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Sound asleep: cardiovascular implications of sleep disordered breathing in preschool children

thesis
posted on 27.02.2017, 23:28 authored by Nisbet, Lauren Claire
Objective: Sleep disordered breathing (SDB) is a spectrum of sleep disorders ranging from primary snoring (PS) to the more severe form, obstructive sleep apnoea (OSA). In both adults and school-age children, SDB is associated with autonomic dysfunction and elevated blood pressure (BP) which pervades both wakefulness and sleep. The surges in BP and heart rate (HR) following obstructive respiratory events are believed to contribute to the development of the elevated BP and loss of the typical nocturnal BP decline (termed nocturnal dipping). SDB is most prevalent during the preschool years, yet the effects of SDB on autonomic function and BP during sleep have not been investigated at this age. This thesis aimed to investigate SDB severity- and sleep-related alterations in cardiovascular function in preschool children with a range of SDB severities in comparison to non-snoring control children, by assessing autonomic function using heart rate variability (HRV) and urinary catecholamine levels; and nocturnal dipping and overnight changes in BP using pulse transit time (PTT), an inverse continuous indicator of BP changes. Additionally, we aimed to characterise the cardiovascular response to obstructive events in preschool children. Methods: 151 snoring children (aged 3-5 y) recruited from children attending the Melbourne Children’s Sleep Centre for assessment of SDB, and 41 non-snoring control children recruited from the community underwent overnight polysomnography, with additional PTT measurement and a 12 h urine collection. Children were grouped according to their clinical history and obstructive apnoea hypopnoea index (OAHI); control (no history of snoring), OAHI≤1 event/h; PS, OAHI≤1 event/h; mild OSA OAHI>1-5 events/h; moderate-severe OSA, (MS) OAHI>5 events/h. HRV was calculated in artifact-free 2 min bins in the time- and frequency-domain for each child. PTT was calculated as the time delay between the electrocardiogram R-wave and the 50% point of the rise in the corresponding finger pulse-wave. PTT was averaged for each 30 s epoch and normalised to each child’s mean wake PTT (before sleep onset), or for nocturnal dipping analysis, PTT and HR during sleep were expressed as percentage change from wake. HRV and PTT data were grouped and averaged for sleep overall, then subdivided into rapid eye movement (REM) and non-REM sleep (NREM1/2, NREM3/4) in each child. Respiratory events and arousals were subsequently removed for ‘stable sleep’ analyses of PTT and HRV. Beat-to-beat PTT and HR were averaged during the two halves of each obstructive respiratory event (early, late), for 10 s before (pre) and during the peak after (post) each event, and expressed as the percentage change from pre- to post-event and late- to post-event. Results: During REM sleep, the MS OSA group had significantly lower PTT (indicating higher BP) than the mild OSA and PS groups (p<0.05 for both). Compared to controls, the MS OSA group had higher low frequency, high frequency and total power HRV during NREM1/2 and REM sleep (p<0.05 for all) and lower sympathovagal balance during NREM3/4 sleep (p<0.05). After removal of respiratory events and arousals, high frequency HRV remained higher in the MS OSA group. There was no group difference in urinary catecholamine levels or in the change in PTT or HR from wake to sleep. The number of sleep stage transitions and awakenings per hour of sleep, indicating sleep fragmentation, was significantly higher in the MS OSA group compared to the mild OSA and PS groups (p<0.05 for both). All severity groups demonstrated a significant post-event increase in HR and fall in PTT (p<0.05 for all), although the response was smaller in the PS than the OSA groups (p<0.05 for both). PTT increased from wake to sleep and was significantly higher during NREM than during REM sleep in all groups (p<0.05 for all). Sympathovagal balance was lowest during NREM3/4 sleep. Conclusions: Preschool children with OSA exhibit significant acute cardiovascular surges with obstructive events. However, despite children with MS OSA demonstrating a significantly lowered PTT during REM sleep, indicating a higher baseline BP during this sleep state, nocturnal dipping of BP is still preserved. Preschool children with OSA also demonstrate increased HRV, largely due to high frequency fluctuations in HR which occur both during and between respiratory events. In contrast to school-age children, preschool children with SDB do not exhibit autonomic dysfunction, nor generalised BP abnormalities. However, the REM-related BP elevation in preschool children with MS OSA may be the first step toward development of day-time BP abnormalities. Increased BP during childhood predicts hypertension in adulthood, and furthermore, circulatory perturbations such as those associated with respiratory events have been implicated in the development of hypertension. Thus, these findings give weight to the suggestion of a cumulative impact of snoring and OSA on the cardiovascular system throughout childhood, which may progress into adulthood. Thus this age may be a ‘window of opportunity’ for early treatment of SDB to prevent future cardiovascular disease.

History

Principal supervisor

Rosemary S.C. Horne

Year of Award

2013

Department, School or Centre

Hudson Institute of Medical Research

Additional Institution or Organisation

The Ritchie Centre

Campus location

Australia

Course

Doctor of Philosophy

Degree Type

DOCTORATE

Faculty

Faculty of Medicine Nursing and Health Sciences