This document summarizes research on the relationship between sleep-disordered breathing (SDB) and cardiovascular and neurological effects in children. It finds that SDB is associated with increased sympathetic tone, blood pressure, and decreased heart rate variability. SDB is also linked to inflammation, oxidative stress, and brain changes that may underlie behavioral and cognitive impairments. Studies show many effects are reversible after adenotonsillectomy, but some neurological impacts may be long-lasting if SDB persists untreated.

1. Gonzalo Pin Arboledas
Unidad de Pediatría Integral Q Valencia
Unidad Valenciana del Sueño.
Hospital Quirón Valencia
www.upiqweb.es

2. VAS:
Respuesta conservada a pr. Subatmosférica e hipercapnea
J Appl Physiol 2004;97:98-108

3. A: incremento gradual de la pr B: Incremento intermitente

4. Mecanismo compensatorio de la mayor estrechez :
VAS menos colapsable.
Respuesta más dinámica tanto al CO2 como a la presión negativa.
Factores que facilitan el colapso:
Vías aéreas altas más estrechas,
Posición más alta de la laringe,
Mayor laxitud de los tejidos y
Mayor flexibilidad cartilaginosa de las estructuras de soporte .
Gryczynska D., Powajbo K., Zakrzewska A.The influence of tonsillectomy on obstructive sleep
apnea children with malocclusion Int J Pediatric Otorhinolaryngol, 1995; 32 (Suppl) S225-
S228

5. “The heart is the chief feature of a functioning mind”. Frank Lloyd Wright (1868-1959)
‘‘The brain runs away with the heart’s best blood.’‘ Jean Ingelow
… existing studies of SDB’s effects are primarily cross-sectional, and
limited by poor sampling, insufficient consideration of confounders, and
imprecise use of statistical tools. The few longitudinal studies are either
before or after tonsillectomy or follow children for ≤ 2 years.

6. Repeated complete upper airway obstruction during sleep might be a
major contributor to the observed behavioral phenotype among
children at the low end of the SDB severity spectrum.
Gozal D et al.Sleep-Disordered Breathing Affects Auditory Processing in 5–7 Year-Old
Children: Evidence From Brain Recordings. Dev Neuropsychol. 2009 September ; 34(5):
615–628. doi:10.1080/87565640903133608

7. children with OSA require more time and an
increased number of learning opportunities to reach
immediate and long-term recall performances that
are reduced compared with controls
acquisition and retention of newly learned
material are compromised
Kheirandish-Gozal L, De Jong MR, Spruyt K, Chamuleau SA, Gozal D. Obstructive sleep apnoea is
associated with impaired pictorial memory task acquisition and retention in children. Eur Respir J.
2010;36(1):164-9.

8. Miano S, Paolino MC, Urbano A, Parisi P, Massolo AC, Castaldo R, Villa MP
Neurocognitive assessment and sleep analysis in children with sleep-disordered
breathing. Clin Neurophysiol. 2011;122(2):311-9.
.
sleep fragmentation and cognitive function
IQ : Controls > SDB
ADHD rating scale scores: SDB > Controls.
SDB: % of wakefulness after sleep onset
N1
Global intelligence correlated positively A2
Arousal
A2 index
Hyperactivity scores correlated positively : A2 index.
CONCLUSIONS: Arousal is a defensive mechanism that
may preserve cognitive function.

9. Baumert M, Kholer M, Kabir M, Sanders P, Kennedy D, Martin J, Pamula Y . Altered cardio-respiratory response to
spontaneous cortical arousals in children with upper airway obstruction. Sleep Medicine.2011 (12): 230-238
Número de arousals corticales: no diferencias.
Duración del arousal:
• Más corto en TRS en N2 y REM.
• AA: sin diferencias.
Cambios FC en el a.espontáneo:
> en TRS en N2

10. …. that the behavioral consequences and cellular losses are produced,
at least in part, by the episodic hypoxia-reoxygenation cycles during
sleep that characterize OSA.
Excessive NADPH oxidase activity may play a role in IH-induced CNS dysfunction
Nair D, Dayyat EA, Zhang SX, Wang Y, Gozal D (2011) Intermittent Hypoxia-Induced Cognitive Deficits Are Mediated by NADPH Oxidase Activity in a Murine Model of Sleep Apnea. PLoS ONE 6(5): e19847.
doi:10.1371/journal.pone.0019847

11. TRS: Porcentajes significativamente elevados de disfuncion global ejecutiva

12. Pr. de conducta e indicaciones de pr. atencionales en los tres grupos de TRS

14. PubMed:
“ADHD”, “attention-deficit/hyperactivity disorder”, “sleep”, sleep disorder” y “children” OR “pediatrics ”.
1994 a Marzo 2012.

16. N= 11.000
Sleep-Disordered Breathing in a Population-Based Cohort: Behavioral Outcomes at 4 and 7 Years.
Pediatrics 2012;129;e857

17. Pediatrics 2012;129;e857
N= 11.000

18. Sleep-Disordered Breathing in a Population-Based Cohort: Behavioral Outcomes at 4 and 7
Years. Pediatrics 2012;129;e857
SDB effects may only become apparent years later.
The most significant long-term effects occurred in
children with the greatest overall levels of snoring,
apnea, and mouth breathing throughout, peaking
at 30 months.
Even very early symptom peaks at 6 and 18
months are associated with 40% and 50%,
respectively, increased behavioral morbidity at 7
years of age.

19. EDAD: 6.5±4.0 a. IAH : >1 < 10

20. DSM-IV Diagnoses and
DSM-IV Diagnoses and
J ,DILLON; S, BLUNDEN; D,RUZICKA; K,GUIRE; D,CHAMPINE; R,WEATHERLY; E, HODGES;B,GIORDANI; R,CHERVIN.
J ,DILLON; S, BLUNDEN; D,RUZICKA; K,GUIRE; D,CHAMPINE; R,WEATHERLY; E, HODGES;B,GIORDANI; R,CHERVIN.
Obstructive Sleep Apnea in Children Before and 11Year After Adenotonsillectomy. Journal ofofthe
Obstructive Sleep Apnea in Children Before and Year After Adenotonsillectomy. Journal the
American Academy of Child & Adolescent Psychiatry.2007 46(11):1425-1436, November 2007
American Academy of Child & Adolescent Psychiatry.2007 46(11):1425-1436, November 2007
Edad: 5 – 12.9 años
Pre-intervención:
Controles Pacientes
Alt. Conducta: 11.1% 36,7% p<.05
p<.05
Síntomatol. TDAH: 7.4% 27.8%
1 año postintervención:
No diferencias significativas

21. … existing studies of SDB’s effects are primarily cross-sectional, and
limited by poor sampling, insufficient consideration of confounders, and
imprecise use of statistical tools. The few longitudinal studies are either
before or after tonsillectomy or follow children for ≤ 2 years.
“The heart is the chief feature of a functioning mind”. Frank Lloyd Wright (1868-1959)
‘‘The brain runs away with the heart’s best blood.’‘ Jean Ingelow

22. Snoring is not associated with adverse effects on blood pressure, arterial
structure or function in 8-year-old children: The Childhood Asthma Prevention
Study (CAPS). Journal of Paediatrics and Child Health. Article first published online: 29 APR 2011 DOI: 10.1111/j.1440-
1754.2011.02014.x
Parentally reported snoring was not independently
associated with adverse measurements of
metabolic markers, vascular structure or function in
8-year-old children.

23. Changes in Heart Rate Variability After Adenotonsillectomy in Children With
Obstructive Sleep Apnea. Chest.2011; 139 (5)
Edad: 4.9 ± 2.4
PRE AA POST AA
IAH 31.9±24.8 4.1±3.7
FC sueño profundo 100.2±15.4 80.5±12.4
FC sueño REM 106.9±16.4 87.0±12.5
Variabilidad BF/AF s. profundo 1.2±1.6 0.5±0.6
Variabilidad BF/AF s. REM 30.0±5.4 1.4±1.7
AA: Asociada a la mejoría la actividad simpática disminuye.

24. TA - DISTENSIBILIDAD ARTERIAL EN
RH.
9,5 +/- 2 a. RONCADORES NO RONCADORES p
T. SISTOLICA 112 +/- 10 105 +/- 8 0.001
T.DIASTOLICA 60 +/- 7 53 +/- 9 0.004
T.MEDIA 81 +/- 7 71 +/- 8 < 0.001
RH:
RH:
Mayor TA diurna
Mayor TA diurna
Menor distensibilidad arterial.
Menor distensibilidad arterial.
Único determinante identificado de la distensibilidad.
Único determinante identificado de la distensibilidad.

25. “aumento de la actividad basal simpática durante la
vigilia y mayor reactividad ante estímulos fisiológicos…
dependiente de la intensidad del SAHS”
Correlación positiva TAS - TAD / IAH
Montesano M; Miano S; Paolino MC; Massolo AC; Ianniello F; Forlani M; Villa MP. Autonomic cardiovascular tests in children with obstructive sleep apnea
syndrome. SLEEP 2010;33(10):1349-1355.

26. DM O’Driscoll, Horne R, Davey M, Hope S, Anderson V, Trinder J, Walker A, Nixon G. Increased sympathetic activity in children with obstructive sleep apnea:
cardiovascular implications. Sleep Medicine.2011;12: 483-488

27. DM O’Driscoll, Horne R, Davey M, Hope S, Anderson V, Trinder J, Walker A, Nixon G. Increased sympathetic activity in children with obstructive sleep apnea:
cardiovascular implications. Sleep Medicine.2011;12: 483-488

28. Acute Cardiovascular changes with obstructive events
in children with sleep disordered breathing Sleep.2009;32,10:12651271

29. O'Driscoll D.M., Horne R.S., Davey M.J., Hope S.A., Anderson V., Trinder J.,
Walker A.M., Nixon G.M. Increased sympathetic activity in children with
obstructive sleep apnea: Cardiovascular implications. Sleep Medicine.
2011;12(5): 483-488
... significant associations between noradrenaline and:
- AHI (r=0.32) and age (r=-0.20, p<0.05 for both).
- Systolic/ diastolic BP z-score (r=0.22 and r=0.20, p<0.05 for both ).
These data indicate that children with OSA have
increased sympathetic tone that may contribute to the
cardiovascular consequences.

30. Baroreflex Sensitivity is Associated with Sleep-Related Breathing Problems in
Adolescents
J Pediatr 2012;160:610-4
SRBPs were associated with attenuated BRS in adolescents,
and this relationship was exacerbated by higher BMI.
“ Although we did not examine the sensitivity and
specificity of either BMI or SRBP scores, our study
suggests that the clinical cut-offs in screening for
SRBP may need to be stratified based on children’s
BMI.”

31. Effects of Sleep Patterns and Obesity on Increases in Blood Pressure in a 5-Year Period:
Report from the Tucson Children's Assessment of Sleep Apnea Study. J Pediatr 2012
increases in BMI and reductions in TST were
associated with higher levels of BP in adolescents,
with a trend for an effect from SDB.

33. Regeneración neuronal
“Second best ”hipótesis
paliativa previa a maduración
NADPH-oxidasa¿?
lóbulo frontal (3-5 a)
Hipoxemia
▲ Resistencia vasc. periférica
Hipercapnia
Activación simpática
Las imágenes doppler son capaces de detectar
Re-oxigenación
BNP
▼ Tono vagal
Menor distensibilidad arter.
S
los cambios subclínicos cardiacos que ocurren
SNA
▲ Catecolaminas Remodelación VI
▼ Variabilidad (<edad)
A durante el intratorácica
▲ Presión
SAHS. Estos cambios generalmente cardiaca
H son reversibles tras la AA ▲ Resistencia
Pediatr Cardiol. 2010
vascular sistémica
▲ RGE
S
8 m:Arousal relacionados con ronquido en ausencia de VD
Remodelación apnea o
(IAH,CO ,arousal)
hipopneas se correlacionan negativamente con score mental. Pediatrics
Stress oxidativo: 2
2006; 117:e496-e502 ▲ reactive oxygen species ▲ IL 6- IL1
Hipertensión
▲ TNFα,MRP8/14
▲ Fac. adhesión -Disfunción
Microdespertares Inflamación (p-selectina)
endotelial.
▲PCR
Alt. Conducta Disf. Cerebral + -Aterogénesis
▲ Adipocitos
TDAH-like fragmentación -Obesidad.
▲ Leptina
BNP: Péptido Cerebral Natriurético Adaptado por Dr. G. Pin y revisada la adaptación por Dr. D. Gozal. (Sleep Medicine 2009;10: S12-S16)