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Study objectivesChildren 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 whether alterations correlated with disease severity.MethodsBrain tissue integrity was examined with mean diffusivity (MD) (3.0 T scanner) in 20 nonsnoring controls (mean age ± SEM, 12.2 ± 0.6 years; 10 males) and 18 children with SDB (12.3 ± 0.7 years; 11 males). Sleep, cognitive, and behavioral measures were compared between groups following overnight polysomnography using Student's 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 (OAHIs).ResultsAge, gender, and sleep variables did not differ between groups. The SDB group showed higher OAHIs, 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 children with SDB. Verbal, performance, and total IQ scores trended lower, and behavioral scores trended higher.ConclusionsPediatric 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.

The role of physiological traits such as ventilatory control instability in children with SDB is currently unclear. Our study indicates that altered ventilatory control sensitivity may contribute to SDB in a subgroup of children, depending on their degree of upper airway anatomical compromise. See related Editorial Background and objective: The contribution of non‐anatomical factors, such as ventilatory control instability (i.e. LG), to the pathogenesis of obstructive SDB in children is unclear. Therefore, we aimed to identify the relationship between LG and severity of SDB, demographic, anthropometric and anatomical characteristics in a clinically representative cohort of children. Methods: Children (aged 3–18 years) with various severities of SDB (n = 110) and non‐snoring controls (n = 36) were studied. Children were grouped according to their OAHI. Anthropometric and upper airway anatomical characteristics were measured. Spontaneous sighs were identified on polysomnography and LG, a measure of the sensitivity of the negative feedback loop that controls ventilation, was estimated by fitting a mathematical model of ventilatory control to the post‐sigh ventilatory pattern. Results: There was no difference in LG between controls and any of the SDB severity groups. However, LG was significantly lower in children with larger tonsils (tonsil grade 4) compared with children with smaller tonsils (tonsil grade 1) (median LG (range): 0.25 (0.20–0.42) vs 0.32 (0.25–0.44); P = 0.009) and in children with a modified Mallampati score of class III/IV compared with class I (0.28 (0.24–0.33) vs 0.37 (0.27–0.44); P = 0.009). Conclusion: A direct relationship was not found between the severity of paediatric SDB and LG. However, an altered ventilatory control sensitivity may contribute to SDB in a subgroup of children depending on their degree of anatomical compromise of the airway. [ABSTRACT FROM AUTHOR]

Background and objective: Frequent central apnoeas are sometimes observed in healthy children; however; the pathophysiology of an elevated central apnoea index (CAI) is poorly understood. A raised CAI may indicate underlying ventilatory control instability (i.e. elevated loop gain, LG) or a depressed ventilatory drive. This pilot study aimed to compare LG in otherwise healthy children with an elevated CAI to healthy controls. Methods: Polysomnographic recordings from children (age > 6 months) without obstructive sleep apnoea and with a CAI > 5 events/h (n = 13) were compared with age and gender‐matched controls with a CAI < 5 events/h (n = 13). Spontaneous sighs were identified during non‐rapid eye movement (NREM) sleep, and breath–breath measurements of ventilation were derived from the nasal pressure signal. A standard model of ventilatory control (gain, time constant and delay) was used to calculate LG by transforming ventilatory fluctuations seen in response to a sigh into a ventilatory‐drive signal that best matches observed ventilation. Results: The high CAI group had an elevated LG (median = 0.36 (interquartile range, IQR = 0.35–0.53) vs 0.28 (0.23–0.36); P ≤ 0.01). There was no difference in either the time constant (P = 0.63) or delay (P = 0.29) between groups. Elevated LG observed in the high CAI group remained after accounting for degree of hypoxia (average oxygen saturation (SpO2) during each analysable window) experienced (0.40 (0.30–0.53) vs 0.25 (0.23–0.37); P = 0.04). Conclusion: An elevated CAI in otherwise healthy children is associated with a raised LG compared to matched controls with a low CAI, irrespective of level of hypoxia. This relative ventilatory instability helps explain the high CAI and may ultimately be able to help guide diagnosis and management in patients with high CAI. While central apnoeas are common in children, a central apnoea index of >5 events/h is outside normal ranges and raises concern regarding origins of such events. Our study indicates that an elevated index of >5 is associated with a hypersensitive ventilatory control system and supports literature that neuroimaging may not be needed. [ABSTRACT FROM AUTHOR]

Key points: Sleep disordered breathing (SDB) affects 4–11% of children and is associated with adverse neurocognitive, behavioural and cardiovascular outcomes, including reduced autonomic control.The relationship between heart rate variability (HRV; a measure of autonomic control) and age found in non‐snoring control children was absent during sleep in children with SDB.Age significantly predicted increasing cerebral oxygenation during wake in non‐snoring control children, whereas during sleep, HRV significantly predicted decreasing cerebral oxygenation.Cerebral oxygenation was not associated with either age or HRV in children with SDB during both wake and sleep.SDB significantly disrupts the normal maturation of autonomic control and the positive association between autonomic control and cerebral oxygenation found in non‐snoring children, and we speculate that the dampened autonomic control exhibited by children with SDB may have an attenuating effect on cerebral autoregulation via the moderating influence of HRV on cerebral blood flow. The repetitive episodes of hypoxia that are features of sleep disordered breathing (SDB) in children are associated with alterations in autonomic control of heart rate in an age‐dependent manner. We aimed to relate heart rate variability (HRV) parameters to age and measures of cerebral oxygenation in children (3–12 years old) with SDB and non‐snoring controls. Children (SDB, n = 117; controls, n = 42; 3–12 years) underwent overnight polysomnography. Total (TP), low‐ (LF) and high‐frequency (HF) power, tissue oxygenation index (TOI) and fractional tissue oxygen extraction (FTOE) were analysed during wake and sleep. Pearson's correlations determined the association between age and HRV parameters, and multiple linear regressions between HRV, age and cerebral oxygenation parameters. During wake, age had a positive association with LF power, reflecting increased parasympathetic and sympathetic activity with increasing age for both control and SDB groups. This association was also evident during sleep in controls, but was absent in children with SDB. In controls, during wake TOI had a positive, and FTOE a negative association with age. During sleep, TP, LF and HF power were significant, negative determinants of TOI and positive determinants of FTOE. These associations were not seen in children with SDB during wake or sleep. SDB disrupts the normal maturation of the autonomic control of heart rate and the association between HRV and cerebral oxygenation exhibited by non‐snoring control children of primary school age. These results highlight the impact SDB has on cardiovascular control and the potential impact on adverse cardiovascular outcomes. Key points: Sleep disordered breathing (SDB) affects 4–11% of children and is associated with adverse neurocognitive, behavioural and cardiovascular outcomes, including reduced autonomic control.The relationship between heart rate variability (HRV; a measure of autonomic control) and age found in non‐snoring control children was absent during sleep in children with SDB.Age significantly predicted increasing cerebral oxygenation during wake in non‐snoring control children, whereas during sleep, HRV significantly predicted decreasing cerebral oxygenation.Cerebral oxygenation was not associated with either age or HRV in children with SDB during both wake and sleep.SDB significantly disrupts the normal maturation of autonomic control and the positive association between autonomic control and cerebral oxygenation found in non‐snoring children, and we speculate that the dampened autonomic control exhibited by children with SDB may have an attenuating effect on cerebral autoregulation via the moderating influence of HRV on cerebral blood flow. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: In adults there is a distinct gender difference in the prevalence and severity of sleep disordered breathing (SDB), however there have been limited studies examining the effects of gender in children with SDB. We aimed to compare the effects of gender on severity of SDB, blood pressure, sleep and respiratory characteristics, quality of life, behavior and executive function.Methods: We included 533 children aged 3-18 years, who underwent standard pediatric overnight polysomnography (PSG) between 2004 and 2016. Blood pressure was recorded prior to each study. Quality of life, behavior and executive function were assessed with parental questionnaires. Children were grouped by gender and SDB severity based on their obstructive apnea hypopnea index (OAHI) into non-snoring controls, Primary Snoring (PS) (OAHI≤1 event/h), Mild obstructive sleep apnea (OSA) (OAHI>1-≤5 events/h) and moderate/severe (MS) OSA (OAHI>5 events/h) and data compared with 2-way ANOVA.Results: A total of 298 boys and 235 girls were studied. There were no differences in age, BMI z-score, SDB severity sleep characteristics or blood pressure between genders. Diastolic blood pressure was elevated in females with MS OSA compared to males (P < 0.05). Quality of life, behavior and executive function scores were all elevated in the SDB groups compared to controls. Females with MS OSA exhibited more internalizing behavioral problems compared to males (59.2 ± 2.4 vs. 51.4 ± 2.3, P < 0.05).Conclusions: In contrast to studies in adults, we identified no gender differences in the severity or consequences of SDB in children, other than females with moderate-severe OSA exhibiting more internalizing problems and higher diastolic blood pressure. [ABSTRACT FROM AUTHOR]

Background: The prevalence of obese children with sleep disordered breathing (SDB) is increasing. Obesity and SDB are independent cardiovascular risk factors, of which arterial stiffness is an early sign. Pulse wave velocity (PWV), is a marker of arterial stiffness and central systolic blood pressure (cSBP) is a better predictor of cardiovascular outcome than peripheral blood pressure. Therefore, we aimed to determine PWV and cSBP in overweight/obese or normal weight children with sleep disordered breathing (SDB), and non-snoring normal weight controls.Methods: Children (3-18 y) with SDB (overweight/obese [BMI z-scores ≥ 1.04], n = 48; normal weight n = 44) referred for clinical assessment of SDB and normal weight non-snoring controls recruited from the community (n = 38) underwent overnight polysomnography. PWV was calculated using photoplethysmography. cSBP was calculated using applanation tonometry in a subset of children older than 8 y (n = 55) who had usable waveforms.Results: Overweight/obese SDB group had higher PWV (mean cm/s (95% CI); wake: 366 (355-380); sleep: 340 (324-357)), than the normal-weight SDB group (wake: 257 (247-267), p = 0.002; sleep: 255 (242-269), p = 0.005), and non-snoring controls (wake: 238 (226-249), p = 0.002; sleep: 235 (220-250), p < 0.001). The normal-weight SDB group had higher PWV than controls (p = 0.03). Overweight/obese children with SDB had higher cSBP (105 (100-110) mmHg) compared with the normal weight children with SDB (96 (90-102)) and the non-snoring controls (97 (91-104); p < 0.05 for both).Conclusion: This study suggests that overweight/obesity substantially worsens the cardiovascular sequelae of SDB, highlighting the imperative to treat obesity and SDB in children early in order to reduce future cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Study Objectives: Both central and obstructive respiratory events are features of sleep disordered breathing. The repetitive hypoxia associated with obstructive events is believed to underpin the adverse neurocognitive and cardiovascular sequelae of this disorder, however whether central events contribute to this has not been investigated. To compare changes in cerebral and peripheral oxygenation, blood pressure and heart rate, associated with central and obstructive events in children aged 3-6 and 7-12 years., Methods: Sixty children referred for suspected sleep disordered breathing underwent overnight polysomnography. Beat-by-beat analysis determined changes from baseline in cerebral oxygenation, peripheral oxygen saturation, fractional tissue oxygen extraction, pulse transit time (a surrogate measure of blood pressure change), and heart rate, associated with central and obstructive respiratory events, during NREM and REM sleep., Results: Eight hundred ninty-two events were analyzed: 493 central and 399 obstructive. Central events had a greater % change from baseline in cerebral oxygenation and heart rate nadir compared with obstructive events and these were greater in NREM compared with REM sleep. The 3- to 6-year-old children experienced a greater % change in TOI compared with the 7-12 year olds, while % change in heart rate was greater in 7-12 year olds., Conclusion: Central respiratory events had similar falls in cerebral oxygenation and heart rate to obstructive events and should be considered when examining the sequelae of sleep disordered breathing, particularly as central events are common in children with sleep disordered breathing., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

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., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

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.

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., (© 2015 American Academy of Sleep Medicine.)