Sleep-disordered breathing (SDB) in children has been associated with a number of physiological, neurocognitive, and

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1 Incidence and Remission of Sleep-Disordered Breathing and Related Symptoms in 6- to 17-Year Old Children The Tucson Children s Assessment of Sleep Apnea Study James L. Goodwin, PhD, Monica M. Vasquez, MPH, Graciela E. Silva, PhD, MPH, and Stuart F. Quan, MD Objective To determine the incidence and remission of sleep-disordered breathing in adolescent children. Study design A total of 319 children completed 2 home polysomnograms approximately 5 years apart. Sleepdisordered breathing (SDB) was determined to be present if a child had a respiratory disturbance index $ 1 event per hour associated with $3% oxygen desaturation. Subjective symptoms such as witnessed apnea, excessive daytime sleepiness, difficulty initiating and maintaining sleep, and habitual loud snoring were considered present if they occurred frequently or almost always. Body mass index percentiles were calculated with childhood growth charts from the Centers for Disease Control and Prevention adjusted for sex and age. Results The mean age at assessment was 8.5 years at baseline and 13.7 years at follow-up, respectively. Incident SDB was more common in boys (odds ratio [OR] = 3.93, P =.008, confidence interval [CI] = ). Children with prevalent SDB were more likely to be boys (OR = 2.48, P =.006) and had a greater increase in body mass index percentile change (OR 1.01, P =.034). Children with prevalent SDB also had 3.41 greater odds for development of obesity from baseline to follow-up in comparison with children with prevalent NoSDB. Conclusions Adolescent boys are more likely to have persistent and incident SDB than girls. Children with prevalent SDB are more likely to have development of obesity. These risks are similar to those observed in adults. (J Pediatr 2010;157:57-61). Sleep-disordered breathing (SDB) in children has been associated with a number of physiological, neurocognitive, and behavioral problems. 1-4 Moreover, there is increasing evidence that SDB has an important adverse impact on a child s physical and cognitive health and social development. 1,5-7 Although there are several studies specifying the prevalence of snoring and other sleep-related problems in children, 8-12 there is little evidence documenting the incidence and remission of symptoms associated with sleep disorders in children, such as witnessed apnea, excessive daytime sleepiness, habitual snoring, and insomnia Furthermore, there are no data to date indicating the incidence and remission rates of SDB in a large sample of children with polysomnography used, as well as identifying factors associated with incidence or remission. This gap in the research literature was highlighted in an extensive recent review of the epidemiology of pediatric obstructive sleep apnea. 16 The Tucson Children s Assessment of Sleep Apnea (TuCASA) study is a longitudinal cohort study designed to investigate the physiological, anatomic, and behavioral correlates of SDB and to document their changes with development. In this analysis, we present data on the incidence, remission, and persistence of SDB and related symptoms. Methods Details of the TuCASA study design have been published previously. 10,17 Briefly, Hispanic and Caucasian children ages 6 to 11 years were recruited to undergo unattended home polysomnography and perform a neurocognitive assessment. Subjects were recruited through the Tucson Unified School District, a very large district with a substantial elementary school population. Parents were asked to complete a short screening questionnaire and to provide their contact information if they were willing BMI CI DIMS EDS NoSDB OR RDI SDB TuCASA WITAP Body mass index Confidence interval Difficulty initiating and maintaining sleep Excessive daytime sleepiness No sleep-disordered breathing Odds ratio Respiratory disturbance index Sleep disordered breathing Tucson Children s Assessment of Sleep Apnea Witnessed Apnea From the College of Medicine (J.G., S.Q.), the Arizona Respiratory Center (J.G., M.V., S.Q.), and the Mel and Enid Zuckerman College of Public Health (J.G., M.V., S.Q.), University of Arizona, Tucson, AZ; the College of Nursing & Health Innovation, Arizona State University (G.S.), Phoenix, AZ; and the Division of Sleep Medicine, Brigham and Women s Hospital and Harvard Medical School (S.Q.), Boston, MA Funded by NHLBI The authors declare no conflicts of interest /$ - see front matter. Copyright Ó 2010 Mosby Inc. All rights reserved /j.jpeds

2 THE JOURNAL OF PEDIATRICS Vol. 157, No. 1 to allow study personnel to contact them to determine whether their child was eligible for the study. A total of 7055 screening questionnaires were sent home with children in a notes home folder. Of these, 2327 (33%) were returned. Recruitment information was supplied on 52% of the returned questionnaires, from which we selected children, on the basis of preestablished inclusion and exclusion criteria, to undergo polysomnography. Unattended home polysomnography was scheduled as soon as possible after recruitment. From 1999 to 2003, 503 children aged 6 to 11 years completed home polysomnography (baseline). Approximately 5 years later (mean 4.7 years), 348 children participated in the second phase of the study; 319 children had home visits where acceptable in-home polysomnography was completed. On both occasions, all of the families completed sleep screening, sleep habits, and morning questionnaires. The TuCASA study was approved by the University of Arizona Institutional Review Board, as well as the Tucson Unified School District Research Committee. The methods for obtaining data have been previously described. 17 In brief, a 2-person, mixed-sex team arrived at the home approximately 1 hour before the child s normal bedtime. Before performing any study procedures, parents gave informed consent, and the child gave assent to the study with language-appropriate Institutional Review Board approved forms. Each child s height, weight, neck circumference, and blood pressure were measured. A parent was asked to complete a comprehensive Sleep Habits Questionnaire that inquired about their child s sleep history and sleep characteristics. A single, unattended overnight polysomnogram was obtained with the Compumedics PS-2 system (Abbotsford, Victoria, Australia). The following signals were acquired as part of the TuCASA montage: C3/A2 and C4/A1 electroencephalogram, right and left electrooculogram, a bipolar submental electromyogram, thoracic and abdominal displacement (inductive plethysmography band), airflow (nasal/oral thermister), nasal pressure cannula, finger pulse oximetry, electrocardiography (single bipolar lead), snoring microphone, body position (Hg gauge sensor), and ambient light. Scoring of sleep was performed by a single registered polysomnographic technologist using Rechtschaffen and Kales criteria. 18 Arousals were identified with criteria published by the American Academy of Sleep Medicine. 19 Apneas were scored if the amplitude (peak to trough) of the airflow signal with the thermistor decreased below at least 25% of the amplitude of baseline breathing (identified during a period of regular breathing with stable oxygen levels), if this change lasted for more than 6 seconds or 2 breath cycles. Hypopneas were designated if the amplitude of any respiratory signal decreased below (approximately) 70% of the amplitude of baseline and if the thermistor signal did not meet the criterion for apnea. Central events were marked if no displacement was noted on both the chest and abdominal inductance channels. However, central events that occurred after movement were not included. Otherwise, events were scored as obstructive. After full scoring, analysis software was used to link each event to data from the oxygen saturation and electroencephalography channels. The Respiratory Disturbance Index (RDI) was defined as the number of respiratory events (apneas and hypopneas) per hour of total sleep time. For this analysis, a 3% oxygen desaturation was required for an event to be counted in the total RDI. In our primary analyses, we considered a child to have SDB if their RDI was greater than or equal to 1 event per hour of total sleep time. Use of this definition is supported by previous evidence that a RDI of one, based on events with a 3% oxygen desaturation, is clinically significant. 12,20,21 We also explored the impact of using definitions of RDI with cutpoints up to 10 events per hour. Witnessed apnea (WITAP) was defined as stopping breathing, struggling to breathe, or having to shake the child awake while sleeping. Excessive daytime sleepiness (EDS) was defined as being sleepy in the daytime or falling asleep at school or while watching television. Snoring was present if the parent reported their child snored loudly. Insomnia (DIMS) was present if the child currently experienced trouble falling asleep, staying asleep, or waking too early. The symptom was defined as present if the parent reported it occurred frequently or almost always. Body mass index (BMI) percentiles were calculated with U.S. Centers for Disease Control and Prevention childhood growth charts adjusted for sex and age. 22 Children were categorized as obese if they exceeded the 95th percentile of BMI for their age, sex, and ethnicity. Variables pertaining to incidence and remission of SDB were defined as follows: incident SDB denotes no SDB at baseline and SDB at follow-up; remission SDB denotes SDB at baseline and no SDB at follow-up; persistent SDB denotes SDB at baseline and at follow-up; persistent no sleep-disordered breathing (NoSDB) denotes no SDB at baseline and no SDB at follow-up; prevalent SDB denotes persistent SDB group + incident SDB group; prevalent NoSDB denotes remission SDB group + persistent NoSDB group. Data Analysis The Student t test and the 2-sample test of proportion were used to compare differences in characteristics at baseline and follow-up. Potential predictors of incident and remissive SDB were also investigated. These variables included change in neck circumference, BMI percentile, sleep efficiency, and total sleep time. Additional variables included parent reported witnessed apnea, snoring, excessive daytime sleepiness, insomnia, sex, and ethnicity. Logistic regression was used to determine predictors of incidence, remission, and persistence or absence of SDB as defined above. Results The mean age at first assessment was 8.5 years (range 6-12), and mean age at second assessment was 13.7 years (range 10-18). The mean time between assessments was 4.6 years (range: ). There were 50.4% males and 49.6% females 58 Goodwin et al

3 July 2010 ORIGINAL ARTICLES Table I. Characteristics of the Tucson Children s Assessment of Sleep Apnea Study Participants at Baseline and Follow-Up* Characteristic Baseline (n = 480) Follow-up (n = 319) P value Age (6-12) ( ) <.001 Respiratory disturbance.89 index $ (1-29.1) (1-30.7) < (0-0.9) (0-0.9) Respiratory disturbance.003 index $1 115 (23.9%) 49 (15.3%) <1 365 (76.1%) 270 (84.6%) Ethnicity.06 Hispanic 203 (42.3%) 114 (35.7%) Non-Hispanic 277 (57.7%) 205 (64.3%) Sex.76 Male 240 (50.0%) 163 (51.1%) Female 240 (50.0%) 156 (48.9%) Obesity.02 Yes 62 (12.9%) 61 (19.2%) No 418 (87.1%) 256 (80.8%) Snoring.03 Yes 72 (15.0%) 31 (9.7%) No 408 (85.0%) 288 (90.3%) Excessive daytime.67 sleepiness Yes 78 (16.35%) 48 (15.1%) No 402 (83.8%) 269 (84.9%) Witnessed apnea.03 Yes 25 (5.2%) 7 (2.2%) No 455 (94.8%) 312 (97.8%) Insomnia.21 Yes 141 (29.9%) 80 (25.3%) No 339 (70.6%) 236 (74.7%) *Representing children with acceptable PSG. at the time of initial enrollment; this sex ratio remained approximately the same at the second assessment. Ethnicity was 58.5% Caucasian and 41.5% Hispanic. Table I shows the characteristics of the cohort at baseline and follow-up. Of note was that the prevalence of both snoring and WITAP, as well as polysomnographically determined SDB, decreased from baseline to follow-up. Snoring declined from 15.0% to 9.7%, and WITAP decreased from 5.2% to 2.2%. Moreover, the percentage of children with a RDI >1 fell from 23.9% to 15.3%. In contrast, the rate of obesity increased from 12.9% to 19.2%. The incidence and remission rates for SDB and symptoms of sleep disturbances are displayed in Table II. Incidence rates for key symptoms of sleep disturbance were as follow: snoring 4.1%, EDS 11.8%, WITAP 0.9%, and DIMS 16.6%. Remission rates were snoring 60.3%, EDS 63.8%, WITAP 84.0%, and DIMS 47.8%. For polysomnographically determined SDB, the incidence rate was 10.0%, and the remission rate was 70.8%. With a logistic regression model and empirically testing each predictor variable, children with Incident SDB were compared with children with prevalent NoSDB. We also compared children with remission SDB with those children who had prevalent SDB. Boys were more likely to have development of SDB (OR = 3.93, P =.008, CI = ). In addition to exploring incident and remissive cases alone, we explored predictors for the combination of incident and persistent cases (prevalent SDB compared with prevalent NoSDB). Children with prevalent SDB were more likely to be boys (OR = 2.48, P =.006, CI [ ]) and had a greater increase in BMI percentile change (OR 1.01, P =.034, ) (Figure). Children with prevalent SDB also had a 3.41 greater odds (P <.001, CI: ) for development of obesity from baseline to follow-up in comparison with children with prevalent NoSDB. Parent-reported symptoms or other measured physiological variables on the night of the PSG were not predictive of future incident SDB or remission of SDB. We examined the number of incident, remission, and persistent cases from baseline to follow-up for higher cut points of RDI, such as 2, 5, and 10 events per hour. Unfortunately, the number of cases were too few to do any meaningful analysis with only 13, 3, and 1 case, respectively, for each of the above cut points. Seventeen children underwent tonsillectomy between the time of their first and second polysomnographic evaluation. Eight children had persistent NoSDB, and 2 children had Persistent SDB, resulting in no change to SDB classification. After tonsillectomy, 3 of the 17 children had incident SDB, and 4 had remission of SDB. Subsequent analyses showed that undergoing tonsillectomy had no influence on our conclusions. Discussion In this analysis, we found that in children between the ages of 6 and 11 years, the incidence of parent-reported sleep symptoms over the ensuing 5 years is relatively low. Moreover, except for symptoms consistent with insomnia, most Table II. Incidence and remission of sleep disturbances Incidence of symptoms Remission of symptoms Reporting no at baseline and follow-up Reporting yes at baseline and follow-up % No./No. at risk % No./No. at risk % No./No. at risk % No./No. at risk Snore 4.1% 12/ % 35/ % 278/ % 23/58 Excessive daytime sleepiness 11.8% 35/ % 30/ % 262/ % 17/47 Witnessed apnea 0.9% 3/ % 21/ % 320/ % 4/25 Insomnia 16.6% 42/ % 43/ % 211/ % 47/90 SDB 10.0% 2 3/ % 63/ % 207/ % 26/89 Incidence and Remission of Sleep-Disordered Breathing and Related Symptoms in 6- to 17-Year Old Children The Tucson Children s Assessment of Sleep Apnea Study 59

4 THE JOURNAL OF PEDIATRICS Vol. 157, No. 1 BMI Percentile Baseline Prevalent No SDB Prevalent SDB Follow-Up Figure. Change in BMI percentile from baseline to follow-up. Children with prevalent SDB had greater increase in BMI percentile than children with prevalent NoSDB. symptoms of sleep disorders remit. In addition, we found that not all children with polysomnographically determined SDB remit and that some children have development of SDB during this interval. Male sex and obesity appear to be the most important risk factors for prevalent SDB in this age group. These data indicate that SDB does not necessarily resolve with the onset of adolescence in children, and risks for SDB in adolescence are similar to those observed in adults. The highest incidence rates we observed were for insomnia-related symptoms (DIMS) and excessive daytime sleepiness. These findings are consistent with the physiological sleep phase delay occurring in adolescents and the potentially hectic social environment in which they live. In this age group, factors such as enhanced autonomy and familial, educational and psychosocial stresses may contribute to poor sleep hygiene. 23,24 Interestingly, remission rates for EDS were higher than remission rates for DIMS. The explanation for these differences is not clear. However, the factors contributing to EDS and DIMS in 6- to 11-year-old children are not the same as in 12- to 18-year-old adolescents. Thus, whereas SDB may be an important contributing cause of EDS in younger children, insufficient sleep may be more relevant in the older age group. Similarly, the aforementioned social environment not only contributes to the higher incidence of DIMS, but also to a relatively low remission rate. In contrast to DIMS and EDS, the incidence rates for snoring and witnessed apnea were much lower. It is difficult to contrast our findings with respect to snoring with prior studies because of differences in the age of the cohorts and length of follow-up. Nevertheless, our snoring incidence rate of 4.1% over an approximate 5 year interval is comparable with the 4.5% rate over a 3-year interval reported by Anuntaseree et al 25 and the 4.3% rate observed by Chervin et al 7 over a 4-year interval. Incidence and remission rates for the symptom of witnessed apnea have not been previously reported. However, the prevalence rate observed at followup in this study (2.0%) is similar to the findings of Sánchez-Armengol et al 26 in a cohort of 12- to 16-year-old children (3%), but higher than those observed by Joo et al 27 in a group of 15- to 18-year-old Korean high school students. It is possible that the older age of the cohort in the latter study accounts for this difference. We observed a 10% incidence rate and a 70.8% remission rate for polysomnographically confirmed SDB in our study. There have been few prior studies documenting the incidence and remission rates of SDB in children, with most occurring in small cohorts recruited from clinical sources. Marcus et al 14 initially studied a small group of children and found that 2 of 20 with primary snoring had evidence of SDB on polysomnography 1 to 3 years later. Similarly, Topol and Brooks 15 found 1 of 13 children had evidence of SDB 3 years later. In contrast, Anuntaseree et al 25 found 5 new cases of SDB in 61 children (9.1%) with habitual snoring 3 years previously. Our study extends these limited observations to a much larger cohort studied after a long duration spanning the time period between preadolescence to adolescence. Our results indicate that there is a small but significant number of preadolescent children who will have development of SDB as they become adolescents. Moreover, although it is generally expected that both snoring, and consequently SDB, should resolve over time in preadolescents in parallel with regression of tonsillar and adenoidal tissue, our finding that the remission rate is only 70.8% indicates that a considerable number of children with SDB will not have spontaneous resolution. Given the increasing data that SDB in children adversely impacts neurocognition and behavior and may increase the risk of hypertension and obesity, our results provide additional evidence that active intervention to treat SDB in preadolescents is indicated. We observed that prevalence of SDB or no SDB was associated with sex and increasing weight. Boys, as well as those children who had excessive weight gain, were more likely to have SDB at the time of the second TuCASA examination. In adults, SDB also is more common in males and those who are obese. Thus our findings support the hypothesis that factors important in the development of SDB in adolescents are similar to those operative in adults. Given the increasing prevalence of obesity in both children and adults in the general population, it is likely that SDB will be a more common occurrence in children, especially adolescents. One limitation of our study is that we used only 1 RDI threshold to classify SDB. Unfortunately, there were too few cases for a meaningful analysis with other definitions. Although we acknowledge that other definitions of SDB have been used (eg, 5 events/hour), an RDI > 1 event per hour has been associated with significant physiological and behavioral outcomes in a number of studies. 12,20,21,28,29 Therefore we believe our analyses have important clinical implications. In summary, our findings in a general population indicate that although symptoms of sleep disorders in preadolescents generally resolve over time, they will not remit in some 60 Goodwin et al

5 July 2010 ORIGINAL ARTICLES children, and a significant number will have development of them. Moreover, SDB in preadolescents may not spontaneously remit, and a significant number will have development of SDB when they are adolescents. Risk factors for SDB in adolescents are similar to those observed in adults. Given the potential for adverse consequences on health and the likelihood of an increasing prevalence of SDB, clinicians should be both vigilant in diagnosis and aggressive in treatment. n Submitted for publication Aug 6, 2009; last revision received Oct 29, 2009; accepted Jan 21, Reprint requests: James L. Goodwin, PhD, 1501 N. Campbell AHSC , The University of Arizona, Tucson, AZ jamieg@arc. arizona.edu. References 1. Owens JA. Neurocognitive and behavioral impact of sleep disordered breathing in children. Pediatr Pulmonol 2009;44: Chervin RAK, Dillon J, Panahi P, Pituch K, Dahl R, Guilleminault C. Inattention, hyperactivity, and symptoms of sleep-disordered breathing. 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