Dissertations in Health Sciences - UEF...Sleep disordered breathing (SDB) is one of the most common sleep disturbances among children; it represents a continuum of symptoms from habitual

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PUBLICATIONS OF THE UNIVERSITY OF EASTERN FINLAND

Dissertations in Health Sciences

ISBN 978-952-61-2247-2ISSN 1798-5706



TIINA IKÄVALKO

PEDIATRIC SLEEP DISORDERED BREATHING – CAUSES AND CONSEQUENCES

The aim of this doctoral thesis was to investigate the risk factors, diagnostic

method and consequences of pediatric sleep disordered breathing (SDB) in a population

sample of children from the Physical Activity and Nutrition in Children (PANIC) Study. The results showed that dentofacial and

pharyngeal morphology but not excess body fat raises the risk for SDB among 7-year-olds. Certain morphological and functional features at the age of 7 years may predict

developing SDB at the age of 10 years. SDB associates with low psychological well-being

in boys aged 7-year.

TIINA IKÄVALKO

Pediatric Sleep Disordered Breathing

– Causes and Consequences

TIINA IKÄVALKO

Pediatric Sleep Disordered Breathing

– Causes and Consequences

To be presented by permission of the Faculty of Health Sciences, University of Eastern Finland forpublic examination in Canthia Auditorium CA102, Kuopio, on Friday, October 14th 2016, at 12 noon

Publications of the University of Eastern Finland Dissertations in Health Sciences

Number 373

Department of Dentistry, Institute of Clinical Medicine, School of Medicine,Faculty of Health Sciences, University of Eastern Finland

Kuopio2016

Grano OyKuopio, 2016

Series Editors:Professor Tomi Laitinen, M.D., Ph.D.

Institute of Clinical Medicine, Clinical Physiology and Nuclear MedicineFaculty of Health Sciences

Professor Hannele Turunen, Ph.D.Department of Nursing Science

Faculty of Health Sciences

Professor Kai Kaarniranta, M.D., Ph.D.Institute of Clinical Medicine, Ophthalmology


Associate Professor (Tenure Track) Tarja Malm, Ph.D.A.I. Virtanen Institute for Molecular Sciences


Lecturer Veli-Pekka Ranta, Ph.D. (pharmacy)School of Pharmacy


Distributor:University of Eastern Finland

Kuopio Campus LibraryP.O.Box 1627

FI-70211 Kuopio, Finlandhttp://www.uef.fi/kirjasto

ISBN (print): 978-952-61-2247-2ISBN (pdf): 978-952-61-2248-9

ISSN (print): 1798-5706ISSN (pdf): 1798-5714

ISSN-L: 1798-5706

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Author’s address: Institute of Dentistry/School of MedicineUniversity of Eastern FinlandKUOPIOFINLAND

Supervisors: Professor Riitta Pahkala, DDS, Ph.D. Institute of Dentistry/School of Medicine University of Eastern Finland KUOPIO FINLAND

Professor Timo Lakka, M.D., Ph.D.Physiology/Institute of BiomedicineUniversity of Eastern FinlandKUOPIOFINLAND

Docent Henri Tuomilehto, M.D., Ph.D.Oivauni Sleep ClinicInstitute of Public Health and Clinical NutritionUniversity of Eastern FinlandKUOPIO

FINLANDProfessor Matti Närhi, DDS, Ph.D.Institute of Dentistry/School of MedicineUniversity of Eastern FinlandKUOPIOFINLAND

Reviewers: Professor Pertti Pirttiniemi, DDS, Ph.D.Department of Oral Development and Orthodontics/Institute of DentistryUniversity of OuluOULUFINLANDOuti Saarenpää-Heikkilä, M.D., Ph.D.Unit of Child Neurology/Department of PediatricsTampere University HospitalTAMPERE

FINLAND

Opponent: Professor Timo Peltomäki, DDS, Ph.D.School of MedicineUniversity of TampereOral and Maxillofacial UnitTampere University HospitalTAMPEREFINLAND

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Ikävalko, TiinaPediatric Sleep Disordered Breathing – Causes and ConsequencesUniversity of Eastern Finland, Faculty of Health SciencesPublications of the University of Eastern Finland. Dissertations in Health Sciences 373. 2016. 83 p.

ISBN (print): 978-952-61-2247-2ISBN (pdf): 978-952-61-2248-9ISSN (print): 1798-5706ISSN (pdf): 1798-5714ISSN-L: 1798-5706

ABSTRACT

Sleep disordered breathing (SDB) is one of the most common sleep disturbances among children; itrepresents a continuum of symptoms from habitual snoring (HS) to obstructive sleep apnea (OSA).The prevalence of OSA among children and adolescents has been reported to range between 0.1 and13% and that of snoring between 2 and 34%. Children with SDB can suffer from diverse symptoms,such as hyperactivity, sometimes excess daytime sleepiness, restless sleep, nightmares, nocturnalenuresis and bruxism. Deviant craniofacial morphology and high body adiposity are known risks forchildhood SDB and treatment modalities aim to influence these factors. When left untreated, SDB canreduce psychological well-being and quality of life, cause impairment in growth and cognition andboth metabolic and cardiorespiratory morbidity. The present study is based on the data of the Physical Activity and Nutrition in Children (PANIC)Study, which is an ongoing physical activity and dietary intervention study in a population sampleof children from the city of Kuopio, Finland. The study population was 512 at the baseline when thechildren were 6–8 years of age, and 440 after 2.2-years´ follow-up when they were 9-11 years. The aimof the study was to investigate the risk factors for pediatric SDB, to evaluate the feasibility of thelateral view photograph of the face for recognizing the facial convexity in order to diagnose thecondition, to assess the role of the SDB for psychological well-being of the children, and to estimatethe possible predictors for developing SDB during follow-up. The results showed that abnormal dentofacial and pharyngeal morphology, but not excess body fat,was associated with SDB in children 6-8 years of age. Children with tonsillar hypertrophy, cross biteand convex facial profile should always be examined as regards their sleeping habits, snoring andpauses in breathing during sleep. Facial convexity is typically determined by the orthodontist but itseemed to be difficult for other health care professionals. SDB was more prevalent in boys with lowpsychological well-being than in boys with normal psychological well-being. The association did notexist in girls. Furthermore, deviant dentofacial morphology, mouth breathing, body adiposity andmale gender seemed to predict SDB in childhood. Orthodontic treatment also seemed to associatewith SDB. In conclusion, the study showed that the causes and consequences of pediatric SDB manifestthemselves with the whole entity of SDB, including the milder forms of the condition. The findingsof the study are useful in identifying children at increased risk for developing SDB. Children withthese features could be candidates for early intervention to prevent the progression of SDB later inlife. This can only happen via better understanding and earlier recognition of the underlyingmechanisms for developing SDB and an intensive collaboration between different medicalspecialities.

National Library of Medicine Classification: WE 705, WF 143, WM 188, WU 140.5Medical Subject Headings: Adipose Tissue; Bruxism; Child; Craniofacial Abnormalities; Early MedicalIntervention; Finland; Mouth Breathing; Quality of Life; Risk Factors; Sleep; Sleep Apnea Syndromes; SleepApnea, Obstructive; Snoring

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Ikävalko, TiinaLasten unenaikaiset hengityshäiriöt – syyt ja seurauksetItä-Suomen yliopisto, terveystieteiden tiedekuntaPublications of the University of Eastern Finland. Dissertations in Health Sciences 373. 2016. 83 s.

ISBN (nid): 978-952-61-2247-2ISBN (pdf): 978-952-61-2248-9ISSN (nid): 1798-5706ISSN (pdf): 1798-5714ISSN-L: 1798-5706

TIIVISTELMÄ

Unenaikaiset hengityshäiriöt (sleep disordered breathing, SDB) ovat yksi yleisimmistä lastenunihäiriöistä. Käsitteellä tarkoitetaan oireiden kirjoa lievimmästä oireesta eli kuorsauksestavaikeimpaan oireeseen eli obstruktiiviseen uniapneaan. Lapsilla ja nuorilla uniapnean esiintyvyysvaihtelee 0.1-13 %:n välillä ja kuorsauksen vastaavasti 2-34 %:n välillä. Unenaikaisistahengityshäiriöistä kärsivillä lapsilla on moninaisia oireita, esimerkiksi yliaktiivisuutta, joskuspäiväaikaista väsymystä, levotonta unta, painajaisia, yökastelua ja bruksismia. Tyypillisiäunenaikaisten hengityshäiriöiden riskitekijöitä ovat poikkeamat hampaiston, kasvojen ja nielunalueen morfologiassa sekä kehon kohonnut rasvapitoisuus. Unenaikaisten hengityshäiriöiden hoitopyrkii vaikuttamaan edellä mainittuihin tekijöihin. Hoitamattomana tila voi heikentää lapsenpsyykkistä hyvinvointia ja elämänlaatua, aiheuttaa oppimisvaikeuksia ja metabolista ja sydän- javerisuonielimistön sairastuvuutta sekä hidastaa kasvua. Tutkimus perustuu Lasten liikunta- ja ravitsemustutkimuksen (Physical Activity and Nutrition inChildren (PANIC) Study) aineistoon. Kyseessä on interventiotutkimus, jossa oli lähtötilanteessatutkittavana 512 6-8-vuotiasta lasta ja 2.2 vuoden seurannan jälkeen 440 9-11-vuotiasta lasta.Tutkimuksen tarkoitus oli tutkia lapsuuden unenaikaisten hengityshäiriöiden riskitekijöitä, arvioidaeri ammattiryhmien kykyä tunnistaa yhtä riskitekijää eli kuperaa kasvoprofiilia, tutkia unenaikaistenhengityshäiriöiden vaikutusta lapsen psykologiseen hyvinvointiin sekä arvioida unenaikaistenhengityshäiriöiden mahdollisia ennusmerkkejä. Tutkimustulokset osoittivat, että poikkeava kasvojen ja pään sekä nielun alueen morfologia oliyhteydessä unenaikaisiin hengityshäiriöihin 6-8-vuotiaiden lasten ikäryhmässä. Jos lapsella onsuurentuneet tonsillat, ristipurenta ja kupera kasvoprofiili, tulisi selvittää myös nukkumistavat sekämahdolliset kuorsaus ja hengityskatkokset. Kehon rasvapitoisuudella ei ollut vaikutusta riskiin.Oikomishoidon erikoishammaslääkäri pystyi tunnistamaan kuperan kasvoprofiilin melkoluotettavasti, mutta muille lasten kanssa työskenteleville terveydenhuollon ammattilaisille se olivaikeaa. Unenaikaiset hengityshäiriöt olivat yleisempiä psyykkisesti huonommin voivilla pojilla.Tytöillä tätä yhteyttä ei havaittu. Unenaikaisten hengityshäiriöiden esiintymistä ja ilmaantumistaseuranta-aikana ennusti poikkeava hampaiston ja kasvojen alueen morfologia, suuhengitys, kehonrasvapitoisuus ja miessukupuoli. Myös oikomishoidolla näytti olevan yhteyttä unenaikaisiinhengityshäiriöihin. Merkittävä johtopäätös oli, että lapsilla unenaikaisten hengityshäiriöiden riskit ja seurauksetilmenevät väestötasolla silloinkin, kun mukana ovat sairauden lievimmät muodot. Tutkimustuloksetovat hyödyllisiä, kun halutaan jo nuorella iällä tunnistaa ne lapset, joilla on riski unenaikaisiinhengityshäiriöihin ja joita kannattaa jo aikaisessa vaiheessa ryhtyä hoitamaan moniammatillisesti.Näin voidaan mahdollisesti estää tilan paheneminen myöhemmällä iällä.

Luokitus: WE 705, WF 143, WM 188, WU 140.5Yleinen Suomalainen asiasanasto: ehkäisevä hammaslääketiede; hengitys; häiriöt; lapset; moniammatillisuus;morfologia; riskitekijät; uni; uniapnea-oireyhtymä; unihäiriöt

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Acknowledgements

This study was carried out at the Institutes of Biomedicine and Dentistry, University ofEastern Finland, Kuopio, during the years 2008–2016.I wish to express my deepest gratitude to my principle supervisor, Professor Riitta Pahkala.I sincerely admire your enthusiasm, vigor and efficiency in doing anything, and especiallyscientific work. Things are certainly not left around waiting on your table. The journey fromthe phone call I received from you in the blueberry forest to this day has been a long one, butyour endless eagerness and warm encouragement have kept me going.I owe my deep gratitude to the principal investigator of the PANIC study, Professor TimoLakka. Your expertise and virtuosity in the academic world have in many ways increasedmy understanding of the area of research. I warmly thank Professor Matti Närhi for all thehelp and constructive comments during these years. Your long knowledge in research hasbeen an important part of my work. I also owe my warmest thanks to docent HenriTuomilehto. Despite your busy schedule and work world-wide, you have supported me andtaught me much about clinical sleep medicine.Likewise, I express my warm gratitude to the official reviewers of my thesis, Professor PerttiPirttiniemi and Outi Saarenpää-Heikkilä, MD, PhD, for their constructive comments andvaluable suggestions to improve the quality of my thesis. I also warmly thank AnnaVuolteenaho, MA, for her skillful revision of the language of my thesis.I warmly and sincerely thank Riitta Myllykangas for all the possible and impossible help youhave given me during these years. Not only your expertise in statistics but also your practicalinsight have been a sine qua non for my work. You have always had the time to listen andunderstand – regarding all areas of life, and I have really enjoyed working with you.The unique PANIC group deserves my special thanks. The Medistudia nerve center has beena place where I have always felt welcome – if I needed any help or advice I got it from you.The researcher group works hard for the best interests of children and I am proud to be apart of it.I am grateful to all my co-authors for their contribution to this work. Especially the co-operation with Professor Soili Lehto has been extremely rewarding.The whole staff of the Institute of Dentistry, University of Eastern Finland, and Oral andMaxillofacial Department, Kuopio University Hospital, is warmly acknowledged for theirhelp, support and kind understanding. During the hectic years while building new dentaleducation in Kuopio the atmosphere has always been one of empathy and open forconstructive discussion, for which I am grateful.I thank all the children and families participating the PANIC study for their time and patienceand I hope the co-operation will continue in the coming years. Furthermore, I thank KuopioSocial and Health Center for providing the facilities and skillful, friendly assistants duringthe examinations.I warmly thank my dear friends and their families for the support and presence they havegiven me during all these years. Despite long silent times I have known in my heart that youare there. I owe you my thanks and love for keeping me in touch with life.I owe my deep thanks to my beloved parents who have supported me in all the stages of mylife, unconditionally and lovingly. Likewise, I owe my warm gratitude to my dear parents-in-law. Especially the times spent in your paradise, the cottage at Konnevesi, have constantly

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given me rest and strength to keep going. I also give my sincere thanks to my relatives forall the joyful moments I have spent with you.I owe my special loving thanks to my dear children. Vertti, my beloved firstborn, you havechallenged me with your intellect and given me inspiration and new fresh views of life.Miina, the middle one, your empathy and sensitive presence warm my heart, not to mentionyour delicious sweet creations that gave me pleasure and (sometimes even too much) energyduring hard times. Kerttu, my dear youngest one, your bounce and rationality is somethingI can only admire – you are a woman who stands on her own two feet. I am proud andprivileged to be the mom of each of you and give my endless love to you.Finally, I cannot express enough gratitude to my dear husband, Harri. The journey of myresearch has been long, but it is nothing compared to our journey of almost 32 years ofmarriage. These years have been filled with work and rest, ordinariness and celebration,going and staying. Altogether, our journey has been filled with love. Thank you for yourendless support and belief in me – not to mention practical love in terms of delicious suppersin late evenings when I came home from work hungry and tired. During all our yearstogether – you have made my day!In appreciation of their financial support for this work, I thank the Institute of Biomedicine,University of Eastern Finland, the Finnish Dental Society Apollonia, the Northern SavoDental Society and the Research Foundation of Respiratory Diseases.

Kuopio, October 2016

Tiina Ikävalko

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List of the original publications

This dissertation is based on the following original publications:

I Ikävalko T, Tuomilehto H, Pahkala R, Tompuri T, Laitinen T, Myllykangas R,Vierola A, Lindi V, Närhi M, Lakka TA. Craniofacial morphology but not excessbody fat is associated with risk of having sleep-disordered breathing –the PANIC study (a questionnaire-based inquiry in 6-8-year-olds). EuropeanJournal of Pediatrics 171: 1747-1752, 2012.

II Ikävalko T, Närhi M, Lakka T, Myllykangas R, Tuomilehto H, Vierola A, PahkalaR. Lateral facial profile may reveal the risk for sleep disordered breathing inchildren - the PANIC-study. Acta Odontologica Scandinavica 73: 550-555, 2015.

III Ikävalko T, Lehto S, Lintu N, Väistö J, Eloranta A-M, Haapala EA, Vierola A,Myllykangas R, Tuomilehto H, Brage S, Pahkala R, Närhi M, Lakka TA. Health-related correlates of psychological well-being among girls and boys 6-8 years ofage - the PANIC study. Submitted.

IV Ikävalko T, Närhi M, Eloranta A-M, Lintu N, Myllykangas R, Vierola A,Tuomilehto H, Lakka T, Pahkala R. Predictors of sleep disordered breathing inchildren – the PANIC study. Submitted.

The publications were adapted with the permission of the copyright owners.

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Contents

1 INTRODUCTION .................................................................................................................. 1

2 REVIEW OF THE LITERATURE ......................................................................................... 32.1 Normal sleep of the children ................................................................................ 3

2.1.1 The functions of sleeping .............................................................................. 32.1.2 Quantity of sleep ............................................................................................ 32.1.3 Cycles of sleep ................................................................................................ 42.1.4 Respiratory patterns of sleep ........................................................................ 5

2.2 Sleep disordered breathing (SDB) – general aspects .......................................... 62.2.1 Historical aspects ........................................................................................... 62.2.2 Definition and classification .......................................................................... 62.2.3 Epidemiology – prevalence of OSA in adults .............................................. 7

2.3 SDB in children ...................................................................................................... 82.3.1 Prevalence ....................................................................................................... 82.3.2 Symptoms ..................................................................................................... 122.3.3 Risk factors ................................................................................................... 122.3.4 Pathophysiology .......................................................................................... 152.3.5 Consequences ............................................................................................... 162.3.6 Diagnostics ................................................................................................... 182.3.7 Treatment of pediatric SDB ......................................................................... 192.3.8 Other orthodontic aspects ........................................................................... 202.3.9 Childhood SDB associations to adult SDB ................................................. 20

3 AIMS OF THE STUDY ........................................................................................................ 23

4 STUDY DESIGN AND STUDY POPULATION ............................................................. 254.1 Ethical considerations ......................................................................................... 254.2 Design of the physical activity and nutrition in children (PANIC) study ..... 254.3 Participants .......................................................................................................... 27

5 METHODS ............................................................................................................................ 295.1 Assessments ......................................................................................................... 29

5.1.1 Dentofacial and pharyngeal morphology .................................................. 295.1.2 Sleep .............................................................................................................. 295.1.3 Body composition and fitness ..................................................................... 305.1.4 Photograph ................................................................................................... 305.1.5 Well-being measurements ........................................................................... 325.1.6 Physical activity and inactivity ................................................................... 325.1.7 Dietary assessments ..................................................................................... 325.1.8 Socioeconomic background and characteristics of the parents ................ 33

5.2 Reliability of the measures ................................................................................. 335.3 Statistical methods .............................................................................................. 33

6 RESULTS ............................................................................................................................... 356.1 Basic characteristics ............................................................................................. 35

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6.2 Risk factors for sleep disordered breathing among children aged 6-8and 9-11- years (Study I, IV) .............................................................................. 39

6.3 Predictors of sleep disordered breathing in children (Study IV) .................... 416.4 Recognizing convexity and vertical proportions of the lateral facial

profile (Study II).................................................................................................. 436.5 Correlates of psychological well-being among girls and boys 6-8 years

of age – the role of sleep disordered breathing (Study III) .............................. 44

7 DISCUSSION ....................................................................................................................... 517.1 Dentofacial and pharyngeal morphology with and risk for sleep

disordered breathing .......................................................................................... 517.2 Prediction of SDB ................................................................................................ 527.3 The psychological consequences of SDB ........................................................... 547.4 Strengths and limitations.................................................................................... 55

8 CONCLUSIONS AND FUTURE PERSPECTIVE ............................................................ 59

REFERENCES .............................................................................................................................. 61

APPENDIX

ORIGINAL PUBLICATIONS I–IV

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Abbreviations

ADHD Attention-deficit/hyperactivity disorder

AHI Apnea/hypopnea index

ATE Adenotonsillectomy

ATH Adenotonsillar hypertrophy

BMI Body mass index

BMI-SDS Body mass index standard deviation score

CI Confidence interval

CP Cerebral palsy

CRP C - reactive protein

DASH Dietary Approach to Stop Hypertension

DXA Dual-energy x-ray absorptiometry

EEG Electro-encephalography

EMG Electro-myography

EOG Electro-oculography

G´ Soft tissue Glabella

h/day Hours/day

HILMO Care register for health care (hoitoilmoitusjärjestelmä)

HS Habitual snoring

ICC Intra-class correlation coefficient

IgA, G, M Immunoglobulin A, G, M

IOTF International Obesity Task Force

kg Kilogram

m Meter

Me` Soft tissue Menton

MetS Metabolic syndrome

min/day Minutes/day

mmHg Mercury millimeter

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n Number of participants

N Non-REM sleep

Na` Soft tissue Nasion

NHP Natural head position

OR Odds ratio

OSA Obstructive sleep apnea

p Probability of rejecting the null hypothesis

PANIC Physical Activity and Nutrition in Children

PCO2 Carbon dioxide pressure

Pg` Soft tissue Pogonion

PS Primary snoring

PSG Polysomnography

PSWB Psychological well-being

R, REM Rapid eye movement

RDI Respiration disturbance index

S Stage

SD Standard deviation

SDB Sleep disordered breathing

Sn Subnasale

SPSS Statistical Package for Social Sciences

UARS Upper airway resistance syndrome

w/kg Watt/kilogram

1 Introduction

Sleep disordered breathing (SDB) is one of the most common sleep disturbances amongchildren; it represents a spectrum of symptoms from simple habitual snoring (HS) toobstructive sleep apnea (OSA). The prevalence of OSA among pediatric population has beenreported to range between 0.1 and 13% and that of snoring between 2 and 34%. The mostcommon risk factor for pediatric SDB is adenotonsillar hypertrophy (ATH) (Arens et al. 2003,Dayyat et al. 2007). Excess body adiposity is a well-recognized risk factor for SDB in adults(Leinum et al. 2009), but it has also been suggested to be a significant risk factor for pediatricSDB (Marcus et al. 1996, Ng et al. 2004, Verhulst et al. 2008). Further, children with deviantcraniofacial morphology, such as a retrusive and vertically growing mandible, narrowmaxilla, distal molar occlusion and lateral cross bite are at risk for developing SDB(Löfstrand-Tideström et al. 1999, Flores-Mir et al. 2013). The early detection of SDB in children must be highlighted, because there is a growing bodyof evidence which associates the disadvantageous health consequences of SDB with otherhealth problems, such as day-time hyperactivity, attention-deficit/hyperactivity disorder(ADHD) type manifestations and other behavioural and cognitional difficulties, night-timeenuresis, systemic low-grade inflammation, metabolic disturbances and altered somaticgrowth and development (Gozal 2001, Marcus et al. 2012). It would be beneficial if children with SDB – the whole spectrum of it – could be recognizedearly in childhood so that they could be candidates for early intervention and treatment toprevent the progression of SDB later on. The objective of this doctoral thesis was toinvestigate the risk factors and consequences of pediatric SDB in a population sample ofFinnish children.

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2 Review of the literature

2.1 NORMAL SLEEP OF THE CHILDREN

2.1.1 The functions of sleepingSleep is defined as a physiological and behavioral state characterized by partial isolation fromthe environment. It is a period of reduced activity and associated with a typical posture, suchas lying down with eyes closed in humans. Sleep results in a decreased responsiveness toexternal stimuli and is a state that is relatively easy to reverse, which distinguishes sleep fromother states of reduced consciousness, such as hibernation and coma (Siegel 2011). Today itis generally accepted that sleep associates with mental and physical health issues – in bothadults and children. The functions of sleeping are multifold: fatigue reversal, biochemicalrefreshment, immune function, memory improvement and psychological well-being(Lavigne et al. 2009). Altogether, sleep is an essential part of our lives and a criticaldeterminant of health. For children, maturational changes contribute to the unique featuresof childhood sleep.

2.1.2 Quantity of sleepA caregiver´s 24-hour cycle concerning the sleep-wake system is a target for newbornchildren. They consolidate their sleep/wake patterns during the first months of life, at thesame time learning to sleep through the night. A study of Henderson shows, that at the ageof 5 months more than half of infants are sleeping simultaneously with their parents(Henderson et al. 2010). The period of sleep children need daily decreases by age – 12–16hours when they are four to twelve months old, 11–14 hours when they are one to two yearsold, 10–13 hours when they are three to five years old, and 9–12 hours at the age of 6-12 years.Compared with adults, teenagers still require more sleep – approximately 8–10 hours(Paruthi et al. 2016). Elderly people tend to go to sleep earlier and wake up earlier, and theirsleep is often light and fragmented (Floyd et al. 2000). Their night time sleep is usuallyshorter, and they usually need to take naps in the daytime (Foley et al. 2007). From birth todeath, the total amount of sleep required daily declines steadily (Figure 1).

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Figure 1. Change of sleep and activity patterns in the course life

It is characteristic of the modern 24/7 society that it may be challenging for both adultsand children to get enough rest and sleep. In fact, an inadequate amount of sleep seems to bea consequence of the modern life-style, associated with the technology of our time (Jenni andO'Connor 2005). A brief history of sleep recommendations for children concludes, thatchildren never get enough sleep according to current recommendations (Matricciani et al.2012). However, it is universally acknowledged that there is a lack of scientific evidence forsleep recommendations for children. In general, the recommended amount of sleep forinfants and toddlers is 12–15 hours, for school-aged children 10–11 hours and for teens 8–9.5hours (Matricciani et al. 2013).

2.1.3 Cycles of sleepA typical daily cycle for humans is approximately 16 hours of wakefulness and activity and8 hours of sleep and resting, in parallel with the rhythm by which society functions. Thepropensity to fall asleep depends on the duration of the preceding wakefulness episode.When the duration of being awake increases, sleep pressure accumulates and reaches acritical point, when sleep onset is reached. The process is called the homeostatic process andruns parallel with the daily 24-hour rhythm (Borbèly 2009). Twice a day (4 PM and 4 AM)there is a strong sleep pressure, and at certain point after sleep deprivation the pressure is sopowerful that an individual will fall asleep regardless of any strategy to fight against sleeping(Lavigne et al. 2009). Light helps humans to control their sleep-wake cycle by sending aretinal signal to the hypothalamic suprachiasmatic nucleus, which is a network of brain cellsand genetic control acting as a pacemaker to the circadian timing system and promoting asleep-wake rhythm in adaptation to the environment (Moore 2013). Within the 24-hour sleep-wake system there is a separate system that governs sleep onsetand maintenance, known as the ultradian rhythm, by which sleep can be divided into fourrecurrent periods. One period consists of non-rapid eye movement (non-REM, N) sleep andrapid eye movement (REM, R) sleep (Iber et al. 2007), which are characterized by typicalelectro-myographic (EMG), electro-oculographic (EOG) and electro-encephalographic (EEG)features. Onset of sleep is usually through N sleep. N1 (stage 1, S1) is a transitional stage betweenwakefulness and sleep. It is the lightest sleep, which can easily be discontinued, and in whichthe arousal threshold is at its lowest. EMG shows a gradual diminution of muscle tonus andEOG slow, possibly asynchronous eye movements. Typical EEG patterns show rhythmic

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alpha waves changing into a relatively low-voltage asynchronous slow activity pattern. Inadults N1 lasts few minutes in one period and constitutes approximately 2-5% of total sleep. N2 (S2) still can be described as light sleep. EMG patterns show further decline in muscleactivity. Heart rate and reactions to stimuli from the outside diminish. EEG is characterizedby the development of high-voltage waves with K-complex and sleep spindles. N2 lasts 15–30 min/period in adults and may constitute half of the total sleep time. N3 (S3 and S4) sleep is the deepest sleep, the one in which EEG slow delta waves dominateand neuronal activity is at its lowest. The temperature of the brain is also at a minimum andthe activation of ventilation and the cardiorespiratory system reduces. N3 constitutes 15-20%of total sleep time, lasting 30-40 minutes/period in adults. R sleep is characterized by intermixed low-voltage cerebral activity, showing sawtoothwaves and typically no K-complex. EMG shows substantially reduced muscle tone, evenatonia. Hallmarks of R sleep are phasic eye movements, which can be registered by EOG. Ingeneral, R sleep can be characterized as an activated brain in a paralyzed body. 20-25%(approximately 30 min/period) of total sleep time is R sleep. Age modifies the pattern of sleep stages. The length of one cycle of an adult is 90-100minutes on average and that of the newborn only 50-60 min. Typically, the proportion of Rsleep decreases by age. A newborn baby has R sleep more than a half of her/his sleeping time,while toddlers have R sleep approximately 20% of total sleep time. N3 is dominating inyoung children, being approximately 25% of total sleep time (Montgomery-Downs et al.2006). (Culebras 2002, Carskadon and Dement 2011)

2.1.4 Respiratory patterns of sleepRespiratory patterns of sleep go through multiple maturational changes from infancy toadulthood. A visible sign of change is a decrease of the breathing frequency during sleep: anewborn baby breaths approximately 40 times per minute, an infant 30 times, a preschoolchild 20 times, a school-aged child and an adolescent 18 times per minute. The rates are notin relation to body weight and boys seem to have higher breathing rates than girls (Ross andRosen 2014). Furthermore, respiration frequency is decreased during sleep compared withdaytime activity and varies in parallel to sleep states. In N sleep minute ventilation decreasesand upper airway resistance increases. During R sleep respiration is irregular in terms of bothfrequency and volume (Ross and Rosen 2014). Short central respiratory pauses are a common finding in healthy children during R sleep.The frequency of the central pauses expressed with apnea episodes per hour of total sleeptime decrease from 2.4 in 1-year-old children to 0.5 in 12-year-olds (Scholle et al. 2011). Ingeneral, overnight polysomnographic (PSG) records of healthy children undergodevelopmental changes during childhood, most of the differences occurring when childrenare approximately 5-6 years old. For example, average obstructive apnea index shows slightincrease and in line with the study of Scholle, central apnea index shows slight decrease.Further, the older children sleep a greater amount of sleep time in supine position(Montgomery-Downs et al. 2006). Generally, the respiratory process is conducted by metabolic and physiologic factors.Carotic and aortic chemoreceptors sense the arterial concentration of oxygen and carbondioxide being responsible for most ventilator responses to variations in concentrations. It isnoteworthy, that in newborns peripheral chemoreceptors adopt a greater role in controllingthe ventilation process compared with adults. During development peripheral

6

chemoreceptors undergo a progressive diminution in sensibility (Marcus et al. 1994, Rossand Rosen 2014).

2.2 SLEEP DISORDERED BREATHING (SDB) – GENERAL ASPECTS

2.2.1 Historical aspectsFat boy Joe, a comically drawn figure in a book by Charles Dickens published in 1837, was achubby, rubicund, perpetually hungry servant boy, who fell asleep snoring loudly in themiddle of his tasks at any time of the day. This was the first time the obvious obesity-hypoventilation syndrome and perhaps also sleep apnea were described in the literature.Later on, the association between obesity and sleeping problems has come to be a target ofinterest, and in the medical literature the condition was described as obesity-hypoventilationsyndrome in 1955 (Auchinloss et al. 1955) and as Pickwickian syndrome in 1956 (Bickelmannet al. 1956). Since the 1980`s, medical research and knowledge of the associations of sleep,breathing and obesity and also other risk factors have increased enormously among healthprofessionals as well as among the general public.

2.2.2 Definition and classificationSDB is a continuum of medical disorders that encompasses the conditions snoring (primaryand habitual), upper airway resistance syndrome (UARS) and OSA (Figure 2). The mildestsymptom and often a hallmark of OSA is snoring. There is no generally accepted,unambiguous definition for snoring. In American English the condition is defined as “tobreathe during sleep with harsh, snorting noises caused by vibration of the soft palate”(American Heritage Dictionary of the English Language 2016). In practice, the humanconception of the typical sound is the golden standard. It is generated at the level of the upperairway, the typical features being a noisy sound when the soft palate vibrates and restrictsthe passage of air to and from the lungs. Primary snoring (PS) means snoring without anypathologies, e.g. daytime sleepiness, sleep disturbances, apnea, hypoventilation, hypoxemiaand hypercarbia (Ng et al. 2006). Habitual snoring (HS) refers to snoring more than threenights per week (Li et al. 2015). UARS is characterized by inspiratory flow limitation, increased upper airway resistanceand frequent cortical arousals, but without apneas, hypopneas or desaturation(Guilleminault et al. 1993). In the literature there are some considerations for UARS to be adistinct entity separately to OSA, because there are some differences in the clinicalpresentation (Stoohs et al. 2008). Further, the progression from UARS to OSA is questionable,and there is no scientific evidence to demonstrate the evolution of this condition. However,currently the International Classification of Sleep Disorders does not define UARS as aspecific entity; it is described as a subgroup of OSA (Iber et al. 2007). OSA, which is the most serious symptom of the condition, is defined as a disorder ofbreathing during sleep characterized by prolonged partial upper airway obstruction,intermittent complete or partial obstruction (obstructive apnea or hypopnea) or both andprolonged and intermittent obstruction that disrupts normal ventilation during sleep(American Academy of Sleep Medicine 2014). In adult OSA patients these events occurthroughout the sleep. In children, obstructive apneas occur mostly during R sleep (Goh et al.

7

2000). The severity of OSA is assessed by the number of apneas and hypopneas per slepthour and expressed by the apnea/hypopnea-index (AHI). OSA is a chronic progressivedisease, the progress of the condition mainly depending on weight gain and, to a lesserdegree, time (Berger et al. 2009).Sleep apnea can also be generated at the level of the central nervous system (central sleepapnea), neurophysiologically being due to a temporary failure in the pontomedullarypacemaker that generates the breathing rhythm. Central apneas (in addition to obstructiveapneas) usually associate with different syndromes (e.g. Prader Willi and Down syndrome)and further, central apneas can be seen with congestive heart failure or chronic opioid use(Javaheri and Dempsey 2013). The present dissertation focuses on the obstructivemanifestation of the condition.

Figure 2. The spectrum of SDB from primary snoring to severe sleep apnea

2.2.3 Epidemiology – prevalence of OSA in adultsGenerally, the most recent estimates of the prevalence of OSA vary between 15–20% amongthe adult population (Peromaa-Haavisto et al. 2015). The prevalence of the condition isincreased in the presence of a certain risk factor; i.e., obesity, increasing age, male gender,family history, craniofacial disorders, tobacco smoking and alcohol consumption. Accordingto Finnish population studies and the register of hospital treatment periods (HILMO) of theFinnish National Research and Development Centre for Welfare and Health (Stakes),approximately 150,000 Finnish adult patients suffered from OSA more than ten years ago(Laitinen et al. 2003), the prevalence being 2.8%. In parallel with the global obesity epidemic,the prevalence of OSA has increased. Furthermore, the condition is still roughlyunderdiagnosed. Globally, the estimates for the prevalence of OSA vary surprisingly little,suggesting that the prevalence is equal in Western societies and developing countries (Kapur2010).

8

2.3 SDB IN CHILDREN

In children, the most severe manifestation of SDB, obstructive sleep apnea, was firstdescribed by Guilleminault in 1976 (Guilleminault et al. 1976). In their work they reportedthe cases of eight children, 5 to 14 years, who suffered from excessive daytime sleepiness,decrease in school performance, abnormal daytime behavior, nocturnal enuresis, morningheadache, abnormal weight and progressive development of hypertension. The symptomswere associated with loud snoring and breathing pauses while sleeping and the conditionwas diagnosed by nocturnal polygraphic monitoring. Since then, the diagnostics and criteriafor pediatric SDB have been under refining. Especially in children, SDB is believed to beunrecognized and underdiagnosed (Alkhalil and Lockey 2011), thus obviously, thediagnostics of pediatric SDB is still a matter of discussion.

2.3.1 PrevalenceSleep disturbances are currently a public health concern throughout the world. Theyinfluence millions of people and their prevalence is increasing both in adults and in children.The frequencies of pediatric SDB and its different manifestations are outlined in Table 1. Thelarge variation in the prevalencies of SDB and its different manifestations is somewhatconfusing. It seems that the condition is difficult to assess because of the disparity of thedefinition and diagnostic methods. Snoring, which can be defined as the mildest form of SDB or on the other hand the hallmarkof SDB, is very common. Almost every child snores when suffering from an upper airwayinfection or allergic rhinitis. On the other hand some children snore every night – withoutany co-existing medical condition. The prevalence of childhood snoring has been reportedto be between 2 and 34%, varying by definition. For comparison, the study using thedefinition of “snoring sometimes or often” the prevalence is 29.0% (Sanchez-Armengol et al.2001) while definition “snoring loudly frequently or almost always” shows the prevalence10.5% (Goodwin et al. 2003). According to a meta-analysis the global prevalence of snoringin children as observed by the parents by any definition is 7.45% (Lumeng and Chervin 2008).

The meta-analysis of population based studies shows that the prevalence of parental-reported apnea in the children usually varies between 0.2 and 4.0%. The same study reportsa wide variation of prevalence of OSA diagnosed with polysomnography, the ranges beingfrom 0.1 to 13.0%, even though most studies agree on ranges from 1 to 4%. The prevalenceof UARS is seldom reported in the literature (Lumeng and Chervin 2008).

The prevalence of the whole entity, – SDB, encompassing all the above-mentionedsymptoms and reported by the parents, has mostly been estimated to vary between theranges 4 and 11% (Lumeng and Chervin 2008, Bixler et al. 2009). The condition is suggestedto be most common among pre-school children, at which age the lymphoid tissue of thepharynx is large in relation to the pharyngeal airway (Linder-Aronson and Leighton 1983).Some studies suggest that in that group, SDB affects up to one third of the children(Castronovo et al. 2003, Bonuck et al. 2011).

Generally, sleep disorders are suggested to be more prevalent in boys (Paavonen et al.2000) and like in adults, boys to have more SDB compared with girls (Gill et al. 2012). Thereare also studies to show no gender difference in the prevalence of SDB (Goodwin et al. 2003,

9

Liukkonen et al. 2008). It must be highlighted, that the epidemiologic data on this issue iscontroversial because of variations in definition and diagnostics, sampling methods, racialaspects and also the effect of age. More effort is definitely needed to harmonize the issue interms of diagnostic criteria and epidemiology.

10

T ab l

e 1.

The

rep

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d pr

eval

ence

s of

chi

ldre

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ith s

ympt

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thor

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nor

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AR

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SG

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2.4

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loud

ly f

requ

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alm

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003)

USA

850

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/PSG

i

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al.

(200

4)Sin

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re10

279

4-7

28.1

sno

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6.0

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e

Got

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a l. (2

004)

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512

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004)

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016)

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1

12

2.3.2 SymptomsChildren with SDB have diverse symptoms that differ from those in adult population.Especially in children there is much individual variation in the symptoms which makes itdifficult to make a diagnosis based on the symptoms. While awake, children with SDB are often mouth breathers (Ali et al. 1993, Kawashima etal. 1999, Xu et al. 2006). Furthermore, hyponasal speech, nasal congestion, swallowingdifficulties, poor appetite and prolonged duration of meals (Ahlqvist-Rastad et al. 1988,Kawasihima et al. 1999, Sakellaropoulou et al. 2012) are reported to be the symptoms ofchildhood SDB. Also morning headache and daytime naps are typical to the children withSDB (Xu et al. 2006, Zarowski et al. 2007). The most common and recognized symptom of childhood SDB while asleep is snoring(Lumeng and Chervin 2008). Nocturnal oral breathing is also typical symptom of SDB(Bonuck et al. 2011). The children with more serious manifestations of SDB have breathingpauses observed by the caregivers (Bonuck et al. 2011). Restless sleep and body movementswith odd sleeping positions, nightmares, excessive vocalization and sweating are typicalnight-time symptoms (Ersu et al. 2004). Furthermore, some studies suggest nocturnalenuresis to associate with childhood SDB (Ersu et al. 2004, Alexopoulos et al. 2014). Theremay also be difficulties in breathing with an inward movement of the upper chest duringinspiration (Wang et al. 1998). The downward motion of the diaphragm causes the abdomento move outward when negative intrathoracic pressure manifests as paradox inwardmovement of the rib cage (Bower and Gungor 2000). This confusing motion of the chest oftenfrightens parents and leads them to consult a doctor. It is suggested that the main symptoms in children might change with age (Sinha andGuilleminault 2010). Infants, among whom the prevalence of snoring is 9%, (Piteo et al. 2011)are described as having “noisy breathing” and poor suck. Toddlers snore loudly and sleeprestlessly, moving around the bed. With pre-school children enuresis and problems withwaking up may become an issue. In children of school-age, diversity of the symptomsincreases. Long-term sequelae of the condition are apparent in this age group, and behavioraland cognitional consequences start to appear. In adolescence, psychological problems, suchas depression become more apparent (Sinha and Guilleminault 2010). Furthermore, studies show that there is an association between childhood SDB and sleepbruxism (Kawashima et al. 1999, Ohayon et al. 2001). Interestingly, high and moderateexposure to second-hand smoke (which is also shown to be a risk factor for childhood SDB)is associated with sleep bruxism in children (Montaldo et al. 2012, Jara et al. 2015).

2.3.3 Risk factorsLymphoid tissue of the pharynxPharyngeal lymphoid tissue consists of adenoid (pharyngeal tonsil), tonsils (palatine tonsils)and lingual tonsils and together they form an entity called Waldeyer´s ring. The majorfunction of this tissue is to participate in the generation of antigen-specific immune responseswith formation of immunoglobulin (IgA, IgG and IgM) -producing plasma-cells. This activeimmunologic cascade leads to physiologic proliferation of the lymphoid tissue in childhood(Gross and Harrison 2000). Adenotonsillar hypertrophy (ATH) is the most common riskfactor for pediatric SDB (Arens et al. 2003, Dayyat et al. 2007). The volume of the adenoid and

13

tonsils increases from birth up to the age of twelve years, the peak of the proportional sizerelated to the skeletal structures occuring around 5-6 years of age (Dayyat et al. 2007). Duringthe first eight years of life, pharyngeal lymphoid tissue is likely to be exposed to stimuli thatpromote cellular proliferation (Papaioannou et al. 2013). For this reason, childhood SDB ismost common during pre-school and early school years (Corbo et al. 2001). Even thoughnasal resistance decreases from 9 to 13 years of age, there is a transient prepubertal increasein the resistance, a phenomenon suggested to result from hormonal changes (Crouse et al.2000). Many environmental and medical factors may irritate and cause proliferation of thelymphoid tissue, e.g. passive smoking (Zhu et al. 2013), seasonal variability (Walter et al.2013), atopy and allergic rhinitis (Ishman et al. 2012) and asthma (Malakasioti et al. 2011). Inaddition, infection by respiratory syncytial virus, sinus problems and recurrent upper airwayinfections may predispose children to ATH (Redline et al. 1999, Goldbart et al. 2007,Tsaoussoglou et al. 2014). Lingual tonsil hypertrophy may be found in SDB children in with and without medicalconditions such as obesity and several craniofacial anomalies. Obesity and 21-trisomy havebeen shown to be risk factors for adenotonsillectomy (ATE) failure, the reason beingundiagnosed lingual tonsil hypertrophy as a possible reason for failure (Kuo and Parikh2014).

Craniofacial morphologyAccording to recent studies, dental malocclusion and craniofacial characteristics of childrenwith SDB seems to differ from those of children without it. A Swedish study examined acohort of 4-year-old children. Children with SDB had smaller cranial base angle and lowerratio of posterior/anterior total face height. They also had a narrow maxilla, a deep palatalheight, a short lower dental arch and more lateral cross bite than the controls. The treatmentof obstruction (ATE) seemed to diminish the mandibular inclination but the tendency for anarrower maxilla persisted (Löfstrand-Tideström et al. 1999, Löfstrand-Tideström andHultcrantz 2007, Hultcrantz and Löfstrand-Tideström 2009, Löfstrand-Tideström andHultcrantz 2010). An Italian study with untreated 4.5-year-old children with apneas showedcharacteristics of skeletal Class II sagittal relation with retrognathic mandible and increasedskeletal discrepancy (Marino et al. 2009). A study in Finnish children with SDB showeddeviations in the dental occlusion compared with non-SDB children, the typicalcharacteristics being increased overjet, a reduced overbite and narrow upper and short lowerdental arches (Pirilä-Parkkinen et al. 2009). Cephalometrically, the same children had aretrusive and vertically growing mandible, long and thick soft palate, low positioned hyoidbone, large craniocervical angle, narrow airway diameter at the level of naso- andoropharynx and large diameter at the tongue level compared with children without SDB(Pirilä-Parkkinen et al. 2010). In summary, a recent systematic review and meta-analysis byFlores-Mir and colleagues suggested retrusive chin, steep mandibular plane, verticaldirection of growth and a tendency toward Class II malocclusion to be the typicalcharacteristics of SDB children (Flores-Mir et al. 2013). Altogether, these features may causean abnormal breathing pattern, and lead to further alterations to the oral and facial muscularbalance. It is likely that skeletal and occlusal development in children is further affected bythis association, possibly resulting in risk of SDB (Peltomäki 2007).

14

Craniofacial anomaliesChildren with many developmental craniofacial anomalies are at increased risk for SDB(Moraleda-Cibrian et al. 2014). Structural and functional changes present in the upper airwayof infants with cleft lip and/or palate confer an increased risk of SDB (Smith et al. 2014). Inolder children with cleft lip and/or palate dysfunction of the palatal structures controllingthe soft tissue and morphological abnormalities of the maxilla and mandible producing asmall nasopharyngeal lumen result in high risk for SDB. The risk is compounded by surgicaloperations to correct the structural anomalies which further decrease the airway dimensions(MacLean et al. 2009). In children with trisomy 21 the risks for SDB are associating generalized hypotonia andpharyngeal collapsibility, independent of age, gender, and body mass index (BMI) (Fung etal. 2012) and macroglossia. The high prevalence of SDB in children with BeckwithWiedermann syndrome is multifactorial and not solely the result of a large tongue (Follmaret al. 2014). Young patients with achondroplasia may suffer from obstructed airways (Reidet al. 1987). Furthermore, syndromes associated with midface hypoplasia (Treacher Collins,Crouzon, Apert and Pfeiffer syndrome) and mandibular micrognathia (Pierre Robin andMarfan syndrome) predisposes to SDB (Spier et al. 1986, Hoeve et al. 2003, Sinha andGuilleminault 2010).

Other risk factorsMultiple medical conditions may increase the risk for SDB. Children with asthma have twiceas much SDB than those without it. The association between asthma and SDB seems to beevident from a physiological context, an inflammatory pathway of the airway being the linkbetween the conditions (Brockmann et al. 2014). Often the obstruction to the upper airwayexists at the level of the nose. Common causes of nasal obstruction include allergic rhinitis,septal deviation, chronic sinusitis and nasopharyngeal stenosis; all raising the risk for SDB(Li and Lee 2009). Infants and toddlers with gastroesophageal reflux may have an increasedrisk for SDB (Koivusalo et al. 2011). In neuromuscular diseases, such as Duchenne musculardystrophy and congenital myopathy, inspiratory muscle weakness may lead to alveolarhypoventilation and reduced pulmonary gas exchange and further, to SDB (Anderson et al.2012). Children with cerebral palsy (CP) have a more than three-fold higher risk of SDBcompared with normally developing children. Interestingly, sleep problems among childrenwith CP include insomnia and excessive daytime sleepiness more often compared tonormally developing children (Sandella et al. 2011). Laryngomalacia in young children alsoraises the risk for SDB (Li and Lee 2009). Furthermore, history of prematurity (Manuel et al.2013) associates with the SDB. The recent systemic review showed a significant association between childhood SDB andsecondhand smoke (i.e. parental smoking) and recommended smoking cessation tocaregivers (Jara et al. 2015). Furthermore, a parental history of SDB raises the risk for thecondition. This familial clustering suggests that genetic factors may constitute a risk factorfor OSA and SDB (Friberg et al. 2009).

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ObesityIt is disquieting that overweight and obesity are becoming more common in children andadolescents in many developed countries (Kipping et al. 2008). In Finland, 10% of childrenand 26% of adolescents are overweight (Vuorela et al. 2009). Furthermore, the sameresearcher group showed that in the last decades the prevalence of overweight and obesityhas even increased among adolescents, especially in boys (Vuorela et al. 2011). Excess bodyadiposity is a well-recognized risk factor for SDB in adults (Leinum et al. 2009), but it has alsobeen suggested to be an important risk factor for pediatric SDB (Marcus et al. 1996, Ng et al.2004, Verhulst et al. 2008). The mechanism by which obesity predisposes to SDB may be themass loading of the upper airway and respiratory muscles causing modification tomorphology and function, reduction of chest compliance, changes in respiratory drive andimpairment of functional residual capacity, all increasing the risk of upper airwayobstruction (Kohler and van den Heuvel 2008). Age and ethnicity modify the impact ofobesity on SDB. In older children there are more associations between body adiposity andSDB compared with younger ones, and in terms of ethnicity, the same association appears tobe more prevalent among African American and Asian children (Kohler and van den Heuvel2008). A large neck circumference of the children is also associated with SDB (Redline et al.1999). It is suggested that two types of SDB exist, one associated with ATH among normalweighted children and the other associating primarily with obesity without ATH (Dayyat etal. 2007). Interestingly, it has recently been demonstrated that deviations in craniofacialmorphology are much more common in normal weight than overweight adult patients withOSA, implying that there may be two different phenotypes of adult SDB; one related to excessadipose tissue and the other to craniofacial abnormalities (Pahkala et al. 2011).

2.3.4 PathophysiologyThe upper airway is a complex structure that is usually divided into four anatomicalsubsegments: nasopharynx (between the nares and hard palate), velopharynx (between thehard palate and soft palate), oropharynx (from the soft palate to the epiglottis) andhypopharynx (from the base of the tongue to the larynx) (Ayappa and Rapoport 2003). Thisstructure is surrounded by more than 20 muscles that actively modify the airway lumen(Fouke et al. 1986). There is also lymphoid tissue, i.e., adenoid, tonsils and lingual tonsils.The main bony structures that determine the area of the airway lumen are the hyoid boneand the mandible. The transition from wake to sleep relaxes the muscles of the upper airway,resulting in collapsibility of the airway structures and an increased resistance to airflow. Inhealthy subjects this increase may be 3-5 mmHg in PCO2 (Horner 2008a). Upper airway obstruction takes place during inspiration in parallel with an increase of thepressure surrounding the structures, and there are three elements that contribute to this:morphological narrowing, abnormal neuromuscular control and inflammation (Sinha andGuilleminault 2010). The airway is narrowest at the level of the oropharynx behind the softpalate. When the upper airways are morphologically narrow, the relaxation during sleep ofpharyngeal muscle tonus may predispose to clinically significant diminutions in inspiratoryairflow and limitation of it (snoring and hypopneas) and even pause of airflow because oftotal airway closure (obstructive apneas). A major contributor to this cascade is posteriormovement of the tongue (Horner 2008a). The neuromuscular control cascades responsible for the tonic sleep-state-dependent inputs

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to the motoneurons innervating the pharyngeal muscles are defined by information gainedfrom animal studies (Horner 2001, Horner 2008b). Serotonin and noradrenaline-containingneurons give excitatory stimuli to the motoneurons of the pharyngeal muscles. Theseneurons are most active in wakefulness, less active in N sleep and least active in R sleep,which may lead to decreased pharyngeal muscle activity in sleep (Chan et al. 2006). There isalso neuromuscular compensation with increasing respiratory effort sustaining patency ofthe upper airway, and this sometimes leads to arousal (Katz and D'Ambrosio 2008). Inflammation, both local and systemic, can lead to increased resistance of the upper airway.Acute or chronic inflammation of lymphoid tissue contributes to chronic activation of thecell-mediated and humoral immune response, resulting in ATH and furthermore, causingobstruction of the airway (Zautner 2012). In terms of systemic inflammation it has beenshown that C-reactive protein (CRP) levels are increased in patients with SDB, independentof body adiposity (Tauman et al. 2004, Kheirandish-Gozal et al. 2006). Episodic hypoxia andarousal launch endothelial dysfunction and systemic inflammation (Kato et al. 2000,Apostolidou et al. 2008), the same process leading to sympathetic activation. This may leadto increased insulin resistance (Punjabi et al. 2004) and blood pressure (O'Brien and Gozal2005).

2.3.5 ConsequencesPsychological effects, cognition and quality of lifeToday, there is a lot of evidence of the behavioral and cognitional difficulties associated withchildhood SDB. SDB of any severity is associated with poor behavior but not with poorcognitive performance (Jackman et al. 2012) and furthermore, SDB is associated with reducedquality of life in 3- to 5-year-olds (Jackman et al. 2013). A study of Gozal shows thatneurocognitive deficits seem to co-exist with the most severe manifestations of SDB (Gozalet al. 2010). Mood disorder symptoms are also shown to associate with SDB (Aronen et al.2009). On the other hand, it has been shown that there is only minimal association with SDBand children´s typical mood, expressive language skills, visual perception, and workingmemory, but there is a significantly stronger association with parent reported emotioninstability (e.g. deterioration in behavior and emotion regulation, school performance,constant and selective attention and alertness) (Beebe 2006). Children with SDB have lowergeneral intellectual ability regardless of severity compared to those with no SDB. Impairmenthas also been observed in academic and executive functioning (Bourke et al. 2011).Furthermore, among preschool children SDB seems to associate with reduced quality of lifeof both the children and their families (Jackman et al. 2013). It has also been shown in alongitudinal study with young children that snoring predicts mental disturbances inadolescence (Gozal 2001). Difficulties in behavior and emotions, such as hyperactivity,aggression, irritability, rebelliousness, conduct problems and impaired concentration arecommon with pediatric SDB (American Thoracic Society 1999). Excessive daytime sleepinessis sometimes observed in children, prevalence varying from 7% to 43% (Carroll et al. 1995,Chervin et al. 2006). Large variation may be explained by the different methods used fordetermining excess daytime sleepiness as well as confounding factors, such as obesity (Gozaland Kheirandish-Gozal 2009). ADHD is a complex, life-lasting disorder which is typically associated with inattentiveness,hyperactivity and impulsivity. The literature shows, that children with ADHD suffer frommore sleep disorders than children without it (Kurnatowski et al. 2008, Chiang et al. 2010,

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Souly et al. 2013). Most parents of ADHD children have reported their children to suffer fromlow quality sleep; typical complaints were snoring, arousals, motor restlessness and legdiscomfort at night (Silvestri et al. 2009). The signs and symptoms of ADHD children arenotably similar to those of SDB. It has been shown, that SDB can lead to mental characteristicsidentical to ADHD (Chervin et al. 2002) and has even been suggested that surgical treatmentof ATH might result in a significant decrease in the severity of ADHD-like symptoms (Amiriet al. 2015). The mechanism of the impairing effect of SDB on psychological context is under debate.Milder and at the same time more common manifestations of the SDB may even have thestrongest effects on psychological functions with pre-school children (Jackman et al. 2012).The study of Jackman suggests, that theoretically snoring itself may be more harmfulrespiratory event among young children than apneas or hypopneas. Snoring may lead tosignificant physiological changes (e.g. inflammation or sleep fragmentation) even to an equalor greater extent than apneas and hypopneas. Literature shows that the milder forms(snoring) may cause problems with sleep fragmentation and severe forms (OSA) by hypoxia(O`Brien et al. 2004). As a consequence, sleep homeostasis may be disturbed. Regardless ofthe severity of the symptom or body adiposity, children with SDB had more deterioration inquality of life and depressive symptoms than children without the condition (Crabtree et al.2004). Further, sleep disturbances cause simply fatigue and stress in both children andparents, and that fact interferes with multiple aspects of children´s lives, including the mentalcontext. In terms of the causality, the recovery of mild/moderate SDB by ATE is associatedwith improved behavior and functioning, suggesting that the relation between SDB anddaytime problems in children is a causal one (Ali et al. 1996).

Growth impairmentGrowth impairment is shown to be a typical feature of advanced SDB (Bonuck et al. 2009).The decline of growth with SDB may occur because of a disruption of growth hormonesecretion in parallel with disruption of the sleep architecture. Nieminen concludes in histhesis that growth impairment in pediatric OSA is associated with reduced concentrations ofinsulin-like growth factors and binding protein, suggesting reduced night-time growthhormone secretion to be secondary to upper airway obstruction (Nieminen 2002). Thealteration of nocturnal secretion of growth hormone may also affect the mandibular ramus,which is in line with morphological differences in the SDB children compared with childrenwith no SDB (Peltomäki 2007). In addition, in the case of SDB child with ATH there may bevarious craniofacial and myofunctional alterations negatively affecting other functions suchas mastication, swallowing, and speech (Souza et al. 2013). Furthermore, there may be specialfeatures such as insufficient lip closure, low position of the tongue, flabby tongue,mastication with half-open lips, position of the lower lip between the incisors and alteredswallowing (Valera et al. 2003). It is suggested that these characteristics may drain the child´scaloric resources which would otherwise be used for somatic growth. Furthermore, SDB maylead to growth failure via increased energy expenditure during restless sleep (Marcus et al.1994, Li et al. 2003).

Cardiovascular consequencesSDB in adults is a risk factor for hypertension and cardiovascular morbidity in the generalpopulation (Peppard et al. 2000). The association of childhood SDB and hypertension is not

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straightforward. There are studies showing that children with any severity of SDB may haveelevated blood pressure (Marcus et al. 1998, Enright et al. 2003, Kwok et al. 2003). On theother hand, a meta-analysis found no evidence that moderate to severe SDB in childhoodincreases the risk of hypertension (Zintzaras and Kaditis 2007). Studies have shown that endothelial function is often altered with childhood OSA (Gozalet al. 2007). The inflammatory cascade which leads to endothelial dysfunction may have animportant role in the relation between SDB and cardiovascular disease. The presence ofcirculating inflammatory markers, such as CRP could support this theory. A recent studywith obese children and adolescents found no association between OSA and CRP levels.However, an association between CRP and measures of adiposity was found. The studysuggests that obesity, but not SDB results in an increased inflammatory status as measuredby CRP (Van Eyck et al. 2014).

Metabolic impactsChildhood OSA, sometimes co-existing with increased body adiposity, increases the risk ofthe metabolic syndrome (MetS) (Waters et al. 2007). MetS is the clustering of a set ofcardiometabolic risk factors thought to put the individual at increased risk of thedevelopment of cardiovascular diseases and type 2 diabetes (Owens and Galloway 2014). Onthe other hand, childhood obesity associates with OSA and high levels of insulin (Gozal etal. 2008). The strongest predictors of MetS in adulthood are childhood elevation of fastinginsulin levels and increased body mass index (BMI) (Brunner et al. 2002). Furthermore,insulin resistance in childhood is associated with increased risk for later cardiovascularmorbidity and mortality (Bao et al. 1996). The treatment of OSA in obese children issuggested to correct the insulin levels (Waters et al. 2007); this relationship between OSA andinsulin resistance has not been observed with normal weight children (Gozal et al. 2008).Altogether, metabolic changes in childhood OSA may be related to obesity, OSA acting as animportant mediator.

2.3.6 DiagnosticsThe diagnosis of childhood SDB is based on the anamnesis and clinical examination of thechildren and further, on supporting deviant findings in a polysomnographic record. A sleephistory screening for the symptoms of SDB should be part of routine health care visits,including oral health examinations. If there is a history of snoring, a detailed anamnesisshould be obtained, e.g. breathing breaks, enuresis, diaphoresis, daytime behavior/learningproblems or restless sleep (Section on Pediatric Pulmonology, Subcommittee on ObstructiveSleep Apnea Syndrome. American Academy of Pediatrics 2002). Physical findings of clinicalexamination are often normal. There may be findings relating to ATH, such as mouthbreathing, hyponasal speech or nasal obstruction. However, a recent meta-analysis suggeststhat clinical assessment of tonsil size by Brodsky classification (Brodsky 1989) is a weakpredictor of the severity of SDB (Kaditis et al. 2016). Sometimes there may be symptoms ofimpaired growth, systemic hypertension or an increased pulmonic component of the secondheart sound indicating pulmonary hypertension, even though these findings are rare andnonspecific (De Luca Canto et al. 2014). The golden standard for the diagnostics of SDB is overnight, attended, in-laboratory PSG(Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome.American Academy of Pediatrics 2002), which is the only diagnostic technique shown to

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quantitate the ventilation and sleep abnormalities associated with the condition. It is anoninvasive test involving the measurement of a number of physiologic functions overnight,typical recordings including electrocardiography, electroencelography, pulse oximetry,oronasal airflow measured by both pressure sensor and thermistor, abdominal and chest wallmovements, partial pressure of carbon dioxide and video recording (Apostolidou et al. 2008).It can be performed at any age, but specific pediatric measuring and scoring criteria shouldbe used. In children, International Classification of Sleep Disorders (3rd edition) classifies AHIof equal or greater than 1 event per hour as abnormal (American Academy on Sleep Medicine2014). However, the relative complexity and high costs of PSG have spurred the quest foralternative diagnostic methods, especially for screening for the condition in children. The history of the symptoms of possible SDB can also be obtained by using thequestionnaires. A meta-analysis reviewed the diagnostic value of alternative methods(clinical history and physical examination) for childhood SDB (De Luca Canto et al. 2014).The authors concluded that in terms of screening for the condition questionnaires could bean acceptable method to determine the children who need to be referred to a sleep medicinespecialist, and they suggested the use of this method especially for dentists. A recent studyassessed the meaning of symptom history in detecting OSA (Kang et al. 2015). The symptomrecord consists of questions such as snoring patterns, night-time and daytime clinicalsymptoms and other OSA-related symptoms. The snoring pattern was evaluated by askingparents about the snoring frequency and duration, and further about the daytime symptoms(sleepiness, attention/hyperactivity problems, depression, low self-esteem, shyness and lowschool performance). The night-time symptoms included breathing pauses, awakenings,enuresis, nightmares and diaphoresis. Other OSA-related symptoms were also included inthe recordings. For example, snoring frequency had a sensitivity of 77% with a specificity of48% and tonsil size a sensitivity of 77% with specificity of 65% in detecting OSA. The resultsof this study suggest combining both history of symptoms and anatomical findings for ascreening scheme of childhood OSA.

2.3.7 Treatment of pediatric SDBOverweight or obese children are encouraged to a healthy way of life and weight loss. Inyoung children the implication of obesity as a risk for SDB is not very significant, althoughhigher body adiposity may predict development of SDB in the coming years (Kohler and vanden Heuvel 2008). ATE is suggested to be an effective and curative treatment modality in cases wherepediatric SDB and ATH co-exist (Laitinen et al. 2003, Wei et al. 2007) but there are also severalstudies which have failed to show any strong association with ATH and SDB (Li et al. 2002,Lam et al. 2006). It is shown that a significant number of children do not achieve completerecovery for SDB after the operation. Residual SDB after ATE may be associated with otherrisk factors, such as body adiposity or deviant craniofacial morphology (Bhattacharjee et al.2010). Furthermore, an American multicenter, single-blinded, randomized and controlledtrial (Marcus et al. 2013) studied children with OSA and ATH, allocating the children intotwo groups: ATE group and watchful waiting group. The results showed that after sevenmonths 42% of the children in the watchful waiting group no longer met the criteria of OSA.The study suggests that watchful waiting may be a rational option if a child has low OSAsymptom burden, little snoring, low AHI and normal waist circumference (Chervin et al.2015). However, the American Academy of Pediatrics suggests ATE as the primary treatment

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for children with SDB and ATH (Marcus et al. 2012). In the case of deviant craniofacial morphology or malocclusion, orthodontic treatment issuggested as a primary treatment in children without ATH and as an additional treatment toATE when SDB persists (Praud and Dorion 2008, Huynh et al. 2016). There are studies toshow that orthodontic treatment, such as maxillary expansion (Guilleminault and Li 2004,Ashok et al. 2014, Machado-Júnior et al. 2016a) and functional treatments advancingmandible (Hanggi et al. 2008, Villa et al. 2012, Machado-Júnior et al. 2016b) may be effectiveas a treatment for pediatric SDB and also as prevention of adult SDB. However, it is alsosuggested that there is not enough evidence to show the efficacy of oral appliances orfunctional appliances in the treatment of pediatric OSA (Carvalho et al. 2007). Children withsevere syndromic craniofacial abnormalities may need invasive surgery, such astracheostomy, osteotomies or osteodistraction (Robison and Otteson 2011).

2.3.8 Other orthodontic aspectsAdequate spatial volume of the upper airways is a prerequisite for physiological respiration.A recent study shows that during development of children from 6 to 17 years of age, upperairway dimensions remain on average outstandingly unchanged, suggesting that the airwaydimensions are established in early childhood (Mislik et al. 2014). Small upper airwaydimensions that have developed in early childhood may expose to SDB and OSA later in life(Papaioannou et al. 2013) when normal soft-tissue changes caused by obesity, ageing orgenetics affect the patency of the oropharynx (Martin et al. 1997). In addition to impairedchildhood growth, spatial volume can be affected by ATH or nasal congestion caused byedema of the nasal mucosa, deviated nasal septum or nasal polyps. The obstruction may leadto postural adaptation (i.e., extension of the head), forward or downward positioning of themandible, tongue positioning forwards and open-mouth posture – all of which arephenomena to ensure adequate airway volume and furthermore, associated with at leastpartial oral breathing (Behlfelt et al. 1990). “Adenoid face” or “long face syndrome” are terms widely used when describing typicalcharacteristics associated with partial oral breathing. The classic facial features are narrowand long dimensions, lip apart posture at rest, short upper lip, flattened nose with smallnostrils, protruding upper incisors and further, self-reported “mouth breathing”. Behindthese traits lies typical malocclusion: increased facial height, over-erupted posterior teeth,backwards and downwards rotated mandible, class II occlusal relationship, open biteanteriorly, increased overjet, narrow V-shaped maxillary arch, high palatal vault and lateralcross bite (Linder-Aronson 1970, Macari et al. 2012). However, the debate about theorthodontic relevance of upper airway obstruction and its assumed effect on facial growthhas been ongoing for over a century, but no final conclusion has yet been reached (Vig 1998).

2.3.9 Childhood SDB associations to adult SDBThere are a few studies to evaluate the possible progression and natural evolution ofpediatric SDB, but without consensus. Among children, as well as among adults, male sexand body adiposity seem to be risk factors for the SDB (Goodwin et al. 2010, Spilsbury et al.2015), which suggests strong support for screening, preventing, and treating overweight inall age groups. On the other hand, milder forms of pediatric SDB do not seem to evolve intomoderate-to-severe SDB in adolescence (Bixler et al. 2016). However, no patient regardlessof age can contract OSA suddenly, over one night - there is always a history of evolution

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from milder symptoms of the condition to the more severe ones. Craniofacial and occlusal development occurs in childhood. Adult patients with SDB havedeviations in craniofacial morphology and dental occlusion similar to those found in childrenwith SDB (Löfstrand-Tideström et al. 1999, Pahkala et al. 2011). It is obvious that withouttreatment, a child with craniofacial and dental risk factors and SDB, even after ATE, mayhave the condition. This raises the question of whether adulthood SDB could be preventedin some individuals by focusing on orthodontic treatment already in childhood.

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3 Aims of the study

The general aim of this doctoral thesis was to investigate the risk factors, diagnostic methodand consequences of pediatric SDB in a population sample of Finnish children.

The specific aims of the doctoral thesis were

1. to study the associations of dentofacial and pharyngeal morphology and body fat withthe risk of having SDB in 6- to 8-year-old children (Study I).

2. to evaluate the lateral view photograph of the face as a tool for assessingmorphological properties as a risk factor for SDB in children and to investigate howreliably a group of health care professionals can visually observe the profile ofchildren from photographs to assess the convexity of their faces. A further aim was tostudy the feasibility of the use of photograph for the visual observation of the facialprofile (Study II).

3. to assess the determinants of psychological well-being in girls and boys attendingtheir first grade at primary school and further, to evaluate the role of SDB in it (StudyIII).

4. to analyze the associations of dentofacial and pharyngeal morphology and body fatwith the risk of having SDB at the age of 9-11 years and to evaluate the influence ofmouth breathing and orthodontic treatment on the condition. (Study IV).

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4 Study design and study population

4.1 ETHICAL CONSIDERATIONS

The Research Ethics Committee of the Hospital District of Northern Savo reviewed andapproved the study protocol. All participating children and their parents gave their informedwritten consent.

4.2 DESIGN OF THE PHYSICAL ACTIVITY AND NUTRITION INCHILDREN (PANIC) STUDY

This dissertation was conducted as a part of the Physical Activity and Nutrition in Children(PANIC) Study. The PANIC study is a long-term controlled exercise and diet interventionstudy in a representative population sample of primary school children from the city ofKuopio, Finland (Figure 3). Altogether 736 children aged 6-8 years who started the first gradein primary schools of Kuopio in 2007–2009 were invited to participate in the baselineexaminations between October 2007 and November 2009. The participants were allocatedinto the exercise and diet intervention group (n=309) and the control group (n=203). Thechildren and their parents in the intervention group received intensive, family-basedphysical activity and diet counselling for two years. The control children did not receive anyintervention during the period. Because the intervention did not have any influence on theresults of the present study (data not shown), the participants were analyzed as one group,without allocation. A follow-up study was carried out with 440 children in 2009-2012 withthe same assessments as in the baseline study. Thereafter, a less intensive intervention willbe continued until adulthood in the intervention group. The participants will be examined inadolescence and in early adulthood.

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Figure 3. Flow chart of the Physical Activity and Nutrition in Children (PANIC) Study population

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The general aim of the PANIC study is to identify the risk factors and risk groups forchronic diseases already in early childhood and to study the effects of physical activity,sedentary behavior, diet, genetic factors, sleep and pain experience on health and well-beingamong children and adolescents. This doctoral dissertation follows a cross-sectional study design using the baselinemeasurements in studies I, II and III. The children in the intervention group had not receivedany exercise or diet intervention at the time of the baseline measurements, and theintervention and control children were treated similarly during the measurements.Therefore, this dissertation treats the baseline data as a cohort. Study IV is a follow-up study.

4.3 PARTICIPANTS

Invitation letters were sent to the children´s principal custodians by mail according to theregistration for the first class of 16 public schools in Kuopio. Private schools and classes forpreparing education for immigrant children and classes for children with special needs wereexcluded from the study. The parents were asked to contact the coordinator of the study toparticipate. If the parents did not get in touch, their willingness to participate was inquiredby telephone. Of the 736 invited children, 512 (70%) participated in the baselineexaminations. The participation rate varied between 55% and 87% among the schoolsincluded. Of the 512 children, 248 (48%) were girls and 264 (52%) were boys. The participantsdid not differ in terms of gender distribution, age or BMI-SDS from other children of the sameage from primary schools of Kuopio based on available school health examination data (datanot shown). Table 2 shows the number of participants, inclusion criteria and outcome variable(s) inStudies I-IV.

Table 2. Number of participants, inclusion criteria and outcome variable(s) in studies I-IV

Study Number ofparticipantsAll, Girls

Inclusion criteria Outcome variable(s)

I 466, 226 Dentofacial and pharyngeal morphology recordsavailableSleep questionnaire availableBody fat percentage measurement available

SDB

II 382, 184 Photograph in the lateral facial projectionavailable

Reliability of the method

III 412, 205 Psychological, physical and social well-beingquestionnaires availableSleep questionnaire availableBody fat percentage measurement availableCardiorespiratory fitness measurement available

Psychological well-being

IV 329, 161 Dentofacial and pharyngeal morphology recordsavailableSleep questionnaire availableBody fat percentage measurement available

SDB, incidence of SDB

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5 Methods

5.1 ASSESSMENTS

5.1.1 Dentofacial and pharyngeal morphologyDentofacial and pharyngeal morphology were clinically evaluated by a standard orthodonticscreening method by one experienced orthodontist (T.I.). The occlusion was assessedaccording to the modified method of Björk (Björk et al. 1964) in the intercuspal position. Therecorded variables included molar occlusion (distal, normal or mesial), overjet (mm),overbite (mm), crowding ( 2 mm), spacing ( 2 mm), anterior and lateral open bite ( 2 mm)as well as cross bite and scissors bite. In cross bite, one or more lower posterior teeth arebuccal to the upper counterpart(s), while in scissors bite, the whole occlusal surface of theupper posterior teeth is buccal to that of the lower antagonistic teeth. The shape of the palatewas visually defined as wide, normal or narrow. The existence of adipose tissue under thechin was assessed visually. Facial profile (convexity, concavity and vertical dimension) wasalso assessed visually. To assess the actual airway between the tonsils the children wereasked to breathe through their nose, which then relaxes the pharynx and palatal area. Thetonsils were considered hypertrophied if there was 1 cm or less space between the tonsils.The definition corresponds to classes 3-4 of the Brodsky classification (Brodsky 1989). Softpalatal morphology was classified according to the Mallampati Classification, which is basedon clinical examination with maximal mouth opening and tongue protrusion in the seatedposition (Mallampati et al. 1985). Dominant mouth breathing was assessed visually duringthe clinical examination. Previous or ongoing orthodontic treatment was checked from thechild´s dental records and classified according to the most prevalent treatment modalities inFinnish children among the studied age groups: Quad helix, head gear, or other (mostlyeruption guidance appliance). Noteworthy, if an examination showed treatment need, a childwas referred to an appropriate professional (i.e., dentist, orthodontist, physician).

5.1.2 SleepSleep, SDB and associated factors were assessed by a questionnaire. The questions in thesleep questionnaire used were based on an established Finnish questionnaire that have beenused to screen for sleep disturbances and SDB (Partinen and Gislason 1995). The parentsfilled out the questions regarding the child’s quantity and quality of sleep, symptoms of SDB,frequency of upper airway infections and previous operative treatments, such as ATE.Unfortunately, the parents did not reliably remember their child`s possible ATE, so thisimportant data could not be used in the present study. SDB was defined as witnessedbreathing pauses (apneas) (sometimes, usually or always/almost always) and/or frequent(most of the sleeping time or frequently) and/or loud (quite loudly, loudly or extremelyloudly) snoring and/or nocturnal mouth breathing (usually or always/almost always)observed by the parents. In other words, if the child had one or more of above-mentionedsymptoms, he/she was defined as having SDB. Sleep duration was assessed using a combined heart rate and movement sensor (Actiheart,

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CamNtech, Cambridge, UK), a single piece monitor that clips onto two standardelectrocardiogram electrodes (Bio Protech Inc., Munmak-eup, South Korea) that were placedon the child’s chest in a standardized manner (Brage et al. 2005). Children were asked to wearthe Actiheart device continuously for at least four consecutive days that included twoweekdays and two weekend days. The duration of sleep was evaluated over an average of4.1 nights and analyzed manually from the heart rate and movement data by one exercisespecialist and confirmed by one physician, if needed. Falling asleep was defined as the timepoint when the accelerometer counts had reached zero and the heart rate had settled downfor at least five minutes. Waking up was defined as the time point when the accelerometercounts and heart rate had increased continuously from zero. Sleep duration was calculatedas the time between these two time points.

5.1.3 Body composition and fitnessBody height was measured with head position being in the Frankfurt plane without shoes bya wall-mounted stadiometer with an accuracy of 1 mm. Body weight was measured by thebioimpedance method using the Inbody 720® device (Biospace Co. Ltd., Seoul, Korea) withan accuracy of 100 g. Both parameters were measured after an overnight fast. BMI wascalculated as weight (kg) divided by height (m) squared. Z-scores for height, weight and BMIwere assessed with an obesity calculator that uses age- and sex-specific British growthreference data from 1990 (Cole et al. 1995). BMI-SDS was calculated using Finnish growthreferences (Saari et al. 2011). Overweight and obesity were defined using the age- and sex-specific BMI cut-offs derived from growth curves corresponding to BMI values 25 and 30 inadults 18 years of age, published by the International Obesity Task Force (IOTF) (Cole et al.2000). Body fat percentage was assessed by the dual-energy x-ray absorptiometry (DXA)method using the Lunar® device (Lunar Prodigy Advance, GE Healthcare, Madison,Wisconsin, USA) in the afternoon in the non-fasting state. The cardiorespiratory fitness of thechildren was tested with an electromagnetic cycle ergometer with a pediatric saddle module(Ergoselect 200 K, Ergoline, Bitz, Germany) as previously described in detail (Lintu et al.2014).

5.1.4 PhotographA standardized method was used for photographing the participants. The photos were takenusing a Canon EOS 300D® digital camera in the lateral projection of the face at a distance oftwo meters. The children were standing in a natural head position (NHP) in front of a mirrorwith a little bubble level taped on their temple to control the correct head position. The paper prints of the photos were gathered into a folder and a short instruction guidealong with the profile figures was formulated. The folder was examined first by a referenceorthodontist (T.I.) and then by seven other healthcare professionals who work with children,i.e., another orthodontist, a dentist with extensive orthodontic experience, a general dentalpractitioner, an otorhinolaryngologist, a pediatrician, an oral hygienist and a public healthnurse. In addition, a dental student examined the folder. The observers classified the profilesvisually as normal/mildly convex, clearly convex or straight/concave based on three modelpictures (Figure 4).

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Figure 4. Formula of normal/mildly convex, evidently convex and straight/concave profiles andinstructions to the observers

The photographic data was digitized and analyzed by Wincepht® 8.0 software in order toanalyze the profiles more objectively and further, to compare the subjective and objectiveassessment. Soft tissue landmarks Glabella (G`), Subnasale (Sn) and Pogonion (Pg`) weredigitally identified to calculate the angle G`- Sn - Pg` indicating the angle of facial convexity(Legan and Burstone 1980). Furthermore, soft tissue Nasion (Na`) and soft tissue Menton(Me`) were identified for the purpose of analyzing the reliability of the measurement of thevertical proportions (Sn`-Me`/Na`-Me`) of the face (Figure 5).

Figure 5. Digitized soft tissue landmarks on lateral facial photographs. Soft tissue Glabella (G`),Subnasale (Sn), Soft tissue Pogonion (Pg`), soft tissue Nasion (Na`) and soft tissue Menton(Me`)

32

5.1.5 Well-being measurementsThe parents completed the questionnaire concerning the child`s well-being during theprevious three months. The questionnaire was developed by the PANIC-researchers to assessthe most important components of well-being in general populations of children. Thequestionnaire was not validated or piloted, but the Cronbach´s Alpha analysis showed highinternal consistencies for the psychological well-being score (Cronbach’s Alpha 0.91), thephysical well-being score (Cronbach’s Alpha 0.83) and the social well-being score(Cronbach’s Alpha 0.76). The questionnaire had three parts: 1) psychological well-being, 2)physical well-being and 3) social well-being. Altogether 19 items were used to inquire aboutpsychological well-being (i.e., timidity, tearfulness, insecurity, anxiety, frustration,depression, restlessness, squeamishness or anger, aggressiveness, difficulties inconcentration, problems in concentration with homework, difficulties with homework,unwillingness go to school, troublemaking in class, discouragement, feeling of inferiority,forgetting things, sleeping difficulties, difficulties in reaching the age-appropriate level indoing things). Physical well-being was inquired with 12 items (i.e., problems with thefollowing activities: sitting, standing, walking, running, lifting or carrying things, eating ordrinking, washing, dressing up, performing housework as well as experiences of physicalpain, physical tiredness, difficulties in reaching the age-appropriate level in doing things).Social well-being was inquired with 6 items, (i.e., difficulties getting along with otherchildren, being bullied, arguing with other children, bullying other children, lack of interestin hobbies, difficulties in reaching the age-appropriate level in doing things). Each item wasrated on a 5-point scale (0=not at all, 1=once or twice in three months, 2=sometimes, 3=often,4= every day or almost every day). The total well-being scores from the questionnaire indicatethe status of physical well-being (range of possible score 0-48), psychological well-being(range of possible score 0-76) and social well-being (range of possible score 0-24).

5.1.6 Physical activity and inactivityThe assessments of the physical activity and sedentary activities were recorded during ausual week – on five week days and two weekend days (Väistö et al. 2014). Parents wereasked for information on regular physical activity, unstructured activity, physical education,physical activity at school and while commuting to and from school and during recess by thePANIC Physical Activity Questionnaire. The total amount of physical activity was calculatedas minutes per day. Habitual sedentary activity was also assessed by the same questionnaire.The amount of total sedentary activity was calculated by summing the time spent on eachsedentary activity type and was expressed as minutes per day weighted by the number ofweekdays and weekend days. Media use was calculated by summing up watching televisionand videos, using a computer, playing video games, using a mobile phone and playingmobile games and reported as minutes per day. The questionnaire was validated byActiheart monitoring (Väistö et al. 2014).

5.1.7 Dietary assessmentsFood consumption and nutrient intake were assessed by food records administered by theparents on four predefined consecutive days, as described previously (Eloranta et al. 2012).The food records were reviewed by a clinical nutritionist and analyzed using The Micro

33

Nutrica® dietary analysis software, Version 2.5 (The Social Insurance Institution of Finland).The Dietary Approach to Stop Hypertension (DASH) Score was used as an indicator of ahealthy diet and calculated as described previously (Fung et al. 2008). The DASH is acommonly used dietary quality index, which was originally developed for treatment ofhypertension in adults, but is also commonly used in children (Moore et al. 2005). In brief,the intake of seven food and nutrient groups, including fruit and fruit juices, vegetables,high-fiber ( 5%) grain products, low-fat (<1%) milk and sour milk products, red meat andsausage, sugar-sweetened beverages and sodium, were categorized into quintiles and scoredfrom 1 to 5. The highest quintile achieved the maximum score of 5 and the lowest quintileachieved the minimum score of 1. Reverse scoring was applied for red meat and sausages,sugar-sweetened beverages and sodium. The resulting 7 component scores were summed tocreate the overall DASH Score. A higher score indicates a higher dietary quality.

5.1.8 Socioeconomic background and characteristics of the parentsThe characteristics of the parents were reported with a structured questionnaire from bothmother and father. Parental socioeconomic status was assessed by the highest educationallevel in the family. Parents selected the appropriate level from three education categories:vocational, polytechnic and university. The total annual income of the households wasencoded into three categories (<€30,000/year, €30,001-€60,000/year and >€60,000/year).Possible unemployment, daily smoking and alcohol consumption (portions/week) werereported.

5.2 RELIABILITY OF THE MEASURES

The inter-examiner reliability for assessing the facial convexity (yes or no), mandibularretrusion (yes or no) and vertical proportions of the face (increased lower facial height yes orno) was measured using Cohen´s Kappa coefficients by comparing the assessments of threeexperienced orthodontists (Landis and Koch 1977). The assessments were performed withsixty randomly selected facial photographs of the studied children (Study I and IV). The intra-examiner reliability of the measures of the angle of convexity and the vertical proportions ofthe face were investigated by comparing the first and second assessment, two weeks apart,of the reference orthodontist (T.I.) using intra-class correlation coefficient (ICC) and its 95%confidence interval (CI) (Study II).

5.3 STATISTICAL METHODS

Statistical analyses were performed using the SPSS statistical software for Windows versions17.0-21.0. All associations and differences in averages were considered statistically significantif the P-value was <0.05. Chi-square or Fisher’s Exact test and Student’s t-test were used to compare the differencesin the prevalence of dental malocclusions and other craniofacial abnormalities, theprevalence of overweight or obesity and the means of BMI z-score and body fat percentagebetween children with and without SDB and between boys and girls (Study I and IV). Chi-square statistics were also used to analyze differences in the prevalence of having asthma or

34

SDB, differences in parental education, level of income, and smoking and employment statusbetween genders and low and normal psychological well-being groups (Study III). Student’st-test or Mann-Whitney U-test (depending on the normality of the variable distribution) wereused to analyze the differences in continuous variables, i.e., body fat percentage,cardiorespiratory fitness, duration of daily media use, duration of daily sedentary andphysical activities, sleep duration, daily supply of energy, the scores of physical,psychological and social well-being between genders as well as between low and normalpsychological well-being (Study III). Multivariate logistic regression analysis was used toinvestigate the associations of craniofacial abnormalities, dental malocclusions and body fatpercentage with the risk of having SDB (Study I and IV). The associations between the mostdeteriorated psychological well-being and parental education, parental daily smoking, SDB,media use and cardiorespiratory fitness were also estimated by logistic regression model(Study III). All independent variables as well as age and sex were entered stepwise into theregression models. Pearson correlation coefficients were calculated between the scores ofphysical well-being, psychological well-being and social well-being (Study III). The changein dental malocclusions and other craniofacial anomalies during the 2.2-year follow-up wasanalyzed by McNemar test (Study IV).

35

6 Results

6.1 BASIC CHARACTERISTICS

The characteristics of the children at the baseline and after 2.2-year follow-up are presentedin Table 3. At the baseline, 15.6% of the girls and 11.4% of the boys had either overweight(11.4% and 6.7%, respectively) or obesity (4.2% and 4.7%, respectively) and after follow-up15.3% of the girls and 18.8% of the boys had either overweight (12.5% and 15.2%,respectively) or obesity (2.8% and 3.6%, respectively). However, at both examinations thebody fat percent was higher among girls. The most common malocclusions at the baselineand after follow-up were dental crowding (51.7% and 42.8%, respectively), distal molarocclusion (29.5% and 25.4%, respectively) and mandibular retrusion (28.4% and 34.1%,respectively). The proportion of children with decreased palatal width was 11.6% at thebaseline and 10.9% after follow-up, while 14.9% had cross bite at the baseline and 8.7% afterfollow-up. Facial convexity at the baseline and increased lower facial height after follow-upwere more frequent among boys. Defined by the highest educational background of the family member, 18.7% of the familieshad a vocational school degree or less, 45.4% had a polytechnic degree and 35.9% a universitydegree. Annual household income was €30,000 in 18.5% of the families, €30,001-€60,000 in44.0% of the families and >€60,000 in 37.5% of the families.

36

Tabl

e 3.

Char

acte

rist

ics

of t

he c

hild

ren

at t

he b

asel

ine

and

afte

r 2.

2-ye

ar fol

low

-up

At

ba s

elin

eA

fter

2.2

-yea

r fo

llow

-up

All

child

ren

(n=

49

1)n

(%)

Gir

ls(n

=2

36)

n (%

)

Boy

s(n

=2

55)

n (%

)

pA

ll ch

ildre

n(n

=4

14)

n (%

)

Gir

ls(n

=2

02)

n (%

)

Boy

s(n

=2

12)

n (%

)

p

Ag e

, ye

ars,

mea

n (

SD

)

BM

I,m

ean

(SD

)

BM

I-SD

S,

Finn

ish

refe

renc

e va

lues

,

mea

n (

SD)

Bod

y fa

t pe

rcen

tage

,m

ean

(SD

)

Sle

ep d

isor

dere

d br

eath

ing

(SD

B)

7.6

(0.4

)

16.2

(2.

2)

0.05

(1.

1)

19.9

(8.

3)

46 (

9.9)

7.6

(0.4

)

16.2

(2.

2)

-0.0

1 (1

.0)

22.5

(7.

8)

17 (

7.6)

7.7

(0.4

)

16.2

(2.

1)

0.10

(1.

1)

17.4

(8.

0)

29 (

12.0

)

0.24

7

0.98

4

0.26

5

<0.

001

0.10

5

10.1

(0.

4)

17.2

(2.

7)

-0.1

3 (1

.1)

23.4

(9.

3)

38 (

11.6

)

10.1

(0.

4)

17.1

(2.

6)

-0.1

5 (1

.0)

25.3

(8.

5)

15 (

9.3)

10.1

(0.

5)

17.4

(2.

8)

-0.1

1 (1

.1)

21.5

(9.

6)

23 (

13.7

)

0.24

2

0.16

4

0.69

4

<0.

001

0.11

8

Dis

tal m

olar

occ

lusi

on

Cro

ss b

ite

Ope

n bi

te

Cro

wdi

ng

Sci

ssor

s bi

te

Con

vex

faci

al p

rofil

e

Incr

ease

d lo

wer

fac

ial h

eigh

t

Man

dibu

lar

retr

usio

n

Dec

reas

ed p

alat

al w

idth

Tons

illar

hyp

ertr

ophy

Ver

tical

ly r

estr

icte

d th

roat

Thic

k ne

ck

Adi

pose

tis

sue

unde

r th

e ch

in

Mou

th b

reat

hing

Ort

hodo

ntic

tre

atm

ent

145

(29.

5)

73 (

14.9

)

14 (

2.9)

254

(51.

7)

4 (0

.8)

159

(32.

4)

103

(21.

0)

139

(28.

4)

58 (

11.6

)

44 (

9.0)

211

(43.

3)

71 (

14.5

)

155

(32.

3)

47 (

9.6)

33 (

6.7)

77 (

32.6

)

33 (

14.0

)

5 (2

.1)

124

(52.

8)

1 (0

.4)

66 (

28.1

)

44 (

18.7

)

58 (

24.7

)

31 (

13.2

)

22 (

9.4)

100

(42.

6)

35(1

4.9)

72 (

31.3

)

19 (

8.1)

17 (

7.2)

68 (

26.7

)

40 (

15.7

)

9 (3

.5)

130

(51.

2)

3 (1

.2)

93 (

36.6

)

59 (

23.2

)

81 (

31.9

)

27 (

10.3

)

22 (

8.8)

111

(44.

0)

36 (

14.2

)

83 (

33.2

)

28 (

11.0

)

16 (

6.3)

0.14

8

0.59

6

0.34

4

0.72

6

0.62

5

0.04

4

0.22

2

0.07

7

0.31

6

0.81

9

0.82

1

0.73

9

0.65

7

0.27

0

0.68

1

105

(25.

4)

36 (

8.7)

5 (1

.2)

177

(42.

8)

11 (

2.7)

154

(37.

3)

94 (

22.8

)

141

(34.

1)

45 (

10.9

)

35 (

8.5)

129

(31.

4)

9 (2

.2)

71 (

17.4

)

23 (

5.7)

79 (

19.5

)

60 (

29.7

)

17 (

8.4)

2 (1

.0)

85 (

42.1

)

3 (1

.5)

72 (

35.8

)

35 (

17.4

)

61 (

30.3

)

22 (

10.9

)

19 (

9.5)

63 (

31.5

)

4 (2

.0)

33 (

16.6

)

8 (4

.1)

44 (

22.4

)

45 (

21.3

)

19 (

9.0)

3 (1

.4)

92 (

43.4

)

8 (3

.8)

82 (

38.7

)

59 (

27.8

)

80 (

37.7

)

23 (

10.8

)

16 (

7.6)

66 (

31.3

)

5 (2

.4)

38 (

18.2

)

15 (

7.2)

35 (

16.7

)

0.05

1

0.84

4

0.52

3

0.78

7

0.12

6

0.54

8

0.01

2

0.11

4

0.97

5

0.48

6

0.96

2

0.53

9

0.67

0

0.18

7

0.14

8

37

Table 4 shows the questions and the distribution of parents´ answers in sleepquestionnaire, based on which the children were defined as having SDB, both at thebaseline and after follow-up. The most frequent answers were “usually breathingthrough the mouth” and “snoring quite loudly”. Observed apneas were few innumber.

Table 4. Prevalence of single signs indicating SDB in the sleep questionnaire filled out by theparents

Childrenexamined at

baseline(n=466)

n %

Childrenexamined at

2.2-year follow-up (n=329)

n %Does your child breathe through the mouth at night? never rarely sometimesusually

always or almost always

95 (20.4)199 (42.7)134 (28.8)

29 (6.2)9 (1.9)

71 (21.6)137 (41.6)95 (28.9)21 (6.4)5 ( 1.5)

Have you noticed any pauses in your child’s breathingpattern during sleep? no rarelysometimes

usually always or almost always

443 (95.1)14 (3.0)6 (1.3)3 (0.6)0 (0.0)

320 (97.3)3 (0.9)6 (1.8)0 (0.0)0 (0.0)

How do you describe your child’s snoring best? no snoring snores rarelysnores in certain positions

snores most of the sleeping time snores frequently

253 (54.3)164 (35.1)

41 (8.8)9 (1.9)0 (0.0)

179 (54.4)126 (38.3)

20 (6.1)3 (0.9)1 (0.3)

How loudly does your child snore? no snoring lowquite loudly

loudly extreme loudly

241 (52.6)194 (42.4)

19 (4.1)3 (0.7)1 (0.2)

180 (54.7)135 (41.0)

13 (4.0)0 (0.0)1 (0.3)

Alternatives in italics included as having SDB

38

At the baseline, 9.9% (n=46) of the children had SDB, and there was no statisticallysignificant difference in the prevalence between the genders. Of the children, 41 (8.8%)snored in certain positions, 38 (8.2%) had nocturnal mouth breathing, 23 (5.0%) snoredloudly, 9 (1.9%) snored frequently and 3 (0.6%) had frequent apneas. After follow-up,11.6% (n=38) had SDB, with no statistically significant difference between genders.Compared with the SDB prevalence of the same children at the age of 7, after follow-up in 5.2% (n=17) SDB persisted, in 6.4% (n=21) new cases appeared and in 4.8% (n=16)previous SDB disappeared (Figure 6).

Figure 6. Changes (%) in SDB from 6-8 to 9-11 years of age

no SDB84 %

appeared6 %

unchanged5 %

disappeared5 %

39

The changes in the dentofacial and pharyngeal morphology, mouth breathing andorthodontic treatment during the follow-up time are shown in the Table 5. In parallelwith an increase in the number of children with previous or ongoing orthodontictreatment, many dental malocclusions have been corrected. Only the prevalence ofmandibular retrusion increased during follow-up time.

Table 5. Dentofacial and pharyngeal abnormalities in children at the age of 7 years and at the age of10 years, longitudinally

At the age of 6-8

years

n (%)

At the age of 9-11

years

n (%)

pa

Distal molar occlusion

Cross bite

Open bite

Crowding

Scissors bite

Convex facial profile

Increased lower facial height

Mandibular retrusion

Decreased palatal width

Tonsillar hypertrophy

Vertically restricted throatb

Thick neck

Adipose tissue under the chin

Mouth breathing

Orthodontic treatment

117 (29.0)

55 (13.6)

13 (3.2)

207 (51.4)

4 (1.0)

132 (32.8)

88 (21.9)

113 (28.1)

48 (12.0)

40 (10.1)

175 (43.9)

57 (14.3)

121 (31.1)

33 (8.2)

28 (6.9)

99 (24.5)

35 (8.6)

5 (1.2)

171 (42.4)

11 (2.7)

149 (37.1)

91 (22.6)

138 (34.3)

45 (11.2)

33 (8.3)

123 (30.8)

9 (2.3)

66 (17.0)

23 (5.7)

79 (19.5)

0.033

0.013

0.039

0.001

0.118

0.060

0.830

0.008

0.771

0.324

<0.001

<0.001

<0.001

0.143

<0.001

aBy McNemar TestbDefined as Mallampati et.al. Class III or IV

6.2 RISK FACTORS FOR SLEEP DISORDERED BREATHING AMONGCHILDREN AGED 6-8 AND 9-11- YEARS (STUDY I, IV)

Characteristics of the children with and without SDB at the baseline and after 2.2-yearfollow-up are presented in Table 6. Children 6-8 years of age with SDB were morelikely to have cross bite, convex facial profile, increased lower facial height,mandibular retrusion, hypertrophic tonsils and mouth breathing than those withoutit. After follow-up, at the age of 9-11 years, children with SDB were more likely tohave convex facial profile, mandibular retrusion and mouth breathing. There were no

40

statistically significant differences in the prevalence of body fat percentage or othercharacteristics between the children with SDB and those without it.

Table 6. Characteristics of the children with SDB and those without it at the baseline andat 2.2-year follow-up

Children examined at baseline(n=466)

Children examined at 2.2-yearfollow-up (n=329)

ChildrenwithSDB

(n=46)

Childrenwithout

SDB(n=420)

p-value

Childrenwith SDB

(n=38)

Childrenwithout

SDB(n=291)

p-value

Distal molar occlusion

Cross bite

Open bite

Crowding

Scissors bite


Increased lower facial height

Mandibular retrusion

Maxillary retrusion

Decreased palatal width


Vertically restricted throata

Mouth breathing

Orthodontic treatment

Thick neck

15 (32.6)

13 (28.3)

3 (6.5)

23 (50.0)

1 (2.0)

24 (54.5)

16 (34.8)

21 (45.7)

0 (0)

8 (17.4)

12 (26.1)

22 (47.8)

13 (28.3)

6 (13.0)

5 (10.9)

124 (29.5)

54 (12.9)

10 (2.4)

217 (51.9)

3 (0.7)

131 (31.3)

85 (20.3)

116 (27.6)

7 (1.7)

45 (10.8)

32 (7.7)

178 (42.7)

31 (7.4)

26 (6.2)

62 (14.8)

0.664

0.005

0.097

0.905

0.308

0.004

0.024

0.012

1.000

0.182

<0.001

0.504

<0.001

0.081

0.468

13 (34.2)

5 (13.2)

0 (0)

13 (34.2)

3 (7.9)

20 (52.6)

12 (31.6)

20 (52.6)

3 (7.9)

8 (21.1)

6 (15.8)

10 (26.3)

7 (18.4)

10 (26.3)

1 (2.6)

68 (23.4)

24 (8.2)

3 (1.0)

127 (43.6)

8 (2.7)

104 (35.7)

58 (19.9)

93 (32.0)

6 (2.1)

31 (10.7)

19 (6.5)

90 (30.9)

12 (4.1)

52 (17.9)

4 (1.4)

0.145

0.356

1.000

0.269

0.122

0.043

0.099

0.012

0.073

0.103

0.053

0.561

0.003

0.211

0.461

Adipose tissue under the chin 16 (34.8) 133 (32.4) 0.748 11 (28.9) 47 (16.3) 0.056

Body fat percentageb 19.7 (8.8) 20.0 (8.3) 0.829 25.5 (10.1) 23.1 (9.1) 0.135b

Data are numbers (percentages) and p-values are from Chi-Square Test or from Fisher’s ExactTestaDefined as Mallampati et al. Class III or IVbData are means (standard deviations) and p-values are from Student’s T-test

The risk factors for SDB at the baseline and after 2.2-year follow-up are presented inTable 7. Children aged 6-8 years with SDB were more likely to have tonsillarhypertrophy, cross bite and convex facial profile than those without it. Children withtonsillar hypertrophy had a 3.7-fold higher risk of suffering SDB than those withnormal size tonsils after adjustment for age, sex and body fat percentage. Furthermore,children with cross bite had a 3.3-fold higher risk of having SDB than those without

41

cross bite, while children with a convex facial profile had a 2.6-fold higher risk ofhaving SDB than those with a normal facial profile. Other craniofacial abnormalitiesor body fat percentage were not associated with the risk of having SDB among thisage group. Children 9-11 years of age with SDB were more likely to have mouthbreathing, adipose tissue under the chin and previous or ongoing orthodontictreatment. Children with mouth breathing had a 5.4-fold higher risk of suffering SDBthan children with nasal breathing.

Table 7. The risk factors for SDB at the age of 6-8 years and at the age of 9-11 years

Relative risk 95% confidence

interval

p-value

Risk factors at the age of 6-8


Cross bite


Risk factors at the age of 9-11

Adipose tissue under the chin

Mouth breathing

3.7

3.3

2.6

2.3

5.4

1.7-8.2

1.5-7.1

1.4-5.1

1.10-5.06

1.93-15.30

0.001

0.003

0.004

0.029

0.001

Data are from stepwise logistic regression models, the effect of gender was considered in eachstep.Only statistically significant determinants are given

6.3 PREDICTORS OF SLEEP DISORDERED BREATHING INCHILDREN (STUDY IV)

Risk factors and prediction of SDBMale gender, distal molar occlusion, mouth breathing and increased body fatpercentage at the baseline were associated with increased risk of having SDB at the2.2-year follow-up (Table 8). Mouth breathing was the strongest baseline predictor ofSDB at the 2.2-year follow-up. Children with mouth breathing at baseline had a 4.4-fold higher risk of SDB at the 2.2-year follow-up than those without it. It is noteworthythat the intervention setting of the PANIC study did not have an impact on the results(data not shown).

42

Table 8. Baseline predictors for having SDB at 2.2-year follow-up among all 329 children


interval

p-value

Male gender 2.2 1.0-4.6 0.042

Distal molar occlusion 2.2 1.1-4.6 0.032

Mouth breathing 4.4 1.7-11.4 0.002

1 SD increase in body fat percentage 1.5 1.1-2.1 0.015

Data are from stepwise logistic regression models, the effect of gender was considered in eachstep.Only statistically significant determinants are given.

Mandibular retrusion, adipose tissue under the chin and a history of orthodontictreatment at baseline were associated with increased risk of developing SDB duringthe 2.2-year follow-up (Table 9). Further, a vertically restricted throat seemed to be aprotective factor against SDB and vice versa, a vertically large or normal throatincreased the risk for SDB. However, there was a clear tendency for the children withvertically large or normal throat to have hypertrophied tonsils. A history oforthodontic treatment was the strongest baseline predictor of developing SDB duringthe 2.2-year follow-up. Children who had a history of orthodontic treatment atbaseline had a 5.0-fold higher risk of SDB than those without it.

Table 9. Baseline predictors for incident SDB at 2.2-year follow-up among 296 childrenwho had no SDB at baseline


interval

p-

value

Mandibular retrusion 3.4 1.3-8.9 0.012

Vertically restricted throata 0.2 0.1-0.7 0.011

Adipose tissue under the chin 2.8 1.1-7.2 0.034

Orthodontic treatment 5.0 1.3-18.4 0.016

aDefined as Mallampati et.al. Class III or IVData are from stepwise logistic regression models, the effect of gender was considered in eachstep.Only statistically significant determinants are given

43

6.4 RECOGNIZING CONVEXITY AND VERTICAL PROPORTIONS OFTHE LATERAL FACIAL PROFILE (STUDY II)

At the baseline the prevalence of SDB in children with the most convex profilesexpressed with the lowest quintile of the angle G`- Sn - Pg` ( 164.2°) was almosttwofold (14.5%) compared with those with a normal profile (8.1%) (p = 0.084). Of allthe profiles clinically classified as convex by the reference orthodontist (T.I.), 67.1%were the most convex profiles expressed with the lowest quintile of the angle G`- Sn -Pg`. Of the convex profiles assessed visually with a photograph by the same examiner,64.3% were in the lowest quintile. The intra-examiner reliability of measures of theangle of convexity (G`- Sn - Pg`) and further, the vertical proportions of the face (Sn`-Me`/N`-Me`) were investigated by comparing the first and second assessment, twoweeks apart, of the reference orthodontist using intra-class correlation coefficient(ICC) and its 95% confidence interval (CI). The ICC (95% CI) between the twomeasurements was 0.980 (0.951-0.992) for the angle of convexity and 0.829 (0.671-0.915) for the vertical proportion of the face. The Kappa values for the measures of facial profile with the photographs betweenthe reference orthodontist and the other health care professionals varied between0.000 and 0.579 and the proportion of agreement varied between 55.6% and 78.8%(Figure 7). The highest Kappa value (0.579) and the highest proportion of agreement(78.8%) were observed between the two orthodontists. The Kappa value for therepeated measurements of the facial profile of the reference orthodontist was 0.920and the proportion of agreement was 93.3%. The Kappa values of the measurementsof the first 200 photos and the last 200 photos did not differ. In order to test the inter-examiner reliability for the measures of facial profile withthe photographs between three experienced orthodontists, the Kappa values variedfrom 0.500 to 0.899 (good to excellent agreement) for facial convexity, from 0.167 to0.533 (poor to good agreement) for mandibular retrusion and from 0.558 to 0.896 (goodto excellent agreement) for vertical proportions of the face.

44

Figure 7. The number of evidently convex profiles identified by eight observers fromfacial photographs (total n=382). On the top of the bars: inter-examiner kappa-valuesand agreement percentages with reference observer

6.5 CORRELATES OF PSYCHOLOGICAL WELL-BEING AMONG GIRLSAND BOYS 6-8 YEARS OF AGE – THE ROLE OF SLEEPDISORDERED BREATHING (STUDY III)

At the age of 6-8 years, the girls had a higher body fat percentage and total sedentarybehavior, a better diet quality assessed by the DASH score, higher psychological andsocial well-being scores and lower levels of cardiorespiratory fitness, total physicalactivity and screen-based sedentary behavior than the boys (Table 10 and 11).

45

Table 10. Classified characteristics of the children

Allchildren(n=412)

n %

Girls(n=205)

n %

Boys(n=207)

n %

p-valuea

fordifference

Asthma

Sleep disordered breathing

Parental education Vocational Polytechnic University

Parental income€30,000

€30,001-€60,000 >€60,000

Parental daily smoking

Mother’s unemployment

Father’s unemployment

Mother’s alcohol consumption, portions/week

Father’s alcohol consumption, portions/week

36 (8.8)

41 (10.0)

77 (18.7)187 (45.4)148 (35.9)

75 (18.5)178 (44.0)152 (37.5)

98 (23.8)

24 (5.8)

26 (6.8)

2.6 (3.1)

6.4 (6.6)

16 (8.0)

16 (7.8)

36 (17.6)104 (50.7)65 (31.7)

41 (20.2)95 (46.8)67 (33.0)

42 (20.5)

15 (7.3)

11 (5.9)

2.4 (2.8)

6.2 (7.0)

20 (9.7)

25 (12.1)

41 (19.8)83 (40.1)83 (40.1)

34 (16.8)83 (41.1)85 (42.1)

56 (27.1)

9 (4.4)

15 (7.8)

2.8 (3.4)

6.6 (6.1)

0.602

0.147

0.088

0.166

0.118

0.215

0.544

0.339

0.481

afrom the Fisher’s Exact Test or Chi-square statistics

46

Table 11. Metric characteristics of children

Allchildren(n=412)

mean(SD)

Girls(n=205)

mean(SD)

Boys(n=207)

mean(SD)

p-valuea

fordifference

Age, years

Body fat percentage

Cardiorespiratory fitness, w/kg lean mass

Total sedentary behavior, min/day

Total physical activity, min/day

Screen-based sedentary behavior, min/day

Sleep durationb, h/night

DASH score

Psychological well-beingc

Physical well-beingd

Social well-beinge

7.6 (0.3)

19.9 (8.1)

3.7 (0.5)

215 (106)

111 (41)

102 (52)

9.7 (0.5)

21.0 (4.4)

10.1 (9.0)

2.8 (3.7)

2.2 (2.6)

7.6 (0.4)

22.6 (7.6)

3.5 (0.5)

224 (107)

103 (38)

90 (47)

9.7 (0.5)

21.6 (4.2)

8.9 (8.2)

2.4 (3.0)

1.7 (2.1)

7.7 (0.4)

17.2 (7.7)

3.8 (0.5)

206 (105)

119 (43)

114 (55)

9.6 (0.5)

20.3 (4.5)

11.4 (9.5)

3.1 (4.2)

2.6 (2.9)

0.364

<0.001

<0.001

0.048

<0.001

<0.001

0.631

0.004

0.006

0.196

<0.001

afrom Student’s T-test or Mann-Whitney U TestbUsing combined heart rate and movement sensorcScore ranging between 0 and 76 according to 19 itemsdScore ranging between 0 and 48 according to 12 itemseScore ranging between 0 and 24 according to 6 items

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SDB was more common in boys with low psychological well-being than in boys withnormal psychological well-being. Cardiorespiratory fitness was lower in girls withlow psychological well-being than in girls with normal psychological well-being. Thelevels of screen-based sedentary behavior were higher and daily parental smokingwas more common in boys with low psychological well-being than in boys withnormal psychological well-being (Table 12 and 13).

Table 12. Classified characteristics of girls and boys with low and normal psychologicalwell-being (PSWB)

Girls (n=205) Boys (n=207)

Low PSWB n %

NormalPSWBn %

p-valuea

LowPSWBn %

NormalPSWBn %

p-valuea

Asthma

Sleep disordered breathing

4 (6.2)

3 (4.5)

12 (8.8)

13 (9.4)

0.513

0.231

6 (7.6)

17 (21.3)

14 (11.0)

8 (6.3)

0.419

0.001

Parental education Vocational Polytechnic or university

16 (24.2) 50 (75.8)

20 (14.4)119 (85.6)

0.08320 (25.0)60 (75.0)

21 (16.5)106 (83.5)

0.137

Parental income €30,000 >€30,000

14 (21.5)51 (78.5)

27 (19.6)111 (80.4)

0.74416 (20.5)62 (79.5)

18 (14.5)106 (85.5)

0.267

Parental daily smoking 13 (19.7) 29 (20.9) 0.847 28 (35.0) 28 (22.0) 0.041

Mother’s unemployment

Father’s unemployment

5 (7.6)

5 (8.3)

10 (7.2)

6 (4.7)

0.922

0.321

5 (6.3)

6 (8.6)

4 (3.2)

9 (7.4)

0.293

0.767

Mother’s alcoholconsumption, portions/week

Father’s alcoholconsumption, portions/week

2.3 (2.8)

5.8 (5.6)

2.5 (2.8)

6.5 (7.6)

0.609

0.620

3.2 (3.8)

7.0 (6.7)

2.6 (3.1)

6.3 (5.7)

0.331

0.606

afrom the Fisher’s Exact Test or Chi-square statistics

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Table 13. Metric characteristics of girls and boys with low and normal psychological well-being (PSWB)

Girls (n=205) Boys (n=207)

LowPSWB

mean(SD)

NormalPSWB

mean(SD)

p-valuea

LowPSWB

mean(SD)

NormalPSWB

mean(SD)

p-valuea

Body fat percentage 23.1 (7.1) 22.4 (7.9) 0.322 18.1 (8.7) 16.6 (7.0) 0.470

Cardiorespiratory fitness, w/kglean mass 3.4 (0.4) 3.6 (0.5) 0.004 3.7 (0.5) 3.9 (0.5) 0.081

Total sedentary behavior,min/day 237 (117) 218 (102) 0.277 229 (123) 192 (89) 0.065

Total physical activity, min/day 100 (36) 104 (38) 0.471 114 (42) 122 (43) 0.173

Screen based sedentarybehavior, min/day 91 (45) 90 (49) 0.491 128 (62) 105 (47) 0.012

Sleep durationb, h/night 9.7 (0.5) 9.7 (0.5) 0.971 9.6 (0.6) 9.7 (0.5) 0.076

DASH score 21.7 (4.1) 21.6 (4.3) 0.913 20.2 (4.9) 20.4 (4.2) 0.810

afrom Mann-Whitney U Test or Student’s T-testbUsing combined heart rate and movement sensor

Boys with SDB were four times more likely to have increased risk of low psychologicalwell-being than boys without SDB (Table 14). Girls who were in the highest third ofcardiorespiratory fitness were less likely to have low psychological well-being thangirls in the lowest third. Boys with at least two hours of screen-based sedentarybehavior per day had two fold higher risk of low psychological well-being than boyswith lower levels of screen-based sedentary behavior. Moreover, boys whose parentssmoked daily had a higher risk of low psychological well-being than boys whoseparents did not smoke. Girls whose parents had lower education had a higher risk oflow psychological well-being than girls whose parents had higher education.

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Table 14. Risk factors for having low psychological well-being in girls and boys

Girls (n=205) Boys (n=207 p-value forinteraction

withgenderORa (95% CI) p ORa (95% CI) p

Age, years 1.20 (0.51-2.83) .674 1.14 (0.49-2.63) .766 0.935

Screen-based sedentarybehavior <2h/day

2h/day1.00

0.66 (0.31-1.42) .2911.00

1.93 (1.04-3.57) .037

0.084

Cardiorespiratory fitness, w/kglean mass <3.48 3.48-3.88 >3.88

1.000.86 (0.43-1.71)0.26 (0.10-0.68)

.663

.006

1.000.66 (0.29-1.49)0.63 (0.29-1.39)

.311

.252

0.410

Sleep disordered breathing No Yes

1.000.32 (0.08-1.24) .099

1.004.24 (1.63-11.00) .003

0.013

Parental education Polytechnic or university Vocational

1.002.34 (1.05-5.25) .039

1.001.07 (0.48-2.36) .868

0.755

Parental daily smoking No Yes

1.000.69 (0.31-1.42) .354

1.002.10 (1.06-4.15) .034

0.105

aThe values are odds ratios (OR) and their 95% confidence intervals (CI) from logistic regressionmodels in which all variables were entered simultaneously.

50

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7 Discussion

7.1 DENTOFACIAL AND PHARYNGEAL MORPHOLOGY WITH ANDRISK FOR SLEEP DISORDERED BREATHING

The present study shows that children with SDB represent different dentofacial andpharyngeal morphology compared with those with no SDB. Typical dentofacialfeatures of SDB children are cross bite, convexity of the facial profile, increased lowerfacial height and mandibular retrusion. The present study is in line with the previousstudies, such as a Finnish study showing 7-year-old children with SDB to have distalposition and posterior rotation of the mandible and increased lower facial height(Pirilä-Parkkinen et al. 2010), and with many other studies (Löfstrand-Tideström et al.1999, Marino et al. 2009). The results of a recent study show that cross bite and openbite associate with SDB (Carvalho et al. 2014). A systematic review and meta-analysissummarize a retrusive chin, steep mandibular plane, vertical direction of mandibulargrowth and a tendency toward Class II malocclusion to be the typical characteristicsof the SDB children (Flores-Mir et al. 2013). The most common malocclusions in both 6- to 8- and 9- to 11-year old children weredental crowding, distal molar occlusion and mandibular retrusion, showing quitetypical distribution of malocclusions among Finnish children (Eskeli 2015). Facialconvexity at the baseline and increased lower facial height after follow-up were morefrequent among boys. The results concerning gender difference among schoolchildren in the prevalence of malocclusions are contradictory (Myllärniemi 1970,Kerosuo et al. 1991, Thilander et al. 2001, Tak et al. 2013). The present study alsoshowed changes in the prevalence of dental malocclusions during the follow-up time,which goes in parallel with an increase in the number of children with previous orongoing orthodontic treatment. Furthermore, both 6- to 8 and 9- to 11-year-old children with SDB were more likelyto have tonsillar hypertrophy than those without it, the association being moresignificant in the younger age group. The result of the present study agrees with otherstudies showing that ATH significantly raises the risk for pediatric SDB (Arens et al.2003, Dayyat et al. 2007). The mass of the lymphoid tissue of the pharynx increasesfrom birth to twelve years, the volume being at maximum related to the skeletalstructures at the age of 5-6 years (Dayyat et al. 2007), and in line with this, SDB is mostcommon in pre-school and early school years (Corbo et al. 2001). Furthermore, thereis a transient prepubertal increase in nasal resistance, a phenomenon suggested toresult from the prepubertal hypertrophy of adenoid tissue or hormonal changescausing mucosal swelling of the nasal passage (Linder-Aronson and Leighton 1983),which further explicates the association of hypertrophied lymphatic tissue with SDB

52

in young school-aged children. However, there are studies to suggest that the importance of obesity as a risk forSDB increases along with age in parallel with ATH and other morphological riskfeatures decreasing in relevance (Kohler and Heuvel 2008). Furthermore, it issuggested that there are two different phenotypes of pediatric SDB; one characterizedby ATH with no obesity (type I) and the other by obesity in the presence of only minorATH (type II) (Dayyat et al. 2007). The present study showed that mouth breathing, often co-existing withlymphadenoid hypertrophy, at the age of 6–8 years was associated with increased riskof SDB after follow-up. Interestingly, children with a vertically large or normal throathad increased risk of SDB. The same children also tended to have hypertrophiedtonsils more often than those with vertically a restricted throat. This may indicate thatthose children had developed a lowered position of the tongue to improve theirbreathing, which is in line with the results of the classical study of Linder-Aronson(Linder-Aronson 1970). On the other hand, a study by Suri suggests that a verticallyrestricted throat significantly predicts a poor outcome of the treatment of SDB withATE which suggests that a delay in treating the hypertrophied adenoid and tonsilsmay promote abnormal craniofacial growth, leading to residual SDB (Suri et al. 2015).The inconsistent results concerning the association of pharyngeal morphology andSDB warrants future studies with a larger study group and PSG-testing fordetermining the sleep disorder to confirm the observations of the present study. This raises the old question of the chicken and the egg. All the aforementionedfactors concerning dentofacial and pharyngeal characteristics of a child with SDB maylead to an abnormal function, including oral breathing, which seems to alter oral andfacial muscular balance and is likely to affect skeletal and occlusal development andfurther, may increase the risk for SDB (Peltomäki 2007). It is noteworthy, that in thepresent study children with SDB represent the whole spectrum of the condition – fromthe mildest manifestation with primary snoring to actual breathing pause, i.e., apneaobserved by the parents. In fact, almost all of the SDB children in the present studywere snorers and/or nocturnal mouth breathers. As both malocclusions and the wholespectrum of SDB are quite prevalent, it is not only to the advantage of individualswith a burden of symptoms and consequences, but also to the advantage of a societyin terms of economics to recognize and understand the close relation between thesetwo different conditions.

7.2 PREDICTION OF SDB

The results of the study indicate that typical features predicting SDB could easily berecognized in health centers by dental professionals within normal oral examinations.Certain morphological and functional features at the age of 6-8 years may predictdeveloping SDB at the age of 9-11 years. Especially high body adiposity and mouth

53

breathing, as well as distal molar occlusion seemed to predispose to the developmentof SDB already in childhood. Furthermore, as in adults (Neelapu et al. 2016), malegender also increased the risk of SDB. Adipose tissue under the chin, mandibularretrusion, vertically normal/large throat and orthodontic treatment were associatedwith incident SDB during the follow-up. Body adiposity has been observed to be an important risk factor for developing SDBin children (Kohler and van den Heuvel 2008, Verhulst et al. 2008). A recent studyshowed that especially an increased amount of visceral fat was associated with severemanifestations of SDB in a population sample of children (Bixler et al. 2016). Inaccordance with the results of these studies, the present study showed that a highbody fat percentage at the age of 6-8 years was associated with a higher risk of havingSDB 2.2 years later, and furthermore, adipose tissue under the chin was associatedwith increased risk of developing SDB during 2.2-year follow-up. In children, theassociations of overweight and obesity with SDB may not be straightforward, and therelationship may be modified by other factors, such as age and craniofacialmorphology (Kohler and van den Heuvel 2008). It can be speculated, that thesignificance of the body adiposity for SDB increases in parallel with age, whichwarrants future studies concerning the PANIC children. The mechanism by which adiposity predisposes to SDB may be the mass loading ofthe upper airway and respiratory muscles (Ng et al. 2006) causing alterations to thestructure and function of these muscles, the reduction of chest wall compliance,changes in respiratory drive and the impairment of functional residual capacity, all ofwhich increase the risk of upper airway obstruction (Kohler and van den Heuvel2008). It is alarming that overweight and obesity are becoming more common inchildren and adolescents in many developed countries (Kipping et al. 2008). InFinland, 10% of children and 26% of adolescents have been found to be overweight(Vuorela et al. 2009). In fact, obese children have been observed to have an increasedrisk of persistent SDB even after ATE, which is the first-line treatment for pediatricSDB (Kohler and van den Heuvel 2008). Interestingly, a history of orthodontic treatment at baseline was associated withincreased risk of developing SDB during the follow-up. This most likely associatedwith the malocclusions and deviant craniofacial morphology that require orthodontictreatment. In line with previous studies the present study showed typical deviationsin dentofacial morphology associating with SDB. In Finland these deviations, such ascross bite, are often diagnosed and early orthodontic treatment initiated in the primaryschool years. However, the impact of different treatment modalities would requirefurther examination since basically, early orthodontic treatment is thought to preventSDB in adulthood by modifying the deviant craniofacial morphology in a morefavorable direction (Hanggi et al. 2008, Ashok et al. 2014).

The physical activity and nutrition intervention of the PANIC study did not haveany effect on the results of the present study, which was a predictable result. The studyshowed, that the obesity, which is a relevant target to healthy lifestyle intervention,was not a risk for SDB among young children. On the other hand, dentofacial and

54

pharyngeal risk factors of SDB cannot be supposed to be affected by the intervention.It is noteworthy that recent papers published within the PANIC study show that anindividualized and family-based lifestyle intervention increased physical activity,attenuated increase in sedentary behavior, enhanced diet quality and further, had abeneficial effect on plasma fatty acid composition in children (Viitasalo et al. 2016,Venäläinen et al. 2016). Further follow-up studies will show if the healthy lifestyleintervention will have an impact on the prevalence or symptoms of SDB in the comingyears. Although some risk features (i.e., retrusive mandible and facial convexity) may notbe unambiguously recognized, most of them are well-known parts of the normalprotocol of oral health professionals when executing regular oral examinations. Itwould be beneficial if children with typical features associated with SDB – the wholespectrum of it – could be recognized early in childhood so that they could becandidates for early intervention and treatment to prevent the progression of SDBover the coming years.

7.3 THE PSYCHOLOGICAL CONSEQUENCES OF SDB

The present study shows that at the age of 6-8 years SDB compromises psychologicalwell-being of boys. There are many recent studies to show that poor behavior, mooddisorder symptoms, emotion instability, impaired psychological functions andreduced quality of life associates with SDB (Beebe 2006, Aronen et al. 2009, Jackmanet al. 2012). The determinants of the quality of life can be affected in both children andtheir families (Jackman et al. 2012) and further predict behavioral and emotionalproblems in adolescence (Gozal 2001). Further, it has been demonstrated thatregardless of the severity of SDB or body adiposity, children with SDB have decreasedquality of life and well-being compared to children without SDB (Rosen et al. 2002,Crabtree et al. 2004). Taken together, these observations underline the importance ofrecognizing the psychological aspects of SDB. The exact mechanisms behind the association of psychological aspects and SDB areunclear. The mechanism may depend on the severity of the condition: milder forms(snoring) with sleep fragmentation and severe forms (OSA) with hypoxia (O´Brien etal. 2004). It is possible, that any dislocation of sleep in a child leads to modification ofneurochemical substrates at the prefrontal cortex level (Beebe and Gozal 2002),resulting in psychological effects. Milder and at the same time more commonmanifestations of SDB may even have the strongest effects on psychological functionsin pre-school children (Jackman et al. 2012). Further, any sleep disturbance, includingSDB may simply cause fatigue and stress in both children and parents, and thisinterferes with multiple aspects of a child´s life, including the mental context. It is unclear, why the results of the present study on the psychological contextconcern only boys. In general, some questionnaire-based studies show boys to havemore SDB compared with girls (Ersu et al. 2004, Gill et al. 2012). The present study

55

showed opposite findings, agreeing with other questionnaire-based studies showingno gender difference in the prevalence of SDB (Liukkonen et al. 2008, Anuntaseree etal. 2014). However, the sample sizes in most studies, including the present study,studying SDB in children have been too modest to examine the gender differences inchildren in more detail. It is possible, that boys are more sensitive to sleepfragmentation. The reason why boys with SDB are doing worse than girls with SDB ismost likely multi-factorial; physiologic or later puberty-related hormonal changesmay potentiate the effect of gender on SDB prevalence. The discrepancy of resultswarrants more future research concerning the gender differences in SDB. The psychological consequences of SDB are likely to manifest themselves in school(Smith et al. 2016), fortunately the phenomenon being at least partly reversible. Schoolchildren with academic scores ranked in the lowest 10th percentile with SDB seemedto get significantly improved grades after ATE compared with those not operated(Gozal 1998). However, there is also a risk for a “learning debt”, since a large surveystudy showed that school children with loud and frequent snoring are likely to havelow grades in school several years after the snoring has been treated (Gozal and Pope2001), the fact that further calls for early intervention to treat SDB. More future studiesare warranted to study the impact of different treatment modalities, such as ATE andorthodontic treatment, to the association of childhood SDB and school performance. The present study suggests observation and recognition of the psychological aspectsof childhood SDB. At home, it is important to be conscious of the fact that SDB is atreatable medical condition, which may largely compromise the well-being of thechild. In schools, among both teachers and school nurses, knowledge of thepsychological and cognitional aspects of this relatively common condition would havelong-lasting effects for the lives of the children. It is possible, that there is a treatabledisease behind poor school performance.

7.4 STRENGTHS AND LIMITATIONS

The strength of the study is the relative large population sample of children aged 6-8and 9-11 years. The results are based on comprehensive and valid assessments ofdental malocclusions and other craniofacial abnormalities, body composition,cardiorespiratory fitness, physical activity, sedentary behavior and parentalsocioeconomic status. However, there are some limitations in the study. Because of the large population-based study sample it was not possible to conductnocturnal polysomnography, which is the golden standard for diagnosing breathing-based sleeping problems in both children and adults (Section on PediatricPulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome. AmericanAcademy of Pediatrics 2002). Instead, SDB was defined as apneas, frequent or loudsnoring or nocturnal mouth breathing observed by the parents and registered by aquestionnaire. The questions in the sleep questionnaire are based on an establishedFinnish questionnaire that has been used to screen for sleep disturbances and SDB

56

(Partinen and Gislason 1995), and modified in the present study for the parents to fillout on behalf of their children. The parents answered the questions concerning thechild’s quantity and quality of sleep and signs of SDB. It is possible, that because ofsleeping in different room that the children, some parents may have been unaware oftheir child´s sleeping pattern as well as mode of breathing, thus causing inaccuracy inreporting. The size of the adenoids was not examined. Reliable methods would have beennasofiberoscopy with local anesthesia or magnetic resonance imaging. However, ashypertrophy of adenoid and tonsils typically coexist and indicate the amount oflymphoid tissue in the pharynx, it may not be relevant to consider them as differentconditions. The shape of the palate was visually defined as wide, normal or narrow.The evaluation with digital study models after scanning the dentition and palatalvault would have given exact metrically measures of the palatal dimensions(Chalmers et al. 2015). Instead, the results are based on visual assessment of anexperienced orthodontist. The aforementioned limitations are caused by theepidemiological character of the present study and the burden of numerous othermedical examinations performed on the children participating in the PANIC study. The associations of certain dental malocclusions, such as scissors bite and open bite,with SDB could not be analyzed because of their low prevalence and thus, insufficientstatistical power. Further, mouth breathing was clinically identified using open lips asa hallmark, which may overestimate the proportion of mouth breathers. Habitualopen-lip posture does not always coexist with mouth breathing, which requiresobjective airway temperature or pressure recordings for a secure diagnosis(Leiberman et al. 1990). Furthermore, reliable assessment of retrusive mandibleseemed to be difficult even for experienced orthodontists in the group of 6- to 8-year-old children. However, the analysis of inter-examiner reliability was based on lateralfacial photographs. Unfortunately, it was not possible to perform a clinical analysis ofmeasurement reliability, which might have given better results. Further, at thebaseline the cross-sectional study design makes it difficult to draw conclusions aboutcausal relationships. The findings may not be directly generalized to all ethnic and agegroups, since almost all children were Caucasian and 6- to 11 years of age. At the time of initiating the PANIC study in 2007, there were no questionnairessuitable for investigating psychological, social and physical well-being in a populationsample of healthy children, as most of the questionnaires available were meant forpediatric patients. Therefore the PANIC researcher group developed a questionnairefor the purpose. An established questionnaire with piloting and validating wouldhave enhanced the generalizability of the presented findings more reliably. Anotherweakness of the questionnaire is that some of the 19 items do not specifically measurepsychological well-being but also reflect social well-being, as indicated by therelatively strong correlation between the psychological and social well-being scores.Moreover, the questionnaire was filled out by the parents. Finally, in general,questionnaires may overestimate the magnitude of the associations and genderdifferences in psychological research because the answers to the questions may reflect

57

the gender-specific attitudes of parents (Eisenberg et al. 1998).

58

59

8 Conclusions and future perspective

The results of this doctoral thesis indicate that children with SDB represent differentdentofacial and pharyngeal morphology compared with those without SDB. Typicalfeatures predicting SDB could be recognized in health centers by dental and otherhealth care professionals working with children. Furthermore, SDB affects thepsychological well-being in childhood. Noteworthy, the above-mentionedphenomena are seen among the whole study group with SDB – even though almostall of the cases in the present study represent milder forms of SDB.

The main findings and conclusions are summarized in respect to the aims of the thesisas follows:

1. Dentofacial and pharyngeal morphology of children with SDB differs fromthose without SDB. Typical features associating with SDB are convexity of thefacial profile, mandibular retrusion and increased lower facial height. Inaddition, tonsillar hypertrophy and dominant mouth breathing associate withSDB. If a child suffers from symptoms of SDB, his or her facial status, dentalocclusion and mode of breathing should be examined. On the other hand,children with risk features should be examined as regards to their sleepinghabits, snoring and pauses in breathing during sleep.

2. The study suggests that certain morphological and functional features, such asdeviant dentofacial and pharyngeal morphology, mouth breathing and bodyadiposity at the age of 6-8 years may predict SDB in the coming years.Furthermore, male gender predicts SDB in childhood. These findings are usefulin identifying children at increased risk for developing SDB.

3. Facial convexity, being an important determinant of pediatric SDB, is difficultto recognize. The fact that the sagittal characteristics are most reliablyrecognized by an orthodontist indicates that one would need to be trained andexperienced for the purpose and furthermore, need sufficient basic knowledgeof the growth and development of the face.

4. SDB associates with low psychological well-being in boys aged 6-8-year. Sinceclinicians make complex management decisions including invasive surgicalinterventions concerning the treatment of pediatric SDB, it is important also torecognize the psychological aspects of the condition. It is possible, that there isa treatable disease behind the poor school performance. The present study

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indicates that there may be modifiable health-related correlates behindemotional and behavioral problems.

The present study suggests that children with current or developing SDB could becandidates for early intervention to prevent the progression of SDB later in life. In thefuture, more longitudinal population-based studies are warranted to confirm thepresent observations among children and further, to clarify the whole picture ofchildhood SDB. Studying pediatric populations provides an incomparableopportunity to recognize early determinants of SDB and its natural evolution. Earlyintervention with lifestyle counselling, surgery and orthodontic treatment may detectthe progression of childhood SDB to adulthood OSA. This can only happen throughbetter understanding and earlier recognition of the underlying mechanisms behindthe development of SDB and an intensive collaboration between different medicalspecialities.

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APPENDIX

PANIC-STUDY

Child’s sleep questionnaireThe questionnaire is filled by either one of the parents

1. How many hours does your child sleep in the night on average____________(½ hour accuracy rate)

2. How quickly does your child fall asleep after going to bed?(1) within 10 minutes or faster(2) within 10-20 minutes(3) within 30 minutes or more

3. How does your child sleep after falling asleep?(1) very peaceful(2) quite peaceful(3) partly peaceful, partly restless(4) quite restless(5) very restless

4. How many times your child awakens during the night?(1) none(2) once(3) twice(4) 3-4 times(5) at least 5 times

5. Is your child usually sleepy during daytime?(1) never or less than once a month(2) less than once a week(3) in 1-2 days a week(4) in 3-5 days a week(5) in 6 days a week or daily

6. How often have your child taken naps during the day during last 3 months?(1) never(2) less than once a week(3) in 1-2 days a week(4) in 3-5 days a week(5) in 6 days a week or daily

7. Does your child seem during daytime more tired compared to the otherchildren at same age?

(1) no, clearly more lively(2) no, quite more lively

(3) no difference(4) yes, quite more tired(5) yes, clearly more tired

8. Does your child have obsessional tendency to fall asleep?(1) never(2) less than once a week(3) in 1-2 days a week(4) in 3-5 days a week(5) in 6 days a week or daily

9. Have your child suffered from insomnia during last 3 months?(1) never(2) less than once a week(3) in 1-2 nights a week(4) in 3-5 nights a week(5) in 6 nights a week or every night

10. Does your child grind teeth during sleep?(1) never(2) less than once a week(3) in 1-2 nights a week(4) in 3-5 nights a week(5) in 6 nights a week or every night

11. Does your child suffer headache in the mornings?(1) never(2) less than once a week(3) in 1-2 mornings a week(4) in 3-5 mornings a week(5) in 6 mornings a week or every morning

12. Have your child had frightening dreams during last 3 months?(1) never(2) less than once a week(3) in 1-2 nights a week(4) in 3-5 nights a week(5) in 6 nights a week or every night

13. Have your child had sleepwalking or talking during sleep during last 3months?

(1) never(2) less than once a week(3) in 1-2 nights a week(4) in 3-5 nights a week(5) in 6 nights a week or every night

14. Does your child usually have blocked nose in the evenings or in the nights?(1) never(2) less than once a week(3) in 1-2 nights a week(4) in 3-5 nights a week(5) in 6 nights a week or every night

15. Have your child had tonsillitis or does she/he often complain of sore throat?(1) never(2) 1-2 times in all(3) 3-5 times in all or 1-2 times during one year(4) 3-5 times in a year(5) more than 5 times in a year

16. Have your child had ear infections?(1) never(2) 1-2 times in all(3) 3-5 times in all or 1-2 times during a year(4) 3-5 times in a year(5) more than 5 times in year

17. Have your child undergone tonsillectomy or/and adenoidectomy?(1) yes, both(2) yes, tonsillectomy(3) yes, adenoidectomy(4) no

18. Does your child breathe through the mouth at night?(1) never(2) rarely(3) sometimes(4) usually(5) always or almost always

19. Have you noticed any pauses in your child’s breathing pattern during sleep?(1) no(2) rarely(3) sometimes(4) usually(5) always or almost always

20. How do you describe your child’s snoring best?(1) no snoring(2) snores rarely(3) snores in certain position(4) snores most of the sleeping time

(5) snores frequently21. How loudly does your child snore?

(1) no snoring(2) low(3) quite loudly(4) loudly(5) extremely loudly

22. How do you describe your child’s snoring compared to the situation a yearago?

(1) much lower(2) lower(3) almost the same(4) some worse(5) much worse

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ISBN 978-952-61-2247-2ISSN 1798-5706



TIINA IKÄVALKO

PEDIATRIC SLEEP DISORDERED BREATHING – CAUSES AND CONSEQUENCES

The aim of this doctoral thesis was to investigate the risk factors, diagnostic

method and consequences of pediatric sleep disordered breathing (SDB) in a population

sample of children from the Physical Activity and Nutrition in Children (PANIC) Study. The results showed that dentofacial and

pharyngeal morphology but not excess body fat raises the risk for SDB among 7-year-olds. Certain morphological and functional features at the age of 7 years may predict

developing SDB at the age of 10 years. SDB associates with low psychological well-being

in boys aged 7-year.

TIINA IKÄVALKO

Documents

Dissertations in Health Sciences - UEF...Sleep disordered breathing (SDB) is one of the most common sleep disturbances among children; it represents a continuum of symptoms from habitual