Abstract
Background
Sleep disordered breathing (SDB) in typically developing (TD) children is associated with adverse cardiovascular effects. As children with Down syndrome (DS) are at increased risk for SDB, we aimed to compare the cardiovascular effects of SDB in children with DS to those of TD children with and without SDB.
Methods
Forty-four children with DS (3–19 years) were age and sex matched with 44 TD children without SDB (TD−) and with 44 TD children with matched severity of SDB (TD+). Power spectral density was calculated from ECG recordings, for low frequency (LF), high frequency (HF), total power and the LF/HF ratio.
Results
Children with DS had lower HF power, and higher LF/HF during sleep and when awake. There were no differences between groups for LF power. SpO2 nadir, average SpO2 drop and SpO2 > 4% drop were larger in the DS group compared to the TD+ group (p < 0.05 for all).
Conclusions
Our findings demonstrate significantly reduced parasympathetic activity (reduced HF power) and increased LF/HF (a measure of sympathovagal balance) in children with DS, together with greater exposure to hypoxia, suggesting SDB has a greater effect in these children that may contribute to an increased risk of adverse cardiovascular outcomes.
Impact
-
Sleep disordered breathing in children with Down syndrome exacerbates impaired autonomic control and increases exposure to hypoxia, compared to typically developing children.
-
In typically developing children sleep disordered breathing has adverse effects on autonomic cardiovascular control.
-
The prevalence of sleep disordered breathing is very high in children with Down syndrome; however, studies on the effects on cardiovascular control are limited in this population.
-
This study supports screening and early treatment of sleep disordered breathing in children with Down syndrome.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Kazemi, M., Salehi, M. & Kheirollahi, M. Down syndrome: current status, challenges and future perspectives. Int. J. Mol. Cell Med. 5, 125–133 (2016).
Arumugam, A. et al. Down syndrome—a narrative review with a focus on anatomical features. Clin. Anat. 29, 568–577 (2016).
Shott, S. R. Down syndrome: common otolaryngologic manifestations. Am. J. Med. Genet. C Semin. Med. Genet. 142C, 131–140 (2006).
Subramanyam, R. et al. Upper airway morphology in Down syndrome patients under dexmedetomidine sedation. Braz. J. Anesthesiol. 66, 388 (2016).
Nixon, G. M., Biggs, S. N., Jitpiriyaroj, S. & Horne, R. S. The relationship between sleep-disordered breathing severity and daytime adaptive functioning in children with Down syndrome. CNS Neurosci. Ther. 22, 936–937 (2016).
Dyken, M. E. et al. Prospective polysomnographic analysis of obstructive sleep apnea in Down syndrome. Arch. Pediatr. Adolesc. Med. 157, 655–660 (2003).
Marcus, C. L. et al. Obstructive sleep apnea in children with down syndrome. Pediatrics 88, 132–139 (1991).
Southall, D. P. et al. Upper airway obstruction with hypoxaemia and sleep disruption in Down syndrome. Dev. Med. Child Neurol. 29, 734–742 (1987).
Stebbens, V. A. et al. Sleep related upper airway obstruction in a cohort with Down’s syndrome. Arch. Dis. Child 66, 1333–1338 (1991).
Shott, S. R. et al. Obstructive sleep apnea: should all children with Down syndrome be tested? Arch. Otolaryngol. Head Neck Surg. 132, 432–436 (2006).
Lin, S. C., Davey, M. J., Horne, R. S. & Nixon, G. M. Screening for obstructive sleep apnea in children with Down syndrome. J. Pediatr. 165, 117–122 (2014).
de Miguel-Diez, J., Villa-Asensi, J. R. & Alvarez-Sala, J. L. Prevalence of sleep-disordered breathing in children with Down syndrome: polygraphic findings in 108 children. Sleep 26, 1006–1009 (2003).
Austeng, M. E. et al. Obstructive sleep apnea in younger school children with Down syndrome. Int. J. Pediatr. Otorhinolaryngol. 78, 1026–1029 (2014).
Hill, C. M. et al. Prevalence and predictors of obstructive sleep apnoea in young children with Down syndrome. Sleep. Med. 27-28, 99–106 (2016).
Fitzgerald, D. A., Paul, A. & Richmond, C. Severity of obstructive apnoea in children with Down syndrome who snore. Arch. Dis. Child 92, 423–425 (2007).
Marcus, C. L. et al. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 130, 731–736 (2012).
Bull, M. J. Committee on Genetics.*** Health supervision for children with down syndrome. Pediatrics 128, 393–406 (2011).
Nisbet, L. C., Yiallourou, S. R., Walter, L. M. & Horne, R. S. C. Blood pressure regulation, autonomic control and sleep disordered breathing in children. Sleep Med. Rev. 18, 179–189 (2014).
O’Driscoll, D. et al. The heart rate response to spontaneous arousal from sleep is reduced in children with Down syndrome referred for evaluation of sleep-disordered breathing. Am. J. Physiol. 298, H1986–H1990 (2010).
O’Driscoll, D. M. et al. Cardiac and sympathetic activation are reduced in children with Down syndrome and sleep disordered breathing. Sleep 35, 1269 (2012).
Ferri, R. et al. Heart rate variability and apnea during sleep in down’s syndrome. J. Sleep Res. 7, 282–287 (1998).
Konstantinopoulou, S. et al. Relationship between obstructive sleep apnea cardiac complications and sleepiness in children with Down syndrome. Sleep Med. 17, 18–24 (2016).
Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability standards of measurement, physiological interpretation, and clinical use. Eur. Heart J. 17, 354–381 (1996).
Billman, G. E. The LF/HF ratio does not accurately measure cardiac sympatho-vagal balance. Front. Physiol. 4, 26 (2013).
Berry, R. B. et al. Rules for scoring respiratory events in sleep: update of the 2007 aasm manual for the scoring of sleep and associated events. Deliberations of the sleep apnea definitions task force of the American Academy of Sleep Medicine. J. Clin. Sleep Med. 8, 597–619 (2012).
American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am. J. Respir. Crit. Care Med. 153, 866–878 (1996).
Ogden, C. L. et al. Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics Version. Pediatrics 109, 45–60 (2002).
Tamanyan, K. et al. Age effects on cerebral oxygenation and behavior in children with sleep disordered breathing. Am. J. Respir. Crit. Care Med. 197, 1468–1477 (2018).
Walter, L. M. et al. Autonomic dysfunction in children with sleep disordered breathing. Sleep Breath. 17, 605–613 (2013).
Nisbet, L. C. et al. Nocturnal autonomic function in preschool children with sleep-disordered breathing. Sleep Med. 14, 1310–1316 (2013).
Trinder, J. Cardiac activity and sympathovagal balance during sleep. Sleep Medicine. Sleep Med. Clin. 2, 199–208 (2007).
Horne, R. S. C. et al. Elevated blood pressure during sleep and wake in children with sleep-disordered breathing. Pediatrics 128, E85–E92 (2011).
Walter, L. M. et al. Impaired blood pressure control in children with obstructive sleep apnea. Sleep Med. 14, 858–866 (2013).
de Carvalho, T. D. et al. Heart rate variability in individuals with Down syndrome—a systematic review and meta-analysis. Auton. Neurosci. 213, 23–33 (2018).
Fernhall, B. et al. Blunted heart rate response to upright tilt in people with Down syndrome. Arch. Phys. Med. Rehabil. 86, 813–818 (2005).
Fernhall, B. et al. Prediction of maximal heart rate in individuals with mental retardation. Med. Sci. Sports Exerc. 33, 1655–1660 (2001).
Fernhall, B. & Otterstetter, M. Attenuated responses to sympathoexcitation in individuals with Down syndrome. J. Appl. Physiol. 2003, 2158–2165 (1985).
Figueroa, A. et al. Impaired vagal modulation of heart rate in individuals with Down syndrome. Clin. Auton. Res. 15, 45–50 (2005).
Guerra, M., Llorens, N. & Fernhall, B. Chronotropic incompetence in persons with Down syndrome. Arch. Phys. Med. Rehabil. 84, 1604–1608 (2003).
de Carvalho, T. D. et al. Cardiac autonomic modulation of children with down syndrome. Pediatr. Cardiol. 36, 344–349 (2015).
Horne, R. S. et al. Nocturnal dipping is preserved in children with sleep disordered breathing regardless of its severity. Pediatr. Pulmonol. 48, 1127–1134 (2013).
Nisbet, L. C. et al. Sleep-disordered breathing does not affect nocturnal dipping, as assessed by pulse transit time, in preschool children: evidence for early intervention to prevent adverse cardiovascular effects? Sleep Med. 15, 464–471 (2014).
Song, P. et al. Global prevalence of hypertension in children: a systematic review and meta-analysis. JAMA Pediatr. 173, 1−10 (2019).
Walter, L. M. et al. Obesity and anthropometric determinants of autonomic control in children with sleep-disordered breathing—which measurements matter? Int. J. Obes. 42, 1195–1201 (2018).
Acknowledgements
The authors wish to acknowledge the assistance of Mr. Aidan Weichard and Ms. Poornima Wijayaratne for assistance in data collection. We would also like to thank all the parents and their children who participated in the study and the staff of the Melbourne Children’s Sleep Centre, where the study was carried out. Financial support was provided by the the Angior Family and Jack Brockhoff Foundations.
Author information
Authors and Affiliations
Contributions
R.S.C.H. conceptualized and designed the study, obtained funding, coordinated and supervised data collection, drafted the initial manuscript, and reviewed and revised the manuscript. A.S., A.B., J.T. and L.M.W. carried out the initial analyses, and reviewed and revised the manuscript. M.J.D. critically reviewed the manuscript for important intellectual content. G.M.N. conceptualized and designed the study, obtained funding and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Patient consent
Participants were asked for their verbal consent and parents or a legal guardian provided written consent.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Horne, R.S.C., Sakthiakumaran, A., Bassam, A. et al. Children with Down syndrome and sleep disordered breathing have altered cardiovascular control. Pediatr Res 90, 819–825 (2021). https://doi.org/10.1038/s41390-020-01285-6
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41390-020-01285-6
This article is cited by
-
Sleep apnea is associated with reduced daytime blood pressure variability in adults with Down syndrome
Scientific Reports (2025)
-
A clinical-translational review of sleep problems in neurodevelopmental disabilities
Journal of Neurodevelopmental Disorders (2024)
-
Sleep-disordered breathing and sleep macro- and micro-architecture in children with Down syndrome
Pediatric Research (2022)
-
Hypoxemia in infants with trisomy 21 in the neonatal intensive care unit
Journal of Perinatology (2021)
