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* Kosair Children’s Hospital Research Institute and Division of Pediatric Sleep Medicine, Department of Pediatrics, University of Louisville, Louisville, Kentucky
Department of Psychological and Brain Sciences, University of Louisville, Louisville, Kentucky
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONREFERENCES |
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Methods. Parents of 5- to 7-year-old snoring children in public schools were surveyed about their child’s sleeping habits. Children with a history of snoring and nonsnoring children were invited for overnight polysomnographic assessment and a battery of neurobehavioral tests. Only children who did not have a history of attention-deficit/hyperactivity disorder and were not considered hyperactive by parental report were tested.
Results. Children with a history of snoring, an obstructive apnea index of <1/hour of total sleep time (hrTST), an apnea/hypopnea index <5/hrTST, and no gas exchange abnormalities were classified as PS (n = 87). Control subjects were defined as children without a history of snoring, an obstructive apnea index <1/hrTST, an apnea/hypopnea index <5/hrTST, and no gas exchange abnormalities (n = 31). Although means for both groups were in the normal range, the PS children were found to perform worse on measures related to attention, social problems, and anxious/depressive symptoms. In addition, although within the normal range, both overall cognitive abilities and certain language and visuospatial functions were significantly lower for the PS group than for the control subjects.
Conclusions. PS seems to be associated with significant neurobehavioral deficits in a subset of children, possibly related to increased susceptibility to sleep fragmentation. Larger studies are urgently required because current guidelines for treatment of snoring in children may require reevaluation.
Key Words: sleep • primary snoring • child • obstructive sleep apnea • neurocognitive function
Abbreviations: OSA, obstructive sleep apnea • PS, primary snoring • AHI, apnea/hypopnea index • hrTST, hour of total sleep time • OAI, obstructive apnea index • ADHD, attention-deficit/hyperactivity disorder • PSG, polysomnographic • SPO2, arterial oxygen saturation • CBCL, Child Behavior Checklist • DAS, Differential Ability Scales • REM, rapid eye movement • NEPSY, Developmental Neuropsychological Assessment • EDS, excessive daytime sleepiness
Habitual snoring during sleep is estimated to affect, on average, 10% to 12% of young children,1–5 with a decrease in frequency after the age of 9 years.6 Snoring, the hallmark symptom of heightened airway resistance during sleep, is the major clinical symptom of obstructive sleep apnea (OSA), a condition characterized by recurrent episodes of gas exchange abnormalities and repeated arousals that affects between 1% and 3% of 2- to 8-year-old children.1,2,7 Children who snore but do not fulfill criteria for OSA are considered to have primary snoring (PS),8 and recently published clinical guidelines "suggest that PS may be a benign condition that does not require therapy."9
Daytime sleepiness, behavioral hyperactivity, learning problems, and restless sleep all are significantly more common in habitual snorers,1,4,10,11 although these studies did not differentiate between children with PS or OSA. Because snoring is so common in children and may resolve over time,12,13 surgical removal of adenotonsillar tissue (tonsillectomy and adenoidectomy), the first line of treatment, is not currently recommended unless OSA is present. In a study encompassing a relatively small number of children, an apnea/hypopnea index (AHI) of >5/hour of total sleep time (hrTST) or an obstructive apnea index (OAI) of >1/hrTST were suggested to represent the cutoff points for normal subjects.14 However, there was no determination that these suggested thresholds were associated with clinically significant disease. Although the rationale to treat any disorder is the prevention of associated morbidities, few studies have critically looked at end-organ injury (eg, neurocognitive function) in children with PS. A preliminary study of a small cohort of children who were referred for evaluation of snoring suggests that reduced neurocognitive performance may be present in children with PS, particularly in the areas of attention, memory, and intelligence.15 Therefore, we undertook this study to assess the neurobehavioral implications of polysomnographically confirmed PS in a large community sample of young children.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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PSG Assessment
Parental informed consent and child assent, in the presence of a parent, were obtained. A standard overnight multichannel PSG evaluation was performed at the Sleep Medicine Center of Kosair Children’s Hospital. Children were studied for up to 12 hours in a quiet, darkened room with an ambient temperature of 24°C in the company of 1 of their parents. All children were in bed with lights out between 9:00 and 9:30 PM and were awakened at 07:00 AM unless they awoke sooner. No drugs were used to induce sleep. The following parameters were measured: chest and abdominal wall movement by respiratory impedance or inductance plethysmography, heart rate by electrocardiogram, and air flow with a sidestream end-tidal capnograph, which also provided breath-by-breath assessment of end-tidal carbon dioxide levels (BCI SC-300, Menomonee Falls, WI) and/or a thermistor. Arterial oxygen saturation (SPO2) was assessed by pulse oximetry (Nellcor N 100; Nellcor Inc, Hayward, CA), with simultaneous recording of the pulse waveform. The bilateral electro-oculogram, 8 channels of electroencephalogram, chin and anterior tibial electromyograms, and analog output from a body position sensor (Braebon Medical Corporation, New York, NY) were also monitored. All measures were digitized using a commercially available polysomnography system (Stellate Systems, Montreal, Canada, or Medcare, Buffalo, NY). Tracheal sound was monitored with a microphone sensor (Sleepmate, Midlothian, VA), and a digital time-synchronized video recording was performed.
Sleep Variables
Sleep architecture was assessed by standard techniques.17 The apnea index was defined as the number of apneas per hrTST. Central, obstructive, and mixed apneic events were counted. Obstructive apnea was defined as the absence of airflow with continued chest wall and abdominal movement for a duration of at least 2 breaths.14,18 Hypopneas were defined as a decrease in nasal flow of 
50% with a corresponding decrease in SPO2 of 4% and/or arousal18 and were scored when the duration was at least 2 breaths. The AHI was defined as the number of apneas and hypopneas per hrTST. The OAI was defined as the number of obstructive apneas per hrTST. The mean oxygen saturation, as measured by pulse oximetry (SPO2), together with SPO2 nadir, was determined. The mean and peak end-tidal carbon dioxide tension was determined. Because criteria for arousal have not yet been developed for children,19 arousals were defined as recommended by the American Sleep Disorders Association Task Force report20 and included respiratory-related (occurring immediately after an apnea, a hypopnea, or a snore), technician-induced, and spontaneous arousals. Arousals were expressed as the total number of arousals per hour of sleep time (arousal index). Periodic leg movements during sleep were scored when there were at least 4 movements of 0.5 to 5 seconds’ duration and between 5 and 90 seconds apart. A periodic leg movements index of 5 per hour of sleep is generally considered as exceeding the normal range in children.21
Neurobehavioral Assessments
A battery of neurobehavioral tests was administered the morning after PSG assessment; the investigator who administered the test was blind to the group assignment of the child. These tests comprised the Conners’ Parent Rating Scale,22 the Child Behavior Checklist (CBCL),23 the Differential Ability Scales (DAS),24 and the Developmental Neuropsychological Assessment (NEPSY).25
Behavioral Variables
The Conners’ Parent Rating Scale-Revised Long Form22 is used to identify behavioral problems in children. This version yields 7 factors—Oppositional, Cognitive Problems/Inattention, Hyperactivity, Anxious-Shy, Perfectionism, Social Problems, and Psychosomatic—and several summary indices, all with a mean T score of 50 and an SD of 10.
The CBCL23 is the most well-developed, empirically derived behavior rating scale available for assessing psychopathology and social competence in children.26 This questionnaire yields 8 factors—Withdrawn, Somatic Complaints, Anxious/Depressed, Social Problems, Thought Problems, Attention Problems, Delinquent Behavior, and Aggressive Behavior—and 3 summary indices, all with a mean T score of 50 and an SD of 10.
Neurocognitive Variables
The DAS24 is a battery of cognitive tests designed to measure reasoning and conceptual ability. Individual DAS subtests are designed to measure separate and distinct areas of cognitive functioning and thus have high specificity. Subtest standard scores are expressed as T scores, with a mean of 50 and an SD of 10. Standard scores for the Verbal Cluster and the Nonverbal Cluster as well as the overall standard score have a mean of 100 and an SD of 15.
The NEPSY25 is designed to assess neurobiological development in 5 functional domains, 4 of which were included in this study: attention/executive functions, language, visuospatial processing, and memory and learning. Standard scores for each subtest and each domain have a mean of 100 and an SD of 15.
Data Analysis
Data are presented as means ± SD unless otherwise indicated. For questionnaire-derived responses, comparisons of the distribution of demographic and risk factors according to group assignment were made with independent t tests (continuous variables) with P values adjusted for unequal variances when appropriate (Levene test for equality of variances) or Fisher exact test (dichotomous outcomes). Although the groups were similar on these demographic and risk factors, analysis of covariance was used for comparisons of PSG and neurobehavioral variables, using age, gender, ethnicity, maternal education, and maternal smoking as covariates. In addition, the effect sizes for each variable were calculated. Correlation analyses, adjusted for multiple correlations, were then performed to evaluate potential relations between sleep measures and neurobehavioral scores. All P values reported are 2-tailed with statistical significance set at <.05 unless otherwise stated.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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For this study, a total of 299 5- to 7-year-old children without parent-reported ADHD or hyperactivity underwent overnight PSG assessment and a battery of neurobehavioral assessments. Children who were found to have an OAI 1, an AHI 5, gas exchange abnormalities (ie, SPO2 nadir 
90% and/or peak end-tidal carbon dioxide levels values 50 mm Hg), or increased arousal index (20/hrTST) on interpretation of their PSG assessment were excluded (n = 181). The remaining children were classified as having PS when their questionnaire reported snoring "almost always," "frequently," or "occasionally" (n = 87) or were included in the control group when their questionnaire reported either no snoring or rare snoring (n = 31). All children in the PS group were observed to snore during the PSG assessment, whereas no child in the control group was observed to snore.
Table 1 shows the demographic data for the 2 groups. No significant differences were found for age, gender, ethnic background, maternal educational achievement, or maternal smoking. However, because these variables may confound the relation between PS and neurobehavioral performance, they were included in the analysis. During PSG assessment (Table 2), PS children exhibited a lower percentage of rapid eye movement (REM) sleep in relation to total sleep time (REM%; P = .002 vs controls) and a higher respiratory arousal index (P = .01 vs controls).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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The spectrum of disease in sleep-disordered breathing ranges from PS through UARS and OSA. The consequences of OSA have been relatively well described and may include behavioral manifestations such as hyperactivity, inattention, and aggression1,27–31; excessive daytime sleepiness (EDS)1,27,28,32; enuresis28; and impaired school performance.16,28,33,34 Surgical removal of enlarged adenotonsillar tissue will improve learning and behavior in children with definitive OSA,16,29,30,35,36 and improvements in hyperactive behavior have been reported in children with PS after surgery.30 However, the level of disease severity associated with neurobehavioral sequelae remains to be defined by appropriate methods. Furthermore, we recently reported that children in the lower 25% of their class at ages 13 to 14 years were more likely to have snored during early childhood and to have required adenoidectomy and/or tonsillectomy for snoring compared with the top 25% of their class.34 These findings suggest that impairments in neurocognitive function associated with snoring in children may not be completely reversible if they occur during a critical period of brain development.
Recently published clinical practice guidelines by the American Academy of Pediatrics suggest that PS may be considered benign9 and that an OAI <1/hrTST should be considered a normal finding.37 However, our current findings suggest that snoring children with an OAI <1/hrTST and an AHI <5/hrTST are at higher risk for impaired neurobehavioral function compared with children without a history of snoring. These findings further strengthen the conclusions of Blunden et al,15 who identified the presence of attention and cognitive deficits in a small group of children who were referred for evaluation of snoring relative to a control group of nonsnorers. Of note, the children who participated in the present study were recruited from the local community, were not being evaluated for sleep disturbances, were not being evaluated or treated for behavioral problems, and therefore were truly representative of the general population.
Neurobehavioral dysfunction in PS children was associated with reduced REM%. The potential impact of reduced REM% on neurobehavioral functioning has not been addressed previously and, although significant, seem to be of small magnitude. Despite a significantly higher respiratory arousal index in the PS group, respiratory sleep fragmentation did not correlate with neurobehavioral function. Sleep fragmentation is commonly observed in adults with OSA, and the resultant EDS markedly affects functions that require concentration and dexterity. However, children with OSA seem to have a reduced propensity for sleep fragmentation and EDS when these measurements are performed using criteria originally developed for adult patients.32,38 Our present findings regarding children who have PS suggest that current techniques used to define arousal are not sensitive enough to detect sleep fragmentation in children19 and/or that neurobehavioral susceptibility to sleep fragmentation is significantly higher in at least some children.
Alternatively, intermittent hypoxia with or without sleep fragmentation could be a determinant of neurocognitive morbidity in snoring children. Although our groups were purposely selected for not having apparent gas exchange abnormalities, it is possible that even mild and infrequent transient oxyhemoglobin desaturations may impose adverse effects, particularly at a critical age for brain development. A unique developmental period of neuronal susceptibility to episodic hypoxia during sleep has recently emerged in a rodent model of sleep-disordered breathing,39 and postnatal ages corresponding to those in which peak prevalence of OSA in children is present were associated with more severe disruption in the acquisition of spatial tasks, as well as with behavioral hyperactivity.40,41 The effects of PS therefore may not become immediately apparent yet may contribute to and have an adverse impact on the acquisition of later skills.34,42
There are several potential limitations of the current study. It is possible that parents of snoring children were more likely to participate if they believed that their child had behavioral problems. However, we attempted to minimize this potential bias by excluding children with reported behavioral problems. Despite such precautionary measures, we still found differences in neurobehavioral functioning between the groups of children. However, the differences in behavioral reports were small and may not be clinically significant. Because esophageal pressure monitoring was not performed, a limitation of the present study consists of the potential misclassification of children with UARS43 in the PS group. However, esophageal pressure monitoring is invasive, often uncomfortable, and frequently not tolerated and as such is not practical for routine use in the clinical setting. Because UARS is characterized by increasing respiratory effort associated with decreases in oronasal airflow and/or arousal,43 it is clear that other methods aiming to improve the detection and classification of respiratory events and arousals in children are critically needed, particularly if such new tools show improved correlation with morbidity. Such methods are now being examined critically and include analysis of spectral electroencephalogram characteristics,19 nasal pressure measurements,44 pulse transit time derivatives,45 and peripheral arterial tonometry.46
A history of snoring in the presence of a "normal" PSG evaluation is associated with lowered neurocognitive function in a subset of 5- to 7-year-old snoring children from a nonreferred community sample. Because the prevalence of snoring in children is relatively high, affecting on average 11% to 12% of all 2- to 8-year-old children,1–5 the potential impact of snoring in the absence of OSA may be greater than previously realized, and larger studies are required to confirm our findings. Thus, the primary reason for polysomnography in snoring children will be to identify sleep-disordered breathing and PS. For the latter group, development of algorithms or novel tests that identify the subgroup of PS children who are susceptible will be required for timely referral and treatment. We suggest that additional research in larger populations of children with PS is urgently required because current guidelines for the treatment of such children may require critical reexamination.
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ACKNOWLEDGMENTS |
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We thank the parents and children for cooperation. We are particularly grateful to Dr Robert J. Rodovsky and Richard Spayd from the Jefferson County Public School System for assistance in this project.
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FOOTNOTES |
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Reprint requests to (D.G.) Kosair Children’s Hospital Research Institute, University of Louisville School of Medicine, 570 S Preston St, Ste 321, Louisville, KY 40202. E-mail: david.gozal{at}0040louisville.edu
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REFERENCES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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