04/12/23 10:11

04/12/23 10:11

Human Sleep and Growth!

Dr. Ahmed Elshebiny , MDDr. Ahmed Elshebiny , MDLecturer of Internal MedicineLecturer of Internal Medicine

Faculty of Medicine, Menoufyia UniversityFaculty of Medicine, Menoufyia University

Former Clinical Research FellowFormer Clinical Research Fellow,,Joslin Diabetes Center, Harvard UniversityJoslin Diabetes Center, Harvard University

04/12/23 10:11

Sleep for growth

Sleep is no less important than food for growth

04/12/23 10:11

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

04/12/23 10:11

Intra-uterineGrowth

PostnatalGrowth

GrowthGrowth

Nutrition

GHGonadal

steroids and GH

(Sam & Meeran Lecture notes Endocrinology& Diabetes, 2009)

InfantilePhase

ChildhoodPhase

Pubertal Phase

04/12/23 10:11

Rate of Growth

04/12/23 10:11

Growth failureCauses 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)

04/12/23 10:11

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)

04/12/23 10:11

What happened to our sleep ?

04/12/23 10:11

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

04/12/23 10:11

04/12/23 10:11

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.

Frequency of Night – Waking

04/12/23 10:11

Sleep Center? Recently VLPO of hypothalamus Sleep active neurons GABA inhibition to arousal systems

( Gaus et al, Neuroscience , 2002)

04/12/23 10:11

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

04/12/23 10:11

Prevalence of Insomnia by age group

04/12/23 10:11

04/12/23 10:11

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

04/12/23 10:11

GH secretion during sleep

04/12/23 10:11

GH secretion during sleep deprivation and daytime sleep

Van Cauter et al, 2000

04/12/23 10:11

Effect of interrupted sleep on GH secretory pattern

(Y. TAKAHASHI, et al)

04/12/23 10:11

SW sleep and nocturnal GH patterns through adult life

Van Cauter et al, 1998 , American Academy of Sleep Medicine

04/12/23 10:11

GHRHGH

SW sleep

Bidirectional Interactions between GH &sleep

REM sleepGhrelin

Somatostatin

04/12/23 10:11

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 )

04/12/23 10:11

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

04/12/23 10:11

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 )

04/12/23 10:11

04/12/23 10:11

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)

04/12/23 10:11

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)

04/12/23 10:11

Potential pathways for the effect of OSA Increased energy expenditure Nocturnal hypoxemia Metabolic alkalosis Impaired growth hormone secretion Feeding problems

04/12/23 10:11

04/12/23 10:11

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)

04/12/23 10:11

04/12/23 10:11

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.

04/12/23 10:11

GHRHGH

SW sleep

Bidirectional Interactions between GH &sleep

REM sleepGhrelin

Somatostatin

04/12/23 10:11

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)

04/12/23 10:11

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)

04/12/23 10:11

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).

04/12/23 10:11

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

04/12/23 10:11

Take home message1. 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.

04/12/23 10:11

04/12/23 10:11