2. Human
Sleep and
!Gr owth
Dr. Ahmed Elshebiny , MD
Lecturer of Internal Medicine
Faculty of Medicine, Menoufyia University
,Former Clinical Research Fellow
Joslin Diabetes Center, Harvard University
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3. Sleep for growth
Sleep
04/12/13 is no less important than food for growth
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4. Key message
Sleep pattern differs by age
Sleep and hormones are interrelated
GH is secreted preferentially in the SW sleep
Sleep disorders can retard growth
Treatment of sleep disorders can lead to catch – up
Bidirectional inter-relation between somatotropic
system and sleep
GH, GHRH , prolactin & somatostatin promote sleep
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7. Growth failure
Causes
Some are constitutional, some are genetic,
nutritional, psychological, are due to chronic
illnesses, and some are the result of hormonal
disorders or may be idiopathic.
Many primary care physicians do not include
sleep OSA as a cause of Growth retardation
Bonuck, et al, International Journal of Pediatric Otorhinolaryngology (2005)
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8. Prevalence of Growth failure
Among children under 2 years of age, a
population-based screening program in
England identified 3% with GF
(Wright et al BMJ, 1998)
In US children aged 24—71months who
are < 5th percentile range between ( 2.7-
5.2 %)
( Third report on nutrition monitoring in US, 1995)
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10. Sleep is an active process
Sleep is not merely the absence of waking.
On the contrary, it is a state during which
specialized physiological activities occur in
the brain and throughout the body.
It is an active process in which metabolism,
tissue restoration, memory consolidation, and
general homeostatic balance is maintained
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12. Frequency of Night – Waking
Newborns – 100%
Six-month-olds – 20-30%
Up to four years: one in three continues to awaken during
the night and require intervention by a parent to return to
.sleep
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13. ?Sleep Center
Recently VLPO of hypothalamus
Sleep active neurons
GABA inhibition to arousal systems
( Gaus et al, Neuroscience , 2002)
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14. Sleep disorders in Children
25 % of children experience some type of
sleep disturbance
Instead of appearing sleepy, the overtired
child may appear overactive & inattentive.
Wake up America, A National Sleep Alert January, 1993
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17. GH secretion during sleep
Growth hormone (GH) is preferentially secreted
during slow-wave sleep .
In normal adult men , sleep onset GH pulse
represents 60-70% of the total daily secretion of the
hormone
There is a quantitative correlation between the
amount of GH secretion during sleep and the
duration of SW sleep
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23. Sleep & Feeding problems co-exist
Problematic sleep and feeding behaviors tend
to coexist in early childhood.
Increased awareness of this coexistence may
improve outcome.
(Pediatrics 2011;127:e615-e621 )
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24. Sleep deprivation & appetite
Total sleep deprivation in humans has been
associated with hyperphagia
Leptin & ghrelin – hormones associated the central
regulation of food intake
Van Cauter E et al 2004
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25. Sleep and intra-uterine growth
In a study of pregnant women in Sri Lanka ,
sleeping for less than or equal to 8 h during
2nd or 3rd or both trimesters is a risk factor
for small for gestational age baby.
(Abeysena, et al., Australian & New Zealand Journal of Obstetrics &
Gynaecology. 49(4):382-7, 2009 )
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27. SDB in children
Sleep disordered breathing is relatively
common in children
While the exact prevalence of SDB in
children is unknown, snoring may occur in
3—12%, while OSA may occur in 1—10%
Bonuck, et al, International Journal of Pediatric Otorhinolaryngology (2005)
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28. Sleep disordered breathing and Growth
failure
SDB, secondary to adenotonsillar
hypertrophy increases the risk of growth
failure in children.
Just 20% of pediatricians screen for SDB
OSA peaks at 2—6 years of age, because of
the relative adenotonsillar hypertrophy found
at this time
Bonuck, et al, International Journal of Pediatric Otorhinolaryngology (2006)
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29. Potential pathways for the effect of
OSA
Increased energy expenditure
Nocturnal hypoxemia
Metabolic alkalosis
Impaired growth hormone secretion
Feeding problems
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31. Effect of Adenotonsillectomy on
growth
Studies found that otherwise healthy children
experiencing GF show significant catch up
following T&A( Tonsillectomy and
adenoidectomy).
The American Academy of Pediatrics
identifies GF as a serious complication of
untreated obstructive apnea
Bonuck, et al, International Journal of Pediatric Otorhinolaryngology (2005)
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33. Sleep disturbance, cortisol and growth
hormones
Sleep disturbance has a stimulatory effect on
the HPA axis and a suppressive effect on the
GH axis.
There is an observed hypocortisolism in
idiopathic hypersomnia and HPA axis relative
activation in chronic insomnia.
Vogontzas et al., Clin Endocrinol (Oxf). 1999 Aug;51(2):205-15.
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35. Central effects of GH
High density of GH binding sites has been
demonstrated in pituitary, hypothalamus and
hippocampus.
The binding sites are also abundant in choroid
plexus
(Lai et al., 1991)
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36. GH deficiency and sleep
GHD is associated with impaired sleep
quality
(Bjo¨rk et al., 1989).
The analysis of sleep microstructure by means
of CAP (cyclic alternating pattern) , in
children with GHD, showed a reduction of
transient EEG amplitude oscillations.
Verrillo et al., Neuroendocrinology. 2011 Apr 5. (online)
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37. Effects of GH, GHRH , Prolactin, and
somatostatin on sleep
GH, PRL & Somatostatin possess REM
sleep-promoting activity.
(Danguir J. Brain Res 367, 26-30 -1986)
GHRH by itself promotes non-REM sleep.
Krueger JM and ObaÂl Jr F. FASEB J 7, 645-652 (1993).
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38. Potential for novel therapeutic
approaches
Pharmacological approaches that stimulate
SW sleep may act as GH secretagogues e.g
oral GHB ( investigational drug for
narcolepsy) and ritanserin( 5HT2 antagonist)
Aging effects on GH and SW sleep?
Improvements of lifestyle indices in GH
deficient adults after treatment with GH may
be related to improvement of sleep quality
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39. Take home message
1. Normal sleep is important to the survival,
growth and development of children.
2. Primary care physicians, parents, and even
teachers, to some extent, should be aware of
sleep disorders that effect children.
3. Appropriate diagnosis and management of
these disorders can significantly improve the
lives of children and their families.
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