An Economic Evaluation of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children who require specialist outpatient care typically wait substantial periods during which their condition may progress, making treatment more difficult and costly. Timely and effective therapy during this period may reduce the need for lengthy specialist care. This study evaluated the cost-effectiveness of an individualized, evidence-informed, web-based program for children with urinary incontinence awaiting a specialist appointment (Electronic Advice and Diagnosis Via the Internet following Computerized Evaluation [eADVICE]) compared to usual care. eADVICE was supervised by a primary physician and delivered by an embodied conversational agent. MATERIALS AND METHODS: A trial-based cost-effectiveness analysis was performed from the perspective of the health care funder as a substudy of eADVICE, a multicenter, waitlist-controlled, randomized trial. Outcomes measures were incremental cost per incremental change in continence status and quality of life on an intention-to-treat basis. Uncertainty was examined using cost-effectiveness planes, scenarios, and 1-way sensitivity analyses. Costs were valued in 2021 Australian dollars. RESULTS: The use of eADVICE was found to be cost saving and beneficial (dominant) over usual care, with a higher proportion of children dry over 14 days at 6 months (risk difference 0.13; 95%CI 0.02-0.23, P = .03) and mean health care costs reduced by $188 (95%CI $61-$315) per participant. CONCLUSIONS: An individualized, evidence-informed, web-based program delivered by an embodied conversational agent is likely cost saving for children with urinary incontinence awaiting a specialist appointment. The potential economic impact of such a program is favorable and substantial, and may be transferable to outpatient clinic settings for other chronic health conditions.

A Randomized Controlled Trial of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children referred to specialist outpatient clinics by primary care providers often have long waiting times before being seen. We assessed whether an individualized, web-based, evidence-informed management support for children with urinary incontinence while waiting reduced requests for specialist appointments. MATERIALS AND METHODS: A multicenter, waitlisted randomized controlled trial was conducted for children (5-18 years) with urinary incontinence referred to tertiary pediatric continence clinics. Participants were randomized to the web-based eHealth program electronic Advice and Diagnosis Via the Internet following Computerized Evaluation (eADVICE), which used an embodied conversational agent to engage with the child at the time of referral (intervention) or 6 months later (control). The primary outcome was the proportion of participants requesting a clinic appointment at 6 months. Secondary outcomes included persistent incontinence, and the Paediatric incontinence Questionnaire (PinQ) score. RESULTS: From 2018 to 2020, 239 children enrolled, with 120 randomized to eADVICE and 119 to the control arm. At baseline, participants' mean age was 8.8 years (SD 2.2), 62% were males, mean PinQ score was 5.3 (SD 2.2), 36% had daytime incontinence, and 97% had nocturnal enuresis. At 6 months, 78% of eADVICE participants vs 84% of controls requested a clinic visit (relative risk 0.92, 95% CI 0.79, 1.06, P = .3), and 23% eADVICE participants vs 10% controls were completely dry (relative risk 2.23, 95% CI 1.10, 4.50, P = .03). The adjusted mean PinQ score was 3.5 for eADVICE and 3.9 for controls (MD -0.37, 95% CI -0.71, -0.03, P = .03). CONCLUSIONS: The eADVICE eHealth program for children awaiting specialist appointments doubled the proportion who were dry at 6 months and improved quality of life but did not reduce clinic appointment requests.

Choline-acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the human infant dorsal motor nucleus of the Vagus (DMNV), and alterations according to sudden infant death syndrome (SIDS) category.

Amongst other molecules, the cholinergic system consists of choline-acetyltransferase (ChAT, - synthesis enzyme), acetylcholinesterase (AChE - primary hydrolysis enzyme), and butyrylcholinesterase (BuChE - secondary hydrolysis enzyme). In the brainstem, the Dorsal Motor Nucleus of The Vagus (DMNV) has high cholinergic expression and is a region of interest in the neuropathology of sudden infant death syndrome (SIDS). SIDS is the unexpected death of a seemingly healthy infant, but postmortem brainstem abnormalities suggesting altered cholinergic regulation have been found. This study aimed to determine the percentage of positive ChAT and AChE neurons within the infant DMNV through immunohistochemistry at the three levels of the brainstem medulla (caudal, intermediate, and rostral), to investigate whether the proportion of neurons positive for these enzymes differs amongst the diagnostic subgroups of SIDS compared to those with an explained cause of Sudden unexpected death in infancy (eSUDI), and whether there were any associations with SIDS risk factors (male gender, cigarette smoke exposure, co-sleeping/bed sharing, and prone sleeping). Results showed that ChAT-positive neurons were lower in the rostral DMNV in the SIDS II cohort, and within the caudal and intermediate DMNV of infants who were exposed to cigarette smoke. These findings suggest altered cholinergic regulation in the brainstem of SIDS infants, with potential contribution of cigarette smoke exposure, presumably via the nicotinic acetylcholinergic receptor system.

Immunohistochemistry for acetylcholinesterase and butyrylcholinesterase in the dorsal motor nucleus of the vagus (DMNV) of formalin-fixed, paraffin-embedded tissue: comparison with reported literature.

The majority of research regarding the expression of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the brain has been conducted using histochemistry to identify enzymatic activity in frozen fixed tissue. However, retrospective human neurochemistry studies are generally restricted to formalin-fixed, paraffin-embedded (FFPE) tissues that are not suitable for histochemical procedures. The availability of commercially available antibody formulations provides the means to study such tissues by immunohistochemistry (IHC). In this study, we optimised IHC conditions for evaluating the expression of AChE and BuChE in the brainstem, focusing on the dorsal motor nucleus of the vagus, in human and piglet FFPE tissues, using commercially available antibodies. Our results were compared to published reports of histochemically determined AChE and BuChE expression. We varied antibody concentrations and antigen retrieval methods, and evaluated different detection systems, with the overall aim to optimise immunohistochemical staining. The primary findings, consistent across both species, are: (1) AChE and BuChE expression dominated in the neuronal somata, specifically in the neuronal cytoplasm; and (2) no change in the protocol resulted in axonal/neuropil expression of AChE. These results indicate that IHC is a suitable tool to detect AChE and BuChE in FFPE tissue using commercial antibodies, albeit the staining patterns obtained differed from those using histochemistry in frozen tissue. The underlying cause(s) for these differences are discussed in detail and may be associated with the principal components of the staining method, the antibody protein target and/or limitations to the detection of epitopes by tissue fixation.

The management of upper airway obstruction in Pierre Robin Sequence.

Pierre Robin Sequence (PRS) is defined by a constellation of characteristics including micrognathia, glossoptosis and airway obstruction. PRS can occur in isolation or can be associated with syndromes and another anomalies. Airway obstruction and feeding difficulties are the major presenting issues, and the severity of the condition ranges from mild, with minimal to no symptoms, to severe, with overt obstruction resulting in apnoeas, severe respiratory distress and cyanosis. The presence of airway obstruction can result in obstructive sleep apnoea and abnormalities in gas exchange, as well as exacerbation of already present feeding difficulties and failure to thrive, secondary to mismatch of caloric intake to energy usage associated with increased effort of breathing. Management of airway obstruction for infants with PRS varies between centres. This paper explores the surgical and non-surgical management options available, their effectiveness and pitfalls in children with PRS. Despite the pros and cons of each management option, it is evident that resource availability and multidisciplinary clinical support are key factors to successful management.

Sleep in children and young adults with cystic fibrosis.

Large gains have been made in the management of respiratory diseases associated with cystic fibrosis (CF). Initial studies evaluating sleep issues in CF focused on respiratory problems of nocturnal hypoxia, alveolar hypoventilation and risk of airway obstruction from nasal polyps with treatment evaluations including long term oxygen therapy or noninvasive ventilation in case of nocturnal hypercapnia. More recent studies include patients whose lung function is better preserved, and have permitted more focus on sleep patterns and sleep quality. This literature identified that reduced sleep duration and poor sleep quality are common and may be explained by chronic pain and cough, frequent stools, gastro-oesophageal reflux, nasal obstruction or sinusitis, and drugs such as corticosteroids or beta-agonists. In the teenage years, poor sleep hygiene, sleep debt and poor sleep quality are associated with depression, poor academic performance, less physical activity, and a decrease in quality of life. Restless leg syndrome also seems to be common in adult patients with CF. These sleep problems seem more important in patients with a low lung function but may also be observed in patients with preserved lung function. The consequences of poor sleep may potentially exaggerate the multi-organ morbidity of CF, such as pain, inflammation, susceptibility to infection, and glucose intolerance, but these aspects are largely under-evaluated. Sleep should be evaluated on a routine basis in CF and prospective studies assessing the benefits of interventions aiming at improving sleep duration and sleep quality urgently needed.

Genes involved in paediatric apnoea and death based on knockout animal models: Implications for sudden infant death syndrome (SIDS).

The mechanism of death in Sudden infant death syndrome (SIDS) remains unknown but it is hypothesised that cardiorespiratory failure of brainstem origin results in early post-natal death. For a subset of SIDS infants, an underlying genetic cause may be present, and genetic abnormalities affecting brainstem respiratory control may result in abnormalities that are detectable before death. Genetic knockout mice models were developed in the 1990s and have since helped to elucidate the physiological roles of a number of genes. This systematic review aimed to identify which genes, when knocked out, result in the phenotypes of abnormal cardiorespiratory control and/or early post-natal death. Three major genes were identified: Pet1- a serotonin transcription factor, the neurotrophin pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor (PAC1). Knockouts targeting these genes had blunted hypercapnic and/or hypoxic responses and early post-natal death. The hypothesis that these genes have a role in SIDS is supported by their being identified as abnormal in SIDS cohorts. Future research in SIDS cohorts will be important to determine whether these genetic abnormalities coexist and their potential applicability as biomarkers.

Sudden Unexpected Death in Infancy [SUDI]: What the clinician, pathologist, coroner and researchers want to know.

The loss of an apparently healthy infant is confronting for any family, puzzling for a clinician and challenging for the pathologist charged with the task of demonstrating a cause for death. The term "cot death" evolved to "sudden infant death syndrome" [SIDS] and now "sudden unexpected death in infancy [SUDI]" as the epidemiology and pathology of infant death changed. Community interventions were successful in changing sleep practices for young babies. The current research focus is on understanding genetic predispositions to unexpected death in early childhood. Whilst much has been achieved in reducing the infant mortality rate from SUDI by between 50%, and 80% in some countries, over the last 30 years, there remain challenges for improving rates of accurate diagnosis and reaching out to more vulnerable families with clearly modifiable risk factors for SUDI. These challenges directly involve the clinician through taking a systematic and detailed history and better standardised death scene evaluations with specifically accredited assessors. Better knowledge regarding circumstances of SUDI cases will help Coroners and researchers provide answers for grieving families now, and in the future contribute to further reductions in the rate of SUDI in communities across the world.

Regional oxygenation, perfusion and body and/or head position: Are preterm infants adversely impacted? A systematic review.

This review addresses regional oxygenation and perfusion changes for preterm infants and changes with body position, with or without head rotation. Future directions for improving neurodevelopmental and clinical outcomes are suggested. The MEDLINE, Embase and Scopus databases were searched up to July 2021. Fifteen out of 470 studies met the inclusion criteria. All were prospective, observational studies with a moderate risk of bias. Significant variation was found for the baseline characteristics of the cohort, postnatal ages, and respiratory support status at the time of monitoring. When placed in a non-supine position, preterm infants showed a transient reduction in cardiac output and stroke volume without changes to heart rate or blood pressure. No studies reported on long-term neurodevelopmental outcomes. Overall, side lying or prone position does not appear to adversely affect regional, and specifically cerebral, oxygenation or cerebral perfusion. The effect of head rotation on regional oxygenation and perfusion remains unclear.

Cheyne-stokes respiration in children with heart failure.

Cheyne-Stokes respiration (CSA-CSR) is a form of central sleep apnea characterized by alternating periods of hyperventilation and central apneas or hypopneas. CSA-CSR develops following a cardiac insult resulting in a compensatory increase in sympathetic activity, which in susceptible patients causes hyperventilation and destabilizes respiratory control. The physiological changes that occur in CSA-CSR include hyperventilation, a reduced blood gas buffering capacity, and circulatory delay. In adults, 25% to 50% of patients with heart failure are reported to have CSA-CSR. The development of CSA-CSR in this group of patients is considered a poor prognostic sign. The prevalence, progression, and treatment outcomes of CSA-CSR in children remain unclear with only 11 children being described in the literature. The lack of data is possibly not due to the paucity of children with severe heart failure and CSA-CSR but because they may be under-recognized, compounded by the absence of routine polysomnographic assessment of children with moderate to severe heart failure. Building on much broader experience in the diagnosis and management of CSA-CSR in adult sleep medicine and our limited experience in a pediatric quaternary center, this paper will discuss the prevalence of CSA-CSR, its' treatment options, outcomes in children, and the potential future direction for research in this understudied area of pediatric sleep medicine.

Expression of reelin with age in the human hippocampal formation.

Reelin plays a key role in neuronal migration and lamination in the cortex and hippocampus. Animal studies have shown that reelin expression decreases with age. The aim of this study was to evaluate the expression of reelin in all layers of the human hippocampal formation across three age groups. We used immunohistochemistry in formalin fixed and paraffin embedded hippocampal tissue from infants (1-10 months; n = 9), children (4-10 years; n = 4), and adults (45-60 years; n = 6) to stain for reelin. Expression was quantified (measured as the number of positive reelin cells/mm2 ) in the granule cell layer of the dentate gyrus (DG), the molecular layer of the dentate gyrus (ML), the hippocampal fissure (HF), stratum lacunosum moleculare (SLM), CA4/Hilus and the stratum pyramidale layer of CA3, CA2, and CA1. Expression of reelin was highest in the HF irrespective of age, followed by the SLM and ML. Minimal to no expression was seen in the stratum pyramidale layer of CA1-3. With age, reelin expression decreased and was statistically significant from infancy to childhood in the HF (p = .02). This study confirms that reelin expression decreases with age in the human hippocampus, and shows for the first time that the major decrease occurs between infancy and early childhood.

Cerebral Oxygenation and Perfusion when Positioning Preterm Infants: Clinical Implications.

OBJECTIVES: To evaluate cerebral tissue oxygenation (cTOI) and cerebral perfusion in preterm infants in supine vs prone positions. STUDY DESIGN: Sixty preterm infants, born before 32 weeks of gestation, were enrolled; 30 had bronchopulmonary dysplasia (BPD, defined as the need for respiratory support and/or supplemental oxygen at 36 weeks of postmenstrual age). Cerebral perfusion, cTOI, and polysomnography were measured in both the supine and prone position with the initial position being randomized. Infants with a major intraventricular hemorrhage or major congenital abnormality were excluded. RESULTS: Cerebral perfusion was unaffected by position or BPD status. In the BPD group, the mean cTOI was higher in the prone position compared with the supine position by a difference of 3.27% (P = .03; 95% CI 6.28-0.25) with no difference seen in the no-BPD group. For the BPD group, the burden of cerebral hypoxemia (cumulative time spent with cTOI <55%) was significantly lower in the prone position (23%) compared with the supine position (29%) (P < .001). In those without BPD, position had no effect on cTOI. CONCLUSIONS: In preterm infants with BPD, the prone position improved cerebral oxygenation and reduced cerebral hypoxemia. These findings may have implications for positioning practices. Further research will establish the impact of position on short- and long-term developmental outcomes.

Ventilatory support at home for children: A joint position paper from the Thoracic Society of Australia and New Zealand/Australasian Sleep Association.

The goal of this position paper on ventilatory support at home for children is to provide expert consensus from Australia and New Zealand on optimal care for children requiring ventilatory support at home, both non-invasive and invasive. It was compiled by members of the Thoracic Society of Australia and New Zealand (TSANZ) and the Australasian Sleep Association (ASA). This document provides recommendations to support the development of improved services for Australian and New Zealand children who require long-term ventilatory support. Issues relevant to providers of equipment and areas of research need are highlighted.

Cognitive parameters in children with mild obstructive sleep disordered breathing.

PURPOSE: Sleep disordered breathing (SDB) in children is commonly described as a continuum from primary snoring (PS) to obstructive sleep apnea (OSA), based on apnea indices from polysomnography (PSG). This study evaluated the difference in neurocognitive and behavioral parameters, prior to treatment, in symptomatic pre-school children with PSG-diagnosed OSA and PS. METHODS: All children had positive Pediatric Sleep Questionnaire (PSQ) results and were deemed suitable for adenotonsillectomy by an ENT surgeon. Neurocognitive and behavioral data were analyzed in pre-school children at recruitment for the POSTA study (The Pre-School OSA Tonsillectomy Adenoidectomy Study). Data were compared between PS and OSA groups, with Obstructive Apnea-Hypopnea Index, OAHI < 1/h or 1-10/h, respectively. RESULTS: Ninety-one children were enrolled, including 52 with OSA and 39 with PS. Distribution of IQ (using Brief Intellectual Ability, BIA) was slightly skewed towards higher values compared with the reference population. No significant differences were found in neurocognitive or behavioral parameters for children with OSA versus those with PS. DISCUSSION: Neurocognitive and behavioral parameters were similar in pre-school children symptomatic for OSA, regardless of whether or not PSG diagnosed PS or OSA. Despite having identical symptoms, children with PS on PSG are often treated conservatively, whereas those with OSA on PSG are considered for adenotonsillectomy. This study demonstrates that, regardless of whether or not PS or OSA is diagnosed on PSG, symptoms, neurocognition, and behavior are identical in these groups. We conclude that symptoms and behavioral disturbances should be considered in addition to OAHI when determining the need for treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials registration number ACTRN12611000021976.

Relationship between sleep respiration, architecture and childhood enuresis: Correlates between polysomnography and questionnaire.

AIM: Nocturnal enuresis (NE) and sleep-disordered breathing (SDB) are common in childhood. While the two disorders are linked, those links are still being clarified. METHODS: This study compared sleep profiles and enuresis-related behaviours between children with NE and those without, who were referred to a tertiary sleep unit with suspected SDB, using the combination of polysomnography (PSG) and questionnaire. Continuous numerical data were analysed after adjusting for body mass index z-score. RESULTS: The study included 52 Children (39 boys, 13 girls) aged 5-14 years. Twenty-one had enuresis (10 monosymptomatic enuresis (MNE) and 11 non-monosymptomatic enuresis (NMNE)) and 31 did not have enuresis. The majority had comorbidities. On PSG, all children with NE had moderate obstructive sleep apnoea (OSA) compared to the control group which were of mild OSA. Children with NMNE had a higher percentage time in stage-3 non-REM sleep when compared to the non-enuretic and MNE groups (P < 0.05). On the questionnaire, more parents of the NE groups reported that their child was 'difficult to wake in the morning' (P < 0.05). CONCLUSION: In this heterogeneous population referred for suspected SDB, children with NE had moderate OSA, yet those with MNE had increased arousals and more often report difficulty waking than children with suspected SDB who do not wet, while children with NMNE exhibit changes in sleep architecture suggesting deeper sleep. These differences may impact treatment choices for children with enuresis.

Motivation for change in the health care of children with developmental disabilities: Pilot continuing professional development-quality improvement project.

AIM: People with developmental disabilities (DDs) experience significant barriers accessing and receiving optimal health care resulting in poorer health-care outcomes. Continuing professional development (CPD) represents an effective means to alter health-care staff behaviour to improve the care of people with DDs. However, given the scepticism regarding the effectiveness of certain CPD models' ability to alter learner's workplace behaviour, the current pilot study developed and determined the feasibility of a novel CPD programme aimed at improving the health care provided to children with DDs. METHODS: Motivation for Change (MFC) is a novel CPD programme based on empirically based behaviour and educational strategies including motivational interviewing, flipped classroom and process mapping. It utilises input of patients, practitioners, and family members during administration of the programme. MFC was administered with 14 staff members in a Sydney Children's Hospital Sleep service. RESULTS: After MFC engagement, staff reported significant improvements in their knowledge of behavioural characteristics of children with DDs, the difficulties they face, how best to support them within the learner's work setting and confidence in working with children with DDs. There was a non-significant decline in their reported need for further training and expressed high level of satisfaction with the MFC programme. CONCLUSION: MFC represents a feasible means of providing CPD to health-care staff but further research is needed to determine objective clinical behavioural change. Evaluation of the impact on patient health outcomes, parent/child satisfaction, staff sustainability and overall system functioning is also needed. It may represent an effective model of CPD for other targets of health-care improvement.

Sleep disordered breathing (SDB) in neonates and implications for its long-term impact.

Sleep-disordered breathing (SDB) is a significant cause of morbidity in neonates and young infants. SDB occurs more commonly in preterm infants and in neonates with underlying syndromes. Recent evidence shows that infants with obstructive sleep apnoea (OSA) or SDB have greater health care resource utilization, including longer hospital stay. Management of SDB includes non-invasive ventilation or surgical interventions tailored to the patient. Screening high risk newborns should allow for early diagnosis and timely therapeutic intervention for this population. However, the thresholds for diagnosing SDB and for guiding and implementing treatment in neonates remain unclear. A collective effort is required to standardize the practice worldwide. This article will discuss neonatal sleep physiology and characteristics of neonatal sleep, with an emphasis on the epidemiology and diagnosis of SDB in neonates and its implications for long term outcomes.

The α3 and α4 nicotinic acetylcholine receptor (nAChR) subunits in the brainstem medulla of sudden infant death syndrome (SIDS).

SIDS occurs in early infancy and predominantly during a sleep period. Abnormalities in nicotine receptor binding and in the expression of the nicotinic acetylcholine receptor (nAChR) subunits α7 and ß2 have been reported in the brainstem of SIDS infants. This study focuses on the α3 and α4 nAChR subunits as α3 is important for early postnatal survival while α4 is crucial for nicotine-elicited antinociception and sleep-wake cycle regulation. Tissue from the rostral medulla of infants who died with a known cause of death (eSUDI, n = 7), and from SIDS classified as SIDS I (n = 8) and SIDS II (n = 27), was immunohistochemically stained for the α3 and α4 nAChR subunits and quantified in 9 nuclei comparing amongst these groups. The association with risk factors of sex, cigarette smoke exposure, upper respiratory tract infection (URTI), prone sleeping and bedsharing was also evaluated. Results showed that only α4 changes (increase) were evident in SIDS, occurring in the hypoglossal and cuneate nuclei of SIDS II infants and the nucleus of the spinal trigeminal tract of SIDS I infants. Amongst the SIDS infants, cigarette smoke exposure was only associated with decreased α4 in cribriform fibre tracts, while sex and bedsharing were associated with increases in α3 in the dorsal motor nucleus of the vagus and solitary nucleus, respectively. Combined, these findings suggest that abnormalities in endogenous acetylcholine synthesis and regulation may underlie the altered α3 and α4 nAChR subunit expressions in the SIDS brainstem medulla since the changes were not related to cigarette smoke exposure.

Cell death in the human infant central nervous system and in sudden infant death syndrome (SIDS).

The brainstem has been a focus of sudden infant death syndrome (SIDS) research with amassing evidence of increased neuronal apoptosis. The present study extends the scope of brain regions examined and determines associations with known SIDS risk factors. Immunohistochemical expression of cell death markers, active caspase-3 and TUNEL, was studied in 37 defined brain regions in infants (aged 1-12 months) who died suddenly and unexpectedly (SUDI). A semi-quantitative mean score of marker expression was derived for each region and scores compared between three SUDI subgroups: explained SUDI (eSUDI; n = 7), SIDS I (n = 8) and SIDS II (n = 13). In eSUDI, active caspase-3 scores were highest in several nuclei of the rostral medulla, and lowest in the hypothalamus and cerebellar grey matter (GM). TUNEL was highest in regions of the hippocampus and basal ganglia, and lowest in the thalamus and cerebellar GM. TUNEL scores were higher in SIDS II compared to eSUDI in the amygdala (p = 0.03) and 5/9 nuclei in the rostral medulla (p = 0.04 - 0.01), and higher in SIDS II compared to SIDS I in the amygdala (p < 0.01), putamen (p = 0.01), lentiform nucleus (p = 0.03) and parietal (p = 0.03) and posterior frontal (p = 0.02) cortex. Active caspase-3 was greater in the hypoglossal nucleus (p = 0.03) of SIDS I compared to eSUDI infants. Co-sleeping, cigarette smoke exposure and the presence of an upper respiratory tract infection in SIDS infants was associated with differences in marker expression. This study affirms the sensitivity of the brainstem medulla to cell death in SIDS, and highlights the amygdala as a new region of interest.

Biochemical markers of cardiac dysfunction in children with obstructive sleep apnoea (OSA).

OBJECTIVES: We explored relationships between biochemical markers and cardiac responses of children with and without obstructive sleep apnoea (OSA) during exercise. We hypothesised that serum markers of sympathetic nervous system activity and low-grade inflammation would correlate with cardiac responses to exercise in children with or without OSA. METHODOLOGY: The study included 40 of 71 children with previously characterised responses to cardiopulmonary exercise testing. Measures included serum cytokine levels using a multiplex bead-based assay (interleukins IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α and IFN-γ). Serum amyloid A (SAA) was quantified by nephelometry, and metanephrine/normetanephrine levels were measured by liquid chromatography, mass-spectroscopy. Comparisons were made between children with and without OSA, and with and without obesity. Relationships between biomarkers and various cardiac parameters were explored by linear regression. RESULTS: Amongst the 40 children in this study, OSA was present in 23. Compared to the 17 children without OSA, those with OSA had higher resting serum IL-6 levels compared to those without (median 3.22 pg/ml vs. 2.31, p < 0.05). Regarding correlations with cardiac function after adjusting for OSA, IL-8 negatively correlated to heart rate (HR) response following exercise (p = 0.03) and IFN-γ negatively correlated with Stroke Volume Index (SVI) (p = 0.03). Both metanephrine and normetanephrine levels positively correlated with SVI (p = 0.04, p = 0.047; respectively) and QI (p = 0.04, p = 0.04; respectively) during exercise when adjusting for OSA. CONCLUSIONS: Children with OSA have raised morning levels of serum IL-6. Separately, higher levels of IFN-γ and IL-8 and lower levels of metanephrine and normetanephrine related to poorer cardiac function during exercise.