Lifestyle and environmental risk factors for unexplained male infertility: study protocol for Australian Male Infertility Exposure (AMIE), a case-control study.

BACKGROUND: Approximately 1 in 20 men are sub-fertile or infertile yet the aetiologies of male infertility remain largely unexplained. It is suggested that lifestyle choices and environmental factors contribute but research is limited. In particular, no study has evaluated early life exposures and subsequent male infertility. To address this knowledge gap, this study aims to characterise a cohort of men with idiopathic infertility and compare their general health, lifestyle choices and environmental exposures from teenage years onwards to men without reproductive abnormalities. METHODS: Two groups of men (N = 500 cases; N = 500 controls), matched for age and socio-economic status, will be recruited from fertility clinics around Australia between June 2021 and June 2024. Men will be eligible if they are between 18 and 50 years, with a female partner less than 42 years, and have identified idiopathic male infertility (case) or are part of a couple with diagnosed female factor infertility but with no indication of compromised male fertility (control). Participants will complete an in-depth survey on general health, lifestyle and environmental exposures, reporting from teenage years onwards. An online medical data capture form will be used to gather fertility assessment information from participant medical records. Biological specimens of saliva (all study participants), blood and urine (optional) will be collected and stored for future genetic and epigenetic analysis. Differences in outcome measures between cases and controls will be determined using appropriate between groups comparisons. The relationship between explanatory variables and infertility will be analysed using multilevel modelling to account for clustering within fertility clinics. DISCUSSION: This study addresses an important gap in research on the aetiology of male infertility and will provide a comprehensive profile of the lifestyle and environmental risk factors for male infertility, leading to provision of up-to-date health advice for male teenagers and adults about optimising their fertility.

Approximately 1 in 20 men are sub-fertile or infertile yet very little is known about the causes of male infertility. Research has suggested that lifestyle choices and environmental factors contribute to infertility, but more needs to be done to identify and verify the full suite of associations.We will recruit up to 1000 Australian male partners within couples who are seeking help from fertility clinics to get pregnant. They will be asked about their general health, lifestyle and environmental exposures at home or work over their lifespan. We will compare findings between men who are sub- or infertile with men who are not. Any differences will help us understand what factors may be associated with risk of infertility in men.This study will provide important information to clinicians and to inform public policy that will lead to prevention and improved treatment strategies for infertile men. The data gathered from this study will enable future research including the genetic and epigenetic basis of male infertility.

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.

Slow wave activity and executive dysfunction in children with sleep disordered breathing.

PURPOSE: This study aimed to examine slow wave activity (SWA), a marker of homeostatic regulation, as a potential mechanism linking sleep disordered breathing (SDB) with executive dysfunction in children. METHODS: Executive function domains of working memory, spatial planning, information processing, and sustained attention were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in children (N = 40; 5-12 years) referred for clinical diagnosis of SDB. Polysomnography records of non-snoring, age-matched controls (N = 34) were retrospectively examined for comparison of SWA. Power spectral analysis of the delta wave determined SWA. Group differences in sleep, respiratory, and SWA outcomes were examined. Mean CANTAB scores were compared to standardized norms and correlated against SWA. RESULTS: Children with SDB showed increased SWA compared to non-snoring controls and scored < 25th percentile for planning accuracy, speed of mental processing, and task efficiency, when compared against population norms. Increasing severity of SDB was associated with an increased difficulty in solving complex tasks and time on task performance. SWA was associated with performance on tasks of early problem solving and efficiency during sustained attention. CONCLUSIONS: SWA, a subtle measure of sleep disruption and sleep regulation, is associated with deficits in problem solving and sustained attention in children with SDB. As current mechanistic theories do not account for deficits observed in children with mild forms of SDB, this study provides a promising alternative.

Improved long-term autonomic function following resolution of sleep-disordered breathing in preschool-aged children.

PURPOSE: Sleep-disordered breathing (SDB) prevalence peaks in preschool children and is associated with deficits in cardiovascular functioning during sleep. No long-term studies have investigated the effects of SDB resolution in mitigating these outcomes. We hypothesized that following 3 years, normalization of alterations to heart rate (HR), pulse transit time (PTT), heart rate variability (HRV), and urinary catecholamines identified at the initial diagnosis would be associated with resolution of SDB. METHODS: Forty-five children with SDB and 28 non-snoring controls underwent polysomnography at baseline (3-5 years) and follow-up (6-9 years). Children were classified into control, resolved, and unresolved SDB. Resolution was defined as an obstructive apnea-hypopnea index (OAHI) ≤1 event/h, no snoring on polysomnography (PSG), or indicated by parents. PTT is an inverse surrogate measure of blood pressure change. HRV was assessed using power spectral analysis. RESULTS: There was no change in PTT or HR between studies for any group. Our HRV data suggest reduced parasympathetic activity in children whose SDB resolved and increased parasympathetic activity in children whose SDB remained the same or worsened at follow-up. We identified a significant correlation between low frequency power and urinary dopamine and adrenaline levels at follow-up in the unresolved group, suggesting increased sympathetic activity in children with unresolved SDB. CONCLUSION: Our findings suggest an association between resolution of SDB and normalization of HRV in the long term in these preschool children and an augmented sympathetic activity in the children with residual SDB. This highlights the autonomic impact of SDB in young children and the importance of detection and treatment.

The efficacy of the OSA-18 as a waiting list triage tool for OSA in children.

PURPOSE: Sleep disordered breathing (SDB) is common in children, resulting in extensive waiting lists for specialist clinics. There is an urgent need for a valid method of triaging patients and the OSA-18, a disease-specific tool, is an attractive candidate for this role. We aimed to examine the OSA-18 as a measurement tool in detail and to determine whether the score or aspects of it could be used as a screening tool for SDB in children. METHODS: Retrospective analysis of 582 children (6 months to 16.4 years)-216 underwent overnight PSG and 366 overnight oximetry. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were conducted. Receiver operating characteristic curve analysis assessed the diagnostic accuracy of the factors for the presence of OSA. Rasch analysis was used to assess the structure of the items (1-18) and categories of response (Likert scale). RESULTS: The CFA with a forced five-factor structure, revealed three factors with Eigenvalues >1, and explained 73.7 % of the variance. EFA resulted in a two-factor structure, explaining 60.3 % of the variance. Assessment of sensitivity and specificity showed a high false-positive rate, irrespective of the factor structure tested. Rasch analysis showed poor discrimination between adjacent categories on the Likert scale. CONCLUSION: This study confirmed that the predictive value of the OSA-18 for SDB severity is weak. Some questions perform better than others statistically, and the seven categories of response introduce significant statistical noise, raising the possibility that modification of the OSA-18 may improve its performance in the prediction of OSA severity.

Risk factors for obstructive sleep apnoea in Australian children.

AIM: This study aims to determine whether demographic or clinical factors predict obstructive sleep apnoea (OSA) severity in Australian children. METHODS: Demographic details and medical histories of 301 Australian children (3-17 years old) referred for assessment of OSA were examined retrospectively. Children underwent overnight polysomnography and were classified as having primary snoring (PS) (obstructive apnoea hypopnoea index (OAHI) ≤ 1 event per hour; n = 150), mild OSA (>1 OAHI ≤ 5 events per hour; n = 76) or moderate/severe (MS) OSA (OAHI > 5 events per hour; n = 75). Information obtained from parent-report questionnaire determined the predictive value of the following factors for determining OSA severity: gender, ethnicity, body mass index, asthma and/or allergic rhinitis, socio-economic status and parental smoking status (mother/father/both). Chi-squared analyses were used to compare the distribution of the demographic and clinical factors across the three groups. Statistically significant risk factors were subsequently entered into logistic regression analysis. RESULTS: Ethnicity and parental smoking were significant risk factors for MS OSA. Children with non-Caucasian ethnicity were 36% more likely than Caucasian children to be diagnosed with MS OSA than PS (P = 0.002). Children with fathers who smoked were 53% more likely to have MS OSA than PS compared with those with fathers who did not smoke (P = 0.008). Obesity was associated with OSA severity in primary school-aged children only. Gender, socio-economic status and history of asthma and/or allergic rhinitis were not risk factors. CONCLUSIONS: Non-Caucasian ethnicity, paternal smoking and obesity in older children were associated with an increased risk of polysomnography-confirmed MS OSA in Australian children.

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.

Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age.

RATIONALE: Apnea of prematurity is a common condition that is usually treated with caffeine, an adenosine receptor blocker that has powerful influences on the central nervous system. However, little is known about the long-term effects of caffeine on sleep in the developing brain. OBJECTIVES: We hypothesized that neonatal caffeine use resulted in long-term abnormalities in sleep architecture and breathing during sleep. METHODS: A total of 201 ex-preterm children aged 5-12 years who participated as neonates in a double-blind, randomized, controlled clinical trial of caffeine versus placebo underwent actigraphy, polysomnography, and parental sleep questionnaires. Coprimary outcomes were total sleep time on actigraphy and apnea-hypopnea index on polysomnography. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in primary outcomes between the caffeine group and the placebo (adjusted mean difference of -6.7 [95% confidence interval (CI) = -15.3 to 2.0 min]; P = 0.13 for actigraphic total sleep time; and adjusted rate ratio [caffeine/placebo] for apnea-hypopnea index of 0.89 [95% CI = 0.55-1.43]; P = 0.63). Polysomnographic total recording time and total sleep time were longer in the caffeine group, but there was no difference in sleep efficiency between groups. The percentage of children with obstructive sleep apnea (8.2% of caffeine group versus 11.0% of placebo; P = 0.22) or elevated periodic limb movements of sleep (17.5% in caffeine group versus 11% in placebo group) was high, but did not differ significantly between groups. CONCLUSIONS: Therapeutic neonatal caffeine administration has no long-term effects on sleep duration or sleep apnea during childhood. Ex-preterm infants, regardless of caffeine status, are at risk for obstructive sleep apnea and periodic limb movements in later childhood.

Pulse transit time as a surrogate measure of changes in systolic arterial pressure in children during sleep.

Pulse transit time has been proposed as a surrogate measure of systolic arterial pressure, as it is dependent upon arterial stiffness. Past research has shown that pulse transit time has a significant inverse relationship to systolic arterial pressure in adults; however, studies in children are limited. This study aimed to explore the relationship between systolic arterial pressure and pulse transit time in children during sleep. Twenty-five children (13.1 ± 1.6 years, 48% male) underwent overnight polysomnography (PSG) with a simultaneous recording of continuous systolic arterial pressure and photoplethysmography. Pulse transit time was calculated as the time delay between the R-wave peak of the electrocardiogram (ECG) to the 50% point of the upstroke of the corresponding photoplethysmography waveform; 500 beats of simultaneous systolic arterial pressure and pulse transit time were analysed in each sleep stage for each child. Pulse transit time was normalized to each subject's mean wake pulse transit time. The ability of pulse transit time to predict systolic arterial pressure change was determined by linear mixed-effects modelling. Significant negative correlations between pulse transit time and systolic arterial pressure were found for individual children for each sleep stage [mean correlations for cohort: non-rapid eye movement (NREM) sleep 1 and 2 r = -0.57, slow wave sleep (SWS) r = -0.76, REM r = -0.65, P < 0.01 for all]. Linear mixed-model analysis demonstrated that changes in pulse transit time were a significant predictor of changes in systolic arterial pressure for each sleep stage (P < 0.001). The model of pulse transit time-predicted systolic arterial pressure closely tracked actual systolic arterial pressure changes over time. This study demonstrated that pulse transit time was accurate in tracking systolic arterial pressure changes over time. Thus, the use of pulse transit time as a surrogate measure of changes in systolic arterial pressure in children is a valid, non-invasive and inexpensive method with many potential applications.

Pediatric Sleep Survey Instrument--a screening tool for sleep disordered breathing.

PURPOSE: The aim of this study was to assess the construct validity and clinical application of the Pediatric Sleep Survey Instrument (PSSI) as a tool to screen for sleep disordered breathing (SDB) in children. METHODS: Polysomnography (PSG) outcomes and PSSI subscale scores were compared between a clinical cohort (N = 87, 5-10 years, 62 M/25 F) and a nonsnoring community sample (N = 55, 5-10 years, 28 M/27 F). Group comparisons assessed the ability of the PSSI subscales to discriminate between the clinical and community cohorts. Receiver operating characteristic (ROC) curves assessed construct validity, with the Apnea/Hypopnea Index (AHI) >5 events/h, OSA-18 score >60, and Pediatric Daytime Sleepiness Scale (PDSS) above the 70th percentile as the target references. RESULTS: The clinical group had more respiratory events, respiratory-related arousals, fragmented sleep, and lower oxygen saturation nadir than the community group (p < 0.001 for all). PSSI subscale scores of Morning Tiredness, Night Arousals, SDB, and Restless Sleep were higher (p < 0.001 for all) in the clinical cohort, confirming the tool's ability to identify clinically relevant sleep problems. ROC curves confirmed the diagnostic accuracy of the SDB subscale against an AHI > 5 events/h (area under the curve (AUC) = 0.7), an OSA-18 score >60 (AUC = 0.7), and a PDSS score in the 70th percentile (AUC = 0.8). The Morning Tiredness subscale accurately predicted a PDSS score in the 70th percentile (AUC = 0.8). A cutoff score of 5 on the SDB subscale showed a sensitivity of 0.94 and a specificity of 0.76, correctly identifying 77 and 100 % of the clinical and community cohorts, respectively. CONCLUSION: The PSSI Sleep Disordered Breathing subscale is a valid tool for screening SDB and daytime sleepiness in children aged 5-10 years.

Circadian rhythm disorders among adolescents: assessment and treatment options.

Delayed sleep phase disorder (DSPD) - a circadian rhythm sleep disorder - is most commonly seen in adolescents. The differential diagnosis between DSPD and conventional psychophysiological insomnia is important for correct therapeutic intervention. Adolescent DSPD sleep duration is commonly 9 hours or more. Depression may be comorbid with DSPD. DSPD has a negative impact on adolescent academic performance. DSPD treatments include bright light therapy, chronotherapeutic regimens, and administration of melatonin as a chronobiotic (as distinct from a soporific). Attention to non-photic and extrinsic factors including healthy sleep parameters is also important to enable better sleep and mood outcomes in adolescents.

Psychological consequences of a diagnosis of infertility in men: a systematic analysis.

Almost half of infertility cases involve male infertility. Understanding the consequence of a diagnosis of male infertility, as a sole or partial contributor to the couples' infertility, to the mental health of men is required to ensure clinical care meets their psychological needs. The aim of this systematic analysis was to synthesize the evidence regarding whether men diagnosed with male factor infertility experience greater psychological distress than (1) men described as fertile and (2) men in couples with other infertility diagnoses. Online databases were searched using a combination of Medical Subject Headings (MeSH) headings and keywords relating to male infertility and psychological distress. The search yielded 1016 unique publications, of which 23 were included: 8 case-control, 14 prospective cohort, and 1 data linkage studies. Seven aspects of psychological distress were identified depression, anxiety, self-esteem, quality of life, fertility-related stress, general psychological stress or well-being, and psychiatric conditions. Case-control studies reported that men with male factor infertility have more symptoms of depression, anxiety and general psychological distress, worse quality of some aspects of life, and lower self-esteem than controls. When men with male factor infertility were compared to men in couples with other causes of infertility, there were few differences in the assessed aspects of psychological distress. Despite methodological limitations within the studies, this systematic analysis suggests that the experience of infertility, irrespective of its cause, negatively affects men's mental health and demonstrates the need for assisted reproduction technology (ART) providers to consider men undergoing assisted reproduction as individuals with their own unique support needs.

Differences in parental attitudes towards sleep and associations with sleep-wake patterns in Caucasian and Southeast Asian school-aged children in Australia.

Caucasian (N = 47) and Southeast (SE) Asian (N = 36) families completed a questionnaire on their attitudes toward sleep, as well as a 7-day sleep diary for their children aged 5 to 11 years. Cultural differences were found in the perceived importance of sleep, particularly compared to homework and belief of how much sleep a child needs. Differences were also found in sleep-wake behaviors and amount of time spent on homework, with SE Asian children reporting a shift in sleep timing and increased homework load compared to Caucasian counterparts. Parental attitudes toward sleep, perception of sleep need, and homework load were not associated with the regulation of actual sleep behaviors in children, regardless of cultural heritage.

The sensitivity of a PDA-based psychomotor vigilance task to sleep restriction in 10-year-old girls.

The impact of sleep restriction on sustained attention in children has not been well quantified. To address this shortcoming, this study tested the sensitivity of a 5-min personal digital assistant-psychomotor vigilance task (PDA-PVT) to sleep restriction in 14 female children [mean (SD) age = 10.6 +/- 0.3 years]. The children underwent PDA-PVT trials at regular intervals both before and after a sleep restriction (5 h time-in-bed) and a control (10 h time-in-bed) condition. Sleep restriction was associated with longer mean response times and increased number of lapses. These results are consistent with findings in the adult literature suggesting an association between inadequate sleep and impaired functioning. In conclusion, the 5-min PDA-PVT is sensitive to sleep restriction in pre-adolescent female children supporting the utility of the PDA-PVT for examining the impact of sleep deprivation on daytime functioning in children.

Impact of high-frequency email and instant messaging (E/IM) interactions during the hour before bed on self-reported sleep duration and sufficiency in female Australian children and adolescents.

INTRODUCTION: Social media interactions via email and instant messaging (E/IM) are common in children and adolescents and may lead to insufficient sleep. This study investigated associations between high-frequency E/IM use to interact with peers, perceived insufficient sleep, and reduced time in bed (TIB) in female children and adolescents. METHODS: The Children's Report of Sleep Patterns was completed by 189 female primary and secondary school students (8-16 years old). Responses were categorized as binary variables (high-frequency use vs not high-frequency use; right amount of sleep vs too little sleep), and TIB was calculated from bed and wake times for the previous 24 hours. RESULTS: High-frequency social media interactions using E/IM during the hour before bed were significantly associated with perceived insufficient sleep (odds ratio [confidence interval]: 2.68 [1.39-5.17]) but not with reduced TIB (-19.07 [-40.02 to 1.89]). CONCLUSIONS: High-frequency social media interactions using E/IM in the hour before bed are a potentially modifiable risk factor for insufficient sleep in female students. Strategies to reduce nighttime usage may improve sleep in children and adolescents.

The impact of central and obstructive respiratory events on cerebral oxygenation in children with sleep disordered breathing.

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.

Age and autonomic control, but not cerebral oxygenation, are significant determinants of EEG spectral power in children.

STUDY OBJECTIVES: Sleep disordered breathing (SDB) in children has significant effects on daytime functioning and cardiovascular control; attributed to sleep fragmentation and repetitive hypoxia. Associations between electroencephalograph (EEG) spectral power, autonomic cardiovascular control and cerebral oxygenation have been identified in adults with SDB. To date, there have been no studies in children. We aimed to assess associations between EEG spectral power and heart rate variability as a measure of autonomic control, with cerebral oxygenation in children with SDB. METHODS: One hundred sixteen children (3-12 years) with SDB and 42 controls underwent overnight polysomnography including measurement of cerebral oxygenation. Power spectral analysis of the EEG derived from C4-M1 and F4-M1, quantified delta, theta, alpha, and beta waveforms during sleep. Multiple regression tested whether age, SDB severity, heart rate (HR), HR variability (HRV), and cerebral oxygenation were determinants of EEG spectral power. RESULTS: There were no differences in EEG spectral power derived from either central or frontal regions for any frequency between children with different severities of SDB so these were combined. Age, HR, and HRV low frequency power were significant determinants of EEG spectral power depending on brain region and sleep stage. CONCLUSION: The significant findings of this study were that age and autonomic control, rather than cerebral oxygenation and SDB severity, were predictive of EEG spectral power in children. Further research is needed to elucidate how the physiology that underlies the relationship between autonomic control and EEG impacts on the cardiovascular sequelae in children with SDB.

Establishing normal values for pediatric nighttime sleep measured by actigraphy: a systematic review and meta-analysis.

Background: Despite the widespread use of actigraphy in pediatric sleep studies, there are currently no age-related normative data. Objectives: To systematically review the literature, calculate pooled mean estimates of actigraphy-derived pediatric nighttime sleep variables and to examine the magnitude of change with age. Methods: A systematic search was performed across eight databases of studies that included at least one actigraphy sleep variable from healthy children aged 0-18 years. Data suitable for meta-analysis were confined to ages 3-18 years with seven actigraphy variables analyzed using random effects meta-analysis and meta-regression performed using age as a covariate. Results: In total, 1334 articles did not meet inclusion criteria; 87 had data suitable for review and 79 were suitable for meta-analysis. Pooled mean estimates for overnight sleep duration declined from 9.68 hours (3-5 years age band) to 8.98, 8.85, 8.05, and 7.4 for age bands 6-8, 9-11, 12-14, and 15-18 years, respectively. For continuous data, the best-fit (R2 = 0.74) equation for hours over the 0-18 years age range was 9.02 - 1.04 × [(age/10)^2 - 0.83]. There was a significant curvilinear association between both sleep onset and offset with age (p < .001). Sleep latency was stable at 19.4 min per night. There were significant differences among the older age groups between weekday and weekend/nonschool days (18 studies). Total sleep time in 15-18 years old was 56 min longer, and sleep onset and offset almost 1 and 2 hours later, respectively, on weekend or nonschool days. Conclusion: These normative values have potential application to assist the interpretation of actigraphy measures from nighttime recordings across the pediatric age range, and aid future research.

Overweight and obese children with sleep disordered breathing have elevated arterial stiffness.

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.