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Nixon G.M.,Melbourne Childrens Sleep Center | Nixon G.M.,Monash Institute of Medical Research | Nixon G.M.,Monash University | Rodda C.P.,Monash University | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Descriptions of the development of symptoms of upper airway obstruction and sudden death of children with Prader-Willi Syndrome (PWS) while on GH therapy have led to concern about GH contributing to obstructive sleep apnea (OSA), especially early in treatment. However, two studies using monitoring with polysomnography (PSG) have not shown deterioration in OSA after 6 wk on GH, except as related to upper respiratory tract infections. Objective: The aim was to describe the evolution of OSA in a girl with PWS on GH treatment in order to highlight important aspects of long-term clinical monitoring for patients with PWS on GH treatment. Patient and Research Design: GH was commenced when the patient was 2.9 yr of age. PSG was performed at baseline and 7 wk after commencing GH, plus at intervals throughout treatment based on symptoms of OSA. Intervention: GH was given at doses ranging from 4.2 to 4.7 mg/m 2 · wk over a period of 3 yr. Main Outcome Measure: OSA was quantified by PSG. Results: OSA was not present at baseline or after 7 wk on GH but developed after 6 months, following a small increase in GH dose. Cessation of GH was accompanied by resolution of OSA. GH was restarted 2 yr later, again associated with the development of OSA that resolved after cessation of GH. Conclusion: This case highlights that OSA may develop late in GH treatment. Children should be monitored for the symptoms of OSA throughout GH treatment, and PSG should be repeated if symptoms develop. Copyright © 2011 by The Endocrine Society.


Nixon G.M.,Melbourne Childrens Sleep Center | Nixon G.M.,Monash Institute of Medical Research | Nixon G.M.,Monash University | Mihai R.,Melbourne Childrens Sleep Center | And 2 more authors.
Journal of Pediatrics | Year: 2011

Objective: To determine predictors of continuous airway pressure (CPAP) adherence in children. Study design: Analysis of CPAP usage data for children between 2004 and 2008. Results: During the study period, 32 children were prescribed CPAP; 2 failed to accept the mask, and 30 (mean ± SD age 9.1 ± 5.3 years) were included in further analysis. In the first 2 to 3 months of treatment, average (± SD) CPAP use was 4.7 ± 2.7 hours/night. Hours of use were not affected by age, sex, baseline obstructive apnea-hypopnea index, intellectual disability, or socioeconomic status (P >.05). Of the children, 10 (33%) used CPAP for one hour or more on more than 6 nights per week and were defined as consistent users. Consistent users treated with CPAP for significantly longer on nights of use than intermittent users (7.2 ± 2.0 hours vs 4.7 ± 2.4 hours, P =.008). The hours of use differed between the two groups after the second night of treatment (P <.05), and this difference persisted for the first 3 months of therapy. Conclusions: Children who attempted to use CPAP at least 6 nights a week were treated with CPAP for a longer time on the nights of use. Usage in the first week of treatment predicted longer term use over 2 to 3 months. Monitoring adherence in the first week of treatment and intervening in cases of low adherence may improve long-term CPAP use. Copyright © 2011 Mosby Inc. All rights reserved.


Walter L.M.,Monash Institute of Medical Research | Nixon G.M.,Monash Institute of Medical Research | Nixon G.M.,Melbourne Childrens Sleep Center | Davey M.J.,Melbourne Childrens Sleep Center | And 3 more authors.
Sleep Medicine | Year: 2011

Study objectives: Sleep-disordered breathing in children is most prevalent in the pre-school years and has been associated with sleep fragmentation and hypoxia. We aimed to compare the sleep and spontaneous arousal characteristics of 3-5-year-old children with obstructive sleep apnoea (OSA) with that of non-snoring control children, and to further characterise the arousal responses to obstructive respiratory events. Methods: A total of 73 children (48 male) underwent overnight polysomnography: 51 for assessment of snoring who were subsequently diagnosed with OSA (obstructive apnoea hypopnoea index (OAHI) > 1 event per h) and 22 control children recruited from the community (OAHI ≤ 1 and no history of snoring). Results: The OSA group had poorer sleep efficiency (p<. 0.05), spent a smaller proportion of their sleep period time in rapid eye movement (REM) (p<. 0.05), and had significantly fewer spontaneous arousals (p<. 0.001) compared with controls. One-quarter of the children with OSA had a sleep pressure score above the cut-off point for increased sleep pressure. In children with OSA, 62% of obstructive respiratory events terminated in a cortical arousal and 21% in a sub-cortical arousal. A significantly higher proportion of obstructive respiratory events terminated in a cortical arousal during non-REM (NREM) compared with REM (p<. 0.001). Conclusions: These findings suggest that in pre-school children OSA has a profound effect on sleep and arousal patterns. Given that these children are at a critical period for brain development, the impact of OSA may have more severe consequences than in older children. © 2011 Elsevier B.V.


Nisbet L.C.,Monash Institute of Medical Research | Yiallourou S.R.,Monash Institute of Medical Research | Nixon G.M.,Monash Institute of Medical Research | Nixon G.M.,Melbourne Childrens Sleep Center | And 6 more authors.
Sleep Medicine | Year: 2013

Background: Obstructive sleep apnea (OSA) is associated with autonomic dysfunction in adults and school-aged children; however, this association has not been investigated in preschool children. We aimed to analyze heart rate variability (HRV) and catecholamine levels in preschool children with OSA. Methods: One hundred and forty-two snoring children aged 3-5. years and 38 nonsnoring control group children underwent overnight polysomnography (PSG). Nocturnal urinary catecholamines were measured in 120 children. Children were grouped according to their obstructive apnea-hypopnea index (OAHI) (control [no snoring], OAHI. ≤. 1. event/h; primary snoring, OAHI. ≤. 1. event/h; mild OSA OAHI. >. 1. ≤. 5. events/h; moderate to severe [MS] OSA, OAHI. >. 5. events/h). The HRV parameters for each child were averaged during rapid eye movement (REM) and non-REM (NREM) sleep. Results: During stable sleep, low-frequency (LF) HRV was similar between groups. High-frequency (HF) HRV was higher in the MS OSA group compared with the control group during all sleep stages (NREM sleep stages 1 and 2 [NREM1/2], 4234±523ms2 vs 2604±457ms2; NREM sleep stages 3 and 4 [NREM3/4], 4152±741ms2 vs 3035±647ms2; REM, 1836±255ms2 vs 1456±292ms2; P<.01 for all). The LF/HF ratio was lower in the MS OSA group compared with the control group (NREM1/2, 0.4±0.06 vs 0.7±0.05; NREM3/4, 0.3±0.06 vs 0.4±0.05; REM, 0.8±0.1 vs 1.3±0.1; P<.01 for all). Catecholamine levels were not different between groups. Conclusions: In preschool children, OSA is associated with altered HRV, largely due to the HF fluctuations in heart rate (HR) which occur during respiratory events and are still evident during stable sleep. The preschool age may represent a window of opportunity for treatment of OSA before the onset of the severe autonomic dysfunction associated with OSA in adults and older children. © 2013.


Nisbet L.C.,Monash Institute of Medical Research | Yiallourou S.R.,Monash Institute of Medical Research | Biggs S.N.,Monash Institute of Medical Research | Nixon G.M.,Monash Institute of Medical Research | And 6 more authors.
Sleep | Year: 2013

Study Objectives: In adults and older children, snoring and obstructive sleep apnea (OSA) are associated with elevated blood pressure (BP). However, BP has not been assessed in preschool children, the age of highest OSA prevalence. We aimed to assess overnight BP in preschool children with snoring and OSA using pulse transit time (PTT), an inverse continuous indicator of BP changes. Design: Overnight polysomnography including PTT. Children were grouped according to their obstructive apnea-hypopnea index (OAHI); control (no snoring, with OAHI of one event or less per hour), primary snoring (OAHI one event or less per hour), mild OSA (OAHI greater than one event to five events per hour) and moderate-severe OSA (OAHI more than five events per hour). Setting: Pediatric sleep laboratory. Patients: There were 128 clinically referred children (aged 3-5 years) and 35 nonsnoring community control children. Measurement and Results: PTT was averaged for each 30-sec epoch of rapid eye movement (REM) or nonrapid eye movement (NREM) sleep and normalized to each child's mean wake PTT. PTT during NREM was significantly higher than during REM sleep in all groups (P < 0.001 for all). During REM sleep, the moderate-severe OSA group had significantly lower PTT than the mild and primary snoring groups (P < 0.05 for both). This difference persisted after removal of event-related PTT changes. Conclusions: Moderate-severe OSA in preschool children has a significant effect on pulse transit time during REM sleep, indicating that these young children have a higher baseline BP during this state. We propose that the REM-related elevation in BP may be the first step toward development of daytime BP abnormalities. Given that increased BP during childhood predicts hypertension in adulthood, longitudinal studies are needed to determine the effect of resolution of snoring and/or OSA at this age.


Walter L.M.,Monash Institute of Medical Research | Nixon G.M.,Monash Institute of Medical Research | Nixon G.M.,Melbourne Childrens Sleep Center | Davey M.J.,Monash Institute of Medical Research | And 5 more authors.
Sleep and Breathing | Year: 2013

Purpose: Sleep disordered breathing (SDB) has adverse effects on cardiovascular health in adults, partly due to changes in autonomic activity. However, there have been limited studies in children. We analysed the impact of SDB and sleep stage on autonomic control of heart rate in 7-12-year-old children, utilizing spectral heart rate variability (HRV) as a measure of autonomic activity. Methods: Eighty children underwent overnight polysomnography. Subjects were grouped according to their obstructive apnoea-hypopnoea index (OAHI): controls, OAHI ≤1 event/h and no history of snoring; primary snorers (PS) OAHI ≤1, Mild (OAHI 1-5) and moderate/severe (MS) OAHI >5. HRV was analysed during Wake, nonrapid eye movement (NREM) 1&2, slow wave sleep (SWS) and REM. Results: Compared with controls, total power, low (LF) and high frequency (HF) power were reduced in all SDB severities during REM. LF/HF ratio was less in MS SDB (median = 0.34; range, 0.20-0.49; p < 0.05) versus controls (0.38; 0.26-0.55; p < 0.05) and PS (0.39; 0.23-0.57; p < 0.05) during SWS. In all groups, total power, LF and HF power were highest during NREM 1&2 while LF/HF ratio was lowest during SWS. Blood pressure was elevated in SDB in all sleep states. Conclusions: HRV was altered in 7-12-year-old children with SDB, which may signify an overall depression of autonomic tone, perhaps a consequence of their elevated blood pressure during sleep coupled with repeated exposure to SDB event-related cardiovascular disturbance. Further research is warranted to elucidate the long-term effects on the cardiovascular system of subjects exhibiting impaired HRV and elevated BP in childhood. © 2012 Springer-Verlag.


Vlahandonis A.,Monash Institute of Medical Research | Nixon G.M.,Monash Institute of Medical Research | Nixon G.M.,Melbourne Childrens Sleep Center | Davey M.J.,Monash Institute of Medical Research | And 3 more authors.
Sleep Medicine | Year: 2013

Objective: Little is known of the long-term prognosis of children treated for sleep disordered breathing (SDB) and even less of children with milder forms of SDB who remain untreated. We aimed to investigate the long-term sleep and respiratory outcomes of children with a range of SDB severities. Methods: 41 children with SDB and 20 non snoring controls (mean age, 12.9±0.2. y), underwent repeat overnight polysomnography (PSG) 4.0±0.3 years after initial diagnosis. SDB severity, presence of snoring, sleep and respiratory parameters, sleep fragmentation index (SFI), the Pediatric Daytime Sleepiness Scale (PDSS), Sleep Disturbance Scale for Children (SDSC), and obstructive sleep apnea 18-item quality of life questionnaire were re assessed. Children with SDB were grouped into resolved (no snoring and obstructive apnea-hypopnea index [OAHI] <1) and unresolved (snoring or an OAHI ≥1). Results: At follow-up OAHI was reduced in both SDB groups (p<0.05); however, 54% (n=22) of children still continued to snore, having either persistent or new OSA (n=4). In this unresolved group, sleep was significantly disrupted; % nonrapid eye movement stage 1 (NREM1) sleep and SFI were increased (p<0.05), and total sleep time (TST) and sleep efficiency were decreased compared to the resolved and control groups (p<0.05). Overall, 29% of children were treated, and of these, 67% had resolved SDB. SDB groups had higher PDSS, SDSC, and OSA-18 scores compared to controls at follow-up (p<0.01). Conclusions: Our study demonstrated that although SDB improved in the long-term, more than 50% of children had residual SDB (mostly primary snoring) and sleep disturbance. As even mild forms of SDB are known to have adverse cardiovascular, learning, and behavioral outcomes, which have implications for the health of these children. © 2013.


Vandeleur M.,Melbourne Childrens Sleep Center | Davey M.J.,Melbourne Childrens Sleep Center | Nixon G.M.,Melbourne Childrens Sleep Center | Nixon G.M.,Monash Institute of Medical Research
Journal of Paediatrics and Child Health | Year: 2013

Aims To examine sleep study findings in children with Prader-Willi syndrome (PWS) referred for polysomnography (PSG) before commencement of growth hormone (GH) and to evaluate the impact of sleep testing on treatment decisions. Methods The sleep unit database was used to identify all cases over an 8-year period (2003-2011). Standard overnight PSG was performed in the sleep laboratory. Obstructive sleep apnoea (OSA) was defined by an obstructive apnoea-hypopnoea index >1/h. Age, symptoms of OSA, tonsillar size and body mass index (BMI) Z-score were obtained through chart review. Results OSA was diagnosed in 15 of 34 (44%) cases identified. Those with OSA were significantly older (P = 0.009) and more likely to have enlarged tonsils (P = 0.05) than those without OSA. There was no difference in BMI Z-score or the presence of symptoms of OSA. GH was deferred in 13 (38%) pending treatment for OSA. Conclusions OSA was frequently present in children with PWS referred simply to meet the requirement for PSG before starting GH. OSA was more likely in older children and those with enlarged tonsils. GH treatment was deferred in 38% of cases. This study supports routine performance of PSG prior to GH, regardless of clinical history. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).


Vlahandonis A.,Monash Institute of Medical Research | Nixon G.M.,Monash Institute of Medical Research | Nixon G.M.,Melbourne Childrens Sleep Center | Davey M.J.,Monash Institute of Medical Research | And 3 more authors.
Sleep Medicine | Year: 2013

Objective: Childhood sleep-disordered breathing (SDB) is associated with elevated blood pressure (BP); however, little is known about the long-term outcomes in this population. We aimed to assess long-term changes in overnight BP in children with SDB. Methods: Forty children with previously diagnosed SDB and 20 nonsnoring control participants underwent repeat overnight polysomnography (PSG) with continuous BP measurement 4. years after the original diagnosis. At follow-up, children aged 11-16. years were categorized into 2 groups of resolved (absence of snoring and obstructive apnea-hypopnea index [OAHI]≤1) or unresolved (continued to snore or had an OAHI >1) SDB. Results: There were no group differences in age, sex, or body mass index (BMI) z score. OAHI was lower at follow-up (P<.05) in both the resolved (n=18) and unresolved (n=22) groups. BP was elevated during wake and sleep in both SDB groups compared to the control group at baseline (P<.01 for all), but it decreased by 5-15mmHg at follow-up during sleep for both SDB groups (P<.05 for all). BP during wake was unchanged in the SDB groups at follow-up but increased in the control group (P<.05). At follow-up, BP did not differ between the control group and the SDB groups during wake or sleep. Improved oxygen saturation (SpO2) during sleep was a significant predictor of a reduction in BP. Conclusions: SDB improved over the 4-year follow-up and both resolved and unresolved groups exhibited a significant reduction in BP during sleep, with levels similar to the control group. Our study highlights the fact that even small improvements can improve the cardiovascular effects of SDB. © 2013.


Yang J.S.C.,Monash Institute of Medical Research | Nicholas C.L.,University of Melbourne | Nixon G.M.,Monash Institute of Medical Research | Nixon G.M.,Melbourne Childrens Sleep Center | And 5 more authors.
Sleep | Year: 2010

Study Objectives: To identify the extent of sleep disruption in children with various severities of sleep disordered breathing (SDB) using both conventional visually scored assessment of sleep stages and arousal indices together with EEG power spectral analysis. Design: Sleep stages and power spectral analysis of the sleep EEG in children with varying severities of SDB with matched control subjects with no history of snoring were compared across the whole night, across sequential hours from sleep onset, and across sleep stages. Measurements: Overnight polysomnography was performed on 90 children (49M/41F) aged 7-12 y with SDB and 30 age-matched healthy controls (13M/17F). Sleep stages were visually scored and the EEG spectra were analyzed in 5-s epochs. Results: Conventional visual scoring indicated that, although sleep duration was reduced in severely affected children, sleep quality during the essential stages of SWS and REM was preserved, as evidenced by the lack of any significant decrease in their duration in SDB severity groups. This finding was supported by the lack of substantial differences in EEG spectral power between the groups over the whole night, within specific hours, and in individual sleep stages. Conclusions: Both conventional scoring and EEG spectral analysis indicated only minor disruptions to sleep quality in children with SDB when assessed across the night, in any specific hour of the night, or in any specific sleep stage. These results suggest that reduced daytime functioning previously reported in children with SDB may not be due to sleep disruption. We speculate that in children, in contrast to adults, a stronger sleep drive may preserve sleep quality even in severe SDB.

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