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

doi:10.1016/j.smrv.2013.04.006

Sleep Medicine Reviews

Volume 18, Issue 2, April 2014, Pages 179-189

https://doi.org/10.1016/j.smrv.2013.04.006 Get rights and content

Summary

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

Introduction

Sleep disordered breathing (SDB) is a common disorder of childhood which ranges in severity from primary snoring (PS) to obstructive sleep apnoea (OSA). OSA affects 1–5% of children¹ and is characterised by prolonged partial and/or intermittent complete upper airway obstruction which disrupts normal ventilation and sleep patterns.² Occurring in 3–15% of children,³ PS describes snoring without associated gas exchange abnormalities or sleep disruption. Despite differences in aetiology, SDB in both adults and children is associated with a number of negative outcomes, including autonomic and cardiovascular dysfunction (for reviews, see4, 5, 6, 7, 8, 9, 10). In adults there is a dose–response relationship between SDB severity (including snoring) and blood pressure (BP) levels,¹¹ but this association is less well described in children. In this review we will explore the relationship between autonomic dysfunction and SDB in children, paying particular attention to the influences of disease severity and/or age.

Section snippets

Autonomic control of heart rate and blood pressure in healthy children

The autonomic nervous system (ANS) plays a major role in homeostasis. The two divisions of the ANS, the parasympathetic nervous system and sympathetic nervous system, innervate similar organs but have opposing effects, and thus different outcomes are effected by a shift in the balance of the two systems. The cardiovascular system in particular is highly regulated by the ANS. Parasympathetic neurons innervate the heart, whilst sympathetic efferents innervate blood vessels, the heart, kidneys and

Autonomic control of heart rate and blood pressure in children with sleep disordered breathing

Over the past 15 y, interest in the paediatric consequences of SDB has risen exponentially. In 2005, a meta-analysis conducted by Ng and colleagues⁵¹ found a significant association between SDB and raised BP, whilst another conducted by Zintzaras and colleagues⁵² in 2007 found no such evidence. In 2008, the meta-analysis of Ng and co-workers was updated; children with a high apnoea hypopnoea index (AHI) had a significantly higher risk of hypertension (odds ratio 3.15, 95% confidence interval

Conclusions

Children with SDB exhibit autonomic dysfunction which pervades both wakefulness and sleep. It is apparent that complex readjustment of autonomic homeostatic mechanisms occurs with adult and paediatric SDB alike. BP dysregulation, in the forms of increased BPV and elevated systolic and/or diastolic BP, have been repeatedly demonstrated in school-aged children and adolescents with SDB, alongside elevated generalised sympathetic activity and impairment of autonomic reflexes, particularly that of

Acknowledgements

The authors have no conflicts of interest to declare. Lauren Nisbet is supported by an Australian Postgraduate Award. Lisa Walter is supported by a project grant from the National Health and Medical Research Council of Australia and Rosemary Horne is a National Health and Medical Research Council of Australia Senior Research Fellow. All of the research was supported by the Victorian Government's Operational Infrastructure Support Program.

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Resolution of sleep disordered breathing (SDB) in typically developing children normalises heart rate variability (HRV), a measure of autonomic control, to that of non-snoring controls. Children with Down Syndrome (DS) have dampened heart rate variability (HRV) but the effect of treatment is not known. To assess the effect of improvement of SDB on autonomic control we compared HRV in children with DS whose SDB improved over 2 y, to those whose SDB did not improve.
24 children (3–19 y) had a baseline and follow-up polysomnographic study 2 y later. Improved SDB was defined as a reduction in obstructive apnea hypopnea index (OAHI) to ≤ 50% of baseline. Children were grouped into Improved (n = 12) and Unimproved (n = 12). Power spectral analysis of the ECG determined low frequency (LF), high frequency (HF) power and the LF/HF ratio. Seven children in the Improved and 2 in the Unimproved group were treated following the baseline study.
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The incidence of sleep-related breathing disorders is underestimated because polysomnography is required to confirm its diagnosis. The pediatric sleep questionnaire-sleep-related breathing disorder (PSQ-SRBD) scale is a self-reported questionnaire completed by a patient's guardian. There is no validated Arabic version of the PSQ-SRBD that can be used in the Arabic-speaking population. Therefore, we aimed to translate, validate, and culturally adapt the PSQ-SRBD scale. We also aimed to evaluate its psychometric properties for the diagnosis of obstructive sleep apnea (OSA).
The cross-cultural adaptation method consisted of the following steps: forward-backward translation, appraisal of a sample of 72 children (aged between 2 and 16 years) by an expert group, and performing Cronbach's alpha coefficient testing, Spearman's rank correlation coefficient testing, Wilcoxon signed-rank testing, and sign testing. The reliability of the Arabic version of the PSQ-SRBD scale was assessed using a test-retest comparison, and a factor analysis of the items was used to verify construct validity. For statistical purposes, p-values <0.05 were considered to indicate significance.
All subscales had adequate internal consistency: 0.799 for snoring and breathing, 0.69 for sleepiness, 0.711 for behavioral problems, and 0.805 for the entire questionnaire. Comparing questionnaire responses administered 2 weeks apart revealed no statistically significant difference in total scores between the two groups (p-values >0.05 by Spearman's rank correlation coefficient test for all domains) and also no statistical difference among 20 out of 22 questions independently (p-value >0.05 by sign test). A factor analysis conducted to assess the structure of the Arabic-SRBD scale revealed good correlational patterns. The mean score before surgery was 0.464 ± 0.166, and this changed to 0.185 ± 0.142 after surgery with a reduction of 0.278 ± 0.184 which was statistically significant (p < 0.001).
The Arabic version of the PSQ-SRBD scale is a valid tool for the assessment of pediatric OSA patients and can be used to follow-up patients after surgery. Future research will determine this translated questionnaire's applicability.
Pediatric obstructive sleep apnea syndrome and hypertension
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Pediatric Obstructive Sleep Apnea Syndrome (OSAS) has been shown to affect not only quality of sleep but overall health. OSAS is associated with the development of blood pressure dysregulation and hypertension (HTN).
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Children with Down syndrome have a very high risk for obstructive sleep apnea (OSA) attributable to multilevel obstruction. Adenotonsillectomy is only partially effective, and positive airway pressure use is met with noncompliance. Successful treatment of OSA in this population may lead to more meaningful improvements in quality of life and other outcomes than in children without Down syndrome. This chapter discusses the general approach to evaluating and managing upper airway obstruction in this high-risk population.
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Obstructive sleep apnea (OSA) is an established risk factor for high blood pressure (BP) in adults. However, it remains unclear whether the same association could be found in children and adolescents. Therefore, we conducted a systematic review and meta-analysis of observational studies to evaluate the associations between childhood OSA and BP outcomes. The review protocol was registered in PROSPERO (CRD42021225683). We performed a systematic literature search to identify relevant cross-sectional and longitudinal studies up to July 6, 2021. Of the 4902 identified articles, a total of 12 cross-sectional studies and 2 cohort studies were included in the final analyses. In the cross-sectional analyses, the mean systolic BP (SBP) were significantly higher in children with mild or moderate-to-severe OSA compared to the healthy controls, and these effects were more pronounced during the nighttime. In prospective studies, moderate-to-severe childhood OSA was associated with a risk of elevated SBP in adulthood (Mean difference = 4.02 mm Hg, 95% CI = 1.32 to 6.72). Taken together, our results suggest that moderate-to-severe childhood OSA is associated with a higher risk of adverse SBP outcomes. Early detection and treatment of OSA may promote cardiovascular health in children and adolescents and possibly in future adulthood.

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^∗: The most important references are denoted by an asterisk.

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Clinical reviewBlood pressure regulation, autonomic control and sleep disordered breathing in children

Summary

Introduction

Section snippets

Autonomic control of heart rate and blood pressure in healthy children

Autonomic control of heart rate and blood pressure in children with sleep disordered breathing

Conclusions

Acknowledgements

Prog Cardiovasc Dis

Sleep Med Rev

Lancet

J Pediatr

J Pediatr

J Auton Nerv Syst

J Pediatr

Chest

Sleep Med

Chest

J Pediatr

Int J Pediatr Otorhinolaryngol

Chest

Sleep Med

Diagnosis and management of childhood obstructive sleep apnea syndrome

Pediatrics

Standards and indications for cardiopulmonary sleep studies in children. American Thoracic Society

Am J Respir Crit Care Med

Epidemiology of pediatric obstructive sleep apnea

Proc Am Thorac Soc

Obstructive sleep apnea: implications for cardiac and vascular disease

J Am Med Assoc

Obstructive sleep apnoea and cardiovascular disease

Intern Med J

Circulation

Obstructive sleep apnoea – an update

Intern Med J

Snoring as part of a dose-response relationship between sleep-disordered breathing and blood pressure

Sleep

The sympathetic control of blood pressure

Nat Rev Neurosci

Temporal response patterns of the human sinus node to brief carotid baroreceptor stimuli

J Physiol

Relationship between spontaneous variations of muscle sympathetic activity and succeeding changes of blood pressure in man

J Auton Nerv Syst

Chemoreceptors, baroreceptors, and autonomic deregulation in children with obstructive sleep apnea

Respir Physiol Neurobiol

Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions

J Hypertens

The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents

Pediatrics

Twenty-four-hour ambulatory blood pressure monitoring in infants and toddlers

Pediatr Nephrol

Twenty-four-hour ambulatory blood pressure monitoring in young children

Pediatr Nephrol

Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: A working group report from the National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents

Pediatrics

Report of the Second Task Force on Blood Pressure Control in Children – 1987. Task Force on Blood Pressure Control in Children. National Heart, Lung, and Blood Institute, Bethesda, Maryland

Pediatrics

Maturation of cardiovagal autonomic function from childhood to young adult age

Circulation

Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology

Eur Heart J

Heart rate variability: origins, methods, and interpretive caveats

Psychophysiology

Assessment of overall blood pressure variability and its different components

Blood Press Monit

Low-frequency power of heart rate variability is not a measure of cardiac sympathetic tone but may be a measure of modulation of cardiac autonomic outflows by baroreflexes

Exp Physiol

Normal ranges of heart rate variability during infancy and childhood

Pediatr Cardiol

Circadian rhythm of heart rate and heart rate variability

Arch Dis Child

Heart rate variability in normotensive healthy children with aging

Clin Exp Hypertens

Central and baroreflex control of heart rate during the wake-sleep cycle in rat

Sleep

Assessment of baroreceptor reflex sensitivity by means of spectral analysis

Hypertension

Can we detect the development of baroreflex sensitivity in humans between 11 and 20 years of age?

Can J Physiol Pharmacol

Pubertal and gender-related changes in the sympathoadrenal system in healthy children

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