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PEDOT-7060; No. of Pages 4 International Journal of Pediatric Otorhinolaryngology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Obstructive sleep apnea in younger school children with Down syndrome Marit Erna Austeng a,b,*, Britt Øverland c, Kari Jorunn Kværner b,d, Els-Marie Andersson e, Stefan Axelsson e, Michael Abdelnoor f, Harriet Akre c a
Østfold Hospital Trust, Department of Otorhinolaryngology, Head and Neck Surgery, Norway Department of Health Economics and Health Management, University of Oslo, Norway Sleep Unit, Department of Otorhinolaryngology/Head and Neck Surgery, Lovisenberg Diakonale Hospital, Norway d Research, Innovation and Education Unit, Oslo University Hospital, Norway e TAKO-Centre, Resource Centre for Oral Health in Rare Medical Conditions, Lovisenberg Diakonale Hospital, Norway f Centre of Clinical Research, Unit of Biostatistics and Epidemiology, Oslo University Hospital, Norway b c
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 November 2013 Received in revised form 27 March 2014 Accepted 29 March 2014 Available online xxx
Objective: We aimed to assess the prevalence of obstructive sleep apnea (OSA) in 8 year old school children with Down syndrome (DS). While the prevalence in otherwise healthy children is below 5%, the prevalence estimates in children with DS are uncertain (30–80%). OSA directly affects cognitive development and school performance. Study design: Population based cross sectional study in a limited geographical area. Methods: Polysomnography (PSG) with video and audio recordings was performed in 8-year-old children with DS in a pediatric sleep unit according to the guidelines of American Academy of Sleep Medicine. Twenty-nine of all 32 children with DS within a restricted area comprising >50% of the Norwegian population and 54% of the children with DS born in Norway in 2002 were enrolled. Results: This study reports an apnea hypopnea index AHI > 1.5 in 28 of 29 children and an obstructive apnea index (OAI) > 1 in 24 of 29 children. 19 children (66%) had an AHI > 5 and 17 children (59%) had an OAI > 5 which indicated moderate to severe OSA. No correlation was found between OSA and obesity or gender. Conclusion: The high prevalence of disease found in these previously undiagnosed 8-year-old children underlines the importance of performing OSA diagnostics in children with DS throughout childhood. These findings suggest that the prevalence of OSA remains high up to early school years. In contrast to earlier publications, this current study has the advantage of being population based, the study is performed on children of a narrow age band to estimate prevalence of disease and the diagnostic gold standard of PSG is applied. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: OSA Pediatric Down syndrome
1. Introduction Obstructive sleep apnea (OSA) is characterized by complete or partly obstruction of the upper airways, which causes a
Abbreviations: AHI, apnea hypopnea index; BMI, body mass index; CAI, central apnea index; OAI, obstructive apnea index; ODI, oxygen desaturation index; OSA, obstructive sleep apnea; PSG, polysomnography. * Corresponding author at: Østfold Hospital Trust, Department of Otorhinolaryngology, Head and Neck Surgery, Postbox 16, 1601 Fredrikstad, Norway. Tel.: +47 917 40 442. E-mail address: [email protected] (M.E. Austeng).
fragmentation of sleep and gas exchange abnormalities. OSA in children is associated with concentration deficit, reduced ability to learn and has been reported to correlate with lower cognitive function, developmental delay and school failure [1]. Treatment of OSA has shown a positive effect on sleep quality, neurocognitive behavior symptoms and quality of life in children [2–4]. Recently revised clinical practical guidelines emphasize that children with craniofacial syndromes are at high risk for OSA [5–7]. In addition to the altered craniofacial anatomy, muscle hypotonia and adenotonsillar hypertrophy may contribute to a higher prevalence of OSA in children with DS [7–9]. The prevalence of OSA in children with DS exceeds that of otherwise healthy children
http://dx.doi.org/10.1016/j.ijporl.2014.03.030 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: M.E. Austeng, et al., Obstructive sleep apnea in younger school children with Down syndrome, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.030
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PEDOT-7060; No. of Pages 4 M.E. Austeng et al. / International Journal of Pediatric Otorhinolaryngology xxx (2014) xxx–xxx
2
treatment. Furthermore, none of the children had an acute bacterial infection or were on antibiotic treatment 2 weeks prior to the sleep test.
6 to15 times according to former studies [6,8,10–16]. However, the rate of OSA in school children has not been reported. The objective of this study was to assess the medical follow up and prevalence of OSA in a population-based sample of younger school children with DS. We also wanted to study the association between OSA and gender, body mass index and performed airway surgery during childhood. Overnight polysomnography (PSG) with video and audio recordings was applied as diagnostic tool.
2.2. Outcome Clinical ear, nose and throat examination was conducted in all children. Height and weight was registered and body mass index (BMI) calculated. Children were categorized into normal weight and overweight (BMI; female BMI < 18.69, male BMI < 18.76) [17]. All patients underwent in patient attended overnight PSG (Embla, Resmed, Norway) with simultaneous video and audio recording. The PSG recordings included a six-channel electroencephalogram (C3/M2, C4/M1, O2/M1, O4/M2, F3/M2, F4/M1), right and left electrooculogram, and submental electromyography. Ribcage and abdominal wall movements were measured using respiratory inductance plethysmography. Flow was measured with nasal pressure transducer and the arterial oxygen saturation was monitored via pulse oximetry. Electrocardiography, body position and electromyography from both legs were also included. Video and audio recordings give supportive information of symptoms of upper airway obstruction other than apneas and hypopneas, like neck extension, gasp for air, mouth breathing and snoring. Sleep was scored according to the guidelines from American Academy of Sleep Medicine [18]. An obstructive apnea was defined as at least two breaths with more than 90% reduction in flow in the presence of ribcage and abdominal movement. A central apnea was defined as at least two breaths with more than 90% reduction without respiratory effort (with subsequent oxygen desaturation of at least 3% or an arousal, or if the event lasts for more than 20 s). Hypopneas were defined as 50% decrease in flow for at least two breaths with subsequent oxygen desaturation of at least 3% or an arousal. The hypopneas were not classified further. Apnea hypopnea index (AHI) was defined as the number of apneas and hypopneas per hour of sleep,
2. Methods 2.1. Population A population based cross sectional study was conducted in Norwegian children with DS born in 2002. The children were recruited in 2010 and health examinations were carried out from November 2010 to November 2011. The Regional Committee for Medical Research Ethics (2010/1950), and the Norwegian Data Inspectorate gave approval to the study. The children were identified through the Departments of Medical Genetics at the Universities of Oslo, Bergen and Tromsø, who have complete national data in genetic registries. Eligibility criteria included a diagnosis of DS based on karyotypic information and physical examination. Further criteria were home address within the Health Authority Region South-East, which includes 57% (32 of 56 children) of all children born with DS in 2002. A total of 29 out of 32 children underwent PSG, a response rate of 90%. To avoid communication difficulties, only children with at least one parent with Norwegian as mother tongue were included. All pediatric rehabilitation center were consulted for possible left outs. To minimize scorer variability, the same experienced sleep specialist analyzed all sleep recordings. Anamnestic data on somatic disease and medical follow up was collected through a parental questionnaire responded by 53 out of 57 parents of children with DS born in Norway in 2002. None of the children were on steroid Table 1 PSG characteristics in 29 children with Down syndrome. Gender
AHI
ODI
CAI
OAI
BMI
Male Female Female Male Female Female Female Female Female Female Male Male Male Male Female Male Female Male Male Female Female Male Female Female Male Female Male Male Male
11.5 1.1 12.8 9.7 30.5 4.0 16.1 15.6 1.9 8.6 7.8 3.4 17.7 6.3 24.2 1.6 6.0 2.9 1.7 1.7 11.2 9.8 16.0 37.0 13.0 2.3 3.1 10.5 9.1
26.1 3.7 18.8 16.4 53.9 3.3 12.4 21.8 2.4 10.8 11.8 3.5 9.9 5.2 24.8 3.3 18.5 5.3 3.0 4.0 13.8 17.1 17.1 38.2 13.4 6.3 3.5 15.9 16.0
0.4 0.0 5.9 .9 6.6 2.7 7.2 .6 .9 2.0 .7 .1 10.9 1.6 4.2 1.2 3.2 2.0 1.4 .5 .3 4.8 .8 .5 .8 1.0 1.1 1.2 3.3
0.8 1.1 6.9 8.8 23.9 1.3 8.9 15 1.0 6.6 7.1 3.3 6.8 4.7 20.0 .4 2.8 .9 .3 1.2 10.9 5.0 15.2 36.5 12.2 1.3 2.0 9.3 5.8
22.6 25.4 18.3 20.5 16.8 16.5 19.5 18.4 16.5 16.9 22.6 17.7 19.2 17.0 19.1 15.4 15.8 19.0 17.5 14.9 16.3 17.8 20.4 16.1 17.6 17.5 * 16.2 *
Tons
Ad
x x
x x x
x
x x x x
x
Mean SaO2
Minimum SaO2
95 95 96 94 96 97 96 96 95 96 96 97 96 97 95 98 94 97 96 96 95 95 97 94 96 95 97 93 94
82 80 87 83 87 92 85 88 90 88 84 91 91 92 85 92 91 92 91 93 85 88 83 85 84 89 93 84 87
AHI = apnea hypopnea index, ODI = oxygen desaturation index, CAI = central apnea index, OAI = obstructive apnea index, BMI = body mass index, Tons = tonsillectomy, Ad = adenoidectomy, SaO2 = oxygen saturation, * = missing.
Please cite this article in press as: M.E. Austeng, et al., Obstructive sleep apnea in younger school children with Down syndrome, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.030
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while oxygen desaturation index (ODI) was defined as the number of oxygen desaturation 3% per hour of sleep. OSA was defined into the following categories: mild (AHI > 1.5), moderate (AHI 5– 10) and severe (AHI > 10) [19]. The obstructive apnea index (OAI) was considered with the same categories as AHI. 2.3. Statistical analysis Statistical analyses were performed using a commercially available software program (SPSS 17.0 for Windows). Descriptive statistics was applied. To measure the strength of linear dependence between variables the Pearson’s correlation coefficient was applied. 3. Results Twenty-nine children underwent PSG, 14 boys and 15 girls. The children slept in average 511 min (range 261–606, SD 73), approximately 8.3 h. The PSGs report an AHI > 1.5 in 28 of 29 (97%) children and an OAI > 1 in 24 of 29 children. 19 children (66%) had an AHI > 5 and 17 children (59%) had an OAI > 5 which indicated moderate to severe OSA. The mean AHI was 10 (SD 8.8), with minimum and maximum values of 1.1 and 37.0 respectively. The mean AHI in the group of children who had the tonsils and/or the adenoids removed was 8.3 (range 1.9–17.7) and mean OAI was 5.36 (0.3–10.6). The difference in mean AHI between the two groups of children, with and without performed airway surgery, was not statistical significant. The distribution of respiratory parameters during sleep is shown in Table 1. Mean AHI in girls was 12.6 and in the boys 7.7, with no significant difference between the genders. The mean ODI was 13.8 (range 2.4–53.9). Corresponding ODI values were 16.6 and 10.7 for girls and boys respectively, a non-significant difference. One third of the children were within the range of normal weight (n = 9), and two thirds (n = 18) were classified as overweight or obese. No difference in ODI or AHI between normal weight and overweight children were found. 5 out of 10 children who had adenoidectomy or tonsillectomies performed in the past had an OAI of 5 or more (Table 1). Anamnestic data collected through a parental questionnaire responded by 53 out of 57 parents of children with DS born in Norway in 2002, suggest that none of the children had been referred to OSA diagnostic prior to our study. 4. Discussion The current study found a high prevalence of OSA in school children with DS at the age of 8. Two-thirds of the children had moderate to severe OSA. The reported prevalence in 8-year-olds in the present study is twenty times higher than reported in otherwise healthy school children (2.2%) [20]. However these study findings are in line with the reported prevalence, 79%, of OSA in 2–5 year olds with DS [8], which suggests that the prevalence of OSA remains high at least up to school age. PSG cut off values have an impact on the outcome. There is no consensus on the PSG cut off values for diagnosing OSA in children AHI < 1.5 and an OAI < 1 are suggested to be normal values in otherwise healthy children, and PSG cut of values up to an AHI > 5 have been applied in prevalence studies in children [6,8,10–16]. Although treatment is recommended to be considered in children with OSA with an apnea index (AI) above 5, there is no consensus on the definition of mild OSA nor on the need for treatment of OSA in children with apnea index values between 1 and 5 measured by PSG [19]. The clinical finding and the PSG recordings has to be regarded to evaluate the sleep quality and possible treatment
3
options in children with an AHI, AI or OAI in the lower spectrum. Some of the PSG recordings reported in Table 1 showed AHI values lower than 5, and as in all recordings on children the AHI together with the central apnoe index CAI has to be regarded to diagnose OSA. However, the video recordings performed as part of the PSG diagnostic in this study revealed that night-time symptoms like neck extension to gasp air, snoring and obstructed breathing, or paradoxical respiration movements was present to some degree in all 29 children. Our findings indicate that a thorough analysis of the video and sound recordings is of major importance in the diagnostics of OSA in children with DS regardless of cut of values set to AHI > 1, 1.5 or 5. The reported wide prevalence range of OSA in children with DS (31–79%) may reflect the diversity of methods applied in the diagnostic procedure such as PSG, questionnaires or oximetry, the differences in age range and the variation of selected cut off values. While some earlier studies chose a narrow age band of preschool children [8] others included children with a wide age range from 1 up to 18 years [10,15]. Such methodical differences complicate the prevalence comparison between studies. The strength of our study is that attended PSG with video and audio recordings was applied, and PSG data was available in all children who agreed to participate. Selection-bias is unlikely and information-bias attempted to be kept at a minimum, as 29 out of 32 (90%) agreed to participate and all children underwent PSG in the same sleep unit with recordings scored according to defined guidelines, by the same experienced sleep specialist. Genetic and socio-demographic factors may affect the outcome in prevalence studies of OSA [21]. The homogeneity of the children in the present study population represents a clear advantage statistically, although it also may represent a limitation to the applicability of our findings to other ethnic groups. However, in the case of DS, the trisomy and associated anatomical changes may represent the dominant influencing factor on disease, and reported findings in subgroups of otherwise healthy children may not be applicable to children with DS. In contrast to reported findings in otherwise healthy children, weight and gender did not affect the severity of disease [6]. We were surprised to find a low reference rate related to OSA diagnostic in this study population of children with DS. Currently attention is being paid to sleep apnea syndrome in children, not only due to its cardiovascular complications [22,23] and suggested relations to metabolic syndrome [24], but also for its impact on cognitive and social development [25,26]. In addition to predisposing craniofacial anatomy, children with DS are associated with high body mass index, which may contribute to OSA. The cardiovascular impact of OSA in children with DS and the long time effect of untreated disease is not documented, however the effect measured in otherwise healthy has caused great concern. Despite the latter, these 29 children were all undiagnosed concerning OSA at the age of 8. Although the children in this study population had not been referred to PSG previous to this study, some children had been referred to surgical treatment with tonsillectomy, adenoidectomy or both (Table 1). According to the parents this treatment had been initiated due to a high rate of infections. The mean AHI in the operated children was slightly lower compared to the remaining study population, with an AHI 8.1 and 10.1 respectively. However we do not know to what degree the surgical treatment has had an impact on the AHI in the children who underwent surgical treatment as, whereas preoperative PSGs were not performed. 5. Conclusion The high prevalence of disease found in these undiagnosed 8year-old children underlines the importance of performing OSA
Please cite this article in press as: M.E. Austeng, et al., Obstructive sleep apnea in younger school children with Down syndrome, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.030
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diagnostics in children with DS throughout childhood. These findings suggest that the prevalence of OSA remains high up to early school years. In contrast to earlier publications, this current study has the advantage of being population based, the study is performed on children of a narrow age band to estimate prevalence of disease and the diagnostic gold standard of PSG is applied. Authors’ contributions Marit Erna Austeng, MD has conceptualized and designed the study, contributed to funding, collected data, carried out the initial analyses, drafted the initial manuscript, and approved the final manuscript as submitted. Britt Øverland, Dr philos has contributed to the design of the study, collected and analyzed data, coordinated and supervised data collection, drafted a part of the initial manuscript, and approved the final manuscript as submitted. Kari Jorunn Kværner, Professor has contributed to the conception and design of the study, contributed to funding, reviewed and revised the early drafts and of the manuscript and approved the final manuscript as submitted. Els-Marie Anderson, Dr has conceptualized and designed parts of the study, collected data, coordinated and supervised parts of the data collection, reviewed and revised drafts of the manuscript and approved the final manuscript as submitted. Stefan Axelsson, Dr has conceptualized and designed parts of the study, collected data, coordinated and supervised parts of the data collection, reviewed and revised drafts of the manuscript and approved the final manuscript as submitted. Harriet Akre, Dr has conceptualized and designed the study, contributed to collection and analyses of data, coordinated and supervised data collection, reviewed and revised the early drafts and of the manuscript and approved the final manuscript as submitted. Michael Abdelnoor, MPH, PhD, has contributed to analyses of data, contributed to parts of the initial manuscript, reviewed and revised the early drafts and of the manuscript and approved the final manuscript as submitted. Conflict of interest None of the authors have any financial or other relationship that might lead to a conflict of interest. References [1] R. Tauman, D. Gozal, Obstructive sleep apnea syndrome in children, Expert Rev. Respir. Med. 5 (June (3)) (2011) 425–440. [2] K. Bonuck, K. Freeman, R.D. Chervin, L. Xu, Sleep-disordered breathing in a population-based cohort: behavioral outcomes at 4 and 7 years, Pediatrics 129 (April (4)) (2012) e857–e865. [3] R.D. Chervin, K.H. Archbold, J.E. Dillon, P. Panahi, K.J. Pituch, R.E. Dahl, et al., Inattention, hyperactivity, and symptoms of sleep-disordered breathing, Pediatrics 109 (March (3)) (2002) 449–456.
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Please cite this article in press as: M.E. Austeng, et al., Obstructive sleep apnea in younger school children with Down syndrome, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.030
PEDOT-7060; No. of Pages 4 International Journal of Pediatric Otorhinolaryngology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Obstructive sleep apnea in younger school children with Down syndrome Marit Erna Austeng a,b,*, Britt Øverland c, Kari Jorunn Kværner b,d, Els-Marie Andersson e, Stefan Axelsson e, Michael Abdelnoor f, Harriet Akre c a
Østfold Hospital Trust, Department of Otorhinolaryngology, Head and Neck Surgery, Norway Department of Health Economics and Health Management, University of Oslo, Norway Sleep Unit, Department of Otorhinolaryngology/Head and Neck Surgery, Lovisenberg Diakonale Hospital, Norway d Research, Innovation and Education Unit, Oslo University Hospital, Norway e TAKO-Centre, Resource Centre for Oral Health in Rare Medical Conditions, Lovisenberg Diakonale Hospital, Norway f Centre of Clinical Research, Unit of Biostatistics and Epidemiology, Oslo University Hospital, Norway b c
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 November 2013 Received in revised form 27 March 2014 Accepted 29 March 2014 Available online xxx
Objective: We aimed to assess the prevalence of obstructive sleep apnea (OSA) in 8 year old school children with Down syndrome (DS). While the prevalence in otherwise healthy children is below 5%, the prevalence estimates in children with DS are uncertain (30–80%). OSA directly affects cognitive development and school performance. Study design: Population based cross sectional study in a limited geographical area. Methods: Polysomnography (PSG) with video and audio recordings was performed in 8-year-old children with DS in a pediatric sleep unit according to the guidelines of American Academy of Sleep Medicine. Twenty-nine of all 32 children with DS within a restricted area comprising >50% of the Norwegian population and 54% of the children with DS born in Norway in 2002 were enrolled. Results: This study reports an apnea hypopnea index AHI > 1.5 in 28 of 29 children and an obstructive apnea index (OAI) > 1 in 24 of 29 children. 19 children (66%) had an AHI > 5 and 17 children (59%) had an OAI > 5 which indicated moderate to severe OSA. No correlation was found between OSA and obesity or gender. Conclusion: The high prevalence of disease found in these previously undiagnosed 8-year-old children underlines the importance of performing OSA diagnostics in children with DS throughout childhood. These findings suggest that the prevalence of OSA remains high up to early school years. In contrast to earlier publications, this current study has the advantage of being population based, the study is performed on children of a narrow age band to estimate prevalence of disease and the diagnostic gold standard of PSG is applied. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: OSA Pediatric Down syndrome
1. Introduction Obstructive sleep apnea (OSA) is characterized by complete or partly obstruction of the upper airways, which causes a
Abbreviations: AHI, apnea hypopnea index; BMI, body mass index; CAI, central apnea index; OAI, obstructive apnea index; ODI, oxygen desaturation index; OSA, obstructive sleep apnea; PSG, polysomnography. * Corresponding author at: Østfold Hospital Trust, Department of Otorhinolaryngology, Head and Neck Surgery, Postbox 16, 1601 Fredrikstad, Norway. Tel.: +47 917 40 442. E-mail address: [email protected] (M.E. Austeng).
fragmentation of sleep and gas exchange abnormalities. OSA in children is associated with concentration deficit, reduced ability to learn and has been reported to correlate with lower cognitive function, developmental delay and school failure [1]. Treatment of OSA has shown a positive effect on sleep quality, neurocognitive behavior symptoms and quality of life in children [2–4]. Recently revised clinical practical guidelines emphasize that children with craniofacial syndromes are at high risk for OSA [5–7]. In addition to the altered craniofacial anatomy, muscle hypotonia and adenotonsillar hypertrophy may contribute to a higher prevalence of OSA in children with DS [7–9]. The prevalence of OSA in children with DS exceeds that of otherwise healthy children
http://dx.doi.org/10.1016/j.ijporl.2014.03.030 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: M.E. Austeng, et al., Obstructive sleep apnea in younger school children with Down syndrome, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.030
G Model
PEDOT-7060; No. of Pages 4 M.E. Austeng et al. / International Journal of Pediatric Otorhinolaryngology xxx (2014) xxx–xxx
2
treatment. Furthermore, none of the children had an acute bacterial infection or were on antibiotic treatment 2 weeks prior to the sleep test.
6 to15 times according to former studies [6,8,10–16]. However, the rate of OSA in school children has not been reported. The objective of this study was to assess the medical follow up and prevalence of OSA in a population-based sample of younger school children with DS. We also wanted to study the association between OSA and gender, body mass index and performed airway surgery during childhood. Overnight polysomnography (PSG) with video and audio recordings was applied as diagnostic tool.
2.2. Outcome Clinical ear, nose and throat examination was conducted in all children. Height and weight was registered and body mass index (BMI) calculated. Children were categorized into normal weight and overweight (BMI; female BMI < 18.69, male BMI < 18.76) [17]. All patients underwent in patient attended overnight PSG (Embla, Resmed, Norway) with simultaneous video and audio recording. The PSG recordings included a six-channel electroencephalogram (C3/M2, C4/M1, O2/M1, O4/M2, F3/M2, F4/M1), right and left electrooculogram, and submental electromyography. Ribcage and abdominal wall movements were measured using respiratory inductance plethysmography. Flow was measured with nasal pressure transducer and the arterial oxygen saturation was monitored via pulse oximetry. Electrocardiography, body position and electromyography from both legs were also included. Video and audio recordings give supportive information of symptoms of upper airway obstruction other than apneas and hypopneas, like neck extension, gasp for air, mouth breathing and snoring. Sleep was scored according to the guidelines from American Academy of Sleep Medicine [18]. An obstructive apnea was defined as at least two breaths with more than 90% reduction in flow in the presence of ribcage and abdominal movement. A central apnea was defined as at least two breaths with more than 90% reduction without respiratory effort (with subsequent oxygen desaturation of at least 3% or an arousal, or if the event lasts for more than 20 s). Hypopneas were defined as 50% decrease in flow for at least two breaths with subsequent oxygen desaturation of at least 3% or an arousal. The hypopneas were not classified further. Apnea hypopnea index (AHI) was defined as the number of apneas and hypopneas per hour of sleep,
2. Methods 2.1. Population A population based cross sectional study was conducted in Norwegian children with DS born in 2002. The children were recruited in 2010 and health examinations were carried out from November 2010 to November 2011. The Regional Committee for Medical Research Ethics (2010/1950), and the Norwegian Data Inspectorate gave approval to the study. The children were identified through the Departments of Medical Genetics at the Universities of Oslo, Bergen and Tromsø, who have complete national data in genetic registries. Eligibility criteria included a diagnosis of DS based on karyotypic information and physical examination. Further criteria were home address within the Health Authority Region South-East, which includes 57% (32 of 56 children) of all children born with DS in 2002. A total of 29 out of 32 children underwent PSG, a response rate of 90%. To avoid communication difficulties, only children with at least one parent with Norwegian as mother tongue were included. All pediatric rehabilitation center were consulted for possible left outs. To minimize scorer variability, the same experienced sleep specialist analyzed all sleep recordings. Anamnestic data on somatic disease and medical follow up was collected through a parental questionnaire responded by 53 out of 57 parents of children with DS born in Norway in 2002. None of the children were on steroid Table 1 PSG characteristics in 29 children with Down syndrome. Gender
AHI
ODI
CAI
OAI
BMI
Male Female Female Male Female Female Female Female Female Female Male Male Male Male Female Male Female Male Male Female Female Male Female Female Male Female Male Male Male
11.5 1.1 12.8 9.7 30.5 4.0 16.1 15.6 1.9 8.6 7.8 3.4 17.7 6.3 24.2 1.6 6.0 2.9 1.7 1.7 11.2 9.8 16.0 37.0 13.0 2.3 3.1 10.5 9.1
26.1 3.7 18.8 16.4 53.9 3.3 12.4 21.8 2.4 10.8 11.8 3.5 9.9 5.2 24.8 3.3 18.5 5.3 3.0 4.0 13.8 17.1 17.1 38.2 13.4 6.3 3.5 15.9 16.0
0.4 0.0 5.9 .9 6.6 2.7 7.2 .6 .9 2.0 .7 .1 10.9 1.6 4.2 1.2 3.2 2.0 1.4 .5 .3 4.8 .8 .5 .8 1.0 1.1 1.2 3.3
0.8 1.1 6.9 8.8 23.9 1.3 8.9 15 1.0 6.6 7.1 3.3 6.8 4.7 20.0 .4 2.8 .9 .3 1.2 10.9 5.0 15.2 36.5 12.2 1.3 2.0 9.3 5.8
22.6 25.4 18.3 20.5 16.8 16.5 19.5 18.4 16.5 16.9 22.6 17.7 19.2 17.0 19.1 15.4 15.8 19.0 17.5 14.9 16.3 17.8 20.4 16.1 17.6 17.5 * 16.2 *
Tons
Ad
x x
x x x
x
x x x x
x
Mean SaO2
Minimum SaO2
95 95 96 94 96 97 96 96 95 96 96 97 96 97 95 98 94 97 96 96 95 95 97 94 96 95 97 93 94
82 80 87 83 87 92 85 88 90 88 84 91 91 92 85 92 91 92 91 93 85 88 83 85 84 89 93 84 87
AHI = apnea hypopnea index, ODI = oxygen desaturation index, CAI = central apnea index, OAI = obstructive apnea index, BMI = body mass index, Tons = tonsillectomy, Ad = adenoidectomy, SaO2 = oxygen saturation, * = missing.
Please cite this article in press as: M.E. Austeng, et al., Obstructive sleep apnea in younger school children with Down syndrome, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.030
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while oxygen desaturation index (ODI) was defined as the number of oxygen desaturation 3% per hour of sleep. OSA was defined into the following categories: mild (AHI > 1.5), moderate (AHI 5– 10) and severe (AHI > 10) [19]. The obstructive apnea index (OAI) was considered with the same categories as AHI. 2.3. Statistical analysis Statistical analyses were performed using a commercially available software program (SPSS 17.0 for Windows). Descriptive statistics was applied. To measure the strength of linear dependence between variables the Pearson’s correlation coefficient was applied. 3. Results Twenty-nine children underwent PSG, 14 boys and 15 girls. The children slept in average 511 min (range 261–606, SD 73), approximately 8.3 h. The PSGs report an AHI > 1.5 in 28 of 29 (97%) children and an OAI > 1 in 24 of 29 children. 19 children (66%) had an AHI > 5 and 17 children (59%) had an OAI > 5 which indicated moderate to severe OSA. The mean AHI was 10 (SD 8.8), with minimum and maximum values of 1.1 and 37.0 respectively. The mean AHI in the group of children who had the tonsils and/or the adenoids removed was 8.3 (range 1.9–17.7) and mean OAI was 5.36 (0.3–10.6). The difference in mean AHI between the two groups of children, with and without performed airway surgery, was not statistical significant. The distribution of respiratory parameters during sleep is shown in Table 1. Mean AHI in girls was 12.6 and in the boys 7.7, with no significant difference between the genders. The mean ODI was 13.8 (range 2.4–53.9). Corresponding ODI values were 16.6 and 10.7 for girls and boys respectively, a non-significant difference. One third of the children were within the range of normal weight (n = 9), and two thirds (n = 18) were classified as overweight or obese. No difference in ODI or AHI between normal weight and overweight children were found. 5 out of 10 children who had adenoidectomy or tonsillectomies performed in the past had an OAI of 5 or more (Table 1). Anamnestic data collected through a parental questionnaire responded by 53 out of 57 parents of children with DS born in Norway in 2002, suggest that none of the children had been referred to OSA diagnostic prior to our study. 4. Discussion The current study found a high prevalence of OSA in school children with DS at the age of 8. Two-thirds of the children had moderate to severe OSA. The reported prevalence in 8-year-olds in the present study is twenty times higher than reported in otherwise healthy school children (2.2%) [20]. However these study findings are in line with the reported prevalence, 79%, of OSA in 2–5 year olds with DS [8], which suggests that the prevalence of OSA remains high at least up to school age. PSG cut off values have an impact on the outcome. There is no consensus on the PSG cut off values for diagnosing OSA in children AHI < 1.5 and an OAI < 1 are suggested to be normal values in otherwise healthy children, and PSG cut of values up to an AHI > 5 have been applied in prevalence studies in children [6,8,10–16]. Although treatment is recommended to be considered in children with OSA with an apnea index (AI) above 5, there is no consensus on the definition of mild OSA nor on the need for treatment of OSA in children with apnea index values between 1 and 5 measured by PSG [19]. The clinical finding and the PSG recordings has to be regarded to evaluate the sleep quality and possible treatment
3
options in children with an AHI, AI or OAI in the lower spectrum. Some of the PSG recordings reported in Table 1 showed AHI values lower than 5, and as in all recordings on children the AHI together with the central apnoe index CAI has to be regarded to diagnose OSA. However, the video recordings performed as part of the PSG diagnostic in this study revealed that night-time symptoms like neck extension to gasp air, snoring and obstructed breathing, or paradoxical respiration movements was present to some degree in all 29 children. Our findings indicate that a thorough analysis of the video and sound recordings is of major importance in the diagnostics of OSA in children with DS regardless of cut of values set to AHI > 1, 1.5 or 5. The reported wide prevalence range of OSA in children with DS (31–79%) may reflect the diversity of methods applied in the diagnostic procedure such as PSG, questionnaires or oximetry, the differences in age range and the variation of selected cut off values. While some earlier studies chose a narrow age band of preschool children [8] others included children with a wide age range from 1 up to 18 years [10,15]. Such methodical differences complicate the prevalence comparison between studies. The strength of our study is that attended PSG with video and audio recordings was applied, and PSG data was available in all children who agreed to participate. Selection-bias is unlikely and information-bias attempted to be kept at a minimum, as 29 out of 32 (90%) agreed to participate and all children underwent PSG in the same sleep unit with recordings scored according to defined guidelines, by the same experienced sleep specialist. Genetic and socio-demographic factors may affect the outcome in prevalence studies of OSA [21]. The homogeneity of the children in the present study population represents a clear advantage statistically, although it also may represent a limitation to the applicability of our findings to other ethnic groups. However, in the case of DS, the trisomy and associated anatomical changes may represent the dominant influencing factor on disease, and reported findings in subgroups of otherwise healthy children may not be applicable to children with DS. In contrast to reported findings in otherwise healthy children, weight and gender did not affect the severity of disease [6]. We were surprised to find a low reference rate related to OSA diagnostic in this study population of children with DS. Currently attention is being paid to sleep apnea syndrome in children, not only due to its cardiovascular complications [22,23] and suggested relations to metabolic syndrome [24], but also for its impact on cognitive and social development [25,26]. In addition to predisposing craniofacial anatomy, children with DS are associated with high body mass index, which may contribute to OSA. The cardiovascular impact of OSA in children with DS and the long time effect of untreated disease is not documented, however the effect measured in otherwise healthy has caused great concern. Despite the latter, these 29 children were all undiagnosed concerning OSA at the age of 8. Although the children in this study population had not been referred to PSG previous to this study, some children had been referred to surgical treatment with tonsillectomy, adenoidectomy or both (Table 1). According to the parents this treatment had been initiated due to a high rate of infections. The mean AHI in the operated children was slightly lower compared to the remaining study population, with an AHI 8.1 and 10.1 respectively. However we do not know to what degree the surgical treatment has had an impact on the AHI in the children who underwent surgical treatment as, whereas preoperative PSGs were not performed. 5. Conclusion The high prevalence of disease found in these undiagnosed 8year-old children underlines the importance of performing OSA
Please cite this article in press as: M.E. Austeng, et al., Obstructive sleep apnea in younger school children with Down syndrome, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.030
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diagnostics in children with DS throughout childhood. These findings suggest that the prevalence of OSA remains high up to early school years. In contrast to earlier publications, this current study has the advantage of being population based, the study is performed on children of a narrow age band to estimate prevalence of disease and the diagnostic gold standard of PSG is applied. Authors’ contributions Marit Erna Austeng, MD has conceptualized and designed the study, contributed to funding, collected data, carried out the initial analyses, drafted the initial manuscript, and approved the final manuscript as submitted. Britt Øverland, Dr philos has contributed to the design of the study, collected and analyzed data, coordinated and supervised data collection, drafted a part of the initial manuscript, and approved the final manuscript as submitted. Kari Jorunn Kværner, Professor has contributed to the conception and design of the study, contributed to funding, reviewed and revised the early drafts and of the manuscript and approved the final manuscript as submitted. Els-Marie Anderson, Dr has conceptualized and designed parts of the study, collected data, coordinated and supervised parts of the data collection, reviewed and revised drafts of the manuscript and approved the final manuscript as submitted. Stefan Axelsson, Dr has conceptualized and designed parts of the study, collected data, coordinated and supervised parts of the data collection, reviewed and revised drafts of the manuscript and approved the final manuscript as submitted. Harriet Akre, Dr has conceptualized and designed the study, contributed to collection and analyses of data, coordinated and supervised data collection, reviewed and revised the early drafts and of the manuscript and approved the final manuscript as submitted. Michael Abdelnoor, MPH, PhD, has contributed to analyses of data, contributed to parts of the initial manuscript, reviewed and revised the early drafts and of the manuscript and approved the final manuscript as submitted. Conflict of interest None of the authors have any financial or other relationship that might lead to a conflict of interest. References [1] R. Tauman, D. Gozal, Obstructive sleep apnea syndrome in children, Expert Rev. Respir. Med. 5 (June (3)) (2011) 425–440. [2] K. Bonuck, K. Freeman, R.D. Chervin, L. Xu, Sleep-disordered breathing in a population-based cohort: behavioral outcomes at 4 and 7 years, Pediatrics 129 (April (4)) (2012) e857–e865. [3] R.D. Chervin, K.H. Archbold, J.E. Dillon, P. Panahi, K.J. Pituch, R.E. Dahl, et al., Inattention, hyperactivity, and symptoms of sleep-disordered breathing, Pediatrics 109 (March (3)) (2002) 449–456.
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Please cite this article in press as: M.E. Austeng, et al., Obstructive sleep apnea in younger school children with Down syndrome, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.030
