Aidan J. Weichard

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.

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.

Oximetry for suspected obstructive sleep apnea-Does removal of awake data affect the result?

Frequency of dips below 90% on overnight oximetry can be used to estimate severity of obstructive sleep apnea (OSA) in children. Movement can result in artifact on oximetry recordings. Clinicians may therefore be tempted to remove periods of wakefulness from the recording to improve accuracy, but removal of such periods of potential artifact is time consuming. The aim of this study was to determine whether removing periods of wakefulness had a significant impact on analysis of overnight oximetry. Children aged 2–18 years (N = 108) with suspected OSA underwent overnight simultaneous oximetry and actigraphy at home on a single night. Actigraphy defined awake periods were “trimmed” from the oximetry data and oximetry variables compared between full and trimmed analysis. There was a statistically but not clinically significant difference between the full and trimmed data for mean SpO2, minimum SpO2, 4% desaturation index, and 3% desaturation index (all P < 0.05). There was no difference between the two analyses for median SpO2 or the frequency of dips below 90%, 85%, or 80%. In conclusion, removal of periods of wakefulness at the start and end of overnight oximetry recordings does not affect the result in the context of testing for suspected OSA in children. Pediatr Pulmonol. 2016;51:1409–1413.

Longitudinal Impact of Resolution of Snoring in Young Children on Psychosocial Functioning.

OBJECTIVE To determine whether sustained resolution of sleep disordered breathing (SDB) in young children, either because of treatment or spontaneous recovery, predicted long-term improvements in quality of life, family functioning, and parental stress. STUDY DESIGN Children diagnosed with primary snoring (n = 16), mild obstructive sleep apnea (OSA, n = 11), moderate-severe (MS) OSA (n = 8), and healthy nonsnoring controls (n = 25) at ages 3-5 years underwent repeat polysomnography at 6-8 years. Parents completed quality of life and parental stress questionnaires at both time points. Resolution of SDB was determined as obstructive apnea hypopnea index (OAHI) ≤1 event/hour, or absence of snoring during polysomnography or on parent report. Linear mixed-model analyses determined the effects of resolution on psychosocial morbidity. OAHI was used to determine the predictive value of changes in SDB severity on psychosocial outcomes. RESULTS Fifty percent of primary snoring, 45% mild OSA, and 63% MS OSA resolved, of which 67% received treatment. Children originally diagnosed with SDB continued to show significant psychosocial impairments compared with nonsnoring controls, irrespective of resolution. A reduction in OAHI predicted improvements in physical symptoms, school functioning, family worry and family relationships, and stress related to a difficult child. CONCLUSIONS Treatment was more likely to result in resolution of SDB if original symptoms were MS. Children originally diagnosed with SDB, irrespective of resolution, continued to experience psychosocial dysfunction suggesting additional interventions are required.

Augmented cardiovascular responses to episodes of repetitive compared with isolated respiratory events in preschool children with sleep-disordered breathing

Background:Childhood sleep disordered breathing (SDB) presents as isolated respiratory events or episodes of consecutive repetitive events. We hypothesized that the surge in blood pressure (BP) and heart rate (HR) would be greater at the termination of events during episodes of repetitive events than following isolated events.Methods:% change in HR and pulse transit time (PTT; inverse surrogate of BP) were calculated from the last half of an event to: (i) between successive repetitive events; (ii) termination of the last repetitive event; (iii) event termination for isolated events.Results:69% of the children exhibiting both isolated and repetitive events had more repetitive than isolated events. %HR change between repetitive events (27 ± 1%) was greater than at event termination for isolated events (17 ± 1%; P < 0.001). %PTT change at the termination of the last repetitive event (−8 ± 2%) was greater than at the termination of isolated events (−2 ± 2%; P < 0.05).Conclusion:Episodes of repetitive respiratory events evoke a greater acute cardiovascular response, including surges in BP and HR between events, than do isolated events. Given that the majority of respiratory events in preschool children occur as repetitive episodes, this finding should be taken into account when assessing the impact of respiratory events for a given child.

Regional brain tissue changes and associations with disease severity in children with sleep-disordered breathing

Study Objectives Children with sleep-disordered breathing (SDB) exhibit behavioral, cognitive, and autonomic deficits, suggestive of neural injury. We assessed whether the tissue alterations resulted from acute or chronic processes, and if alterations correlated with disease severity. Methods Brain tissue integrity was examined with mean diffusivity (MD) (3.0-Tesla scanner) in 20 non-snoring controls (mean age±sem, 12.2±0.6y; 10 male) and 18 children with SDB (12.3±0.7y; 11 male). Sleep, cognitive, and behavioral measures were compared between groups following overnight polysomnography using Students t-tests. Whole-brain MD maps were realigned and averaged, normalized, smoothed, and compared between groups using ANCOVA (covariates; age, gender, and socioeconomic status). Partial correlations were calculated between whole-brain smoothed MD maps and obstructive apnea hypopnea indices (OAHI). Results Age, gender, and sleep variables did not differ between groups. The SDB group showed higher OAHI, body mass indices, and systolic blood pressure. Significantly reduced MD values (acute changes) appeared in the hippocampus, insula, thalamus, temporal and occipital cortices, and cerebellum, but were increased (chronic damage) in the frontal and prefrontal cortices in the SDB group over controls. Both positive and negative correlations appeared with extent of tissue changes and disease severity. Externalizing and Total Problem Behaviors were significantly higher in SDB children. Verbal, performance and total IQ scores trended lower, and behavioral scores trended higher. Conclusions Pediatric SDB is accompanied by predominantly acute brain changes in areas that regulate autonomic, cognitive, and mood functions, and chronic changes in frontal cortices essential for behavioral control. Interventions need to be keyed to address acute vs chronic injury.

Association between slow-wave activity, cognition and behaviour in children with sleep-disordered breathing

BACKGROUND It has been suggested that impaired dissipation of slow-wave activity (SWA) in children with sleep-disordered breathing (SDB) may be a potential mechanism for daytime dysfunction. We aimed to examine whether resolution of SDB resulted in normalisation of SWA dissipation and whether this was associated with improved cognition and behaviour. METHODS Children (aged 3-6 y) diagnosed with SDB and age-matched non-snoring control children were followed up for 3 y after a baseline study. At the follow-up, children were categorised into control (N = 13), resolved SDB (N = 15) and unresolved SDB (N = 14). Delta activity on the electroencephalogram over the sleep period was used to calculate SWA and a battery of cognitive assessments and behaviour questionnaires were conducted at both time points. RESULTS There was no change in the average SWA between the baseline and follow-up and no differences between the groups. Cognitive and behavioural performance in the resolved group did not improve to control levels. However, decreased SWA at the beginning of the sleep period (β = -0.04, p = 0.002) and a decrease in obstructive apnoea-hypopnoea index (β = -2.2, p = 0.022) between the baseline and follow-up predicted improvements in measures of sustained attention. Increased SWA at the beginning of the sleep period between the baseline and follow-up predicted worsening of externalising behaviour (β = 0.02, p = 0.039). CONCLUSIONS This study suggests that resolution of SDB is not associated with changes in the dissipation of SWA. However, the association between decreases in SWA and improvements in cognitive and behavioural outcomes suggest that irrespective of disease, children whose quantitative sleepiness improves have improved attention and reduced externalising behaviours.

Age Effects on Cerebral Oxygenation and Behavior in Children with Sleep-disordered Breathing

Rationale: Childhood sleep‐disordered breathing ranges in severity from primary snoring to obstructive sleep apnea and is associated with behavioral and neurocognitive deficits. It remains unknown why children with primary snoring, who do not experience peripheral oxygen desaturation or sleep fragmentation, experience similar daytime deficits as those with obstructive sleep apnea or why effects are age‐dependent. Objectives: To examine cerebral tissue oxygenation and oxygen extraction as an explanation for daytime deficits in children with primary snoring. Methods: Children referred for suspected sleep‐disordered breathing and nonsnoring control subjects underwent overnight polysomnography with near‐infrared spectroscopy. Children were categorized into 3‐ to 6‐year (n = 87) and 7‐ to 12‐year (n = 72) old groups, and according to the obstructive apnea‐hypopnea index into primary snoring (≤1 event/h), mild (>1‐5 events/h), and moderate/severe obstructive sleep apnea (>5 events/h). Cognitive and behavioral performance were assessed. Measurements and Main Results: In the 3‐ to 6‐year group, there were no differences in cerebral oxygenation or oxygen extraction between severity groups. In the 7‐ to 12‐year group, cerebral oxygenation was significantly lower, although these differences were small, in control subjects versus primary snoring during quiet wakefulness before sleep onset, N1, and REM. Oxygen extraction was significantly higher in control subjects versus primary snoring during N1 sleep, with no differences between primary snoring and obstructive sleep apnea groups. Cerebral oxygenation was not associated with cognitive performance in either age group or behavior in the 3‐ to 6‐year group; however, it was associated with behavior in the school‐aged children. Conclusions: Children with sleep‐disordered breathing are able to maintain cerebral oxygenation, and the small changes observed are not related to cognitive deficits. However, in older children these differences were related to behavioral measures.

Sleep: A Window Into Autonomic Control in Children Born Preterm and Growth Restricted

Study Objectives Preterm birth and fetal growth restriction (FGR) are both associated with risk of hypertension in adulthood. Mechanisms leading to this pathology are unclear. In children aged 5-12 years, who were born preterm and FGR, we used sleep as a tool to assess autonomic control with assessment of cardiovascular structure and function. Methods Eighteen children born preterm and FGR, 15 children born preterm with appropriate birth weights for gestational age (AGA), and 20 AGA term-born children were studied. Children underwent overnight polysomnography with the addition of continuous noninvasive blood pressure (Finometer™). Spectral measures of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity were assessed and overnight urinary catecholamine levels measured. Echocardiographic studies (Vivid7, GE Healthcare) were performed and vascular compliance assessed (Miller Instruments™). Statistical comparisons were adjusted for age and body size. Results Compared to term children, preterm AGA children had increased high frequency HRV (p < .05) and BPV (p < .05) during sleep, reflecting increased parasympathetic activation and blood pressure changes related to respiration. Preterm FGR children had smaller left ventricular lengths, ascending aorta, and left ventricular outflow tract diameter (p < .05 for all) and vascular compliance was positively correlated with gestational age (r2 = 0.93, p < .05). Conclusions FGR combined with preterm birth did not alter autonomic control but altered heart structure in children. In contrast, preterm birth alone altered autonomic control but had no change in heart structure. These changes in children born preterm and FGR may contribute, in part, to increased risk of cardiovascular disease later in life but by different mechanisms.

Being Born Too Small and Too Early May Alter Sleep in Childhood

Study Objectives Fetal growth restriction (FGR) occurs in up to 10% of pregnancies and is associated with increased risk of prematurity and neurodevelopmental impairment. FGR also alters sleep state distribution in utero and maturation in infancy. Currently, limited data on the long-term associations of FGR and childhood sleep exist. Accordingly, we assessed the associations between preterm birth and FGR and sleep in children aged 5-12 years. Methods 17 children born preterm and FGR, 15 children born preterm but appropriately grown (AGA) and 20 term AGA children (controls) were studied using overnight polysomnography. Sleep macro-architecture was assessed using standard criteria and sleep micro-architecture was assessed using spectral analysis of the EEG (C4-M1) with Total, Delta (0.5Hz-3.9Hz), Theta (4.0Hz-7.9Hz), Alpha (8.0Hz-11.9Hz), Sigma (12.0Hz-13.9Hz) and Beta Power (14.0Hz-30Hz) calculated. Results For sleep macro-architecture, preterm FGR children had higher N2% compared to term AGA children (p<0.05). Preterm AGA children had reduced total sleep time, NREM% and sleep efficiency compared to term AGA children (p<0.05 for all). For sleep micro-architecture, preterm FGR children had a higher amount of Total, delta and alpha power compared to both groups (p<0.05). Sigma and beta power were lowest in the preterm AGA group compared to both groups (p<0.05 for both). Conclusions Prematurity and FGR were associated with altered sleep macro- and micro-architecture measures indicative of reduced sleep quantity and quality in childhood. As sleep disturbance can impact both behavior and neurodevelopment in children, sleep in FGR and preterm children warrants further investigation.