Sleep Medicine 14 (2013) 1317–1322

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Sleep Medicine

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Original Article

The effect of childhood obstructive sleep apnea on ambulatory bloodpressure is modulated by the distribution of respiratory events duringrapid eye movement and nonrapid eye movement sleep

1389-9457/$ - see front matter � 2013 Elsevier B.V. All rights reserved.http://dx.doi.org/10.1016/j.sleep.2013.09.017

⇑ Corresponding author. Tel.: +852 2632 2917; fax: +852 2636 0020.E-mail address: junau@cuhk.edu.hk (C.T. Au).

Chun Ting Au a,⇑, Crover Kwok Wah Ho b, Yun Kwok Wing b, Albert Martin Li a

a Department of Pediatrics, Prince of Wales and Shatin Hospitals, The Chinese University of Hong Kong, Shatin, Hong Kongb Department of Psychiatry, Prince of Wales and Shatin Hospitals, The Chinese University of Hong Kong, Shatin, Hong Kong

a r t i c l e i n f o a b s t r a c t

Article history:Received 7 March 2013Received in revised form 29 August 2013Accepted 1 September 2013Available online 17 October 2013

Keywords:Obstructive sleep apneaRapid eye movementREM-related OSABlood pressurePolysomnographyChildren

Objective: We aimed to investigate if different childhood obstructive sleep apnea (OSA) subtypes, namelyrapid eye movement (REM)-related, nonrapid eye movement (NREM)-related and stage-independentOSA would exert different effects on ambulatory blood pressure (ABP).Methods: Data from our previous school-based cross-sectional study were reanalyzed. Subjects who hadan obstructive apnea–hypopnea index (OAHI) between 1 and 10 events per hour and a total REM sleepduration of >30 min were included in our analysis. REM-related and NREM-related OSA were definedas a ratio of OAHI in REM sleep (OAHIREM) to OAHI in NREM sleep (OAHINREM) of >2 and <0.5, respectively.The others were classified as stage-independent OSA.Results: A total of 162 subjects were included in the analysis. In the mild OSA (OAHI, 1–5 events/h) sub-group, no significant differences in any ABP parameters were found between OSA subtypes. On the otherhand, in subjects with moderate OSA (OAHI, 5–10 events/h), the REM-related OSA subtype had a signif-icantly lower daytime systolic blood pressure (SBP) z score (�0.13 ± 0.90 cf 1.15 ± 0.67; P = .012) andnighttime SBP z score (0.29 ± 1.06 cf 1.48 ± 0.88, P = .039) than the stage-independent OSA subtype. Lin-ear regression analyses revealed that OAHINREM but not OAHIREM was significantly associated with bothdaytime (P = .008) and nighttime SBP (P = .042) after controlling for age, gender, and body size.Conclusion: Children with obstructive events mainly in REM sleep may have less cardiovascular compli-cations than those with stage-independent OSA.

� 2013 Elsevier B.V. All rights reserved.

1. Introduction

In recent years, a number of studies have shown that pediatricobstructive sleep apnea (OSA) is associated with elevated bloodpressure (BP) [1–4]. Our group documented that children withOSA had significantly higher daytime and nocturnal BP comparedto nonsnoring control subjects. In addition, moderate to severeOSA, defined as an obstructive apnea–hypopnea index (OAHI) of>5 events per hour, was associated with a higher risk for nocturnalhypertension, whereas the effect of mild OSA was only modest [4].

It has been found that obstructive respiratory events more com-monly are found in rapid eye movement (REM) sleep [6,7] in chil-dren with OSA, possibly attributed to the reduced muscle tone andblunted arousal and ventilatory responses during this sleep state[6–9]. A previous study revealed that 55% of obstructive apneasin children occurred during REM sleep [10]. Patients with obstruc-tive respiratory events mainly during REM sleep are defined as

having REM-related OSA. Clinically, the diagnosis of REM-relatedOSA has not been standardized. For research purposes, a subjectis classified as having REM-related OSA when the diagnostic crite-ria of OSA are fulfilled and the ratio of OAHI in REM sleep(OAHIREM) to OAHI in non-REM (NREM) sleep (OAHINREM) is >2[11–13]. Although REM-related OSA in children is common, re-search in this topic is limited. There are no published data on itsprevalence based on a community sample. A pediatric study [14]that involved sleep laboratory attendants showed that nearly 70%of patients had higher OAHIREM than OAHINREM. From adult studies,the prevalence of REM-related OSA is approximately 10–36%among patients with OSA [11–13,15].

The clinical significance of REM-related OSA is controversial.Some studies suggest that REM-related OSA is associated withexcessive daytime sleepiness [16,11,17], and others argue thatthe main correlate with adverse outcomes is OAHINREM rather thanOAHIREM [18–20]. There currently is no evidence to suggestdifferential effects on 24-h ambulatory BP (ABP) monitoring bythe different OSA subtypes. Our study aimed to investigate if differ-ences in ABP were present in children with OSA, with different

1318 C.T. Au et al. / Sleep Medicine 14 (2013) 1317–1322

distributions of respiratory events among REM and NREM sleep.We stratified the study population into mild (OAHI, 1–5 events/h) and moderate OSA (OAHI, 5–10 events/h) subgroups to controlfor the effect of overall OSA severity on ABP.

2. Methods

2.1. Study design

Data from our previous school-based cross-sectional study,which investigated the association between OSA and ABP, werereanalyzed [4]. The study included 306 children aged 6–13 yearsrecruited from primary schools that were randomly selected fromtwo local districts, Sha Tin and Tai Po. All subjects underwentanthropometric measurements, overnight polysomnography(PSG) and ABP monitoring. ABP monitoring was performed over a24-h period during which overnight PSG also was performed. Bodymass index (BMI) was converted to BMI z score according to nor-mal reference [21]. Written informed consent and assent were ob-tained from parents and subjects, respectively. The study wasapproved by the Joint Chinese University of Hong Kong, New Ter-ritories East Cluster.

2.2. Clinical research ethics committee

Based on the PSG results, subjects were divided into fourgroups: (1) healthy control subjects without OSA (OAHI <1 event/h), (2) mild OSA (OAHI, 1–5 events/h), (3) moderate OSA (OAHI,5–10 events/h), and (4) severe OSA (OAHI, >10 events/h) [4]. Inour retrospective analysis subjects within each group, except forthe control group, were further stratified into different OSA sub-types, namely REM-related, NREM-related, and stage-independentOSA for comparisons. REM-related OSA and NREM-related OSAwere defined as OAHIREM/OAHINREM of >2 and <0.5, respectively.

Table 1Anthropometric and polysomnographic data of different obstructive sleep apnea subtypes

Control (OAHI<1/h)

Mild OSA (OAHI 1–5/h)

REM-related

NREM-related

Sleep stage:independent

n = 127 n = 90 n = 18 n = 24

Age, y 10.4 ± 1.7 10.6 ± 1.6 10.2 ± 1.7 10.7 ± 1.6Male gender, n (%) 72 (56.7) 62 (68.9) 12 (66.7) 18 (75)Height, cm 139 ± 10 140 ± 11 138 ± 10 141 ± 11BMI, m/kg2 17.4 ± 2.9 18.9 ± 3.5 18.8 ± 3.4 17.7 ± 3.8BMI z score 0.21 ± 0.98 0.63 ± 1.00 0.69 ± 0.94 0.11 ± 1.16REM sleep, % 21.0 ± 3.9 21.6 ± 3.6 20.1 ± 3.9 19.9 ± 4.2Stage 1, % 6.5 ± 3.0 8.2 ± 3.6 7.7 ± 4.8 8.9 ± 2.7Stage 2, % 49.4 ± 5.4 48.0 ± 5.0 49.9 ± 4.9 48.3 ± 5.7SWS, % 23.1 ± 5.4 22.2 ± 4.8 22.3 ± 5.7 22.9 ± 6.0TST, min 474 ± 58 467 ± 59 478 ± 61 462 ± 75ODI, events /h 0.1 (0–0.4) 0.4 (0.2–

0.9)0.7 (0.2–1.2)

0.8 (0.5–1.3)

ArI, events/h 6.1 ± 2.5 7.1 ± 2.7 8.1 ± 4.9 8.9 ± 3.0⁄

Respiratory ArI,events/h

0.3 (0.1–0.7) 1.3 (0.9–2.3)

2.0 (1.5–2.7)⁄

2.2 (1.3–3.2)⁄

SpO2 nadir in REM, % 93 ± 2 94 ± 2 92 ± 4 92 ± 2SpO2 nadir in NREM,

%93 ± 2 93 ± 2 92 ± 2 91 ± 2⁄

SpO2 nadir, % 92 ± 2 92 ± 3 91 ± 4 91 ± 2OAHITST, events /h 0.3 ± 0.3 2.3 ± 1.1 1.8 ± 0.7 2.2 ± 1.0OAHIREM, events/h 0 (0–1.0) 7.0 (4.3–

9.8)0.2 (0–0.6)⁄ 2.1 (1.1–2.7)⁄

OAHINREM, events/h 0 (0–0.3) 0.6 (0.3–1.0)

2.0 (1.6–3.1)⁄

2.1 (1.3–2.6)⁄

Abbreviations: OSA, obstructive sleep apnea; h, hour; OAHI, obstructive apnea–hypopneabody mass index; SWS, slow-wave sleep; TST, total sleep time; ODI, oxygen desaturatioOAHINREM, OAHI in NREM sleep.* Significantly different from REM-related OSA group.

The other subjects with a ratio between 0.5 and 2 were classifiedas stage-independent OSA. To avoid an overestimated OAHIREM incases with inadequate total REM sleep, subjects with less than30 min of total REM sleep were excluded.

The severe OSA cases also were excluded, as there were onlythree subjects in each of NREM-related and the stage-independentgroups. Such small sample size would provide unreliable results.Moreover, their OAHI widely varied from 11.3 events per hour to80.9 events per hour and combining severe and moderate groupswas not an option as that would distort the results by greatlyincreasing the variance of OAHI.

2.3. Polysomnography

Overnight PSG was performed in a dedicated sleep laboratorywith CNS 1000P polygraph (CNS, Inc., Chanhassen MN) as de-scribed in our previous publication [22]. All computerized sleepdata were further manually edited by experienced PSG technolo-gists and clinicians according to standardized criteria [23]. Allstudies were standardized to record the time in bed for9.5 h ± 5 min, starting at 21:30 ± 15 min and ending at7:00 ± 15 min the next day.

2.4. ABP monitoring

Subjects underwent 24-h ABP monitoring on the same day asovernight PSG using an oscillometric monitor (SpaceLabs 90217,SpaceLabs Medical, Redmond, Washington, USA), which has beenvalidated for use in children [24]. Systolic BP (SBP) and diastolicBP (DBP) were measured every 60 min during the nighttime from09:30 pm to 07:00 am and every 30 min from 07:00 am to09:30 pm (daytime period). The exact cutoff dividing daytimeand nighttime BP was individually defined according to the PSGtracings. Individual mean SBP and DBP were calculated for daytime

.

Moderate OSA (OAHI 5–10/h)

Pvalue

REM-related NREM-related

Sleep stage:independent

Pvalue

n = 15 n = 8 n = 7

.558 10.1 ± 1.7 10.2 ± 1.8 9.3 ± 1.4 .490

.808 13 (86.7) 5 (62.5) 5 (71.4) .398

.635 139 ± 11 140 ± 12 138 ± 11 .966

.336 19.1 ± 3.2 20.3 ± 2.4 18.6 ± 2.6 .503

.074 0.82 ± 0.98 1.24 ± 0.98 0.87 ± 0.94 .598

.070 21.3 ± 3.4 21.0 ± 4.8 21.4 ± 7.1 .988

.535 6.6 ± 3.4 8.3 ± 3.2 10.8 ± 4.4⁄ .056

.355 46.9 ± 6.8 47.8 ± 6.8 44.1 ± 3.4 .489

.841 25.2 ± 5.1 22.9 ± 6.4 23.8 ± 4.1 .574

.714 505 ± 53 463 ± 44 456 ± 71 .095

.049 1.4 (0.5–2.3) 1.2 (0.5–4.5)

3.7 (0.9–5.7) .220

.030 8.8 ± 3.5 10.9 ± 2.4 13.7 ± 5.0⁄ .024

.005 3.7 (2.2–5.0) 6.9 (6.0–8.7)⁄

7.2 (5.1–9.3) .004

.758 91 ± 4 93 ± 2 92 ± 3 .435

.011 93 ± 3 90 ± 5 93 ± 1 .109

.288 90 ± 4 90 ± 5 91 ± 2 .780

.291 6.9 ± 1.2 7.2 ± 1.4 7.9 ± 1.0 .253<.001 23.2 (18.4–

29.6)1.7 (0–2.7)⁄ 8.6 (5.2–10.0)⁄ <.001

<.001 1.5 (1.1–2.7) 8.3 (7.0–9.4)⁄

8.1 (7.1–8.7)⁄ <.001

index; REM, rapid eye movement; NREM, nonrapid eye movement; y, years; BMI,n index; ArI, arousal index; SpO2, oxygen saturation; OAHIREM, OAHI in REM sleep;

Table 2Daytime and nighttime ambulatory blood pressure data of different obstructive sleep apnea subtypes.

Control (OAHI<1/h)

Mild OSA (OAHI 1–5/h) Moderate OSA (OAHI 5–10/h)

REM-related

NREM-related

Sleep stage:independent

P value fortrend

REM-related

NREM-related

Sleep stage:independent

P value fortrend

n = 127 n = 90 n = 18 n = 24 n = 15 n = 8 n = 7

Daytime SBP,mmHg

111 ± 8 113 ± 8 112 ± 8 113 ± 9 .779 112 ± 7 119 ± 7 122 ± 7⁄ .003

Daytime DBP,mmHg

71 ± 5 71 ± 5 71 ± 5 73 ± 6 .295 72 ± 4 75 ± 6 75 ± 2 .097

Nighttime SBP,mmHg

99 ± 9 102 ± 8 101 ± 9 102 ± 7 .932 101 ± 9 104 ± 7 110 ± 9 .022

Nighttime DBP,mmHg

58 ± 6 59 ± 5 59 ± 4 60 ± 5 .829 59 ± 6 59 ± 7 63 ± 6 .229

Nocturnal SBPdipping,%

10.5 ± 5.3 9.5 ± 5.8 10.3 ± 6.9 9.4 ± 4.7 .928 10.3 ± 5.7 12.3 ± 4.2 9.5 ± 5.7 .892

Nocturnal DBPdipping,%

17.5 ± 6.9 16.6 ± 6.7 16.1 ± 7.0 17.3 ± 5.1 .728 18.1 ± 6.6 21.2 ± 6.3 16.8 ± 6.9 .854

Abbreviations: OSA, obstructive sleep apnea; h, hour; OAHI, obstructive apnea–hypopnea index; REM, rapid eye movement; NREM, nonrapid eye movement; DBP, diastolicblood pressure; SBP, systolic blood pressure.* Significantly different from REM-related OSA group.

C.T. Au et al. / Sleep Medicine 14 (2013) 1317–1322 1319

and nighttime periods. All mean BP variables were converted intoBP z scores using the reference ranges relative to gender and heightpublished by Wuhl et al. [25]. Nocturnal dipping of SBP and DBPwere derived by calculating the difference between daytime andnighttime BP and expressed as a percentage of mean daytime BP.

2.5. Statistical analysis

The mean ± standard deviation, median (interquartile range),and number (percentage) were presented for parametric, nonpara-metric, and categorical data, respectively. Data from the controlgroup were shown for reference. Normally distributed and nonnor-mally distributed data were compared using one-way analysis ofvariance and the Kruskal–Wallis test, respectively. Two group pair-wise comparisons were performed with post hoc testing of analysisof variance for normally distributed data and the Mann–Whitney Utest with Bonferroni correction (significance at P < .016) for non-

Fig. 1. Scatter plot of ambulatory blood pressure of d

normally distributed data. The v2 test or Fisher exact test withBonferroni correction (significance at P < .016) were performed toinvestigate the difference in proportions between groups. Linearcontrast tests were used to examine the linear trends across groupsfor continuous variables. Linear regression analyses were used toexamine the association of OAHIREM and OAHINREM with ABP mea-sures. All analyses were performed using the statistical softwarepackages SPSS (version 13.0 for Windows; SPSS Inc., Chicago, Illi-nois, USA).

3. Results

3.1. Mild OSA subgroup

In the mild OSA subgroup, one child who had less than 30 minof total REM sleep was excluded. Among the remaining 132 chil-

ifferent mild obstructive sleep apnea subtypes.

Fig. 2. Scatter plot of ambulatory blood pressure of different moderate obstructive sleep apnea subtypes. P values were obtained from linear contrast tests. ⁄Significantlydifferent from rapid eye movement sleep-related obstructive sleep apnea group. (P < .05, post hoc testing of analysis of variance).

Table 3Results of multiple linear regression analysis showing the association of obstructiveapnea–hypopnea index in rapid eye movement sleep and obstructive apnea–hypopnea index in nonrapid eye movement sleep with daytime and nighttimesystolic blood pressure (n = 162).

Daytime SBP Nighttime SBP

b SE P value b SE P value

Age, y �1.009 0.572 .080 �0.581 0.591 .327Body height, cm 0.244 0.090 .008 0.331 0.093 <.001Male gender 3.020 1.252 .017 �0.833 1.292 .520BMI z score 2.458 0.588 <.001 1.272 0.608 .038OAHIREM, events/h �0.022 0.078 .781 0.054 0.080 .505OAHINREM, events/h 0.652 0.245 .008 0.517 0.253 .042

Abbreviations: SBP, systolic blood pressure; SE, standard error; y, years; BMI, bodymass index; OAHIREM, obstructive apnea–hypopnea index in rapid eye movementsleep; OAHINREM, OAHI in nonrapid eye movement sleep; h, hour.

1320 C.T. Au et al. / Sleep Medicine 14 (2013) 1317–1322

dren, 90 subjects had REM-related OSA, 18 subjects had NREM-re-lated OSA, and 24 subjects had stage-independent OSA. No signif-icant differences in age, gender, and body size were found betweenthese subtypes (Table 1).

From the PSG results, the REM-related OSA group had a signif-icantly lower arousal index (P = .031) and higher oxygen saturationnadir during NREM sleep (P = .015) than the stage-independentOSA group. However, no significant difference in overall OAHIcould be found (Table 1). For ABP parameters, there were no signif-icant differences or linear trends across different OSA subtypes (Ta-ble 2 and Fig. 1).

3.2. Moderate OSA subgroup

In the moderate OSA subgroup, 15, 8, and 7 subjects were foundto have REM-related, NREM-related, and stage-independent OSA,respectively. No significant differences in age, gender, and bodysize were found between these subtypes. The REM-related OSAgroup had significantly less stage 1 sleep (P = .046) and lower arou-sal index (P = .019) than the stage-independent OSA group (Ta-ble 1). The ABP data revealed that there were significantincreasing linear trends in both daytime (P for trend = .003) andnighttime SBP (P for trend = .022) across different OSA subtypes,namely from the REM-related to NREM-related to the stage-inde-pendent group. Post hoc analyses demonstrated that the REM-re-lated OSA group had significantly lower daytime SBP (P = .014)and a trend of lower nighttime SBP (P = .052) than the stage-inde-pendent OSA group (Table 2). These linear trends across differentOSA subtypes and differences between the REM-related andstage-independent OSA subtypes remained significant, even afterconverting the ABP parameters into z scores (P for trend = .003and P for trend = .015; P = .012 and P = .039, respectively) (Fig. 2).

3.3. Multivariate analysis

Multiple linear regression analysis showed that OAHINREM butnot OAHIREM was significantly associated with both daytime

(P = .008) and nighttime SBP (P = .042) after adjusting for age, gen-der, height, and BMI z score (Table 3). No two-way interaction ef-fect between OAHIREM and BMI z score or between OAHINREM andBMI z score could be found on ABP measures.

4. Discussion

To our knowledge, our study is the first to investigate ABP inchildren with different OSA subtypes. The main finding was thatdaytime and nighttime SBP were lowest in children with REM-re-lated OSA (mean, 112 and 101 mmHg) and highest in childrenwith stage-independent OSA (mean, 122 and 110 mmHg), despitethe groups having similar overall OAHI. On the contrary, no sim-ilar differences were observed in children with mild OSA. In addi-tion, OAHINREM but not OAHIREM was shown to be independentlyassociated with daytime and nighttime SBP in linear regressionanalysis after adjusting for confounders. Each 1-unit increase inOAHINREM was associated with an increase of 0.7 mmHg in

C.T. Au et al. / Sleep Medicine 14 (2013) 1317–1322 1321

daytime SBP and 0.5 mmHg in nighttime SBP. Such effect sizemay be clinically significant, as a previous study demonstratedthat a small increase in BP in children was associated with leftventricular abnormalities [3]. Furthermore, it was suggested thatelevated childhood BP, though not exceeding the threshold ofhypertension, could mediate adulthood hypertension and meta-bolic syndrome [26].

Our results also showed that children with REM-related OSAhad less respiratory event–related arousals and lower proportionof stage 1 sleep than the other two subtypes. This finding isconsistent with a previous study which demonstrated that arou-sal threshold in response to inspiratory resistance load in REMsleep was substantially higher than that in NREM sleep [9]. Thisphysiologic phenomenon may serve as a protective mechanismagainst arousal-related swings in sympathetic activity and henceBP. In addition, it was found that children with REM-relatedOSA tended to also have lower oxygen desaturation index,though the difference was not statistically significant. This find-ing may offer another explanation for the lower BP seen in theREM-related group, as intermittent hypoxia would lead to in-creased sympathetic activity, endothelial dysfunction, and sys-temic inflammation, all of which would cause elevation of BP[27].

Our findings were consistent with results from previous studies.Elevated BP was significantly correlated with OAHINREM but notwith OAHIREM in children aged 5–12 years [2]. One study showedthat morning awakening from stage 2 sleep was associated withgreater heart rate and BP surges compared to awakening fromREM sleep in young adults, indicating that awakening from REMsleep led to a lesser degree of autonomic activation [28]. Anotherstudy demonstrated that acute surges in heart rate and BP imme-diately after obstructive events were more pronounced duringNREM compared to REM sleep in children aged 7–12 years [29].These results and our findings suggest that disturbances in REMrather than NREM sleep maybe less harmful for cardiovascularoutcomes.

Interestingly, significant differences in ABP between differentOSA subtypes could only be found in moderate but not mild OSA.One possible explanation is that the differences in OAHINREM be-tween different OSA subtypes among the mild group were not asgreat as those found in the moderate OSA group. This findingwas particularly true during the nighttime, as the frequency ofABP measurement was only taken once per hour; therefore, thechance of picking up significant postrespiratory BP surges was rel-atively low in the mild group compared to the moderate group. It ispossible that important BP differences in the mild OSA group wereunderestimated.

Because our study comprised a community-based cohort, mostof the cases had relatively mild OSA compared to subjects recruitedfrom hospital attendants. The use of community-based samplesshould make the data more applicable to the general population.However, the small sample size in the moderate OSA group limitedthe generalizability of the results and should be interpreted withcaution. A prospective study with a larger sample size is requiredto confirm our findings. Nevertheless, the effect size observed inthe moderate OSA group was so large that it was unlikely to be arandom effect.

Synchronization between ABP monitoring and PSG was not per-formed at the data collection stage. It would be interesting toexamine if children exhibited differential BP levels in differentsleep stages depending on their OSA subtype. Another limitationof our study was that ABP was intermittently measured insteadof continuously. In children with REM-related OSA, obstructiverespiratory events are concentrated in REM sleep, which accountsfor only approximately 25% of total sleep time in school-aged chil-dren [30,31]. BP in REM sleep might be continuously elevated, due

to the frequent respiratory events. However, because the hourlymeasurements had a higher probability to be taken during NREMsleep, the increased BP in REM sleep would be diluted and wouldresult in a lower overall BP. Nevertheless, our results showed thatchildren with REM-related OSA did not only have a lower night-time BP but also a lower daytime BP, supporting the fact that itwas unlikely to be a biased result.

Overall OAHI is conventionally used as a marker of OSA severityin both children and adults. However, linear associations betweenOAHI and adverse outcome measures were only found in somestudies [2–4] but not the others [5,32]. To determine a subject’sOSA severity by solely relying on OAHI is continuously being ques-tioned. The definitions of REM-related and NREM-related OSA inour study were totally arbitrary, and our design was not poweredto validate such definitions. Nevertheless, our results suggest thatwe may need to pay more attention to the distribution of respira-tory events among REM and NREM sleep, as it may modulate theadverse effect of OSA on BP in children.

Our findings have important implications as the majority ofchildren with OSA had REM-related OSA, which did not seem tolead to significant BP abnormalities. It is possible that we havebeen overstating and even overtreating this problem in children.Our results will need to be replicated, and further studies examin-ing other recognized OSA-related complications such as neurocog-nitive and metabolic abnormalities are needed.

Conflict of interest

The ICMJE Uniform Disclosure Form for Potential Conflicts ofInterest associated with this article can be viewed by clicking onthe following link: http://dx.doi.org/10.1016/j.sleep.2013.09.017.

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