia, extrapolate costs across Australia, and identify the cost determinants. Methods A population-based longitudinal study was conducted with a bottom-up costing approach using linked datasets containing all paediatric tonsillectomy and tonsillectomy with adenoidectomy surgeries performed in the state of Victoria between 2010 and 2015. Results The total average annual cost of tonsillectomy hospitalisation in Victoria was A$21 937 155 with a median admission cost of A$2224 (interquartile range (IQR) 1826-2560). Inflation-adjusted annual tonsillectomy costs increased during 2010-2015 (P < 0.001), not explained by the rising number of surgeries. Hospital readmissions resulted in a total average annual cost of A$1 427 716, with each readmission costing approximately A$2411 (IQR 1936-2732). The most common reason for readmission was haemorrhage, which was associated with the highest total cost. The estimated total annual expenditure of both tonsillectomy and resulting readmissions across Australia was A$126 705 989. Surgical cost in the upper quartile was associated with younger age, male sex, lower socioeconomic status, surgery for reasons other than infection alone, overnight vs day case surgery, public hospitals and metropolitan hospitals. Surgery for obstructed breathing during sleep had the strongest association to high surgical cost. Conclusions This study highlights the cost of paediatric tonsillectomy and associated hospital readmissions. The study findings will inform healthcare reform and serve as a basis for strategies to optimise patient outcomes while reducing both postoperative complications and costs.

Hospital revisits after paediatric tonsillectomy: a cohort study.

BACKGROUND: Tonsillectomy, with or without adenoidectomy, is the leading reason for paediatric unplanned hospital readmission, some of which are potentially avoidable. Reducing unplanned hospital revisits would improve patient safety and decrease use of healthcare resources. This study aimed to describe the incidence, timing and risk factors for any surgery-related hospital revisits (both emergency presentation and readmission) following paediatric tonsillectomy and adenotonsillectomy in a large state-wide cohort. METHODS: We conducted a population-based cohort study using linked administrative datasets capturing all paediatric tonsillectomy and adenotonsillectomy surgeries performed between 2010 and 2015 in the state of Victoria, Australia. The primary outcome was presentation to the emergency department or hospital readmission within 30-day post-surgery. RESULTS: Between 2010 and 2015, 46,583 patients underwent 47,054 surgeries. There was a total of 4758 emergency department presentations (10.11% total surgeries) and 2750 readmissions (5.84% total surgeries). Haemorrhage was the most common reason for both revisit types, associated with 33.02% of ED presentations (3.34% total surgeries) and 67.93% of readmissions (3.97% total surgeries). Day 5 post-surgery was the median revisit time for both ED presentations (IQR 3-7) and readmission (IQR 3-8). Predictors of revisit included older age, public and metropolitan hospitals and peri-operative complications during surgery. CONCLUSIONS: Haemorrhage was the most common reason for both emergency department presentation and hospital readmission. The higher risk of revisits associated with older children, surgeries performed in public and metropolitan hospitals, and in patients experiencing peri-operative complications, suggest the need for improved education of postoperative care for caregivers, and avoidance of inappropriate early discharge.

Ventilatory control instability as a predictor of persistent periodic breathing in preterm infants.

BACKGROUND: Periodic breathing (PB) is common in preterm infants. We aimed to characterize the contribution of ventilatory control instability to the presence and persistence of PB longitudinally. METHODS: Infants born between 28 and 32 weeks of gestation were studied using daytime polysomnography at: 32-36 weeks postmenstrual age (PMA) (N = 32), 36-40 weeks PMA (N = 20), 3 months corrected age (CA) (N = 18) and 6 months CA (N = 19). Loop gain, a measure of sensitivity of the ventilatory control system, was estimated by fitting a mathematical model to ventilatory patterns associated with spontaneous sighs. RESULTS: The time spent in PB decreased from 32-36 weeks PMA to 6 months CA (P = 0.005). Across all studies, studies with PB (N = 62) were associated with higher loop gain compared to those without PB (N = 23) (estimated marginal mean ± SEM: 0.445 ± 0.01 vs 0.388 ± 0.02; P = 0.020). A threshold of loop gain >0.415 (measured at 32-36 weeks PMA) provided a sensitivity of 86% and a specificity of 75% to detect the presence of PB at 6 months CA. CONCLUSIONS: The course of PB in preterm infants is related to changes in loop gain. Higher loop gain at 32-36 weeks PMA was associated with a greater risk of persistent PB at 6 months CA. IMPACT: The developmental trajectory of periodic breathing and its relationship to ventilatory control instability is currently unclear. Unstable ventilatory control is a determinant of periodic breathing in preterm infants up to 6 months corrected age. Infants who display greater ventilatory control instability at 32-36 weeks postmenstrual age may be at increased risk of persistent periodic breathing at 6 months corrected age. Assessment of ventilatory control stability may assist in the early identification of infants at risk of persistent periodic breathing and its potential adverse effects.

Sleep-disordered breathing and sleep macro- and micro-architecture in children with Down syndrome.

BACKGROUND: Children with Down syndrome (DS) are at increased risk of sleep-disordered breathing (SDB), which is associated with intermittent hypoxia and sleep disruption affecting daytime functioning. We aimed to compare the impact of SDB on sleep quality in children with DS compared to typically developing (TD) children with and without SDB. METHODS: Children with DS and SDB (n = 44) were age- and sex-matched with TD children without SDB (TD-) and also for SDB severity with TD children with SDB (TD+). Children underwent overnight polysomnography with sleep macro- and micro-architecture assessed using electroencephalogram (EEG) spectral analysis, including slow-wave activity (SWA, an indicator of sleep propensity). RESULTS: Children with DS had greater hypoxic exposure, more respiratory events during REM sleep, higher total, delta, sigma, and beta EEG power in REM than TD+ children, despite the same overall frequency of obstructive events. Compared to TD- children, they also had more wake after sleep-onset and lower sigma power in N2 and N3. The DS group had reduced SWA, indicating reduced sleep drive, compared to both TD groups. CONCLUSIONS: Our findings suggest that SDB has a greater impact on sleep quality in children with DS compared to TD children. IMPACT: SDB in children with DS exacerbates disruption of sleep quality, compared to TD children. The prevalence of SDB is very high in children with DS; however, studies on the effects of SDB on sleep quality are limited in this population. Our findings suggest that SDB has a greater impact on sleep quality in children with DS compared to TD children, and should be screened for and treated as soon as possible.

Smartphone videos to predict the severity of obstructive sleep apnoea.

OBJECTIVE: Diagnosis of obstructive sleep apnoea (OSA) is made on overnight polysomnography (PSG). Given the widespread availability of smartphone video technology, we aimed to develop and test a standardised scoring system for smartphone videos and compare these scores to PSG results. METHODS: Children aged 1-16 years undergoing PSG for suspected OSA were included. Parents were asked to take 1-2 min videos of the breathing they were concerned about. Videos were scored using a newly developed and tested tool on five components: inspiratory obstructive noises (1-4), presence of obstructive events (0-1), increased work of breathing (0-1), mouth breathing (0-1) and neck extension (0-1). Video scores and the Obstructive Apnoea Hypopnoea Index (OAHI) were compared using Spearman correlation. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for different cut-off scores to achieve the best results. RESULTS: Videos from 43 children (28 men (65.1%), median age 5.7 years (range 2.6-14.0 years), median OAHI 3.8/hour (range 0-82 events/hour) were included. Nine children (20.9%) had a video score of <3, all of whom had an OAHI of ≤5 events/hour. For a video score of ≥3, sensitivity was 100%; specificity was 36%; positive predictive value was 53%; and negative predictive value 100% for moderate to severe OSA (OAHI>5 events/hour) . CONCLUSION: We have developed and validated a simple clinical tool (the Monash Obstructive Sleep Apnoea Video Score) to quantify abnormalities in breathing seen on short video recordings made on a smartphone. A low score rules out moderate-severe OSA and may be valuable in the triage of children with symptoms of OSA.

Sociodemographic associations of geographic variation in paediatric tonsillectomy and adenoidectomy.

Geographic variation of paediatric tonsillectomy, with or without adenoidectomy, (A/T) has been described since the 1930s until today but no studies have investigated the factors associated with this variation. This study described the geographical distribution of paediatric A/T across the state of Victoria, Australia, and investigated area-level factors associated with this variation. We used linked administrative datasets capturing all paediatric A/T performed between 2010 and 2015 in Victoria. Surgery data were collapsed by patient residence to the level of Local Government Area. Regression models were used to investigate the association between likelihood of surgery and area-level factors. We found a 10.2-fold difference in A/T rates across the state, with areas of higher rates more in regional than metropolitan areas. Area-level factors associated with geographic variation of A/T were percentage of children aged 5-9 years (IRR 1.07, 95%CI 1.01-1.14, P = 0.03) and low English language proficiency (IRR 0.95, 95% CI 0.90-0.99, P = 0.03). In a sub-population analysis of surgeries in the public sector, these factors were low maternal educational attainment (IRR 1.09, 95% CI 1.02-1.16, P < 0.001) and surgical waiting time (IRR 0.99635 95% CI 0.99273-0.99997, P = 0.048). Identifying areas of focus for improvement and factors associated with geographic variation will assist in improving equitable provision of paediatric A/T and decrease variability within regions.