dentofacial morphology in obese and non-obese · pdf fileii dentofacial morphology in obese...

Dentofacial Morphology in Obese and Non-Obese Children With and Without Obstructive Sleep Apnea

by

David Justin Simone

A thesis submitted in conformity with the requirements for the degree of Master of Science (Orthodontics)

Graduate Department of Dentistry University of Toronto

© Copyright by Dr. David Justin Simone 2016

ii

Dentofacial Morphology in Obese and Non-obese Children With and Without Obstructive Sleep

Apnea

David Simone

Master of Science (Orthodontics)

Graduate Department of Dentistry

University of Toronto

2016

Abstract

Introduction: Several craniofacial abnormalities have been suggested to contribute to

obstructive sleep apnea. These characteristics vary significantly among the literature and are

limited by the infrequent use of polysomnogprahy, the gold standard for diagnosing and

quantifying obstructive sleep apnea.

Objective: To compare the prevalence of facial and/or dental imbalances in children with and

without obstructive sleep apnea in cohorts of obese and non-obese children.

Methods: A prospective, cross-sectional study of children (ages 4-16) who were referred for a

polysomnogram at The Hospital for SickKids. Facial features and malocclusion was assessed

clinically by one dentist, blinded to the PSG results.

Results/Conclusions: Horizontal excess (overjet) was the only dentofacial finding which was

significantly more common in children with obstructive sleep apnea as compared to those

without obstructive sleep apnea (p=0.04). Dentofacial characteristics were also not different

between children using positive airway pressure therapy and children not on positive airway

pressure therapy

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Acknowledgments

I am grateful to all the people who have supported me and helped me throughout this

process. I would first like to thank my supervisors, Dr. Reshma Amin and Dr. Bryan Tompson,

without whom this project wouldn’t have been successful without your endless guidance and

advice. I would also like to thank my committee members, Dr. Fernanda Almeida, Dr. Nelly

Huynh, and Dr. Indra Narang, for your contribution to this project. You are all responsible for

guiding me in the proper direction to complete this project.

Secondly, I would like to thank the numerous people who dedicated their time that

allowed this project to be completed in a timely manner. I would like to thank Nicole Sidhu,

Nadia Kabir, Aman Sayal, and Tanvi Naik for helping with entering data into the database,

coordinating patient schedules, and preparing appropriate consents for patients. I would like to

thank Allison Zweerink for informing me of the schedules of the nightly polysomnograms and

Derek Stephens for your help with the statistical analyses.

Finally, I would like to thank my beautiful wife, Joanna and my two precious daughters,

Amalia and Violette. This project is dedicated to you. Without your infinite support and never-

ending love, I would not have been able to get through the last three years. Thank you for

picking up the slack when I was busy concentrating on school related work. Without a doubt, I

would not have been able to get through any of this without you.

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Table of Contents

Abstract ……………………………………………………………………………..... ii

Acknowledgments ……………………………………………………………………. iii

_Table of Contents …………………………………………………………………….. iv

List of Tables. ………………………………………………………………………… vi

List of Figures ………………………………………………………………………... vii

List of Abbreviations ………………………………………………………………… viii

List of Appendices …………………………………………………………………… x

Chapter 1: Background ………………………………………………………….. 1

1.1 Obstructive Sleep Apnea ………………………………………………… 1

1.2 Obesity …………………………………………………………………… 2

1.3 Epidemiology of OSA …………………………………………………… 3

1.4 Pathophysiology of OSA ………………………………………………… 3

1.5 Obesity and OSA ………………………………………………………… 10

1.6 Complications of Pediatric OSA ………………………………………… 12

1.7 Diagnosis ………………………………………………………………… 14

1.8 Pediatric Obstructive Sleep Apnea Treatment …………………………… 18

1.9 OSA and Craniofacial and Dentofacial Development …………………… 24

1.10 Rationale …………………………………………………………………. 25

1.11 Study Aim ………………………………………………………………… 26

Chapter 2: Materials and Methods ……………………………………………... 27

2.1 Subjects……………………………………………………………………... 27

2.2 Study Procedures …………………………………………………..………. 27

v

2.3 Demographics and Anthropometric Measures ……………………….……. 28

2.4 Sleep Questionnaires ………………………………………………………. 29

2.5 Clinical Orthodontic Examination ……………………………………….… 30

2.6 Polysomnogram …………………………………………………………..... 35

2.7 Statistical Analysis ……………………………………………………….... 36

2.8 Study Outcomes ……………………………………………………………. 37

2.9 Hypothesis ……………………………………………………………….… 37

Chapter 3: Results …………………………………………….............................. 38

3.1 Intra-rater Reliability ………………………………………………………. 38

3.2 Study Participants ………………………………………………………….. 39

3.3 Polysomnography Results …………………………………………………. 42

3.4 Questionnaire Results ……………………………………………………… 45

3.5 Dentofacial Morphology……………………………………………………. 49

Chapter 4: Discussion ……………………………………………........................... 55

Appendix A ……………………………………………............................................ 61

Appendix B ……………………………………………............................................ 62

Appendix C ……………………………………………............................................ 71

Appendix D ……………………………………………............................................ 72

Bibliography……………………………………………........................................... 73

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List of Tables

Table 1.1 Signs and Symptoms of Pediatric Obstructive Sleep Apnea ……………….…………………. 26

Table 2.1 Inclusion and Exclusion Criteria ……………………………………………………………… 38

Table 2.2 Summary of Study Procedures ……………………………………………............................... 39

Table 2.3 Centers for Disease Control and Prevention Weight Categories …………................................ 39

Table 2.4 Frontal View Examination …………………………………………………………………….. 41

Table 2.5 Profile View Examination …………………………………………………………………….. 42

Table 2.6 Functional Assessment ……………………………………………………............................... 43

Table 2.7 Intra-Oral Examination ………………………………………………………………………... 44

Table 3.1 Intra-rater reliability …………….………………………………………................................... 49

Table 3.2 Subject Groups ……………………………………………………………................................ 51

Table 3.3 Demographics of the Four Study Cohorts (excluding PAP group)………. …………………… 52

Table 3.4 Demographics of OSA vs. No OSA Groups (excluding PAP group) …………………………. 53

Table 3.5 PSG Results across the Four Cohorts (excluding PAP group) ……………….………………... 53

Table 3.6 PSG results of OSA vs. No OSA Groups (excluding PAP group) ……………….……………. 55

Table 3.7 Spruyt and Gozal Questionnaire results across the Four Cohorts (excluding PAP group)…….. 57

Table 3.8 Frequencies of Spruyt and Gozal Scores of OSA vs. No OSA groups (excluding PAP group).. 57

Table 3.9 Pediatric Sleep Questionnaire Results across the Four Cohorts (excluding PAP group)……… 59

Table 3.10 Frequencies of PSQ Scores of OSA vs. No OSA groups (excluding PAP group) …………….. 59

Table 3.11 Prevalence of Dentofacial Characteristics across the Four Cohorts (excluding the PAP group). 61

Table 3.12 Dentofacial Morphology of OSA vs. No OSA Groups (excluding PAP group) ………………. 62

Table 3.13 Univariate Analysis for Various Dentofacial Characteristics (excluding the PAP group)……... 63

Table 3.14 Dentofacial Morphology of Obese & OSA vs. Obese & PAP groups ……………….………… 64

Table 3.15 Multiple Regression Model for the Presence of OSA in the Study Cohort Excluding Children Using PAP Therapy……………….……………….……………….……………….…………...

65

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List of Figures

Figure 4.1 ROC Curve for Spruyt Gozal Score ……………………………………. 58

Figure 4.2 ROC Curve for PSQ Score……………………………………………… 60

viii

List of Abbreviations

SDB: Sleep Disordered Breathing

OSA: Obstructive Sleep Apnea

CA: Central Apnea

HS: hypoventilation syndrome

AT: Adenotonsillectomy

PSG: Polysomnogprahy

REM: Rapid Eye Movement

ICSD: International Classification of Sleep Disorders

AASM: American Academy of Sleep Medicine

BMI: Body Mass Index

CDC: Centers for Disease Control and Prevention

AHI: Apnea-Hypopnea Index

MRI: Magnetic Resonance Imaging

EMG: Electromyography

Pcrit: Critical Nasal Pressure

CRP: C-reactive protein

IL-6: Interleukin-6

GCR: Glucocorticoid receptor gene

TNF-α: Tumour necrosis factor-alpha

ICS: Intranasal Corticosteroid

OM: Oral Montelukast

ADHD: Attention-deficit/hyperactivity disorder

ANP: atrial natriuretic peptide

ADH: antidiuretic hormone

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PSQ: Pediatric Sleep Questionnaire

EEG: Electroencephalography

EOG: Electrooculography

HRQOL: Health Related Quality of Life

LDL: Low density lipoprotein

HDL: High density lipoprotein

OAI: Obstructive Apnea Index

PAP: Positive Airway Pressure

CPAP: continuous pressure airway pressure

BPAP: Bi-level positive airway pressure

RME: Rapid Maxillary Expansion

CBCT: Cone-beam computed tomography

AI: Apnea Index

SRDB: Sleep related breathing disorder

IOTN: Index of Orthodontic Treatment Need

NPAF: Nasal Pressure Airflow

SaO2 : Oxygen saturation

EtCO2: End-tidal Carbon Volume

TcCO2 : Transcutaneous carbon dioxide

OAHI: Obstructive apnea-hypopnea index

CAI: Central apnea-hypopnea index

ANOVA: Analysis of Variance

ICC: Intraclass Correlation Coefficient

OR: Odds ratio

ROC: Receiver Operating Curve

x

List of Appendices

Appendix A Spruyt and Gozal Sleep Questionnaire

Appendix B Pediatric Sleep Questionnaire (PSQ)

Appendix C Pediatric Polysomnogram Set up

Appendix D Pediatric Polysomnogram Data Recording

1

Chapter 1 Background

Sleep disordered breathing (SDB) is a broad term encompassing abnormalities in

respiratory pattern, gas exchange and sleep architecture during sleep.1 SDB includes: i)

obstructive sleep apnea (OSA), episodes of complete or partial airway obstruction; ii)

central apnea (CA), prolonged pauses in the absence of respiratory effort; and iii)

hypoventilation, persistent low tidal volume breathing or bradypnea causing hypercarbia

and hypoxemia.2 OSA is the most common subtype of SDB affecting 1-5% of healthy

children.3 Adenotonsillar hypertrophy is the most common cause of OSA in healthy

children. The first-line treatment for OSA is adenotonsillectomy (AT).

1.1 Obstructive Sleep Apnea

OSA is defined by the American Thoracic Society as a “functional disturbance in

sleep characterized by transient and partial/complete obstruction of the airways which

interrupts sleep, resulting in disruption of normal gas exchange (intermittent hypoxia and

hypercapnia) and sleep fragmentation1.” OSA in children was first described

systematically in 19762 using clinical symptoms and polysomnogpraphy (PSG). Since

then the recognition of abnormal breathing during sleep has progressed tremendously in

the last two decades, with the realization that childhood OSA is both common and

serious. The understanding of the pathophysiology has improved, although much

remains to be known. There is increased recognition of the relationship between

respiratory abnormalities during sleep and adverse consequences.

Children with OSA tend to have a different pattern of breathing during sleep than

adults. Children have a higher arousal threshold than adults3. As a result, they frequently

do not arouse in response to obstructive events, and most studies have demonstrated the

preservation of sleep architecture34 or only minimal changes in sleep architecture. This is

in contrast with OSA in adulthood which is associated with significant sleep

fragmentation and decreased slow wave and rapid eye movement (REM) sleep4,55,6. In

children, OSA is characteristically more severe in REM sleep secondary to the relative

muscle atonia: a state specific deficit in upper airway function

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With this increasing recognition of SDB in children, many classification systems

have been developed. However, the International Classification of Sleep Disorders

(ICSD) is most frequently used. The ICSD was first published in 1990 by the American

Academy of Sleep Medicine (AASM) along with the Japanese Society of Sleep Research,

Latin America Sleep Society and European Sleep Research Society. It was further revised

in 2007 (Second Edition), and then again most recently in 2014 (Third Edition). OSA is

classified within the sub-group of ‘Sleep-Related Breathing Disorders6.’

1.2 Obesity

Obesity is defined as a Body Mass Index (BMI) at or above the sex-specific 95th

percentile of BMI for age, based on the 2000 Centers for Disease Control and Prevention

(CDC) Growth Charts7. There has been an increasing trend in childhood obesity

worldwide. In 1978, childhood obesity among Canadian children and adolescents aged 3-

19, was 5%. In 2013, the prevalence has increased to 13%7.

Obesity in children and adolescents is now recognized as a major medical and

public health problem that affects nearly every major organ system8. Childhood obesity

has both immediate and long-term effects on physical and mental health. Children with

obesity are more likely to have risk factors for cardiovascular disease, such as high

cholesterol or high blood pressure. In a population-based sample of 5- to 17-year-olds,

70% of children with obesity had at least one risk factor for cardiovascular disease.9 In

addition, children and adolescents with obesity are at greater risk for bone and joint

problems, sleep apnea, and social and psychological problems such as stigmatization and

poor self-esteem10. Over the long-term, children with obesity are more likely to be obese

as adults11,12 are therefore at higher risk of developing cardiovascular disease, Type 2

diabetes, stroke, several types of cancer, and osteoarthritis13.

Craniofacial morphology has also been shown to differ between obese and normal

adolescents. In 2005, Sadeghianrizi et al14 compared craniofacial morphology in obese

and normal adolescents using lateral cephalometric radiographs. They found that obese

adolescents exhibited significantly larger mandibular and maxillary dimensions than

normal adolescents. IN general, obesity was associated with bimaxillary prognathism and

relatively greater facial measurements14.

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1.3 Epidemiology of OSA

OSA is a common condition in children of all ages, from neonates to adolescents,

and can result in severe complications if left untreated. Diagnostic criteria for OSA

among adults is defined as an apnea-hypopnea index (AHI) of 5 or greater events per

hour on nocturnal PSG and evidence of disturbed sleep, daytime sleepiness, or other

daytime symptoms15. The diagnostic criteria for OSA in children is heterogeneous across

studies. At present, an AHI of 1 to 5 events per hour is most frequently used to define

OSA in children 15. From the available studies, the estimated prevalence rates of OSA in

healthy children range between 1.2% and 5.7%16-18 depending on the AHI threshold for

OSA diagnosis. If these prevalence rates were applied to the 2011 Census of Canada

population estimates, that would translate between 93,425 and 443,772 Canadian children

aged 0-19 years being diagnosed with OSA, which is equivalent to 1300-5700 children

per 100,000 children as being diagnosed with OSA.

Children between 2 and 8 years of age are at increased risk of OSA as this

coincides with the peak of adenotonsillar hypertrophy in childhood17,19. In general,

infants or older children outside this age window are likely have additional or other

underlying etiologic factors such as dentofacial abnormalities or neuromuscular disease

predisposing them to the development of OSA16,17,19,20.

In contrast to adults, where OSA is more common in men than women, OSA in

children appears to occur equally amongst the sexes20-22. OSA has been shown to have a

higher prevalence amongst African American children than Caucasian children15,23 and

Asians have more severe OSA than matched Caucasians24.

1.4 Pathophysiology of OSA

While the clinical features of OSA are well understood, the understanding of its

pathogenesis remains incomplete. OSA is a result of a balance between structural factors

and functional factors and both appear to play a role. Upper airway anatomy as well as

collapsibility is important in the pathogenesis of OSA. The patency of the upper airway is

determined by a balance between the intraluminal negative pressure of the airway and the

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soft tissue structures that support the upper airway23,25. When the collapsing forces are

great enough to obstruct the airway, an obstructive apnea or hypopnea can occur.

1.4.1 Upper Airway Anatomy

The upper airway is composed of muscle and soft tissue but lacks rigid or bony

support. Most notably, it contains a collapsible portion that extends from the hard palate

to the larynx. It has the ability to change shape and momentarily close for speech and

swallowing during wakefulness. This also renders the upper airway vulnerable to collapse

during sleep.

High-resolution magnetic resonance imaging (MRI) has been utilized to

determine the size of the upper airways structure in children26,27. As compared with

control subjects, children with OSA have a smaller oropharynx, larger adenoids, tonsils

and retropharyngeal nodes26. Arens et al.27have shown with regional analysis of MRIs

that the upper airway in children with OSA is most restricted where the adenoids and

tonsils overlap. However, with segmental analysis, the upper airway has been shown to

be restricted throughout the initial two-thirds of its length and that the narrowing is not in

a discrete region adjacent to either the adenoid or tonsils, but rather in a continuous

fashion along both27. Furthermore, Schiffman et al28 used MRI to determine the mandible

dimensions of children with OSA (24 subjects with mild to moderate OSA), and

demonstrated that a smaller mandible is not a feature in children with OSA.

The tonsils and adenoids grow progressively during childhood and usually

reach maximal size by the age of 1229. MRI has also shown that in children with habitual

snoring, enlarged tonsils and adenoids restrict the upper airway and that soft palate

volume is also larger in children with OSA30. Surgical treatment for OSA in these

children have been shown to reduce symptoms and improve, quality of life, and PSG

findings, thus providing evidence of beneficial effects of early AT31. However,

adenotonsillar hypertrophy is only one of the potential determinants of OSA in children

given that OSA persists in select patients after AT32.

In children with certain medical conditions, such as Down Syndrome, the

prevalence of OSA is much higher (30%-55%) than in otherwise healthy children33.

Craniofacial abnormalities which predispose these children to OSA include midfacial

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hypoplasia and mandibular hypoplasia, glossoptosis, an abnormally small upper airway

with superficially positioned tonsils and relative tonsillar and adenoidal hypertrophy,

hypopharyngeal collapse, tracheal stenosis, and laryngomalacia23,33.

Furthermore, cephalometric studies in children with OSA frequently report

narrower maxilla34, mandibular retrognathia35,36, longer lower facial height35-37, and

caudal placement of the hyoid bone38. A reduced upper airway sagittal width has also

been reported based on a reduced distance on lateral cephalometric radiographs as

measured from the posterior nasal spine to the adenoids. On average, this distance is

2.60-5.60mm shorter in children with OSA compared with healthy controls39 However,

other studies report no differences in measures of maxillary and mandibular width,

length, or volume between patients with OSA and normal control subjects40. Thus, the

contribution of skeletal abnormalities to the development of OSA in otherwise normal

children is controversial32.

In 2013, Flores-Mir et al, conducted a systematic review and meta-analysis to

consolidate the current knowledge of craniofacial morphological characteristics

associated with upper airway constriction resulting is OSA in children. Their study only

included cephalometric values and did not include a complete description of dentofacial

characteristics. The authors identified nine articles and found that three cephalometric

variables, the angle between the mandibular plane and sella nasion line (MP-SN), the

angle from SN to B point (SNB) and the angle from A point to nasion point to B point

(ANB), were significantly different between children with and without OSA. Children

with OSA had a steeper mandibular plane angle (MP-SN = +4.2°), a more retrusive

mandible (SNB = -1.79°), and were more likely to show a class II skeletal pattern (ANB

= +1.38°)41. Similar findings were found in the systematic review by Katyal et al39. The

authors demonstrated that children with OSA and primary snoring showed increased

weighted mean differences in the ANB angle of 1.64° and 1.54°, respectively, compared

with the controls. The increased ANB angle was primarily due to a decreased SNB angle

in children with primary snoring by 1.4°. In this meta-analysis, PSG was performed to

determine the presence and severity of OSA.

1.4.2 Upper Airway Collapsibility

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The pathophysiology of OSA in children is a complex interaction between an

airway predisposed toward collapse and neuromuscular compensation. Even though

anatomical determinants have been shown to be of critical importance to the development

of OSA, they do not completely account for the pattern of SDB32. Most children with

severe OSA are able to maintain normal sleep state distribution, particularly REM and

slow wave sleep, despite having obstructive apneic episodes4,42. This suggests that there

may be a compensation to maintain airway patency during obstructive episodes via

neuromuscular activation, ventilatory control, and arousal threshold32.

The significance of neuromuscular modulation in maintaining airway patency is

highlighted with three clinical observations: (1) apnea is observed predominantly in REM

and stage 2 sleep rather than in wakefulness or slow wave sleep4; (2) although sedated

and anesthetized children with OSA have narrower and more collapsible airways

compared with normal control children, there is considerable overlap40,43; and (3) during

sleep, most children with OSA intermittently attain a stable breathing pattern, suggesting

that reflex neuromuscular activation below the arousal threshold is possible44.

The pharyngeal dilator muscles responsible for modulating airflow through the

upper airway include the genioglossus, hyoglossus, and styloglossus. These muscles act

in unison and produce forward movement of the tongue, increase oropharyngeal airway

size and stiffness32. During wakefulness, children with OSA have an increased

genioglossus electromyography (EMG) recording levels compared with non-OSA control

children45 suggesting a reflex activation of the muscle via mucosal mechanoreceptors to

negative airway pressure. During the initial onset of sleep, this EMG activity decreases in

both OSA children and control subjects with a subsequent increase in airway resistance

and collapsibility of the airway. However, the EMG activity remains below the wakeful

baseline during stage 2 of sleep in normal children, suggesting a mechanically stable

airway. In contrast, most children with severe OSA have an increase in EMG activity

during sleep stage 2, suggesting the need for neuromuscular compensation to maintain

airway patency46.

During collapse of the upper airway, minute ventilation decreases, which induces

a compensatory increase in respiratory effort. This results in large negative luminal

pressure during inspiration. As a result, a ‘negative pressure reflex’ causes activation of

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pharyngeal dilator muscles to decrease airway collapsibility and increase minute

ventilation32. Marcus et al.47reported that children with OSA rely on arousal mechanisms

to sustain minute ventilation, which disrupts sleep homeostasis, whereas normal children

who were subjected to inspiratory resistance loading, were able to respond to the loading

with an increased inspiratory time and sustain loads without arousing for several minutes.

That is, normal children were able to perform the negative pressure reflex without

arousal, whereas, the negative pressures reflex is diminished or completely lost in

patients with OSA32.

In adults, the critical nasal pressure (Pcrit) at which the upper airway collapses is

higher in patients with OSA than in those with primary snoring. In 1994, Marcus et al48

compared the Pcrit between prepubertal children with OSA and those with primary

snoring. Pcrit was determined by correlating the maximal inspiratory airflow with the

level of positive or negative nasal pressure applied via a nasal mask. As in adults, they

found that the maximal inspiratory airflow varied in proportion to the upstream (nasal)

rather than the downstream (esophageal) pressure changes. Pcrit was 1 ±3 cmH2O in

OSA compared with -20 ± 9 cmH2O in primary snorers. They concluded that Pcrit, a

measure of airway collapsibility, correlated with the degree of upper airway obstruction

and was reduced postoperatively, consistent with increased upper airway stability.

The negative pressure reflex is important in maintaining upper airway patency by

exciting pharyngeal muscle dilators through neuromuscular compensation. It is plausible

that mucosal inflammation or edema could impair the afferent limb of this reflex. It is

hypothesized that snoring induces a mucosal inflammatory response resulting in swelling,

affecting upper airway resistance and/or collapsibility32. .

1.4.3 Inflammation

It has been previously established that OSA induces a systemic proinflammatory

response which can result in end-organ dysfunction49. Sleep apnea in children is

associated with increased inflammatory responses and increased plasma levels of C-

reactive protein(CRP) and interleukin-6 (IL-6)50. In 2014, Mutlu et al51 investigated the

clinical significance of preoperative serum CRP, interleukin-6 (IL-6), fetuin-A, cystatin

C, adiponectin and tumor necrosis factor-alpha (TNF-α) levels in children with

8

adenotonsillar hypertrophy and compared the results with post surgical values. They

found that levels of cytokines in children with SDB secondary to adenotonsillar

hypertrophy decreased after surgical treatment. They concluded that the risks of

development of cardiovascular disease are decreased in association with lower levels of

cytokines. 51.

Goldbart et al.52 have demonstrated the presence of upper airway inflammation in

children with OSA. They found increased expression of leukotriene receptors in tonsillar

tissue from children with OSA compared with children with recurrent throat infections.

In a subsequent study, Goldbart et al53 found an upregulation of the glucocorticoid

receptor gene (GCR) expression in OSA derived adenoid and tonsil tissues compared

with tissue from children with recurrent throat infections. Translational studies

incorporating intranasal corticosteroids54, leukotriene receptor antagonists55, or both56,

for the treatment of pediatric OSA have demonstrated a reduction in OSA severity. The

largest study to date looking at the anti-inflammatory therapy for mild OSA was

published in 2014 by Kheirandish-Gozal et al57. A combination of intranasal

corticosteroid (ICS) and oral montelukast (OM) for 12 weeks normalized PSG sleep

findings in 62% of their 752 sample size diagnosed with mild OSA. Thus, a combination

of ICS and OM as treatment of mild OSA appears to be effective and have lasting

effects57.

Tauman et al.58 first correlated the increase in CRP levels among American

children with OSA with AHI, arterial oxygen saturation, and arousal index measures.

Although CRP is a nonspecific marker of inflammation, recent epidemiologic studies

suggested that CRP may participate directly in atheromatous lesion formation through

reduction of nitric oxide synthesis and induction of the expression of particular adhesion

molecules in endothelial cells59. It was noted that these increases were prominent among

children who presented with neurobehavioral complaints. They suggested that

intermittent hypoxia and sleep fragmentation of OSA may underlie these systemic

inflammatory responses. However, a subsequent group from Greece found conflicting

results that CRP levels are not significantly different between control subjects and

children with OSA60.

Since the association of plasma CRP concentrations with OSA in childhood has

9

been inferred from several studies demonstrating increased circulating levels of CRP with

increasing severity of OSA, Bhattacharjee et al61 used CRP to assess if residual disease

persists post AT in children with OSA. They found that pre-AT AHI and post-AT CRP

levels were most significantly associated with residual OSA61.

OSA has also been associated with insulin resistance, hyperglycemia and

dyslipidemia in children62. Koren et al63 found that AT improved insulin sensitivity and

HDL levels, but not fasting glucose or other lipoprotein levels despite a parallel increase

in BMI z scores. This suggests that OSA is causally involved in creating an adverse

metabolic state independent from obesity because the metabolic changes did not differ

significantly between children without obesity and children with obesity or between boys

and girls. Fasting insulin was most strongly associated with post-AT AHI, such that more

children with insulin resistance were more likely to have residual OSA.

Koren et al64 followed up this study to assess the independent contributions of

OSA to insulin resistance and dyslipidemia in large pediatric cohort(n=459). They found

that although obesity was the primary driver of most associations between OSA and

metabolic measures, sleep duration was inversely associated with glucose levels, with

stage 3 Non REM sleep (N3) and REM sleep being negatively associated and sleep

fragmentation positively associated with insulin resistance measures. In children with

mild OSA, the presence of obesity increased the odds for insulin resistance, while higher

AHI values emerged among obese children who were more insulin-resistant64. Thus the

exclusive presence of interactions between OSA and obesity in the degree of insulin

resistance is coupled with synergistic contributions by sleep fragmentation to insulin

resistance in the context of obesity. Insufficient N3 or REM sleep may also contribute to

higher glycemic levels independent of obesity64.

It is difficult to distinguish between inflammatory mechanisms leading to SDB as

opposed to the systemic/local inflammation resulting from the presence of SDB.

However, most data support the concept of a disease that is associated with inflammation

that is ameliorated after surgery at the systemic and the local airway level. In contrast,

there are no data that confirm pre-existing inflammation in children with newly

diagnosed OSA65.

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1.5 Obesity and OSA

Since its initial description in 1976, obesity and OSA has become widely

recognized as a highly prevalent condition in children2. The last two decades has

witnessed a shift from the classic presentation of children with OSA (i.e. adenotonsillar

hypertrophy and failure to thrive) to a majority of children being overweight or obese,

even though adenotonsillar hypertrophy continues to play a role in the latter group66.

Early descriptions of childhood OSA rarely described obese patients. Most

children were of normal weight and failure to thrive was a common complication67.

However, with the epidemic of childhood obesity continually rising, the epidemiology of

childhood OSA is shifting towards obesity as being an important risk factor. The risk of

OSA is greatly increased by obesity in children, with an estimated prevalence ranging

from 19 to 61% depending on the definition of OSA, the degree of obesity and the age of

the study population68.

Compared to the estimated 3% prevalence of OSA in 2- to 8-year-old children15,

the risk of OSA in obese children has been estimated to be as high as 36%69, and may

exceed 60%70 when habitual snoring is present. The presence of both OSA and obesity

sets into motion a viscous cycle, where the presence of OSA affects metabolic

requirements which can perpetuate the tendency towards obesity71,72. In addition,

sleepiness will reduce the likelihood of engaging in physical activity and enhance eating

behaviors that favor calorie-dense foods66,72.Clinic-based and epidemiological studies

have confirmed that obesity is an important risk factor for OSA73 and is one of the

strongest predictors of SDB in both adults and children74. In a case-control study design,

Redline et al75 examined risk factors for SDB in children aged 2-18 years (n = 399), and

found that the risk among obese children was increased four to five fold.

The proposed physiologic mechanisms that may contribute to OSA in obese

children include anatomic and functional factors restricting the upper airway, alterations

in chest wall mechanics affecting lung volumes and upper airway collapsibility, and

inflammatory and metabolic factors that may perpetuate the disorder66,76.

11

Adenotonsillar hypertrophy has been recognized as an important anatomic cause

of restriction of the upper airway and contributing to the development of OSA in children

with obesity77-81 However, residual OSA after AT has been reported in 54-76% of these

children82 compared with approximately 15-20% in children without obesity80,83.

Nandalike et al84 were the first to quantify the volumetric changes in the upper airway in

children with obesity and OSA after AT. They found that AT increased the volume of the

nasopharynx and oropharynx, reduced tonsils, but had no effect on the adenoid, lingual

tonsil, or retropharyngeal nodes. They also noted a small significant increase in the

volume of the soft palate. These findings could explain the lower success rate of AT

reported in children with obesity and OSA.

With regards to obesity, the pathophysiologic mechanisms for OSA are both

mechanical and functional. Mechanically, deposition of adipose tissue within the base of

the tongue and the pharynx results in decreased airway size and increase airway

resistance85. Functionally, there is a reduced lung volume due to displacement of the

diaphragm by the obese abdomen and a decreased central ventilatory drive78. Using MRI,

Arens et al77 determined the anatomic risks factors associated with OSA in obese children

as compared with obese control subjects without OSA. As compared with control

subjects, subjects with OSA had a smaller oropharynx (P= 0.05) and larger adenoid (P =

0.01), tonsils (P = 0.05), and retropharyngeal nodes (P = 0.05). The size of lymphoid

tissues correlated with severity of OSA whereas BMI did not have a modifier effect on

these tissues. Subjects with OSA demonstrated increased size of parapharyngeal fat pads

(P= 0.05) and abdominal visceral fat (P =0.05). The size of these tissues did not correlate

with severity of OSA and BMI did not have a modifier effect on these tissues. In

conclusion, upper airway lymphoid hypertrophy is significant in obese children with

OSA. The lack of correlation of lymphoid tissue size with obesity suggests that this

hypertrophy is caused by other mechanisms. Although the parapharyngeal fat pads and

abdominal visceral fat are larger in obese children with OSA they could not find a direct

association with severity of OSA or with obesity77.

Recent evidence suggests that OSA is associated with a state of chronic

inflammation characterized by increased oxidative stress, pro-inflammatory cytokine

production, and metabolic deregulation86. It has been shown to also contribute to the

12

pathogenesis and progression of nonalcoholic fatty liver disease, via the deleterious

effects of chronic intermittent hypoxia on liver metabolism and inflammation87. Alkhouri

et al86 demonstrated that circulating markers of hepatocyte apoptosis were significantly

altered in children with OSA. More specifically, levels of soluble CD163, a marker of

macrophage activation, increased significantly in children with OSA and improved after

OSA treatment. These findings indicate that children with OSA have increased apoptotic

and inflammatory pressures86.

1.6 Complications of Pediatric OSA

It is now well established that SDB may lead to serious and measurable end-organ

dysfunction. This is especially important in children because of the risk of life-long

negative sequelae. The effects of untreated SDB include neurocognitive deficits,

cardiovascular complications, inflammation, growth impairment, reduction in health

related quality of life (HRQOL) and increased healthcare resource utilization.

1.6.1 Neurocognitive Complications

One of the most well-established long term sequelae of pediatric OSA is

behavioral and neurocognitive dysfunction1. Behavioral dysregulation is the most

commonly encountered comorbidity of OSA1. Sixty-one articles including over 29 000

children have directly explored the relationship between OSA and behavioral and

neurocognitive function88. The vast majority of studies consistently report some

association between OSA and hyperactivity, attention deficits and impulsivity1. Poor

school performance, impaired executive functioning, and an inverse relationships

between memory and learning have all been reported in children with OSA1.To

investigate a causal relationship between decrements in cognition and OSA, in the past

decade 19 studies have assessed neurocognition pre and post treatment for OSA1. The

majority of the studies have demonstrated significant improvements post treatment with

three studies demonstrating sustained improvements at more than a year post treatment88.

1.6.2. Cardiovascular Complications

The cardiovascular complications of SDB are of immediate importance because

earlier diagnosis and treatment can reverse these processes and prevent its consequences

13

in adult life1. Recurrent episodes of upper airway obstruction, which are characteristic of

OSA result in intermittent hypoxia, intrathoracic pressure swings and sleep

fragmentation. This results in autonomic system activation supported by the followings

findings: increased urinary cathecholamines, decreased pulse transit time and alterations

in blood pressure regulation in OSA1. Right ventricular dysfunction has also been

demonstrated1.Cardiac benefits of treatment for SDB have been shown. Plasma levels of

B-type natriuretic peptide, a marker of ventricular strain, has been found to be elevated in

children with SDB and to decrease after AT1. Similarly, there is evidence of

echocardiographic improvement of elevated pulmonary pressure also after AT1.

1.6.3 Inflammatory Complications

OSA also appears to cause low grade systemic inflammation and local

inflammation. This is thought to be the result of the intermittent hypoxia and sleep

fragmentation leading to the production of free radicals and systemic oxidative stress.

Increased circulating levels of CRP, as well as adhesion molecules have also been shown.

Anti-inflammatory therapy targeting upper airway inflammation has been shown to

improve residual OSA post AT1.

1.6.4 Somatic Growth Failure

OSA can also impair somatic growth. Failure to thrive has been reported in up to

50% of children presenting for AT89. The suggested etiologies include decreased caloric

intake, increased work of breathing as well as a reduction in growth factors such as

insulin like growth factor-1 and growth hormone. Selimoglu has demonstrated significant

increases in insulin like growth factor-1 six months after adenotonsillectomy90.

Furthermore, elevations in low density lipoprotein (LDL) cholesterol along with

reduced levels in high density lipoprotein (HDL) cholesterol were observed in both obese

and non-obese children with OSA, with significant improvements after OSA

treatment91,92.

14

1.6.5 Quality of Life and Healthcare Resource Utilization

Childhood SDB leads to significant decreases in HRQOL and these scores

significantly improve following treatment93.Healthcare resource utilization is a powerful

index of disease morbidity in children1. Healthcare resource utilization is significantly

increased and usage is elevated several years before an OSA diagnosis94. The total

number of admissions in children with OSA is 40% higher as compared to matched

controls.

In summary, SDB is associated with serious and measurable end-organ

dysfunction. Treatments for SDB are available and the benefits of treatment have been

demonstrated which argues for timely diagnosis and treatment of SDB to avoid long-term

negative sequelae.

1.7 Diagnosis

The management goals for childhood OSA are to 1) identify children who are at

risk for OSA; 2) diagnose children with OSA; and 3) treat children with OSA to prevent

negative sequelae of untreated disease. Diagnostic tools that have been studied include

clinical history and physical examination, patient questionnaires, and PSGs. Given the

resource intensive nature of PSGs in combination with the limited access to PSGs, the

pediatric sleep medicine field has tried to identify tools that can be used clinically to

screen for OSA.

1.7.1 Signs and Symptoms

The most common signs and symptoms, based on history and physical

examination of the child, associated with childhood OSA are summarized in Table 1.1.

Several studies have evaluated the use of history alone as a screening tool for the

diagnosis of OSA. Preutthipan et al95 aimed to determine whether parents’ observations

(such as observed cyanosis, snoring extremely loudly, shaking the child, being afraid of

apnea) could predict the severity of OSA. Although they found that some parent’s

observations are more frequently reported in children with OSA, neither any single nor

combination of observations accurately predicted the severity of OSA. They found an

15

overall poor sensitivity and specificity when evaluating various historical factors in

children with OSA.

Snoring is the most common clinical symptom of OSA. It is a sensitive, non-

specific, screening symptom for OSA29. If a history of nightly snoring is elicited, a more

detailed history regarding labored breathing during sleep, observed apnea, restless sleep,

diaphoresis, enuresis, cyanosis, excessive daytime sleepiness, and behavior or learning

problems (including attention-deficit/hyperactivity disorder (ADHD)) should be

obtained96.

In children with OSA, findings on physical examination during wakefulness are

most often normal. However, there may be non-specific findings related to adenotonsillar

hypertrophy, such as mouth breathing, nasal obstruction during wakefulness, adenoidal

faces, and hyponasal speech96.

Table 1.1 Signs and Symptoms of Pediatric OSA97

Daytime Symptoms Physical Examination

• Morning headaches • Daytime sleepiness • Diagnosis of ADHD • Learning problems • Irritability • Hyperactivity

• Underweight or overweight • Tonsillar hypertrophy • Adenoidal faces • Micrognathia/retrognathia • High-arched palate • Signs of cor pulmonale • Hypertension

Nocturnal Symptoms

• Snoring • Witnessed apneas • Gasping • Paradoxical Breathing • Neck hyperextension • Nocturnal Diaphoresis • Nocturnal enuresis

ADHD is a behavioral abnormality commonly seen in children and adolescents.

Its main symptoms include inattention, hyperactivity, and impulsivity98. Attention deficit

and hyperactivity are known possible symptoms or correlates of OSA99. Chervin100 and

O’Brien18 reported that children with mild symptoms of ADHD showed a high

16

prevalence of snoring and sleep problems. However, these associations may be missed in

children, because ADHD is a common primary diagnosis in itself. In conclusion, OSA

can mimic the signs of ADHD. Furthermore, unlike in adults, children with OSA,

especially younger children, rarely have excessive daytime sleepiness, and parental

reports of sleepiness vary with the questionnaire used99. If misdiagnosed as ADHD,

children may be subject to long-term methylphenidate, a commonly used medication for

ADHD, whereas recognition and treatment of the underlying sleep disorder should be

treated, to prevent unnecessary medication use.101.

A higher prevalence of nocturnal enuresis has been reported in children with

OSA. Although, the exact etiology is not yet known, it has been postulated that increased

enuresis may be because of the dampening effects of OSA on the arousal response,

changes in bladder pressure or possibly the secretion of hormones involved in fluid

regulation, such as atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) 102,103.

Nonetheless, in the majority of children with OSA, the physical examination is

normal. In addition, the presence of adenotonsillar hypertophy has not been shown to

reliably predict OSA104,105.

1.7.2 Questionnaires

Questionnaires have been developed as screening tools for the diagnosis of OSA.

At present, two of the more commonly used questionnaires to screen for SDB are the

Pediatric Sleep Questionnaire (PSQ)106 and the Spruyt and Gozal 6-item Sleep

Questionnaire107.

The PSQ (see Appendix B) was first published and validated in 2000 by Chervin

et al106. It consists of 22 item parent-reported questionnaire. It is composed of four

subscales for SDB, snoring, sleepiness, and behaviour. The PSQ performed slightly better

than other published questionnaires as a screening tool for the detection of OSA with a

sensitivity of 0.85 and a specificity of 0.87 when using an established cut-off score of

0.33 for the original validation study29. In a follow up study, using PSG to diagnose OSA,

Chervin et al108 subsequently found a lower sensitivity, 0.78 and specificity 0.72.

17

In 2012, Spruyt and Gozal107 (see Appendix A) developed a set of six

hierarchically arranged questions that aided in the screening of children at high risk for

SDB. A total of 1,133 children between the ages of 5- to 9-years-old were evaluated

using the questionnaire. All sleep-related questions used the Likert-type responses

“never” (0), “rarely” (once per week; 1), “occasionally” (twice per week; 2), “frequently”

(three to four times per week; 3) and “almost always” (>4 times per week; 4) for the

preceding 6-month time frame. Overall, the questionnaire had a sensitivity of 59.03%,

specificity of 82.85%, positive predictive value of 35.4 and negative predictive value of

92.7.

A 2002 systematic review by Schechter et al.109, looked at the use of

questionnaires as screening tools for OSA. The authors concluded that questionnaires had

an unacceptably low sensitivity and specificity for predicting OSA. This was further

confirmed in a more recent systematic review in 2014 by De Luca Canto et al110. These

authors concluded that the PSQ had sufficiently high sensitivity and specificity to be used

as a screening tool for OSA but not as a true diagnostic tool for pediatric OSA.

1.7.3 Polysomnography

The gold standard test to diagnose OSA is an overnight PSG, also known as a

level I study111. The overnight PSG is attended by a sleep technologist during which at

least seven physiological channels are measured. An overnight PSG monitors

electroencephalography (EEG), chin and leg electromyography (EMG),

electrooculography (EOG) and cardiorespiratory variables, including respiratory effort,

heart rate, oximetry and carbon dioxide levels for approximately 8 to 10 hours. The PSG

determines the AHI which describes the severity of OSA. AHI is defined as the number

of apneas and hypopneas per hour of total sleep time. Apnea is defined as a drop in the

peak airflow > 90% of baseline, with the drop lasting at least the duration of two breaths

during baseline breathing and is associated with the presence of respiratory effort

throughout the entire period of absent airflow. Hypopnea is defined as a drop in the peak

airflow > 30% of baseline, for the duration of at least two breaths in associations with

either > 3% oxygen desaturation or an arousal112. An AHI greater than 1.5 events per

hour is a positive diagnosis for OSA113-115.

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Though PSGs are the gold standard test for the diagnosis of pediatric OSA, there

are many challenges related to performing a PSG. These include: inconvenience to the

patient and, the relative scarcity of sleep laboratories with a resulting extended wait

period between referral and actual testing. In 2014, Katz et al116 aimed to describe

pediatric sleep physician and diagnostic testing resources for SDB in Canadian children.

They found marked disparities across the province/territories with many provinces having

no practitioners or access to PSGs. In the provinces that had access to PSGs, reported

wait times ranged from <1 month to 1.5-2 years. This study clearly demonstrated a lack

of resources and services for pediatric SDB across Canada, with pronounced disparities.

Even if only affected children were tested with PSG, the authors estimate there are 7.5

times more children with OSA than the current testing capacity in Canada116.

1.8 Pediatric Obstructive Sleep Apnea Treatment

Treatment for OSA must be individualized based on the clinical assessment,

anatomy of the upper airway and severity of the disease.

1.8.1 Adenotonsillectomy

The most common cause of childhood OSA is adenotonsillar hypertrophy117. The

first line treatment for OSA in these children is AT.

Early studies showed that pre-pubertal adolescents initially considered to have

been cured of OSA by AT subsequently had recurrence as teenagers. Guilleminault et al.

showed that subjects initially treated with AT had narrowing behind the base of the

tongue and oral-facial anatomical abnormalities that either did not exist initially or had

not been identified previously118..Tasker et found that a narrow upper airway and snoring

persisted 12 years after AT119. In another study Guilleminault et al. (n =207)

demonstrated that complete resolution of OSA following AT was present in only 51% in

non-obese pre-pubertal children that were studied with PSG 3 months post-operatively120.

More recently, in a large, multicenter retrospective study, Bhattacharjee et al. (n=500)

found that although AT led to significant improvements in indices of SDB in children,

residual disease was present in a large proportion of children (70%), particularly among

older (>7 yr) or obese children121. .

19

Marcus et al31 were the first to perform a randomized controlled study evaluating

the benefits and risks of AT, as compared with watchful waiting, for the management of

OSA. This Childhood Adenotonsillectomy Trail (CHAT) was designed to evaluate the

efficacy of early AT versus watchful waiting. A total of 464 obese and non-obese

otherwise healthy children between the ages of 5 to 9 years old age were included.

Children with an AHI score of more than 30 events per hour, an obstructive apnea index

(OAI) score of more than 20 events per hour, or arterial oxyhemoglobin saturation of less

than 90% for 2% or more of the total sleep time were not eligible, owing to the severity

of the PSG findings. The primary study outcome was the change in the attention and

executive-function score on the Developmental Neuropsychological Assessment

(NEPSY; scores range from 50 to 150, with 100 representing the population mean and

higher scores indicating better functioning)122. This test has well-established

psychometric properties122 and comprised three tasks (tower building, visual attention,

and auditory attention) performed under the supervision of a psychometrist. Secondary

outcomes for this study were caregiver and teacher ratings of behaviour, symptoms of

OSA, sleepiness, global quality of life, disease-specific quality of life, generalized

intellectual functions, and PSG indexes. They found that compared with a strategy of

watchful waiting, surgical treatment for obstructive sleep apnea in school-age children

did not significantly improve attention or executive function as measured by

neuropsychological testing but did reduce symptoms and improve secondary outcomes of

behavior, quality of life, and PSG findings, thus providing evidence of beneficial effects

of early AT31.

Substantial subgroup differences with regard to the normalization of PSG

findings post AT in Marcus’ et al31 randomized trial of AT were observed within each

study group. Regardless of the assigned treatment (surgery or watchful waiting),

normalization of PSG findings was seen less frequently in black children than in children

of other races, in children with obesity than in children without obesity, and in children

with a baseline AHI score above the median than in those with a baseline AHI score at or

below the median31. Among obese children, those randomly assigned to early AT had

greater reductions in symptoms and greater improvement in behavioral and PSG

outcomes than did those in the watchful waiting group31. However, there persistence of

20

OSA post AT was higher in the children with obesity as compared with the children

without obesity (33% vs. 15%)31.

Overall, the results of published data on the success of AT ranges from 24 to 100

percent in the literature123. In 2009, Friedman et al.123 performed an updated systematic

review of AT for the treatment of pediatric OSA. The meta-analysis included 1079

subjects with a mean age of 6.5 years of age. The effect measure was the percentage of

pediatric patients with OSA who were successfully treated with AT based on

preoperative and postoperative PSG data. When “cure” was defined as an AHI of <1, AT

was successful only 66.3% of the time. However, although complete resolution is not

achieved in most cases, it still offers significant improvements in AHI, making it a

valuable first-line treatment for pediatric patients.

Adenotonsillectomy yields improvements in children with OSA however

complete normalization occurs in only 25% of the patients, with obesity and AHI at

diagnosis being the major determinate for the success for surgical outcome81. Therefore,

obesity should be considered as an important, potential, contributor to residual airway

obstruction after surgery with its own, independent, contribution to the pathophysiology

of OSA124.

1.8.2 Positive Airway Pressure

Positive Airway Pressure (PAP) therapy is recommended for children with

moderate to severe OSA post AT or if a child is not a candidate for AT.

PAP therapy for OSA was first developed more than three decades ago125. PAP

works by counteracting the sleep-induced negative transmural pressure that promotes

collapse and narrowing of the collapsible upper airway. PAP therapy maintains upper

airway patency via the delivery of pressurized air through an interface that is worn over

the nose or the nose and mouth. This creates a “pneumatic splint” which prevents partial

or complete collapse of the upper airway during sleep125. The aim of PAP therapy is to

normalize the obstructive AHI, improve sleep quality and normalize gas exchange. There

are two types of PAP therapy that are delivered by a mask: 1) continuous pressure airway

pressure (CPAP) and 2) Bi-level positive airway pressure (BPAP) therapy. For both

21

CPAP and BPAP, the non-invasive interfaces include nasal pillows, nasal, oronasal and

full face options.

Although PAP therapy has been increasingly prescribed in children over the past

few decades due to advances in both the technology itself as well as the number of

interfaces that are available for children, the greatest barrier to PAP therapy is adherence.

In a recent study, DiFeo et al. prospectively studied children and adolescents and

concluded that PAP adherence is primarily related to family and demographic factors

rather than the severity of apnea or measures of psychosocial functioning126. This is an

additional challenge as the entire family often needs to be engaged for the child to be

adherent with PAP. Access to pediatric PSG is currently limited by a 12 -month waiting

period for PSG at Sick Kids alone, with similar wait times across Canada.

At present, the literature is insufficient and contradictory in describing the long

term effects of PAP therapy, on the development of the face, jaw, and teeth88. A few case

reports have suggested that early childhood long-term treatment using either CPAP or

BPAP carries a high risk of facial growth impairment, in particular, midface hypoplasia

and Class III malocclusions127,128. However, more recently, a small sample size, cross-

sectional study failed to show any statistically significant difference between long-term

PAP use and dentofacial abnormalities in children with persistent OSA129. This is an area

of needed further study.

1.8.3 Orthodontic Treatment

Persistent OSA post AT has also led to the consideration of orthodontic

modalities to treat OSA. There are several craniofacial abnormalities where imbalanced

development may contribute to OSA such as posterior crossbite, Class II skeletal and

dental patterns, and anterior open bite. Aside from aesthetic and occlusion benefits,

orthodontic treatment can help guide facial growth in order to correct facial imbalances,

improve swallowing, reposition tongue posture and re-establish nasal breathing130.

Early detection and treatment of children with OSA and facial imbalances may

prevent the sequelae of this disease. Early orthodontic treatment could prevent a need for

AT and provides another treatment option for children with OSA that are not adherent to

22

PAP therapy.

1.8.3.1 Rapid Maxillary Expansion

Rapid Maxillary Expansion (RME) is a common orthodontic procedure used to

correct maxillary arch constriction by opening the mid-palatal suture. It is a common

treatment modality to correct posterior crossbites in the primary, mixed, or permanent

dentition.

The precise role of maxillary constriction in the pathophysiology of OSA is

unclear. However, it is known that a significant number of children with OSA have nasal

obstruction (nasal septal deviation with or without turbinate hypertrophy) associated with

a narrow maxilla. Maxillary constriction is thought to increase nasal resistance and alter

tongue position, leading to narrowing of the retroglossal airway and subsequently the

development of OSA131.

There is no evidence to support that RME enlarges oropharyngeal airway volume.

Zhao et al132 retrospectively studied 24 adolescent patients (mean ±SD age 12.8 + 1.88

years) with maxillary constriction using hyrax palatal expanders and compared that to 24

control patients (mean ±SD age 12.8 + 1.85) undergoing routine orthodontic treatment

without palatal expansion. They used cone-beam computed tomography (CBCT) to

assess changes in the volume, length, and minimum cross-sectional area of the

oropharynx. They found no statistically significant differences between the groups.

On the other hand, RME has been shown to increase nasal width and nasal cavity

dimensions. Pirelli at el.133 investigated the effect of RME on 31 children (19 boys, 12

girls) with maxillary constriction, without adenoid hypertrophy, with OSA demonstrated

by PSG. RME was performed for 10 to 20 days with 6 to 12 months of retention. The

mean AHI fell from 12.2 events per hour to less than one event per hour, demonstrating a

resolution of the SDB.

In a further study, Pirelli et al.134 evaluated if RME in 42 children with a case

history of oral breathing, snoring, and night time apneas could improve the patency of

nasal breathing and OSA. Selection criteria included no adenotonsillar hypertrophy,

BMI<24, and narrow maxillary arch determined by posterior-anterior cephalometric

23

evaluation. Investigations were carried out before orthodontic treatment, one month after

treatment (T1) and after the end of orthodontic treatment (T2). All results were analyzed

by postero-anterior cephalometric evaluation in T0, T1, and T2. The results reported that

in all 42 patients, RPE therapy widens the nasal fossa and releases the septum restoring

normal nasal airflow with a disappearance of obstructive sleep disordered breathing134.

1.8.3.2 Functional Appliance Therapy

Functional appliances are removable or fixed intraoral devices which alter the

muscles forces against the teeth and craniofacial skeleton. They depend on altered

neuromuscular action to effect bony growth and occlusal development. They have been

used in children with OSA because functional appliances posture the mandible forward

and potentially enlarge the upper airway and increase the upper airspaces, improving the

respiratory function135.

In 2007, a Cochrane based review assessed the effectiveness of using functional

orthopaedic appliances for the treatment of OSA in children136. Out of 384 potentially

relevant studies, only 1 paper was included 137, demonstrating the lack of

methodologically sound research in this area. For example, there was an important

methodological problem with many papers not showing important information necessary

to assess their quality. Papers did not present information such as: how participants were

allocated to interventions, who generated the allocation, how sample size was determined

etc136.

Villa et al137, compared active oral appliance vs. no treatment and studied 32

children, with total apnea index (AI) of more than 1 event/hr diagnosed by PSG. A

decrease of at least 50% in the total AHI was considered treatment success. In 9/14

treated subjects, the AHI fell 50%. Although this study showed some results that favored

the intervention, the results must be considered with caution due to methodological

problems such as non-randomized generation of allocation, no allocation concealment, no

blinding, no sample size calculation reported, number of patients randomized different

from patients analyzed, high number of loss to follow up and no intention-to-treat

analysis was performed.

In conclusion, the available information is not enough to answer whether oral

24

appliances or functional appliances are effective in the treatment of sleep apnea in

children136.

1.9 OSA and Craniofacial and Dentofacial Development

Facial growth and development is primarily dictated by genetic factors, but

environmental inputs also contribute, in particular, with respect to the mode of breathing.

Children who suffer from respiratory problems and OSA commonly exhibit disturbances

in dentofacial morphology. The growth of the dentofacial regions follows the functional

matrix theory; that is, growth occurs in response to functional needs and possibly in

response to the growth of the nasal cartilage138.

Linder-Aronson139 proposed the cause-and-effect pathway of reduced nasal

breathing during wakefulness and resultant craniofacial abnormality. When nasal

breathing is reduced, possibly from enlarged adenoids or an anatomical defect (i.e.

decreased nasal width or nasal septal deviation), mouth breathing is inevitable as the

primary mode of respiration.

Mouth breathing leads to an altered pattern of muscle recruitment in the oral and

nasal capsule, which ultimately results in skeletal changes 140.The important role of

abnormal nasal resistance during the early developmental period was demonstrated from

studies on infant rhesus monkeys140.A small silicone head was placed within the nostrils

of infant rhesus monkeys in order to induce nasal resistance for the first 6 months of

life140,141. The blockage of the nasal passage led to narrowing of the dental arches,

decrease in maxillary length, anterior cross bite, maxillary overjet and an increase in

anterior facial height140. These changes were shown to be reversible if the experimental

nasal resistance was withdrawn while the infant monkey was still in its developmental

phase.

In children, mouth breathing is most commonly associated with: an extended

posture of the head (3 to 5 degree extended craniocervical posture); retrognathic

mandible; a larger anterior facial height; a steeper mandibular plane; a lowered position

of the hyoid bone; an antero-inferior posture of the tongue compared to normal children

and a high palatal vault142. This pattern of findings has been termed “long face

25

syndrome,” and is similar to the reported cephalometric findings in children with OSA35-

37. Comparable changes in the craniofacial structure have been described in a group of

subjects with large tonsils, which has been termed the “adenoidal face”139. The adenoid

face is characterized by an incompetent lip seal, a narrow upper dental arch, retroclined

mandibular incisors, increased anterior face height, a steep mandibular plane angle, and

retrognathic mandible compared with faces of healthy controls139. Thus, not only does

upper airway obstruction predispose to OSA, but it also has an adverse effect on

craniofacial development, posing an increased future risk of OSA32.

The literature reports mixed results with regards to the resolution versus the

persistence of craniofacial abnormalities after treatment for OSA. On the one hand, some

studies have shown that cephalometric variables normalize after treatment of OSA in

children. In a five year follow up study after AT in children with OSA, resolution of

maxillary and mandibular inclination abnormalities and lower face height was

observed37. On the other hand, it has been shown that open bites and cross-bites are

observed 2 years after AT in most patients143. As a general rule, if treatment is initiated at

a young enough age (before 6 years of age), the long-term dentoalveolar development is

more likely to normalize143. Dentofacial anomalies can also present as malocclusions that

can be observed during intra-oral examination. Posterior crossbite, Class II skeletal and

dental patterns, and anterior open bite have been found to be more prevalent in OSA

children versus healthy controls143. The remainder of the reported occlusal characteristics

varies significantly among the literature in children with OSA, emphasizing the need for

further research on this topic. The specific reported prevalence’s of posterior crossbite in

children with OSA ranges between 16.7% - 68.2%39,144 versus reported controls 2.4%-

23.2%39,145. The prevalence of Class II skeletal and dental patterns in OSA children

ranges in the literature between 29.3%-88%144,145 versus controls 4.9%-28%145,146. Lately,

the reported prevalence of anterior open bite in OSA children ranges between 5%-

20%67,144 and 0% in the control groups145.

1.10 Rationale

A formal dental evaluation is not standard of care for either children referred to sleep

clinics for query obstructive sleep apnea or those prescribed PAP therapy for the

treatment of OSA. Sleep physicians perform a cursory craniofacial examination including

26

a basic assessment of maxillary constriction and mandibular hypoplasia. Given the

emerging evidence in the literature demonstrating an improvement in OSA with

orthodontic treatment, as well as the limited literature suggesting midfacial hypoplasia

and class III malocclusions as a result of ongoing PAP therapy, a needed first step is to

understand the prevalence of malocclusion and dental anomalies in children referred to a

sleep center for query OSA. It is also important to understand how this prevalence differs

in children that are currently being treated for OSA with PAP therapy. Determining the

prevalence of dental abnormalities and malocclusion in these cohorts of children will

inform future interventional studies to look at the relative efficacies of different treatment

interventions.

1.11 Study Aim

The aim of our study is to report on the prevalence of dentofacial abnormalities in

children with suspected OSA who have been referred for a PSG at Sick Kids.

.

27

Chapter 2 Materials and Methods

2.1 Subjects

Ethics approval was obtained from both the University of Toronto Health

Sciences Research Ethics Board (#31147) and the Hospital for Sick Children's Research

Ethics Board (REB #1000047032). Children referred to the sleep laboratory at the

Hospital for Sick Children, Toronto, Ontario, Canada for overnight PSG between March

2015 to April 2016 were invited to participate in the study (n=100). The subjects were

selected according to the inclusion and exclusion criteria listed in Table 2.1. Informed

consent was obtained verbally and in writing from all study participants and/or their

parents/legal guardian. Study assent was obtained when appropriate.

Table 2.1 Inclusion and Exclusion Criteria.

Inclusion Criteria Exclusion Criteria

• Age 4-18 years

• Referred for an overnight PSG study at the sleep laboratory at the Hospital for Sick Children

• Craniofacial abnormality related to an underlying genetic syndrome

• Children and/or parental caregivers not proficient in English

2.2 Study Procedures

The study procedures are summarized in Table 2.2. A complete description is

provided in the methods section below for each study procedure. All study procedures

were completed at the clinically scheduled overnight sleep study.

28

Table 2.2 Summary of Study Procedures

Study Procedure Description Time To Complete

Enrollment and Consent into study Consent obtained from parent/guardian and patient (if appropriate)

3-5 Minutes

Demographic and Clinical Measures Patient and parent information collected 2-3 Minutes

Sleep Questionnaires Spruyt and Gozal Questionnaire Pediatric Sleep Questionnaire

10 Minutes

Clinical Orthodontic Examination All dental examinations completed by Dr. David Simone. Extra-oral and intra-oral exam data collected.

5-10 Minutes

Polysomnogram* PSG undertaken by trained technologists according to the international guidelines111

8-10 hours

* The polysomnogram was clinically indicated and not a research specific study procedure

2.3.Demographics and Anthropometric Measures

The following demographic and anthropometric information was collected from

each patient: 1) age; 2) date of birth; 3) gender; 4) country of origin of mother; 5) country

of origin of father; 6) body type, 7) height, and (8) weight.

Each patient’s BMI was calculated using the formula BMI = Weight (kg)/ Height2

(m2). Each patient's BMI was then converted into a percentile for the population

according to the patient’s age and gender using the published data by the CDC147. Weight

status category was determined from each patient’s BMI percentile according to the

CDC’s guidelines (Table 2-3)148.

Table 2.3 CDC Weight Categories

Weight Status Category Percentile Range

Underweight Less than the 5th percentile

Normal/Healthy Weight 5th percentile to less than 85th percentile

Overweight 85th to less than the 95th percentile

Obese Equal to or greater than the 95th percentile

29

2.4 Sleep Questionnaires

2.4.1 Spruyt and Gozal Questionnaire 107

The Spruyt and Gozal questionnaire was developed in 2012 and intended to be a

screening tool for SDB (see Appendix A). All study participants completed this

questionnaire. The questionnaire consists of six questions.

For the development and validation of the questionnaire, 1,133 urban children

with habitual snoring between the ages of 5 to 9 years of age that had undergone a PSG

were included. This sample was analyzed based on established AHI cutoffs. The

investigators developed a set of six ordered questions that allows for fair discrimination

along the SDB spectrum. The questions can be found in Appendix A.

Questions 1-4 and question 6 use Likert-type responses including: 1) never; 2)

rarely; 3) occasionally; 4) frequently; 5) almost always “Question 5 uses the following

scale with regards to snoring: 1) mildly quiet; 2) medium loud; 3) loud; 4) very loud and ;

5) extremely loud.

The total score for the questionnaire represents the average score of all six

questions, according to the following formula (where Q1= raw score to question 1, Q2 =

raw score to question 2, and so forth): A = (Q1+Q2)/2; B = (A+Q3)/2; C = (B+Q4)/2; D

= (C+Q5)/2; and the cumulative score = (D+Q6)/2. Based on the original validation

study, a score greater or equal to 2.72 out of 4 was indicative of a high risk for OSA107.

2.4.2 Pediatric Sleep Questionnaire

Parents/guardians were also asked to complete the PSQ. The PSQ was developed

and validated for sleep disorders in 2000 by Chervin et al106,108. Chervin et al studied

children aged 2-18 years who had PSG confirmed sleep related breathing disorders

(SRDB). Items thought to be predictive of SRBDs in children were formulated based on

clinical experience. This produced a 22-item questionnaire that was strongly associated

with diagnosis of SRBD (P<0.0001) (see Appendix B). The following options were

available for each of the 22 items on the PSQ: yes, no or don’t know. The number of

symptom-items endorsed positively (“yes”) was divided by the number of items

answered positively or negatively; the denominator therefore excluded items with

missing responses and items answered as don’t know. The result was a score, that ranged

30

from 0.0 to 1.0. Scores > 0.33 were considered positive and suggestive of pediatric SDB.

This threshold was based on a validation study demonstrating optimal sensitivity and

specificity at the 0.33 cut-off108.

2.5 Clinical Orthodontic Examination

All study participants underwent a comprehensive, clinical orthodontic

examination by the same examiner (D.S.), blinded to any reported signs and symptoms of

query OSA. The examination consisted of dental, skeletal, functional and esthetic

characteristics which were subdivided into four sections: (1) Frontal View, (2) Profile

View, (3) Functional, (4) Intra Oral. The examination lasted approximately 5-10 minutes.

2.5.1 Frontal View

Table 2.4 outlines the examination in the frontal view. Facial type and lower face

height were categorized as brachycephalic if the lower third was shorter than the average,

mesocephalic if the lower third was longer than the average, or dolichocephalic if the

lower third was much larger than the average. Mandibular symmetry was assessed if the

chin point was deviated from the facial midline, in the absence of a functional shift, and

the relationship of the dental midline to the facial midline. Incisor and gingival display at

both rest and smile were measured clinically using a flexible plastic ruler with 1mm

accuracy.

Table 2.4 Frontal View Examination

Front View

1. Type facial (if borderline, choose mesocephalic)

☐Mesocephalic ☐Brachycephalic ☐Dolichocephalic

2. Lower Face Height ☐Normal ☐Increased ☐Decreased

3. Symmetry ☐Symmetric ☐Mandible shift to Right ☐Mandible shift to Left

4. Dental Midlines (midline – use cusp of upper lip)

Upper : ☐on with facial midline ☐shift to Right ☐ shift to Left; Amount : ____mm

Lower : ☐on with facial midline ☐ shift to Right ☐ shift to Left; Amount : ____mm

5. Incisor display at rest ____mm

6. Gingival display on smile ____mm

7. Incisor display on smile ____mm

31

2.5.2 Profile View

Table 2.5 outlines the examination from the profile view. Facial profile was

assessed by measuring the angle formed by a line dropped from soft tissue nasion (i.e.

bridge of nose) to subnasale (i.e. base of the upper lip) and a second line extending from

subnasale to soft tissue pogonion (i.e. chin point). An acute angle would indicate a

convex profile; an obtuse angle would indicate a concave profile; and a straight line

would indicate a straight profile. Lip position was determined relative to a straight line

drawn from the tip of the nose to the most anterior curvature of the soft tissue chin. Lip

strain on closing was assessed by the activity of the mentalis muscle.

Table 2.5 Profile View Examination

Profile View

8. Facial Profile ☐Straight ☐Concave ☐Convex

9. Skeletal position - Maxilla ☐Retrognathic ☐Normal ☐Prognathic

10. Skeletal position - Mandible ☐Retrognathic ☐Normal ☐Prognathic

11. Nasiolabial Angle ☐Normal 90º-100 º ☐Acute (< 90 º) ☐Obtuse (>100 º)

Lip Position:

12. With respect to esthetic line: Upper lip

☐Normal ☐Retrusive ☐Protrusive

13. With respect to esthetic line: Lower lip ☐Normal ☐Retrusive ☐Protrusive

14. Lip strain to close ☐Yes ☐No

2.5.3 Functional

Table 2.6 outlines the Functional Assessment portion of the examination. Tonsil

size was evaluated according to the Standardized Tonsillar Hypertrophy Grading

Scale149. Tonsil size 0 denoted surgically removed tonsils. Size 1 implied tonsils hidden

within the pillars. Tonsil size 2 implied the tonsils extending to the pillars. Size 3 tonsils

were beyond the pillars but not to the midline. Tonsil size 4 implied tonsils extend to the

midline149.

32

Table 2.6 Functional Assessment

Functional

15. Tonsils ☐Removed ☐1+ ☐2+ ☐3+ ☐4+ (kissing tonsils)

16. History of Mouth Breathing

☐Yes: If YES specify: ☐During Day Time ☐During Night Time ☐ No

2.5.4 Intra-Oral

Table 2.7 outlines the intra-oral portion of the clinical examination. The intra-oral

examination included both vertical and horizontal discrepancies, molar and canine

Angle’s classification, presence of crossbites, and maxillary and/or mandibular crowding

or spacing.

Angles classification of occlusion was assessed for both left and right sides of the

dentition. Subjects in the permanent dentition were classified as having a Class I, Class

II, or Class III malocclusion. Class I occlusion is defined as the mesiobuccal cusp of the

permanent maxillary first molar occluding in the buccal groove of the permanent

mandibular first molar. Class II malocclusion is defined as the mesiobuccal cusp of the

permanent maxillary first molar occluding from a half to full cusp mesial to the buccal

groove of the permanent mandibular first molar. Subjects were classified as Class III

when the mesiobuccal cusp of the permanent maxillary first molar occluded from a half

to full cusp distal to the buccal groove of the permanent mandibular first molar. Subjects

in the primary or mixed dentition were classified as flush terminal plane, mesial step, or

distal step occlusion. Flush terminal plane is defined when the distal surfaces of maxillary

and mandibular primary second molars that lie in the same vertical plane. Mesial step is

defined when the primary mandibular 2nd molar is mesial in relation to the maxillary 2nd

molar and distal step when the primary mandibular 2nd molar is posterior to the distal

surface of the maxillary 2nd molar.

The presence of deep-bites, open-bites, crossbites, and scissor-bites as well as

crowding, were assessed and classified according to the method described by Björk et al.

(1964)150. Vertical excess (i.e. overbite) was measured by taking the average

measurement of both central incisors. Overbite was expressed as the percentage that the

upper incisors vertically overlap the lower incisors. Horizontal excess (i.e. overjet) was

33

also measured by taking the average measurement of both central incisors and measuring

the horizontal (anterior-posterior) overlaps of the maxillary central incisors over the

mandibular central incisors. Posterior crossbites were recorded if the buccal cusp of the

upper tooth occluded edge-to-edge, or lingually, to the buccal cusp of the corresponding

lower tooth. Posterior crossbites included cross bites of the primary or permanent molars

and canines as well as permanent premolars. Crowding or spacing of the arch was

evaluated by calculating the amount of overlap or space between the interproximal

contacts of erupted teeth. In mixed dentition, this was done with the assumption that

unerupted permanent canines, first premolars and second premolars will occupy 7mm of

the mesio-distal arch dimension. The overall crowding or spacing was divided into mild

(1-3 mm), moderate (4-9 mm), or severe (>10 mm). Intercanine width and intermolar

width was measured using a Boley gauge with 0.01mm accuracy. Intercanine width was

measured from the cusp tips of the maxillary right and left primary and permanent

canines. Intermolar width was measured from the junction of the lingual groove at the

gingival margin between the maxillary left and right primary second molars and

permanent first molars.

The Index of Orthodontic Treatment Need (IOTN) esthetic scale ranks

malocclusion in terms of the perceived esthetic impairment in order to identify those who

would most likely benefit from orthodontic treatment151.

Table 2.7 Intra-Oral Examination

Intra oral

17. Oral Habits ☐Yes ☐No If YES, since When :____________years

Which? ☐Nail Biting ☐Biting lip/cheek ☐Bruxism ☐Sucking Thumb/finger ☐Other:______________________

18. Horizontal Excess (taken at average of both central incisors, labial to labial)

Overjet: ☐☐☐mm

19. Vertical Excess (taken at average of both central incisors, labial to labial)

Overbite: ☐☐☐%

20. Anterior OpenBite Open bite: ☐☐☐mm

21. Posterior Openbite R ☐☐☐mm

22. Posterior OpenBite L ☐☐☐mm

34

23. Odontogram 8 7 6 5 4 3 2 1 1 2 3 4 5 6 7 8

E D C B A A B C D E

E D C B A A B C D E

8 7 6 5 4 3 1 1 2 3 4 5 6 7 8

24. Dental crossbite (including edge-to-edge bite)

Anterior crossbite: ☐Yes; If YES, # of maxillary teeth involved: ____ ☐No

Posterior crossbite: ☐Yes ☐Unilateral; If YES, # of maxillary teeth involved: ___

☐Bilateral

☐No

25. Narrow Palate ☐Yes ☐No

26. CR/CO shift ☐Yes, specify: ☐Posterior - anterior ☐Vertically

☐To the right ☐To the left

☐No

27. Intermolar distance (measured from mid-palatal groove @ gingival margin)

☐☐☐mm

28. Intercanine distance (measured from cusp tip)

☐☐☐mm

29. Tongue size ☐Normal ☐Microglassia ☐Macroglossia

30. Arch Shape Upper: ☐U shape ☐V shape Lower : ☐U shape ☐V shape

31. Palatal Depth ☐☐☐mm

32. Stage of dentition ☐Primary ☐Mixed ☐Permanent (No primary teeth present)

33. Molar Classification (according to R and L sides)

Permanent: (<1/2 cusp = cl.1) Right: ☐I ☐II ☐III Left: ☐I ☐II ☐III

Primary/mixed: Right: ☐Mesial step ☐Flush ☐Distal Step Left : ☐Mesial step ☐Flush ☐Distal Step

34. Canine Classification (<1/2 cusp = cl.1)

Right: ☐I ☐II ☐III Left: ☐I ☐II ☐III

35. Space Analysis ☐crowding Upper: ☐<3 mm ☐4-9 mm ☐>10mm

Lower: ☐<3 mm ☐4-9 mm ☐>10mm ☐spacing

Upper: ☐<3 mm ☐4-9 mm ☐>10mm Lower: ☐<3 mm ☐ 4-9 mm ☐>10mm

35

36. IOTN esthetic scale (match for overall occlusal attractiveness)

2.6 Polysomnogram

Subjects underwent a standard level one overnight baseline PSG using XLTEC

(Oakville, Canada) data acquisition and analysis system. Sleep architecture and

respiratory data were assessed 27 and information was obtained from PSG and scored

according to the AASM scoring guidelines by a registered polysomnogprahic

technician28. A standard overnight PSG lasting approximately 8-10 hours included a 4-

lead EEG (C3, C4, O1, and O2), two bilateral EOG leads referenced to A1 or A2, one

submental and two tibial EMGs. Respiratory measurements included chest wall and

abdominal movement using inductance pneumography; airflow using a nasal cannula

connected to a Nasal Pressure Airflow (NPAF) by Braebon; oxygen saturation (SaO2)

using a Massimo pulse oximeter (Irvine, CA); transcutaneous carbon dioxide

36

measurement (TcCO2) using a LINDE carbon dioxide sensor (Munich, Germany). Video

and audio recordings were obtained for each study. The raw data from the

polysomnograms were scored according to the AASM guidelines, as is current clinical

practice152. Scoring involved the quantification of sleep staging, respiratory events,

oxygen saturations and carbon dioxide recordings. Sleep architecture was assessed by

standard techniques. Information obtained from each PSG included: sleep onset latency

and REM onset latency, total sleep time, sleep efficiency, time spent in each sleep stage

(percentage), and number and classification of arousals and snoring. Respiratory events

included obstructive apneas and hypopneas, mixed apneas as well as central apneas and

hypopneas.

The diagnosis and severity of OSA in children was based on the frequency of

obstructive apneas, obstructive hypopneas, mixed apneas, central apneas and central

hypopneas per hour during sleep as well as gas exchange characteristics. These were

recorded as the obstructive apnea-hypopnea index (OAHI), central apnea-hypopnea index

(CAI), baseline mean oxygen saturation and percentage of time the C02 is >50mmHg.

OSA and central apnea (CA) severity will be graded according to accepted clinical

criteria. An OAHI of <1.5 and CAI <1 is normal, an OAHI of >1.5 to <5 and CAI of >1

to <5 indicates mild OSAS and CAI, an OAHI or CAI of >5 to <10 indicates moderate

OSA and CA, and an OAHI or CAO of ≥10 indicates severe OSA and CA152. Nocturnal

hypoventilation (C02 recording >50mmHg for >25% of the night), if present, was

reported from the PSG. All PSGs were reported by one of the three clinical sleep

physicians at The Hospital for Sick Children.

2.7 Statistical Analysis

Descriptive statistics were used to summarize the study results. Intra-rater

reliability testing was assessed for the orthodontic clinical examination. ICC was used for

the continuous rating scale and Kappa statistics for the categorical. 95% confidence

intervals are given for the estimates.

To calculate intra-rater reliability, ten patient records from the Graduate

Orthodontic Clinic of the University of Toronto were randomly selected as the sample for

error analysis. An orthodontic examination was performed on 10 different patients at 2

37

different time points, 6 months apart, using the same full orthodontic methodology

(photographs, radiographs and study models). After 6 months, the orthodontic

examination was repeated on the same 10 patients using the same full orthodontic

records. Intra-rater reliability was calculated using the student’s t-test for linear

measurements and percent agreement for categorical measurements.

Data (for the primary analysis) are presented as the mean + standard deviation for

continuous variables and as percentages for categorical variables. Independent

Students t tests were used to compare continuous data and Analysis of Variance

(ANOVA) was used to compare differences between multiple (more than 2) groups. Chi-

square test was used to compare the categorical data. ROC analysis was used to find the

area under the curve, sensitivity, specificity and the confidence around them. Odds ratios

(OR) associated with the presence or absence of characteristics and mean values with

95% CI values were also calculated. Univariate and Multiple Logistic regression was

used to assess the relationship between independent predictor variables and binary

outcomes (OSA). Variables were considered significant at the 5% significance level.

Data were analyzed using SAS/STAT Software, version 9.4 (North Carolina).

2.8 Study Outcomes

The primary outcome was the prevalence of dentofacial abnormalities and

malocclusions in a cohort of children with and without obesity who were referred for a

polysomnogram because of a history of query OSA. Our secondary outcome measure

was the identification of clinical factors that can predict the obstructive apnea-hypopnea

index (OAHI), a measure of the OSA severity, in this referred cohort of children.

2.9 Hypothesis

Our study hypothesis was that there will be an increased prevalence of dentofacial

abnormalities and malocclusions in children with and without obesity with a PSG

diagnosis of OSA as compared to those without a PSG diagnosis of OSA.

38

Chapter 3 Results

3.1 Intra-rater Reliability

A total of 29 data collection points were used to determine the intra-rater

reliability. The results for percent agreement for categorical and continuous variables

between the two different time points were assessed using kappa and intraclass

correlation coefficients (ICC), respectively (see Table 3.1). To interpret our results we

used a benchmark cut-off proposed by Landis and Koch:153 Cohen’s kappas ≥ 0.80

represent excellent agreement; coefficients between 0.61 and 0.80 represent substantial

agreement; coefficients between 0.41 and 0.61 moderate agreement; and <0.41 represent

fair to poor agreement.

Table 3.1 Intra-rater reliability. Percent agreement, Kappa and Intraclass Correlation Coefficient of repeated orthodontic examination measurements recorded 6 months apart

Measurement Percent Agreement (%) kappa

Profile 100 1.00

Symmetry 100 1.00

Anterior Openbite 100 1.00

Crossbite 100 1.00

Maxillary Teeth Involved 100 1.00

Posterior Openbite 100 1.00

Stage of Dentition 100 1.00

Permanent Molar Classification Right 100 1.00

Permanent Molar Classification Left 100 1.00

Spacing Mandible 100 0.76

Spacing Maxilla 100 0.66

Skeletal Position Maxilla 90 0.69

Upper Lip with respect to E-Line 90 1.00

39

Lower Lip with respect to E-line 90 1.00

Facial Type 90 1.00

Mandibular Arch Shape 90 1.00

Canine Classification Right 90 0.69

Canine Classification Left 90 0.69

Upper Dental Midline 80 0.56

Lower Dental Midline 80 0.61

Skeletal Position Mandible 80 0.69

Maxillary Arch Shape 80 0.60

Nasiolabial Angle 80 0.76

Lower Face Height 80 0.60

Narrow Palate 70 0.35

ICC 95% Confidence Interval

Lower Bound Upper Bound

Overjet (mm) 0.90 0.65 0.98

Overbite (% overlap of incisors) 0.98 0.91 0.99

Intermolar Distance (mm) 0.94 0.79 0.99

Intercanine Distance (mm) 0.96 0.86 0.99

Overall, the agreement for the categorical variables assessed ranged from

0.35(poor agreement) to 1.0 (excellent agreement). Profile, symmetry, anterior openbite,

crossbite, posterior openbite, stage of dentition and molar classification had the highest

Cohen’s kappa (k=1.0), while upper dental midline and narrow palate had the lowest (k=

0.56 and k= 0.35). All continuous measurements had excellent agreement (ICC ranging

from 0.90-0.98).

3.2 Study Participants

One hundred and two children were screened for the study. Two patients declined

study participation. A reason for declining consent was not given. One hundred children

with a mean (standard deviation) age 10.5 (SD 3.8) years participated in the study over

40

the recruitment period of 13 months (March 2015 - April 2016). The subjects were

divided into five different groups (see Table 3.2) based on: 1) PSG diagnosis of OSA, 2)

CDC weight status category (BMI percentile range) and 3) history of treatment with PAP

therapy.

Based on the PSG findings, subjects were divided into an OSA group (OAHI >1.5

events per hour) and a non-OSA group (OAHI <1.5 events per hour). On the basis of

weight status category, BMI- for-age percentile growth charts were used to divide

subjects into a non-obese group (BMI< 95th percentile) and an obese group (BMI > 95th

percentile). The fifth group included children that were prescribed PAP therapy.

Table 3.2 Subject Groups

Group # Group Category

1 Non-Obese and No OSA

2 Non-Obese and OSA

3 Obese and No OSA

4 Obese and OSA

5 PAP treatment

See Table 3.3 for the demographic information for the four study cohorts,

excluding the PAP treatment group. The mean BMI, BMI percentile, height, weight, and

presence of mouth breathing were significantly different between the cohorts. The Non-

Obese and OSA group had the highest percentage of snorers (90.7%), mouth breathers

(100%), and children with increased tonsillar size> 3 (50%). However, mouth breathing

was not statically significant between the cohorts (p=0.062).

41

Table 3.3 Demographics of the Four Study Cohorts (excluding PAP group)

Table 3.4 compares the demographic information for the subjects with and

without OSA (excluding the PAP group). When the subjects were divided based on OSA

diagnosis, there were no significant demographic differences between the groups.

Non-Obese and No OSA

Non-Obese and OSA

Obese and No OSA

Obese and OSA

P value

Sample Size (n) 21 11 28 27

Age (years) 9.4 (3.6) 8.18(4.69) 10.93(3.74) 11.0(3.92) 0.13

Male (%) 17 (81) 7(63.6) 16(57.1) 21(77.8) 0.12

BMI (kg/m2) 19.54 (3.85) 17.17 (3.17) 30.53 (8.25) 33.39(9.73) <0.0001

BMI Centile 75.81 (20.45) 53.27 (26.63) 98.11 (1.13) 98.11(1.42) <0.0001

Height (cm) 136.33 (22.24) 128.55 (25.01) 150.07 (17.34) 150.63(20.10) 0.0038

Weight (kg) 39.22 (20.26) 31.0 (19.58) 70.73(31.59) 108.42(33.31) <0.0001

Snoring 14 (66.7) 10 (90.9) 22(78.6) 24(88.9) 0.20

Mouth Breather 15(71.4) 11 (100) 22(78.6) 15(55.6) 0.0355

Increased Tonsillar Size >3 6(28.6) 5(50) 3(10.7) 5(18.5) 0.06

* Statistics shown for categorical variables are n (%) from the population with available data as continuous variables are mean (SD), unless otherwise specified.

42

Table 3.4 Demographics of OSA vs. No OSA Groups (excluding PAP group)

OSA

(n=38)

No OSA

(n=49)

p-value

Age (Years) 10.2(4.3) 10.3(3.7) 0.91

Male 28(73.7) 33(67.4) 0.52

BMI (kg/m2) 28.69(11.17) 25.82(8.64) 0.19

BMI Centile 85.13(24.85) 88.55(17.30) 0.45

Height (cm) 144.2(23.58) 144.2(20.55) 0.99

Weight (kg) 66.51(41.54) 57.23(31.31) 0.26

Snoring 34(89.5) 36(73.5) 0.06

Mouth Breather 26(68.4) 37(75.5) 0.46

Increased Tonsillar Size >3 10(27.0) 9(18.4) 0.34

* Statistics shown for categorical variables are n (%) from the population with available data as continuous variables are mean (SD), unless otherwise specified.

3.3 Polysomnography Results

See Table 3.5 for a summary of the PSG findings across the four cohorts.

Significant findings included sleep state distribution %N1 sleep, sleep stage distribution

% REM sleep, total arousal index, respiratory events arousal index, oxygen desaturation

index, maximum respiratory rate, mean respiratory rate, maximum transcutaneous carbon

dioxide (tcCO2), percent of sleep time with end-tidal carbon dioxide (EtCO2) above

50mmHg,OAHI index and AHI index. The OAHI and AHI were significantly different

across the four groups and were the highest in the Obese and OSA group with a mean

(SD) OAHI of 12.31(15.42), (p=<0.0001) and 13.15(15.33), (p=<0.0001), respectively.

Table 3.5 PSG Results across the Four Cohorts (excluding PAP group)


Non-Obese and OSA

Obese and No OSA

Obese and OSA P value

Total Sleep Time (TST) (minutes) 426.7 (45.6) 414.9 (66.7) 360.2 (113.5) 365.1 (63.1) 0.14

Sleep Efficiency (%) 84.8 (9.1) 87.0 (10.1) 81.8 (16.3) 82.9 (11.2) 0.65

43

Sleep stage distribution % N1 4.5 (3.0) 4.9 (3.5) 5.5 (3.3) 7.6 (4.9) 0.03



Sleep stage distribution % REM 19.4 (3.1) 20.5 (6.3) 18.0(5.0) 15.5 (6.6) 0.04

Wake after sleep onset (WASO),

(minutes)

36.9 (3.2) 31.4 (31.4) 38.5 (59.5) 53.0 (42.4) 0.45

Sleep onset latency, (minutes) 29.4 (3.2) 21.7 (21.7) 37.3 (27.1) 25.7 (30.1) 0.37

REM latency, (minutes) 128.40 (53.7) 139.6 (73.7) 154.8 (72.8) 141.6 (59.2) 0.55

Total arousal index (# events/

hour) 9.8 (2.3) 15.4 (4.5) 9.3 (4.2) 17.6 (8.1) <0.0001

Spontaneous arousal index

(#events/hour) 11.8 (13.3) 8.6 (3.4) 7.9 (3.5) 9.2 (3.9) 0.32

Respiratory events arousal index

(#events/ hour) 0.6 (.6) 6.5 (4.7) 0.8 (0.8) 7.9 (7.7) <0.0001

Oxygen saturation mean (%) 97.8 (0.6) 97.4 (0.9) 97.9 (0.9) 97.1 (2.6) 0.22

Oxygen saturation minimum, (%) 91.5 (2.8) 87.6 (9.7) 92.3 (3.9) 86.5 (13.0) 0.05

Oxygen desaturation index, (#

events/hour) 0.8 (0.6) 4.5 (6.0) 0.8 (0.8) 10.0 (22.0) 0.03

Time spent ≤ 90% oxygen

saturation (minutes) 0.03 (0.06) 2.0 (5.7) 0.0 (0.1) 10.2 (36.5) 0.24

Respiratory rate mean (bpm) 17.0 (2.0) 15.0 (5.1) 16.9 (2.4) 18.3 (3.3) 0.03

Respiratory rate minimum (bpm) 13.5 (2.2) 13.8 (2.3) 13.8 (2.4) 14.6 (2.4) 0.41

Respiratory rate maximum (bpm) 20.6 (2.7) 21.1 (1.6) 20.7 (3.7) 23.9 (4.5) 0.005

Heart rate mean (bpm) 80.0 (12.3) 79.6 (14.9) 75.2 (11.4) 78.0 (10.1) 0.13

Heart rate minimum (bpm) 53.7 (7.7) 58.0 (11.2) 55.2 (7.8) 57.7 (8.4) 0.32

Heart rate maximum (bpm) 109.3 (13.6) 121.5 (15.1) 114.2 (20.4) 111.7 (11.1) 0.20

EtCOⁿ minimum (mmHg) 33.4 (4.7) 30.9 (3.4) 31.2 (5.5) 29.8 (9.3) 0.39

EtCOⁿ maximum (mmHg) 49.7 (2.5) 50.2 (6.7) 50.2 (3.4) 52.3 (7.7) 0.42

TcCOⁿ minimum (mmHg) 35.1 (4.2) 37.3 (11.0) 33.7 (4.9) 34.2 (9.1) 0.54

TcCOⁿ maximum (mmHg) 47.1 (4.0) 55.5 (19.34) 47.7 (4.3) 49.0 (6.7) 0.048

% TST EtCO2 > 50 mmHg 0.4 (0.4) 29.3 (0) 1.8 (3.5) 4.8 (12.8) 0.03

% TST TcCO2 > 50 mmHg 14.1 (15.7) 28.7 (0) 4.9 (10.9) 14.6 (22.1) 0.44

CAI (#events/ hour) 0.62 (0.46) 0.87 (1.34) 0.66 (0.77) 0.67 (0.91) 0.88

OAHI (#events/ hour) 0.40 (0.63) 9.46 (9.20) 0.51 (0.59) 12.31 (15.42) <0.0001

AHI (#events/hour) 1.12 (0.71) 10.51 (9.35) 1.18 (0.88) 13.15 (15.33) <0.0001

* Statistics shown for categorical variables are n (%) from the population with available data as continuous variables are mean (SD), unless otherwise specified. TST, total sleep time; REM, rapid eye movement; WASO, wake after sleep onset; bpm, beats per minute; EtCOⁿ, end-tidal carbon dioxide; TcCOⁿ, transcutaneous carbon dixode

44

Table 3.6 summarizes the PSG findings for the subjects with and without OSA

(excluding PAP group). The significant differences between these groups were sleep

stage distribution % N1 sleep, total arousal index, respiratory events arousal index,

minimum oxygen saturation , oxygen desaturation index, maximum respiratory rate ,

heart rate mean, OAHI and AHI Index.

Table 3.6 PSG results of OSA vs. No OSA Groups (excluding PAP group)

OSA

(n=38)

No OSA

(n=39)

P value

Total Sleep Time (TST) (minutes) 379.5(67.26) 376.9(93.70) 0.88

Sleep Efficiency (%) 84.09(10.88) 83.08(13.65) 0.71

Sleep stage distribution % N1 6.86(4.65) 5.07(3.21) 0.0469



Sleep stage distribution % REM 16.98(6.79) 18.59(4.65) 0.22

Wake after sleep onset (WASO) (minutes) 46.71(40.37) 37.83(47.85) 0.36

Sleep onset latency, (minutes) 24.56(27.71) 33.88(30.17) 0.14

REM latency, (minutes) 141.0(62.68) 143.5(63.70) 0.86

Total arousal index (#events/hour) 16.99(7.30) 9.48(3.53) <0.0001

Spontaneous arousal index (#events/hour) 9.02(3.76) 9.55(9.21) 0.72

Respiratory events arousal index (#events/hour) 7.51(6.94) 0.72(0.74) <0.0001

Oxygen saturation mean (%) 97.16(2.20) 97.86(0.78) 0.07

Oxygen saturation minimum (%) 86.82(12.01) 91.93(3.45) 0.01

Oxygen desaturation index (#events/hour) 8.42(18.91) 0.80(0.71) 0.02

Time spent ≤ 90% oxygen saturation (minutes) 7.82(30.96) 0.02(0.06) 0.13

Respiratory rate mean (bpm) 17.35(4.17) 16.90(2.20) 0.55

Respiratory rate minimum (bpm) 14.36(2.36) 13.67(2.31) 0.17

Respiratory rate maximum (bpm) 23.0.5(4.10) 20.67(3.28) 0.004

Heart rate mean (bpm) 78.50(11.52) 73.35(11.87) 0.045

Heart rate minimum (bpm) 57.78(9.12) 54.53(7.68) 0.08

45

Heart rate maximum (bpm) 114.5(13.01) 112.1(17.78) 0.49

EtCOⁿ minimum (mmHg) 30.12(7.91) 32.08(5.23) 0.25

EtCOⁿ maximum (mmHg) 51.65(7.34) 49.99(3.08) 0.26

TcCOⁿ minimum (mmHg) 35.12(9.65) 34.29(4.63) 0.63

TcCOⁿ maximum (mmHg) 50.93(12.01) 47.44(4.16) 0.10

% TST EtCO2 > 50 mmHg 6.72(13.98) 1.50(3.16) 0.21

% TST TcCO2 > 50 mmHg 15.51(21.64) 6.35(11.47) 0.17

CAI (#events/hour) 0.73(1.04) 0.65(0.65) 0.64

OAHI (#events/hour) 11.49(13.85) 0.46(0.60) <0.0001

AHI (#events/hour) 12.38(13.80) 1.15(0.80) <0.0001

* Statistics shown for categorical variables are n (%) from the population with available data as continuous variables are mean (SD), unless otherwise specified. TST, total sleep time; REM, rapid eye movement; WASO, wake after sleep onset; bpm, beats per minute; EtCOⁿ, end-tidal carbon dioxide; TcCOⁿ, transcutaneous carbon dioxide

3.4 Questionnaire Results

3.4.1 Spruyt and Gozal Questionnaire

A total of 77 subjects were included in the statistical analyses for the Gozal and

Spruyt questionnaire. 13 subjects were excluded because the patients were using PAP

therapy. 10 questionnaires were excluded to due missing data. Table 3.7 shows the total

number of subjects who scored >2.72 on the Spruyt and Gozal questionnaire across all

four cohorts. The obese groups (No-OSA and OSA) on average had a higher percentage

of subjects who scored higher on the questionnaire (13.64% and 14.77%, respectively)

than the non-obese groups. However, the Spruyt and Gozal questionnaire scores were not

different between the four cohorts (p=0.94).

46

Table 3.7 Spruyt and Gozal Questionnaire results across the Four Cohorts

(excluding the PAP therapy group)


Non-Obese and OSA

Obese and No OSA

Obese and OSA

P value

Total Spruyt and Gozal Score >2.72

4 (4.55)

4(4.55)

12(13.64)

13(14.77)

0.94

* Statistics shown for categorical variables are n (%) from the population with available data as continuous variables are mean (SD), unless otherwise specified

The specificity and sensitivity for the Spruyt and Gozal questionnaires for the

diagnosis of OSA was calculated from the 2x2 contingency table (see Table 3.8). The

Spruyt and Gozal scores were compared for children with and without OSA. Children

receiving PAP therapy were excluded.

Table 3.8 Frequencies of Spruyt and Gozal Scores of OSA vs. No OSA groups

(excluding PAP group)

OSA

Spruyt and Gozal Score > 2.72

Yes No

Yes 17 16

No 19 25

From the above table, it was found that this questionnaire was able to correctly

identify children who have OSA (AHI>1.5) with a sensitivity of 47.22% and a specificity

of 60.98% . Also, the odds ratio of having sleep apnea with a Spruyt and Gozal score of

greater than 2.72 was 1.40 (95% CI 0.56-3.46, p = 0.47). The odds ratio was not

significant. The graph in Fig 3.1 shows the receiver operating curve (ROC) for the Spruyt

and Gozal questionnaire to correctly diagnose children with and without OSA. The area

under the curve was 0.54. It is evident from the plotted data that the ROC curve closely

approximates a straight line. The Spruyt and Gozal questionnaire was a poor screening

test for OSA in our study cohort.

47

Figure 3.1 ROC Curve for the Spruyt and Gozal Questionnaire to Screen for OSA

3.4.2 Pediatric Sleep Questionnaire

13 patients from the cohort were excluded because they were using PAP therapy.

The remaining 87 subjects were included in the PSQ statistical analysis. Questionnaire

scores > 0.33 were considered positive and suggestive of pediatric OSA. This threshold

is based on a validation study that demonstrated that the PSQ's optimal sensitivity and

specificity for the detection of OSA is at this cutoff. 108. Table 3.9 reveals the total

number of subjects who scored >0.33 on the PSQ questionnaire for all four cohorts.

Children with obesity had the highest proportion of children that were PSQ screen

positive but this difference was not significantly difference (p=0.62).

48

Table 3.9 Pediatric Sleep Questionnaire Results across the Four Cohorts (excluding

PAP group)

Non-Obese and

No OSA Non-Obese and

OSA Obese and No

OSA Obese and

OSA P value

Total PSQ Score >0.33

16(18.4)

9(10.3)

22(25.3)

19(21.8)

0.62


Specificity and sensitivity for the PSQ to detect OSA was calculated from the 2x2

contingency table (see Table 3.10). The PSQ scores were compared for children with and

without OSA. Children receiving PAP therapy were excluded.

Table 3.10 Frequencies of PSQ Scores of OSA vs. No OSA groups (excluding PAP

group)

OSA

PSQ > 0.33

Yes` No

Yes 28 38

No 10 11

From the above table, it was found that this questionnaire was able to correctly

identify children who have OSA (AHI>1.5) with a sensitivity of 73.88% and a specificity

of 22.45%. Also, the odds ratio of diagnosing OSA based on a PSQ score of greater than

0.33 was 0.8105 (95% CI 0.3025-2.1720, p = 0.68). However, the odds ratio was not

significant. The graph in Fig 3.2 shows the ROC for the PSQ questionnaire to correctly

identify children with and without OSA. The area under the curve was 0.56. It is evident

from the plotted data that the ROC curve closely approximates the straight line. The PSQ

questionnaire was a poor screening test for OSA in our study cohort.

49

Figure 3.2 ROC Curve for the PSQ Score Questionnaire to Screen for OSA

3.5 Dentofacial Morphology

Dentofacial characteristics were grouped into variables describing anterior-

posterior, transverse, vertical, and perimeter characteristics of the patient’s morphology.

Table 3.11 summarizes the prevalence of dentofacial morphology characteristics of the

four study cohorts. The only statistically significant differences between the four groups

were overjet (p=0.02), maxillary intermolar width (p=0.02), and maxillary intercanine

width (p=0.0005).

50

Table 3.11 Prevalence of Dentofacial Characteristics across the Four Cohorts

(excluding the PAP therapy group)

ANTERIOR-POSTERIOR Non-Obese and No OSA

Non-Obese and OSA

Obese and No OSA

Obese and OSA

P value

Convex Profile 28.6 % 9.1 % 28.6 % 29.6 % 0.97

Retrognathic Mandible 28.6 % 9.1 % 32.1 % 29.6 % 0.92

Anterior Crossbite 9.5 % 9.1 % 25.0 % 18.5 % 0.80

Overjet(mm) 2.7 (1.6) 2.3 (1.1) 1.6 (2.0) 3.3 (2.4) 0.02

Class II Molar 25 % 16.7 % 12.5 % 23.5 % 0.66

Class II Canine 40 % 4.6 % 21.4 % 17.0 % 0.62

Distal Step 38.5 % 18.8 % 41.7 % 24.3 % 0.93

TRANSVERSE & VERTICAL Non-Obese and No OSA

Non-Obese and OSA

Obese and No OSA

Obese and OSA

P value

Dolichocephalic Facial Pattern 0 % 0 % 3.6 % 3.7 % 0.74

Increased Lower Face Height 19.1 % 9.1 % 36.7 % 48.1 % 0.22 Overbite (% overlap of Incisors) 46.7(37.2) 60.0(37.1) 30.9(3.1) 43.7(45.4) 0.21

Anterior Openbite 0 % 9.1 % 10.7 % 0 % 0.16

Posterior Crossbite 14.3 % 2.7 % 17.9 % 11.1 % 0.51

Narrow Palate 9.5 % 18.2 % 39.3 % 18.5 % 0.71

Maxillary Intermolar Width (mm) 36.0 (3.5) 33.9(5.2) 37.7(3.4) 37.8(3.8) 0.02

Maxillary Intercanine Width (mm) 31.2 (2.8) 29.4(3.0) 32.9(2.5) 33.4(3.2) 0.0005

PERIMETER Non-Obese

and No OSA Non-Obese and OSA

Obese and No OSA

Obese and OSA

P value

Maxillary or Mandibular Crowding > 4mm

4.7% 27.3% 32.14% 29.6% 0.36


To better understand the relationship the relationship between SDB and

dentofacial morphology, we evaluated the differences between subjects with OSA (AHI

>1.5; n=38) as compared to those without OSA. (AHI <1.5; n=49). Children receiving

PAP therapy were excluded from this analysis. Table 3.12 summarizes these findings.

The only significant dentofacial difference found between OSA and non-OSA children

was overjet. The mean (SD) overjet in OSA children was 3.0mm(2.14mm) and

2.06mm(1.94mm) in non-OSA children (p=0.04). Although there was only one

statistically significant difference between the two-groups, there was a trend towards

children with OSA having a higher percentage of dolichocephalic facial type, increased

lower face height, and mandibular or maxillary crowding >4mm. Linear measurements

51

that were higher in children with OSA included overbite, inter-molar distance and inter-

canine distance.

Table 3.12 Dentofacial Morphology of OSA vs. No OSA Groups (excluding PAP

group)

OSA

(n=38)

No OSA

(n=49)

P value

Dolichocephalic Facial Type 1 (2.6) 1(2.0) 0.74

Increased LFH 14 (36.8) 14(28.6) 0.72

Convex Profile 9 (23.7) 14(28.6) 0.61

Retrognathic Mandible 9 (23.7) 15(30.6) 0.40

Anterior Open Bite 1 (2.6) 3(6.1) 0.63

Anterior Crossbite 6 (15.8) 9(18.4) 0.75

Posterior Crossbite 6 (15.8) 8(16.3) 0.95

Narrow Palate 7 (18.4) 13(26.5) 0.37

Distal Step 7 (18.4) 10(20.4) 0.93

Canine Class II 10 (26.3) 14(28.6) 0.62

Maxillary or Mandibular Crowding >4mm 11 (28.9) 10(20.4) 0.36

Overbite (% overlap of incisors) 48.42(43.34) 37.65(37.57) 0.22

Overjet (mm) 3.0 (2.14) 2.06 (1.94) 0.04

Inter-canine distance (mm) 32.24 (3.63) 32.16(2.69) 0.91

Inter-molar Distance (mm) 36.71 (4.54) 36.96(3.49) 0.77


Univariate analysis was then performed with OAHI > 1.5/hr (i.e. positive

diagnosis for OSA) as the predictor outcome for the various dentofacial characteristics.

Table 3.13 provides the p-values and odds-ratios from the univariate analysis. Overall

there was no statistical significant association between AHI and dentofacial

characteristics.

52

Table 3.13 Univariate Analysis for Various Dentofacial Characteristics (excluding

the PAP therapy group)

Variable Odds Ratio 95% Confidence Interval

P -value

Dolichocephalic vs. Mesocephalic Facial Type

Brachycephalic vs. Mesocephalic Facial Type

0.750

0.550

0.032-17.506

0.115-2.625

0.74

Convex vs. Normal Profile Type

Concave vs. Normal Profile Type

0.769

0.765

0.092-6.449

0.087-6.716

0.97

Increased Lower Face Height vs. Normal Face Height

Decreased Lower Face Height vs. Normal Face Height

0.441

0.500

0.174-1.118

0.072-3.477

0.22

Retrognathic vs. Normal Mandible 0.956 0.383-2.386 0.92

Distal Step 0.943 0.268–3.315 0.93

Class II Canine 1.273 0.494–3.276 0.62

Anterior Crossbite 1.157 0.379-3.534 0.80

Posterior Crossbite 0.673 0.206-2.206 0.51

Narrow Palate 0.822 0.298-2.271 0.71

Maxillary or Mandibular Crowding >4mm 0.629 0.235-1.689 0.36

Overbite (% overlap of incisors) 1.005 0.994-1.016 0.21

Overjet (mm) 1.005 0.996-1.570 0.02

Furthermore, to determine if an association existed between dentofacial

morphology and the use of PAP therapy, children with obesity and recently diagnosed

OSA (i.e. not using PAP therapy) were compared to children with obesity and OSA who

have been using PAP therapy for a minimum period of at least 1 year. Table 3.14

summarizes the findings between the two groups. There were no statistical differences

between the two groups.

53

Table 3.14 Dentofacial Morphology of Obese & OSA vs. Obese & PAP groups

Obese and OSA (n=27)

Obese CPAP (n=13)

P-Value

Dolichocephalic Facial Type 1(3.70) 0(0) 0.99

Increased LFH 13(48.2) 8(61.5) 0.51

Convex Profile 8(29.6) 5(38.5) 0.58

Retrognathic Mandible 8(29.6) 6(46.2) 0.30

Anterior Open Bite 0(0) 0(0) 0.99

Anterior Crossbite 5(18.5) 6(46.2) 0.13

Posterior Crossbite 3(11.1) 4(30.1) 0.13

Narrow Palate 5(18.5) 2(16.67) 0.89

Distal Step 5(50.0) 1(100) 0.34

Canine Class II 18(66.7) 9(69.23) 0.87

Maxillary or Mandibular Crowding >4mm 3(11.11) 4(31) 0.12

Overbite (% overlap of incisors) 43.70(45.41) 33.08(45.35) 0.49

Overjet (mm) 3.30(2.399) 1.69(2.29) 0.06

Inter-canine distance (mm) 33.41(3.21) 34.38(3.92) 0.44

Inter-molar Distance (mm) 37.85(3.80) 40.31(4.66) 0.11


A multiple regression model was developed using generated variables with p-

values < 0.05 from the univariate analyses. Table 3.15 demonstrates the multiple

regression analysis.

54

Table 3.15 Multiple Regression Model for the Presence of OSA in the Study Cohort

Excluding Children Using PAP Therapy

Variable Odds Ratio 95% Confidence Interval

P -value

Overjet (mm) 1.328 1.001-1.761 0.049

Respiratory Rate Max 1.234 1.018-1.496 0.03

BMI 1.027 0.968-1.089 0.38

Total Arousal Index 1.313 1.137-1.517 0.0002

Overjet, maximum respiratory rate, and total arousal index were significant

predictors of OSA as demonstrated form the multiple regression analysis. The odds ratio

of having an increased overjet and OSA was 1.328 (95% CI 1.001-1.761, p = 0.049). The

odds ratio of having an increased maximum respiratory rate and OSA was 1.234 (95% CI

1.018-1.496, p = 0.03). The odds ratio of having an increased total arousal index was

1.313 (95% CI 1.137-1.517, p = 0.0002). BMI was not a significant predictor for OSA.

55

Chapter 4

Discussion

We are reporting on the first pediatric study to systematically describe the

prevalence of dentofacial characteristics in a referred cohort of children with and without

PSG proven OSA using the currently recommended AASM guidelines. A key finding of

our study was that the prevalence of an overjet (i.e. horizontal excess) was significantly

higher in the children with OSA as compared to those without OSA. Furthermore, the

presence of an overjet, maximum respiratory rate, total arousal index all significantly

predicted the presence of OSA in our study cohort.

We evaluated dentofacial morphology in three planes: vertical, transverse, and

anterioposterior. When the study population was subdivided into four groups based on a

diagnosis of OSA and CDC BMI centile criteria for obesity, three dentofacial

characteristics were significantly different between the groups. These included overjet

(i.e. horizontal excess), maxillary intermolar width and maxillary intercanine width.

However, after the study cohort was subdivided based on an OSA diagnosis, only the

presence of an overjet remained clinically significant. This increase in overjet may be

explained by the presence of a Class II skeletal pattern and/or dental pattern, which has

found to be more prevalent in OSA children versus healthy controls142. Also, an increased

overjet in OSA children can be explained by long-term changes in the position of the

head, mandible, and tongue in order to maintain airway adequacy during sleep142.

Our finding of an increased overjet is consistent with previous studies on the

effects on OSA and dentofacial morphology. Pirilä-Parkkinen et al.145 conducted a

similar study in 2008, looking at the effects of SDB on developing dental arches. Their

findings, like ours, found children with OSA had a significantly increased overjet,

however, they also found a reduced overbite, narrower upper arch and shorter lower

dental arch when compared with the controls. The difference in findings may be

explained by the fact that their protocols followed the older guidelines published by the

American Thoracic Society in 1996 for scoring OSA diagnosed by PSG. The use of older

guidelines for scoring OSA may result in over- or under-diagnosis of OSA, leading to

different results based on OSA criteria and diagnosis. Our study used the most up-to-date

56

guidelines published by the AASM88 and found overjet as the only significant

dentofacial predictor of OSA.

Katyal et al39 conducted a systematic review in 2013 on dentofacial morphology

using lateral cephalograms in pediatric OSA . Katyal et al. found an increase in weighted

mean differences in the ANB angle of 1.64 degrees (P<0.0001) and 1.54 degrees

(P<0.00001), respectively, in children with OSA and primary snoring, compared with the

controls. The authors concluded that an increased ANB angle of less than 2 degrees in

children with OSA and primary snoring, compared with the controls, could be regarded

as having marginal clinical significance. Though our study did not look at cephalometric

measurements and ANB angles, our finding of increased overjet was found to be

significantly associated with a higher AHI, but it is not yet clear if this result is clinically

significant.

An interesting finding of our study was the incidence of convex profile,

retrognathic mandible, anterior open bite, anterior crossbite, posterior crossbite, narrow

palate, distal step and Class II canine were higher in the non-OSA group when compared

with OSA group. This is unexpected as based on the results of the systematic review, the

prevalence of these dentofacial characteristics would be expected to be higher in the

group with OSA. However, our findings may be explained by the fact that pediatric OSA

is a multifactorial disease and that craniofacial morphology is frequently not the only

factor contributing to the disease process154.

Although, PAP therapy is an effective therapy for OSA in children, there are

some notable long-term sequelae that have been reported in the literature. The

craniofacial skeleton in the growing child is responsive to changing functional demands

and environmental factors. Orthopedic modification of facial bones through the sustained

application of near-constant forces over long periods of time has been a mainstay of

orthodontic and dentofacial orthopedic therapy155. The successful use of PAP therapy

requires the application of such forces to the midface area. This prompts concern about

potential side effects on antero-posterior skeletal development in that area. The possible

effect of PAP therapy might depend on the skeletal age at which treatment begins. The

rate of normal forward and downward displacement of the midface varies with age129. A

review of the literature reveals that greater skeletal changes in the midface are possible in

younger patients and children because the early mixed dentition is particularly vulnerable

57

to the effects of PAP therapy on the development of the face, jaw, and teeth88,156,157. In

our study, the ages of children receiving PAP therapy ranged from 4 to 16 years of age.

However, all the subjects, with the exception of one child, were between 10 to 16 years

of age. Thus the majority of children were in the late-mixed to permanent dentition phase.

Case reports have suggested that long-term treatment with CPAP or BPAP during

early childhood carries a high risk of facial growth impairment, in particular, midface

hypoplasia and Class III malocclusions127,128. However, more recently, a small sample

size, cross-sectional study failed to show any statistically significant difference between

long-term PAP use and craniofacial morphologic pattern in children with persistent

OSA129. Our study was in line with this most recent cross-sectional study. We did not

find any statistically significant differences between the children with obesity not using

PAP therapy and children with obesity, using PAP therapy. However, all of the children

prescribed PAP therapy were greater than 10 years of age (with the exception of one

subject), and, therefore, the majority of the skeletal structures have already developed.

Interestingly, anterior crossbite was significantly more prevalent in the PAP group

(46.2% vs. 18.5%), though not statistically significant (p=0.13). This can be explained by

the increased force of the facemask on the anterior teeth. This is an area of future study to

determine of the anterior crossbite continues to progress in this cohort with subsequent

years of PAP therapy usage.

The intra-rater reliability of the orthodontic examinations for dentofacial

characteristics demonstrated excellent agreement for the majority of the measurements

with (K ≥ 0.80). The intra-rater reliability was poor for narrow palate (k=0.35). The

continuous measurements for overjet, overbite, intermolar and intercanine distance had

excellent agreement with ICC ranging from 0.90-0.98. Therefore, based on our results,

the orthodontic clinical examination seems to be a quick, reliable assessment that could

be done in any busy sleep medicine clinic. Furthermore, there is the potential to translate

this clinical examination traditionally performed by skilled dentists into a screening

examination that could be performed by sleep medicine clinicians.

The high reliability of the clinical dental examination has been previously

described in the literature. Dwokrin et al.158 demonstrated excellent reliability of

assessing molar classification in adults (K=0.78), We reported perfect agreement

58

(K=1.0) for the molar classification in the permanent dentition. A possible explanation

for this discrepancy is that Dworkin et al. used a more rigorous scale divided into ¼ cusp

increments to diagnose molar classification whereas out study used ½ cusp increments.

Carvalho et al. has also previously reported the inter- and intra-observer agreement for

diagnosis of dental malocclusion; the Cohen’s kappa coefficients ranged from 0.808

(overbite ≥ 4mm, yes or no), to 1.0 (openbite, yes or no)159.

With regards to orthodontic diagnosis and classification, it is possible that several

indicators of malocclusion (eg. molar classification, canine classification, overjet,

overbite) which directly affect the extra-oral facial characteristics (i.e. facial type, profile,

etc) may change spontaneously due to difference in mandibular position as determined by

the patient and/ or examiner160. However, since our percent agreement among

measurements were based upon orthodontic records as opposed to chair-side

examination, the disagreement in measurements between the two different time-points

were most likely due to differences in observation rather than differences in examination

technique.

Our study sample as a whole had a 74% prevalence of snoring, which is much

higher than the reported 7 to 28% prevalence of primary snoring in the literature.88

However, our study cohort was a referred population of children with suspected OSA

rather than a population based cohort. More specifically, our sample had a higher

percentage of snorers in both obese groups and OSA groups, of which a significant

difference was found. When analyzing the overall score for the 6-item questionnaire to

predict OSA, there was a higher prevalence of predictive scores in the obese groups

(OSA and Non-OSA) than the non-obese groups (OSA and non-OSA). However, the

sensitivity and specificity of the Spruyt and Gozal questionnaire used in our study was

47.22% and 60.98%, respectively, making it a poor predictor of OSA. This is somewhat

comparable to the sensitivity, 59.03%; and specificity, 82.85%, reported by Spruyt et al

94 in their questionnaire validation study. Similar trends were seen when analyzing the

overall scores from the PSQ. The obese groups (non-OSA and OSA) showed a

prevalence of 25.3% and 21.8%, respectively, however, with no statistical significance.

The sensitivity and specificity was also poor at 73.88% sensitivity and 22.45%

specificity. This supports the general consensus in the literature stating that patients’

59

complaints of snoring alone is insufficient to discriminate apneic and non-apneic

snorers161-163. In conclusion, our study clearly demonstrates that sleep questionnaires have

limited accuracy as screening tools for OSA in children.

There were no statistically significant differences between the groups in age,

gender, and percentage of mouth breathers. In an epidemiological study done in 2008 by

Lumeng et al. in children with OSA, the available data appeared insufficient to prove that

SDB differs systematically by age 15. This is in line with our findings. Lumeng et al also

reported that there is a higher percentages of boys who are affected by SDB (50-100%

higher) than girls15. Though our results are non-significant for gender, there is a much

higher percentage of boys in both OSA groups, 63.6% vs. 36.4% (Non-Obese) and

77.8% vs. 22.2% (Obese). The prevalence of mouth breathing in our study was 71%,

which is much higher than was Izu. et al164 found of 42% in OSA children. Though

mouth breathing was most prevalent in the non-obese/OSA group (100%), there was a

high prevalence amongst all the groups.

There were a few notable limitations to our study and the results should be

interpreted with caution. First, it was a cross-sectional study with a relatively small

sample size in each of our cohorts, and significant differences could be identified with a

larger sample size.. Our recruitment potential was limited due to the fact that we were

only including children with and without obesity that did not have any other

comorbidities. Over 80% of the children seen in the sleep center at SickKids have

comorbidities. Secondly, we did not have a true 'non snoring' control group as our non

OSA comparator group also had symptoms suggestive of OSA warranting a referral to a

sleep center but did not have a PSG diagnosis of OSA. Finally, our study used clinical

examination as the sole method of evaluating dentofacial morphology. Although, a more

objective measure of dentofacial morphology would have been beneficial to directly

calibrate the clinical examination, the authors could not justify exposing children to

radiation for screening purposes. From the literature, orthodontic examinations have been

shown to have high intra- and inter-observer reliability. 145,159 In addition, the author

performed all of the orthodontic examinations and was demonstrated to have high intra-

rater reliability. Therefore, we could not justify the radiation exposure from lateral

cephalograms or cone beam Computed Tomograms for our study participants.

60

Future studies in this area of research would be to conduct a similar study but

with a larger sample size and a true control group, using objective forms of data

collection such as lateral cephalograms and/or facial scans. Theoretically this would give

more credibility for cause and effect, however, due to the relative scarcity of sleep labs

and the long wait times for a polysomnogram, it would be highly unethical to use this

resource on healthy children for the purpose of research, while those with signs and

symptoms of SDB are expected to wait. Since overjet was the most significant

dentofacial predictor of OSA, areas of future study would also include a longitudinal

assessment of overjet pre and post adenotonsillectomy. In addition, the severity of the

OSA based on PSG could be assessed pre and post treatment of overjet in children with

OSA. Finally, a longitudinal assessment of children using PAP therapy starting from a

young age (<6 years of age) would be able to better demonstrate if any possible changes

occur in craniofacial development from the use of prolonged PAP therapy.

In summary, the results from the studying of intra-rater reliability of clinical

measures of malocclusion and facial characteristics demonstrated excellent agreement for

the majority of the measurements. Sleep questionnaires proved to be unsuccessful at

predicting the presence of obstructive sleep apnea. OSA was only statistically related to

horizontal excess (overjet). All other dentofacial characteristics were not statistically

significant. Even though overjet was found to be statistically significant, the clinical

significance between the mean difference in overjet between the OSA and Non-OSA

groups is yet to be determined. There were no significant differences in dentofacial

morphology between children with obesity using PAP therapy and children with obesity

not using PAP therapy. Pediatric OSA is a multifactorial disease and craniofacial

morphology is not the only factor contributing to the disease process. Thus if a health

professional notices signs and symptoms of sleep-disordered breathing, the patient should

be referred to a sleep medicine specialist to properly diagnose by PSG, and not rely solely

on craniofacial abnormalities, or sleep questionnaires as diagnostic procedures.

61

Appendices

Appendix A: Spruyt and Gozal Sleep Questionnaire107

Last Name: _________________________ First Name : ______________________________

Gender: F ! M ! Date of birth : Month ____ Day ____ Year ____ Age : ______

Over the last 6 months: Please mark each of the following items.

Never Rare

(1 night/week)

Occasional

(2 nights/week)

Frequent

(3 to 4 nights/week)

Almost Always

(more than 4 nights/week)

1 – Do you ever shake your child to make him/her breathe again when asleep? ! ! ! ! !

2 – Does your child stop breathing during sleep? ! ! ! ! !

3 – Does your child struggle to breathe while asleep? ! ! ! ! !

4 – Are you ever concerned about your child's breathing? ! ! ! ! !

Hardly noticeable Moderately strong Strong Very Strong Extremely Strong

5 – How loud is your child snore? ! ! ! ! !

Never Rare

(1 night/week)

Occasional

(2 nights/week)

Frequent

(3 to 4 nights/week)

Almost Always

(more than 4 nights/week)

6 – How often does your child snore? ! ! ! ! !

62

Appendix B: Pediatric Sleep Questionnaire108

PEDIATRIC SLEEP QUESTIONNAIRE Version 070424 Child’s Name: , . (Last) (First) (M.I.) Name of Person Answering Questions: . Relation to Child: . Your phone number, days: , and evenings: . Area Code Number Area Code Number

Relative’s name and number in case we cannot reach you: ___________________. __________. Area Code Number

Instructions: Please answer the questions on the following pages regarding the behavior of your child during sleep and wakefulness. The questions apply to how your child acts in general, not necessarily during the past few days since these may not have been typical if your child has not been well. If you are not sure how to answer any question, please feel free to ask your husband or wife, child, or physician for help. You should circle the correct response or print your answers neatly in the space provided. A “Y” means “yes,” “N” means “no,” and “DK” means “don’t know.” When you see the word “usually” it means “more than half the time” or “on more than half the nights.”

63

GENERAL INFORMATION ABOUT YOUR CHILD: Office

use only GI1

Today’s Date: . Month Day Year

GI2

Where are you completing this questionnaire? _____________.

GI3

Date of Child’s Birth: .

Month Day Year

GI4

Sex: Male or Female? ______________.

GI5

Current Height (feet/inches) : .

GI6

Current Weight (pounds) : .

GI7

Grade in school (if applicable):____________.

GI8

Racial/Ethnic Background of your Child (please circle): 1.) American Indian 2.) Asian-American 3.) African-American 4.) Hispanic 5.) White/not Hispanic 6.) Other or unknown

GI9

A. Nighttime and sleep behavior: WHILE SLEEPING, DOES YOUR CHILD …

Office use only

… ever snore?

Y N DK A1

… snore more than half the time?

Y N DK A2

… always snore?

Y N DK A3

… snore loudly?

Y N DK A4

… have “heavy” or loud breathing?

Y N DK A5

… have trouble breathing, or struggle to breathe? HAVE YOU EVER …

Y N DK A6

… seen your child stop breathing during the night? If so, please describe what has happened:

Y N DK A7

… been concerned about your child’s breathing during sleep?

Y N DK A8

… had to shake your sleeping child to get him or her to breathe, or wake up and breathe?

Y N DK A9

… seen your child wake up with a snorting sound? DOES YOUR CHILD …

Y N DK A11

… have restless sleep?

Y N DK A12

… describe restlessness of the legs when in bed? … have “growing pains” (unexplained leg pains)? … have “growing pains” that are worst in bed? WHILE YOUR CHILD SLEEPS, HAVE YOU SEEN …

Y N DK Y N DK Y N DK

A13 A13a A13b

… brief kicks of one leg or both legs? … repeated kicks or jerks of the legs at regular intervals (i.e., about every 20 to 40 seconds)? AT NIGHT, DOES YOUR CHILD USUALLY …

Y N DK Y N DK

A14 A14a

… become sweaty, or do the pajamas usually become wet with perspiration?

Y N DK A15

… get out of bed (for any reason)?

Y N DK A16

… get out of bed to urinate? If so, how many times each night, on average?

Y N DK _______ times

A17 A17a

Does your child usually sleep with the mouth open?

Y N DK A21

Is your child’s nose usually congested or “stuffed” at night?

Y N DK A22

Do any allergies affect your child’s ability to breathe through the nose? DOES YOUR CHILD …

Y N DK A23

… tend to breathe through the mouth during the day?

Y N DK A24

… have a dry mouth on waking up in the morning?

Y N DK A25

… complain of an upset stomach at night?

Y N DK A27

… get a burning feeling in the throat at night?

Y N DK A29

… grind his or her teeth at night?

Y N DK A30

… occasionally wet the bed?

Y N DK A32

Has your child ever walked during sleep (“sleep walking”)?

Y N DK A33

Have you ever heard your child talk during sleep (“sleep talking”)?

Y N DK A34

Does your child have nightmares once a week or more on average?

Y N DK A35

Has your child ever woken up screaming during the night?

Y N DK A36

Has your child ever been moving or behaving, at night, in a way that made you think your child was neither completely awake nor asleep? If so, please describe what has happened:

Y N DK A37

Does your child have difficulty falling asleep at night?

Y N DK A40

How long does it take your child to fall asleep at night? (a guess is O.K.)

________ minutes

A41

At bedtime does your child usually have difficult “routines” or “rituals,” argue a lot, or otherwise behave badly?

Y N DK A42

DOES YOUR CHILD … … bang his or her head or rock his or her body when going to sleep?

Y N DK A43

… wake up more than twice a night on average?

Y N DK A44

… have trouble falling back asleep if he or she wakes up at night?

Y N DK A45

… wake up early in the morning and have difficulty going back to sleep?

Y N DK A46

Does the time at which your child goes to bed change a lot from day to day?

Y N DK A47

Does the time at which your child gets up from bed change a lot from day to day? WHAT TIME DOES YOUR CHILD USUALLY …

Y N DK A48

… go to bed during the week?

A49

… go to bed on the weekend or vacation?

A50

… get out of bed on weekday mornings?

A51

… get out of bed on weekend or vacation mornings?

A52

B. Daytime behavior and other possible problems: DOES YOUR CHILD …

Office Use Only

… wake up feeling unrefreshed in the morning?

Y N DK B1

… have a problem with sleepiness during the day?

Y N DK B2

… complain that he or she feels sleepy during the day?

Y N DK B3

Has a teacher or other supervisor commented that your child appears sleepy during the day?

Y N DK B4

Does your child usually take a nap during the day?

Y N DK B5

Is it hard to wake your child up in the morning?

Y N DK B6

Does your child wake up with headaches in the morning?

Y N DK B7

Does your child get a headache at least once a month, on average?

Y N DK B8

Did your child stop growing at a normal rate at any time since birth? If so, please describe what happened:

Y N DK B9

Does your child still have tonsils? If not, when and why were they removed?: HAS YOUR CHILD EVER …

Y N DK B10

… had a condition causing difficulty with breathing? If so, please describe:

Y N DK B11

… had surgery? If so, did any difficulties with breathing occur before, during, or after surgery?

Y N DK Y N DK

B12

B12a

… become suddenly weak in the legs, or anywhere else, after laughing or being surprised by something?

Y N DK B13

… felt unable to move for a short period, in bed, though awake and able to look around?

Y N DK B15

Has your child felt an irresistible urge to take a nap at times, forcing him or her to stop what he or she is doing in order to sleep?

Y N DK B16

Has your child ever sensed that he or she was dreaming (seeing images or hearing sounds) while still awake?

Y N DK B17

Does your child drink caffeinated beverages on a typical day (cola, tea, coffee)? If so, how many cups or cans per day?

Y N DK _______ cups

B18 B18a

Does your child use any recreational drugs? If so, which ones and how often?:

Y N DK B19

Does your child use cigarettes, smokeless tobacco, snuff, or other tobacco products? If so, which ones and how often?:

Y N DK B20

Is your child overweight? If so, at what age did this first develop?

Y N DK _______ years

B22 B22a

Has a doctor ever told you that your child has a high-arched palate (roof of the mouth)?

Y N DK B23

Has your child ever taken Ritalin (methylphenidate) for behavioral problems?

Y N DK B24

Has a health professional ever said that your child has attention-deficit disorder (ADD) or attention-deficit/hyperactivity disorder (ADHD)?

Y N DK B25

C. Other Information 1. If you are currently at a clinic with your child to see a physician, what is the problem that brought you? 2. If your child has long-term medical problems, please list the three you think are most significant. _____. . . 3. Please list any medications your child currently takes: Medicine Size (mg) or amount per dose Taken when? __________ ___________________________ ____________ Effect: . __________ ___________________________ ____________ Effect: . __________ ___________________________ ____________ Effect: . __________ ___________________________ ____________ Effect: .

4. Please list any medication your child has taken in the past if the purpose of the medication was to improve his or her behavior, attention, or sleep: Medicine Size (mg) or amount per dose Taken how often? Dates Taken __________ __________________________ ________________ __________ Effect: . __________ __________________________ ________________ __________ Effect: . __________ __________________________ ________________ __________ Effect: . __________ __________________________ ________________ __________ Effect: . 5. Please list any sleep disorders diagnosed or suspected by a physician in your child. For each problem, please list the date it started and whether or not it is still present. Please list any psychological, psychiatric, emotional, or behavioral problems diagnosed or suspected by a physician in your child. For each problem, please list the date it started and whether or not it is still present.

7. Please list any sleep or behavior disorders diagnosed or suspected in your child’s brothers, sisters, or parents: Relative Condition ____________________ ________________________ ____________________ ________________________ ____________________ ________________________ D. Additional Comments: Please use the space below to print any additional comments you feel are important. Please also use this space to describe details regarding any of the above questions. Instructions: Please indicate, by checking the appropriate box, how much each statement* applies to this child:

This child often…

Does not apply 0

Applies just a little 1

Applies quite a bit 2

Definitely applies most of the time 3

… does not seem to listen when spoken to directly.

… has difficulty organizing tasks and activities.

… is easily distracted by extraneous stimuli.

… fidgets with hands or feet or squirms i

… is “on the go” or often acts as if “driven by a motor”.

… interrupts or intrudes on others (e.g., butts into conversations or games.

* Derived from DSM-IV.

THANK YOU

Appendix C Pediatric Polysomnogram Set up

Appendix D Pediatric Polysomnogram Data Recording

73

73

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