Lauren C. Nisbet

Preschool Children with Obstructive Sleep Apnea: The Beginnings of Elevated Blood Pressure?

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 childs 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.

Blood pressure regulation, autonomic control and sleep disordered breathing in children

Sleep disordered breathing (SDB) ranges in severity from primary snoring (PS) to obstructive sleep apnoea (OSA). In adults, SDB is associated with adverse cardiovascular consequences which are mediated, in part, by autonomic dysfunction. Although SDB is common in children, fewer paediatric studies have investigated these cardiovascular effects. Initial research focused on those with OSA, indeed children with PS were occasionally utilised as the comparison control group. However, it is essential to understand the ramifications of this disorder in all its severities, as currently the milder forms of SDB are often untreated. Methodologies used to assess autonomic function in children with SDB include blood pressure (BP), BP variability, baroreflex sensitivity, heart rate variability, peripheral arterial tonometry and catecholamine assays. The aim of this review was to summarise the findings of paediatric studies to date and explore the relationship between autonomic dysfunction and SDB in children, paying particular attention to the roles of disease severity and/or age. This review found evidence of autonomic dysfunction in children with SDB during both wakefulness and sleep. BP dysregulation, elevated generalised sympathetic activity and impairment of autonomic reflexes occur in school-aged children and adolescents with SDB. The adverse effects of SDB seem somewhat less in young children, although more studies are needed. There is mounting evidence that the cardiovascular and autonomic consequences of SDB are not limited to those with OSA, but are also evident in children with PS. The severity of disease and age of onset of autonomic consequences may be important guides for the treatment of SDB.

Time course of EEG slow-wave activity in pre-school children with sleep disordered breathing: A possible mechanism for daytime deficits?

BACKGROUND Daytime deficits in children with sleep disordered breathing (SDB) are theorized to result from hypoxic insult to the developing brain or fragmented sleep. Yet, these do not explain why deficits occur in primary snorers (PS). The time course of slow wave EEG activity (SWA), a proxy of homeostatic regulation and cortical maturation, may provide insight. METHODS Clinical and control subjects (N=175: mean age 4.3±0.9 y: 61% male) participated in overnight polysomnography (PSG). Standard sleep scoring and power spectral analyses were conducted on EEG (C4/A1; 0.5-<3.9Hz). Univariate ANOVAs evaluated group differences in sleep stages and respiratory parameters. Repeated-measures ANCOVA evaluated group differences in the time course of SWA. RESULTS Four groups were classified: controls (OAHI ≤ 1 event/h; no clinical history); PS (OAHI ≤ 1 event/h; clinical history); mild OSA (OAHI=1-5 events/h); and moderate to severe OSA (MS OSA: OAHI>5 events/h). Group differences were found in the percentage of time spent in NREM Stages 1 and 4 (p<0.001) and in the time course of SWA. PS and Mild OSA children had higher SWA in the first NREM period than controls (p<0.05). All SDB groups had higher SWA in the fourth NREM period (p<0.01). CONCLUSIONS These results suggest enhanced sleep pressure but impaired restorative sleep function in pre-school children with SDB, providing new insights into the possible mechanism for daytime deficits observed in all severities of SDB.

Nocturnal autonomic function in preschool children with sleep-disordered breathing

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 3-5years 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⩽1event/h; primary snoring, OAHI⩽1event/h; mild OSA OAHI>1⩽5events/h; moderate to severe [MS] OSA, OAHI>5events/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±523ms(2) vs 2604±457ms(2); NREM sleep stages 3 and 4 [NREM3/4], 4152±741ms(2) vs 3035±647ms(2); REM, 1836±255ms(2) vs 1456±292ms(2); 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.

Long-Term Cognitive and Behavioral Outcomes following Resolution of Sleep Disordered Breathing in Preschool Children

This study aimed to determine the long term effects of resolution of SDB in preschool children, either following treatment or spontaneous recovery, on cognition and behavior. Children diagnosed with SDB at 3-5y (N = 35) and non-snoring controls (N = 25), underwent repeat polysomnography (PSG) and cognitive and behavioral assessment 3 years following a baseline study. At follow-up, children with SDB were grouped into Resolved and Unresolved. Resolution was defined as: obstructive apnea hypopnea index (OAHI) ≤1 event/h; no snoring detected on PSG; and no parental report of habitual snoring. 57% (20/35) of children with SDB received treatment, with SDB resolving in 60% (12/20). 43% (15/35) were untreated, of whom 40% (6/15) had spontaneous resolution of SDB. Cognitive reduced between baseline and follow-up, however this was not related to persistent disease, with no difference in cognitive outcomes between Resolved, Unresolved or Control groups. Behavioral functioning remained significantly worse in children originally diagnosed with SDB compared to control children, regardless of resolution. Change in OAHI did not predict cognitive or behavioral outcomes, however a reduction in nocturnal arousals, irrespective of full resolution, was associated with improvement in attention and aggressive behavior. These results suggest that resolution of SDB in preschool children has little effect on cognitive or behavioral outcomes over the long term. The association between sleep fragmentation and behavior appears independent of SDB, however may be moderated by concomitant SDB. This challenges the assumption that treatment of SDB will ameliorate associated cognitive and behavioural deficits and supports the possibility of a SDB phenotype.

Characterization of the acute pulse transit time response to obstructive apneas and hypopneas in preschool children with sleep-disordered breathing.

BACKGROUND Surges in heart rate (HR) and blood pressure (BP) at apnea termination contribute to the hypertension seen in obstructive sleep apnea (OSA). Because childhood OSA prevalence peaks in the preschool years, we aimed to characterize the cardiovascular response to obstructive events in preschool-aged children. METHODS Clinically referred children aged 3-5 years were grouped by obstructive apnea-hypopnea index (OAHI) into the following: primary snoring (PS) (OAHI≤1 event/h [n=21]), mild OSA (OAHI>1-≤5 [n=32]), and moderate to severe (MS) OSA (OAHI>5 [n=28]). Beat-to-beat pulse transit time (PTT), an inverse continuous indicator of BP changes, and HR were averaged during the two halves (early and late) and during the peak after (post) each obstructive event and were expressed as percentage change from late- to post-event. RESULTS We analyzed 422 events consisting of 55 apneas and 367 hypopneas. A significant post-event increase in HR and fall in PTT occurred in all severity groups (P<.05 for all). A greater response was associated with OSA, nonrapid eye movement sleep (NREM), cortical arousal, hypopneas, and oxygen desaturation (P<.05 for all). CONCLUSIONS Obstructive events elicit acute cardiovascular changes in preschool children. Such circulatory perturbations have been implicated in the development of hypertension, and our findings complement previous studies to suggest a cumulative impact of snoring on the cardiovascular system from childhood into adulthood.

Long-term improvements in sleep and respiratory parameters in preschool children following treatment of Sleep Disordered Breathing

STUDY OBJECTIVE Sleep disordered breathing (SDB) in preschool-aged children is common, but long-term outcomes have not been investigated. We aimed to compare sleep and respiratory parameters in preschool children to examine the effects of treatment or non-treatment after 3 years. METHODS Children (3-5 years) diagnosed with SDB (n = 45) and non-snoring controls (n = 30) returned for repeat overnight polysomnography (39% of original cohort), 3 years following baseline polysomnography. Children with SDB were grouped according to whether they had received treatment or not. SDB resolution was defined as an obstructive apnea hypopnea index (OAHI) ≤ 1 event/h, no snoring detected on polysomnography and habitual snoring not indicated by parents on questionnaire. RESULTS Fifty-one percent (n = 23) of the children with SDB were treated. Overall, SDB resolved in 49% (n = 22), either spontaneously (n = 8) or with treatment (n = 14). SDB remained unresolved in 39% (n = 9) of those treated and 64% (n = 14) of the children who were untreated. Two of the non-snoring controls developed SDB at follow-up. The treated group had significantly lower OAHI (p < 0.01), respiratory disturbance index (p < 0.001), total arousal and respiratory arousal indices (p < 0.01 for both) at follow-up compared with baseline. There were no differences between studies for the untreated group. CONCLUSIONS Although treatment resulted in an improvement in indices related to SDB severity, 39% had SDB 3 years following diagnosis. These findings highlight that parents should be made aware of the possibility that SDB may persist or recur several years after treatment. This is relevant regardless of the severity of SDB at baseline and the treatment given.

Sleep-disordered breathing does not affect nocturnal dipping, as assessed by pulse transit time, in preschool children: evidence for early intervention to prevent adverse cardiovascular effects?

OBJECTIVE Sleep-disordered breathing (SDB) is associated with reduced nocturnal dipping of blood pressure (BP) and sleep disruption in adults, and these features confer an increased risk of cardiovascular events. As SDB prevalence in children peaks during the preschool years, we investigated nocturnal dipping and sleep fragmentation in preschool children with SDB. METHODS Children (3-5 years; n=163) grouped by obstructive apnoea hypopnoea index (OAHI): control, no snoring history and OAHI ≤1 event/h; primary snoring, OAHI ≤1 event/h; mild SDB, >1-≤5 events/h; moderate-severe SDB, >5 events/h. Pulse transit time (PTT), an inverse continuous indicator of BP changes, and heart rate (HR) during total sleep time and the first period of rapid eye movement (REM), non-REM (NREM)1/2 and NREM3/4 sleep were expressed as percentage change from wake before sleep onset. The sleep fragmentation index (SFI) was calculated as the number of sleep stage transitions or awakenings per hour of sleep. RESULTS There were no group differences in the change in PTT or HR from wake to total sleep time or to individual sleep stages or in the proportion of children in the quartile with the smallest change in PTT during total sleep. Children with moderate-severe SDB had higher SFI than primary snoring (PS) or mild SDB groups (p<0.05 for both) and controls (p=0.07). CONCLUSIONS In contrast to adults, nocturnal dipping is preserved in young children with SDB, despite increased sleep fragmentation. As there is evidence that nocturnal dipping is similarly preserved at the school age, childhood may pose a window of opportunity for resolution of SDB when the cardiovascular effects are less marked.

Effect of body position and sleep state on obstructive sleep apnea severity in children with Down syndrome.

STUDY OBJECTIVES To investigate the influence of sleep position and sleep state on obstructive sleep apnea (OSA) severity in in children with Down syndrome (DS). DESIGN Retrospective review. SETTING Sleep disorders laboratory of a tertiary medical center. PARTICIPANTS Children with Down syndrome and typically developing children matched for age, gender, apneahypopnea index (AHI), and year of polysomnogram. MEASUREMENTS AND RESULTS Sleep variables from baseline polysomnography. Sensor-recorded position (supine, prone, lateral) was expressed as the percentage of total sleep time. The AHI was calculated in each sleep state (NREM, REM), position, and position-sleep state combination. Of 76 DS subjects (55% male) the median age and AHI were 4.6 years (range 0.2-17.8 years) and 7.4 events/h (range 0-133). In all subjects, AHI was higher in REM than NREM (p < 0.05); however, the NREM AHI was higher in DS subjects than controls (p < 0.05). Compared to controls, the percentage of prone sleep was greater in DS subjects (p < 0.05), but the percentage of supine or non-supine (prone plus lateral) sleep was no different. For DS subjects alone, NREM AHI was higher in supine than non-supine sleep (p < 0.05). CONCLUSION In DS and non-DS children alike, respiratory events are predominantly REM related. However, when matched for OSA severity, children with DS have a higher NREM AHI, which is worse in the supine position, perhaps indicating a positional effect compounded by underlying hypotonia inherent to DS. These findings illustrate the clinical importance of NREM respiratory events in the DS population and implications for treatment options.

Seasonal variability in paediatric obstructive sleep apnoea

Background Allergy and respiratory viral infection may contribute to the pathogenesis of sleep disordered breathing (SDB) through promoting adenotonsillar growth. We investigated the seasonal variation of SDB in children by analysing the change in the obstructive apnoea hypopnoea index (OAHI) throughout the year. Participants 257 3–12-year-old children referred for assessment of SDB underwent overnight polysomnography (PSG). Results Mean seasonal OAHI was significantly higher in winter (5.1±0.8 events/h) and spring (4.6±0.9 events/h) compared with autumn (2.4±0.8 events/h; p<0.01 and p<0.05, respectively) and summer (2.0±0.5 events/h; p<0.05 for both). There were no differences in OAHI between summer and the other seasons or between winter and spring. Conclusions We identified more severe obstructive sleep apnoea in clinically referred children during winter and spring and suggest that inflammation from respiratory viruses may contribute to adenotonsillar hypertrophy, worsening airway obstruction. Clinicians should take season into account when interpreting PSG results.