Longitudinal effects of early exposure to intermittent hypoxia on autonomic cardiovascular control in very preterm infants.

INTRODUCTION: Cardiorespiratory control is immature in infants born preterm compared to those born at term. Animal studies have shown that repetitive hypoxia associated with periodic breathing can alter autonomic control. We aimed to elucidate if the amount of time spent with apnoea and periodic breathing in the neonatal unit was associated with longitudinal changes in autonomic control assessed using heart rate variability. METHODS: Twenty-nine very preterm infants (10 M 19F) were studied during supine daytime sleep on 4 occasions. Study 1: 32-36 weeks post menstrual age (PMA) (n = 29), Study 2: 36-40 weeks PMA (n = 27), Study 3: 3-months corrected age (CA) (n = 20) and Study 4: 6-months CA (n = 26). The percentage total sleep time (%TST) spent having apnoeas in active (AS) and quiet sleep (QS) at each study was calculated. Total power, low frequency (LF, sympathetic + parasympathetic activity) high frequency (HF, parasympathetic activity), and LF/HF (sympathovagal balance) were calculated. Infants were divided into two groups based on the %TST spent with apnoeas above and below the median in AS and QS at Study 1. Data were normalised and compared with two-way ANOVA with Bonferroni post-hoc tests. RESULTS: When apnoeas were included in the analysis, in QS Total power and HF power were higher, and when apnoeas were excluded HF power was higher in QS but lower in AS in the above median group at Study 4. 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.

The surge in heart rate and blood pressure at respiratory event termination is dampened in children with down syndrome.

BACKGROUND: Children with Down syndrome (DS) have a high prevalence of sleep disordered breathing (SDB) and altered cardiovascular autonomic control. We aimed to analyze the effect of DS on the surge in heart rate (HR) and pulse transit time (PTT, an inverse surrogate measure of blood pressure change) at respiratory event termination. METHODS: 44 children (3-19 y) with DS and 44 typically developing (TD) children matched for SDB severity, age and sex underwent overnight polysomnography. Multilevel modelling determined the effect of DS on HR and PTT changes between a 10s pre-event to the latter half of each respiratory event (late-event) and 15s post-event during NREM and REM, accounting for SDB severity and event length. RESULTS: The children with DS had a significantly smaller % change in HR late-event to post-event (NREM: DS 26.4 % ± 17.5 % (mean ± SD), TD 30.7 % ± 21.0 %; REM DS 16.9 % ± 15.3 %, TD 21.0 % ± 14.0 %; p < 0.05 for both) compared with TD children for obstructive events, and central events (13.2 % ± 17.0 %, TD 18.8 % ± 17.0 %; p < 0.01) during REM. %change in PTT was significantly smaller in the DS group during NREM and REM from pre-event and late-event to post-event compared with TD children for obstructive and central events. CONCLUSION: These results suggest children with DS have dampened HR and BP responses to respiratory events compared with TD children. Whether this is symptomatic of autonomic dysfunction or a protective factor for the cardiovascular system in children with DS remains to be elucidated.

Effect of sleep disordered breathing severity in children with Down syndrome on parental wellbeing and social support.

INTRODUCTION: Sleep disorders, particularly sleep disordered breathing (SDB), are common in children with Down syndrome (DS). We investigated the relationship between SDB severity and parental psychological wellbeing and their perception of social support. METHODS: 44 children with DS (3-19 years) underwent overnight polysomnography and were categorised into three groups: primary snoring, Mild and Moderate/Severe obstructive sleep apnoea (OSA). Parents completed questionnaires about their child's behaviour (Child Behavior Checklist), sleep symptoms (Pediatric Sleep Survey Instrument) and SDB-related quality of life (OSA-18), together with the DUKE-UNC Functional Social Support (DUKE) and Psychological General Well-Being Index (PGWBI) questionnaires for themselves. 34 children completed a follow-up study after 2 years. RESULTS: There were no significant differences between SDB severity groups for parental perceived social support or psychological wellbeing. Total scores on the DUKE were below average and PGWBI scores were indicative of moderate psychological distress in all three groups. Reduced perceived levels of social support were significantly correlated with externalising child behaviour and sleep disturbance. Diminished parental psychological wellbeing was also significantly correlated with increased sleep disturbances and reduced quality of life in children. At follow-up there were no significant changes in any questionnaire outcome, however parents of children with improved SDB severity had improved PGWBI vitality scores. CONCLUSION: The degree of parent-reported sleep disturbance in children with DS was linked to suboptimal perceived parental social support and poor psychological wellbeing. Our results emphasise the need for enhanced awareness of the detrimental effects of sleep problems in children with DS on parental wellbeing.

Assessing sleep in children with Down syndrome: Comparison of parental sleep diaries, actigraphy and polysomnography.

BACKGROUND: This study compared measurements of sleep and wake assessed with actigraphy, sleep diary and polysomnography in children with Down syndrome (DS) and also compared measures of actigraphic sleep recording in children with DS and typically developing (TD) children. METHODS: Children with DS aged 3-19 years (N = 44) referred for assessment of sleep disordered breathing (SDB) underwent overnight polysomnography, together with 1 week of actigraphy with sleep diary. Actigraphy data from the children with DS were compared with data collected from TD children, matched for age and sex. RESULTS: 22 children (50%) with DS completed >3 consecutive nights of actigraphy with a matched sleep diary. There were no differences between bedtimes, wake times or time in bed on weeknights, weekends or over 7 nights between actigraphy and sleep diary. Total sleep time was over estimated by the sleep diary by almost 2 h and the number of night awakenings under-reported. Compared to matched TD children (N = 22), there was no difference in total sleep time, however children with DS fell asleep more quickly (p < 0.001), had more awakenings (p = 0.001) and more time awake after sleep onset (p = 0.007). Children with DS exhibited less variability in both bedtimes and wake times, and fewer had >1 h sleep schedule variability. CONCLUSIONS: Parental sleep diaries over-estimate total sleep time but accurately report bed and wake times compared to actigraphy in children with DS. Children with DS have more regular sleep patterns than TD children of the same age, which is important for optimising daytime functioning. The reasons behind this warrant further investigation.

Sleep disordered breathing improvement prevents worsening of autonomic dysfunction in children with Down syndrome.

BACKGROUND: Resolution of sleep disordered breathing (SDB) in typically developing children normalises heart rate variability (HRV), a measure of autonomic control, to that of non-snoring controls. Children with Down Syndrome (DS) have dampened heart rate variability (HRV) but the effect of treatment is not known. To assess the effect of improvement of SDB on autonomic control we compared HRV in children with DS whose SDB improved over 2 y, to those whose SDB did not improve. METHODS: 24 children (3-19 y) had a baseline and follow-up polysomnographic study 2 y later. Improved SDB was defined as a reduction in obstructive apnea hypopnea index (OAHI) to ≤ 50% of baseline. Children were grouped into Improved (n = 12) and Unimproved (n = 12). Power spectral analysis of the ECG determined low frequency (LF), high frequency (HF) power and the LF/HF ratio. Seven children in the Improved and 2 in the Unimproved group were treated following the baseline study. RESULTS: In the Unimproved group at follow-up, LF power was lower compared to baseline during N3 and Total Sleep (p < 0.05 for both). HF power was lower during REM (p < 0.05). HRV remained unchanged between studies in the Improved group. CONCLUSION: Autonomic control worsened as indicated by lower LF and HF power in children whose SDB was not improved. In contrast, in those children with improved SDB, autonomic control remained the same, suggesting improvement in SDB severity prevents further worsening of autonomic control in children with DS.

The effects of sleep disordered breathing on sleep spindle activity in children and the relationship with sleep, behavior and neurocognition.

STUDY OBJECTIVES: Obstructive sleep disordered breathing (SDB), has adverse neurocognitive and behavioral sequelae in children, despite conventional measures of sleep disruption being unaffected. There is growing evidence that sleep spindles may serve as a more sensitive marker of sleep quality. We investigated the relationship between sleep spindles and sleep fragmentation and neurocognition across the spectrum of SDB severity in children. METHODS: Children 3-12 years old referred for clinical assessment of SDB and age matched control children from the community were recruited and underwent polysomnography. Sleep spindles were identified manually during N2 and N3 sleep. Spindle activity was characterised as spindle number, density (number of spindles/h) and intensity (spindle density x average spindle duration). Children completed a battery of tests assessing global intellectual ability, language, attention, visuospatial ability, sensorimotor skills, adaptive behaviors and skills and problem behaviors and emotional difficulties. RESULTS: Children were grouped into control, Primary Snoring, Mild OSA and Moderate/severe OSA, N = 10/group. All measures of spindle activity were lower in the SDB groups compared to the Control children and this reached statistical significance for Mild OSA (p < 0.05 for all). Higher spindle indices were associated with better performance on executive function and visual ability assessments but poorer performance on auditory attention and communication skills. Higher spindle indices were associated with better behavior. CONCLUSION: The reduced spindle activity observed in the children with SDB, particularly Mild OSA, indicates that sleep micro-architecture is disrupted and that this disruption may underpin the negative effects of SDB on attention, learning and memory.

Heart rate surge at respiratory event termination in preterm and term born children with sleep disordered breathing.

BACKGROUND: Repetitive surges in heart rate (HR) at respiratory event termination underpin the altered autonomic HR control associated with sleep disordered breathing (SDB). As children born preterm are at greater risk of adverse cardiovascular outcomes, we aimed to determine whether the HR response to obstructive respiratory events was elevated compared to term-born children. METHODS: Fifty children (3-12 years) born preterm, were matched for SDB severity, age and gender with term born children. Multilevel modelling determined the effect of preterm birth and arousal on HR changes between a 10s baseline to the latter half of respiratory events and 15s post event during NREM and REM. RESULTS: 1203 events were analysed (NREM: term 380; preterm 383; REM: term 207; preterm 233). During NREM fewer events terminated in arousal in the preterm compared with term group (preterm 68%; term 84%; χ2 = 27.2, p < 0.001). There were no differences in REM. During NREM, HR was lower in the preterm group at all event phases, with and without associated arousals (P < 0.01 for all). % change in HR from baseline to post event was higher in the preterm compared with term group (preterm: median 23% IQR (12%,34%); term: 18% (10%,29%); p < 0.01) and late event to post event (preterm: 30% (21%, 32%); term 28% (20%,39%); p < 0.01) in events associated with arousals. CONCLUSION: The greater magnitude of surges in HR following respiratory events terminating with arousal in preterm born children, although small, occur repeatedly throughout the night and may contribute to adverse cardiovascular outcomes, although further studies are required.

Nocturnal dipping of heart rate is impaired in children with Down syndrome and sleep disordered breathing.

BACKGROUND: Children with Down syndrome (DS) are at increased risk for sleep disordered breathing (SDB), which can have adverse effects on the cardiovascular system. In adults with SDB, nocturnal dipping of heart rate (HR) and blood pressure (BP) is reduced, and this is associated with an increased risk of future cardiovascular events. We aimed to compare nocturnal dipping of HR and pulse transit time (PTT) (a surrogate inverse measure of BP change) in children with DS and SDB to those of typically developing (TD) children with and without SDB. METHODS: 19 children with DS (3-18 years) were age and sex matched with 19 TD children without SDB (TD-) and with 19 TD children with matched severity of SDB (TD+). Nocturnal dipping was assessed as the percentage change in HR and PTT from wake before sleep onset to total sleep, N2, N3 and REM sleep across the night and to the first cycle of sleep. RESULTS: Children with DS exhibited reduced nocturnal dipping of HR during total sleep, N2, N3 and REM sleep and increased PTT (reduced BP dipping) in N2 sleep. Fewer children with DS exhibited a greater than 10% fall in HR between wake and N2 or REM sleep compared to TD+ children. CONCLUSIONS: Our findings demonstrate significantly reduced nocturnal dipping of HR in children with DS compared to TD children matched for SDB severity, suggesting SDB has a greater cardiovascular effect in these children. Further studies are required to fully understand the mechanisms involved and to assess if treatment of SDB improves nocturnal dipping.

Continuous oximetry recordings on the first post-operative night after pediatric adenotonsillectomy-a case-control study.

BACKGROUND: Children with obstructive sleep apnea (OSA) with recurrent dips in oxygen saturation (SpO2) during sleep are known to be at increased risk of post-operative airway compromise after adenotonsillectomy (AT). We aimed to determine the extent of desaturation on the first post-operative night in children known to have recurrent desaturation pre-operatively and to compare the extent of desaturation in that group with results in children known to have normal oximetry recordings pre-operatively. METHODS: Prospective sequential recruitment of 57 children who had overnight oximetry performed on the first night after adenotonsillectomy was undertaken, including 28 with a McGill Oximetry Score (MOS) of 2-4 pre-operatively (high risk group) and 29 with a normal/inconclusive pre-operative MOS (low risk group). Oximetry parameters (mean SpO2, SpO2 nadir, and rates of SpO2 dips below 90% and dips of ≥4%) were compared to the pre-operative oximetry result. Demographic and clinical factors, and the occurrence of post-operative complications, were derived from the medical record. RESULTS: In the high risk group, the MOS improved in 23/28 children, but remained abnormal in 82%. Conversely, in the low risk group 26/29 (90%) had a normal post-operative oximetry. The remaining 3, all of whom had severe OSA on pre-operative polysomnography, had a lowered baseline SpO2 post-operatively. Mean SpO2 was slightly lower post-operatively in both groups. In the high risk group, all other SpO2 measures improved post-operatively. Respiratory adverse events were more common in the high risk group as expected (39% compared to 3% in the low risk group, p = 0.001). An adverse event requiring clinical intervention was significantly more likely if the post-operative oximetry was abnormal (result unknown to the treating team), occurring in 73% of children with an abnormal compared with 32% of children with a normal post-operative oximetry (p = 0.002). CONCLUSION: Most children with an abnormal oximetry pre-operatively continued to have an abnormal oximetry on the first night after AT, albeit somewhat improved. While adverse events were more frequent in children with an abnormal post-operative oximetry, half (54%) did not suffer a clinical respiratory adverse event despite having repetitive desaturations on downloadable oximetry. These findings support close clinical observation of children at high risk of complications post-operatively, especially those with abnormal oximetry pre-operatively, rather than focusing on recurrent dips in SpO2 on post-operative oximetry downloads in the absence of clinically evident complications.

Craniofacial photography and association with sleep-disordered breathing severity in children.

PURPOSE: Sleep-disordered breathing (SDB) in children has been associated with craniofacial characteristics. Facial photography provides a radiation-free means of estimating facial morphology through facial landmark analysis. Our objective was to determine whether facial analysis provides information about SDB severity. Specifically, we aimed to determine whether facial photographic measurements differ with SDB status, or were associated with SDB severity. METHODS: Single-center cohort of children undergoing overnight polysomnography for assessment of SDB; non-snoring controls were recruited from the community to undergo polysomnography. Standardized front and lateral facial photographs were analyzed according to previously published protocols. Multivariate analysis of variance was used to determine if facial measurements differed between SDB groups and controls. Linear regression was performed to determine if facial measurements were associated with SDB severity. RESULTS: Seventy-eight children (9 controls, 17 primary snoring, 23 mild SDB, 27 moderate-severe SDB) were included. Facial angles and upper-to-lower face height ratio showed variation between SDB groups (p = 0.038). Facial measurements related to SDB severity, specifically an increased cervicomental angle (p = 0.001), and increased lower-to-upper face height (p = 0.006). CONCLUSION: Evaluation of craniofacial features using clinical photography is feasible. Preliminary investigation shows some relationship with SBD severity. Further work is needed to determine if craniofacial photography is useful for stratifying SDB risk in children.

Sleep and sleep disordered breathing in children with down syndrome: Effects on behaviour, neurocognition and the cardiovascular system.

Down syndrome (DS), the most common human chromosomal malformation, has an estimated annual incidence of one in 1000 live births worldwide. Sleep problems are common in children with DS, reported by parents in up to 65% of school-aged children, significantly higher rates than in typically developing (TD) children. Problems include difficulty in sleep initiation and maintenance together with obstructive sleep apnoea (OSA) which affects up to over 90%, of DS children compared with 1-5% in the general paediatric population. Any sleep problem has the potential to exert significant negative effects on daytime behaviour, learning and quality of life in TD children and there is now a growing body of evidence that children with DS are similarly affected. In addition to adverse effects on daytime functioning, OSA has adverse effects on the cardiovascular system and this is a particularly significant issue given the high rates of hypertension and premature cardiac disease in people with DS. This review discusses the effects of sleep problems and OSA on daytime functioning and cardiovascular function in children with DS and evidence of the effectiveness of treatment in improving outcomes and quality of life for these children.

Risk factors for obstructive sleep apnoea in Australian children.

AIM: This study aims to determine whether demographic or clinical factors predict obstructive sleep apnoea (OSA) severity in Australian children. METHODS: Demographic details and medical histories of 301 Australian children (3-17 years old) referred for assessment of OSA were examined retrospectively. Children underwent overnight polysomnography and were classified as having primary snoring (PS) (obstructive apnoea hypopnoea index (OAHI) ≤ 1 event per hour; n = 150), mild OSA (>1 OAHI ≤ 5 events per hour; n = 76) or moderate/severe (MS) OSA (OAHI > 5 events per hour; n = 75). Information obtained from parent-report questionnaire determined the predictive value of the following factors for determining OSA severity: gender, ethnicity, body mass index, asthma and/or allergic rhinitis, socio-economic status and parental smoking status (mother/father/both). Chi-squared analyses were used to compare the distribution of the demographic and clinical factors across the three groups. Statistically significant risk factors were subsequently entered into logistic regression analysis. RESULTS: Ethnicity and parental smoking were significant risk factors for MS OSA. Children with non-Caucasian ethnicity were 36% more likely than Caucasian children to be diagnosed with MS OSA than PS (P = 0.002). Children with fathers who smoked were 53% more likely to have MS OSA than PS compared with those with fathers who did not smoke (P = 0.008). Obesity was associated with OSA severity in primary school-aged children only. Gender, socio-economic status and history of asthma and/or allergic rhinitis were not risk factors. CONCLUSIONS: Non-Caucasian ethnicity, paternal smoking and obesity in older children were associated with an increased risk of polysomnography-confirmed MS OSA in Australian children.