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.

Autonomic cardiovascular control is unaffected in children referred for assessment of excessive daytime sleepiness.

There is conflicting evidence for impaired autonomic control of heart rate (HR) in adults with narcolepsy and idiopathic hypersomnolence (IH). Despite these chronic hypersomnia conditions primarily being diagnosed around the age of puberty, there are limited studies in children. The present study investigated cardiovascular control using heart rate variability (HRV) and the extent of nocturnal HR dipping during sleep in children and adolescents with narcolepsy and IH. Children having an overnight polysomnographic study followed by a multiple sleep latency test (MSLT) for investigation of excessive daytime sleepiness (EDS) between May 2010 to December 2023 were included: 28 children diagnosed with narcolepsy, 11 with IH, and 26 subjectively sleepy children who did not meet the diagnostic criteria for either narcolepsy or IH. Each clinically referred child was matched for age and sex with a control. Time domain and frequency domain HRV were calculated from ECG recorded at 512 Hz. There were no differences in either time domain or spectral analysis of HRV between clinical groups or between clinical groups and their control group. The expected sleep state differences in HRV were observed in all groups. There was also no difference in HR nocturnal dipping between groups. Despite evidence for abnormal autonomic function in adults with narcolepsy and IH, our study did not identify any abnormalities in HR, HR control, or nocturnal dipping of HR in children referred for assessment of EDS. This suggests that autonomic dysfunction may be a feature of these conditions that develops in later life.

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.

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.

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.

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.

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.

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.

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.

Children with Down syndrome and sleep disordered breathing have altered cardiovascular control.

BACKGROUND: Sleep disordered breathing (SDB) in typically developing (TD) children is associated with adverse cardiovascular effects. As children with Down syndrome (DS) are at increased risk for SDB, we aimed to compare the cardiovascular effects of SDB in children with DS to those of TD children with and without SDB. METHODS: Forty-four children with DS (3-19 years) were age and sex matched with 44 TD children without SDB (TD-) and with 44 TD children with matched severity of SDB (TD+). Power spectral density was calculated from ECG recordings, for low frequency (LF), high frequency (HF), total power and the LF/HF ratio. RESULTS: Children with DS had lower HF power, and higher LF/HF during sleep and when awake. There were no differences between groups for LF power. SpO2 nadir, average SpO2 drop and SpO2 > 4% drop were larger in the DS group compared to the TD+ group (p < 0.05 for all). CONCLUSIONS: Our findings demonstrate significantly reduced parasympathetic activity (reduced HF power) and increased LF/HF (a measure of sympathovagal balance) in children with DS, together with greater exposure to hypoxia, suggesting SDB has a greater effect in these children that may contribute to an increased risk of adverse cardiovascular outcomes. IMPACT: Sleep disordered breathing in children with Down syndrome exacerbates impaired autonomic control and increases exposure to hypoxia, compared to typically developing children. In typically developing children sleep disordered breathing has adverse effects on autonomic cardiovascular control. The prevalence of sleep disordered breathing is very high in children with Down syndrome; however, studies on the effects on cardiovascular control are limited in this population. This study supports screening and early treatment of sleep disordered breathing in children with Down syndrome.