Valerie McLaughlin Crabtree

Sleep Disturbances in Children with Attention Deficit Hyperactivity Disorder

The objective of the study was to compare polysomnographic patterns in two groups of preadolescent children with attention deficit hyperactivity disorder (ADHD) (a sleep clinic referral sample and a community sample) with control children. A prospective and observational study in the sleep clinic and the community was undertaken. Forty-seven ADHD children referred to the sleep clinic (ADHDcl), 53 ADHD children from a community survey (ADHDcom), and 49 control children underwent overnight polysomnography. Significant differences between the groups were observed for rapid-eye-movement (REM) sleep latency and percentage, and periodic limb movement index with associated arousals (PLMa). REM sleep latency was shorter in controls than ADHDcl and ADHDcom (p < 0.01) and REM% was highest in controls and lowest in ADHDcl (p < 0.001). PLMa was higher in ADHDcl than the other groups (p < 0.001), but there were no differences in PLMa between ADHDcom and controls. ADHD children display significant alterations in their sleep patterns, and ADHDcl are more likely to have an elevated PLMa than ADHDcom. In addition, REM sleep is affected by ADHD. We postulate that ADHDcl may represent a subset of children with ADHD at high risk for hyperactivity during sleep.

Periodic limb movement disorder of sleep in children

To characterize periodic limb movement disorder (PLMD) in a cohort of prepubertal children we examined sleep‐related identifiable differences between children with PLMD and attention‐deficit/hyperactivity disorder (ADHD), PLMD alone, and age‐matched controls. Children were selected from a chart review of all children referred to a pediatric sleep medicine center and from a community survey of 5–7‐year‐old‐children. Polysomnography (PSG) and parental report data from all children identified as having periodic limb movement index (PLMI) >5 were reviewed and compared with a cohort of age‐matched controls. A total of 8.4% of children in the clinic‐referred sample, and 11.9% of the children recruited from the community had PLMI >5. Of those, 44.4% were identified as having ADHD. Children with PLMD had significantly lower percentage of rapid eye movement (REM) than control children (P < 0.001). Children in the PLMD/ADHD group had a significantly greater number of arousals associated with PLM (PLMa) than children with PLMD only (P < 0.05). While a relationship between ADHD and PLMD was observed, it was weaker than previous reports (Chervin, R. D. et al. Sleep, 2002; 25: 213; Chervin, R. D. and Archbold, K. H. Sleep, 2001; 24: 313; Picchietti et al. J. Child Neurol., 1999; 13: 588; Picchietti et al. Mov. Disord., 1999; 14: 1000; Picchietti and Walters Sleep, 1999; 22: 297). Children in the PLMD/ADHD group were more likely to have PLMas than were children with PLMD only. We postulate that rather than a direct relationship between ADHD and PLMD, this link may be mediated by the presence of reduced REM sleep and more importantly by the sleep fragmentation associated with PLM‐induced arousals.

APOE ε4 allele, cognitive dysfunction, and obstructive sleep apnea in children

Background: Obstructive sleep apnea (OSA) in children is associated with severity-dependent changes in neurocognitive functioning. However, the severity of OSA accounts for only approximately 40% of the variance in cognitive performance. Thus, genetic determinants of individual susceptibility may also contribute to the morbidity of OSA. Considering the unique susceptibility of apolipoprotein E (ApoE) knock-out mice to an experimental model of OSA, we examined whether the APOE ε4 allele contributes to increased neurocognitive morbidity in pediatric OSA. Methods: Consecutive habitually snoring and nonsnoring 5- to 7-year-old children underwent overnight polysomnography, neurocognitive testing, and a blood draw the next morning. Children were divided into OSA or no OSA, and OSA children were further subdivided into those with ≥2 abnormal cognitive subtest scores and those with normal cognitive scores. The presence of the APOE ε4 allele was determined from blood genomic DNA. Results: Among all children without OSA, APOE ε4 was present in 3 of 199 children, whereas in those with OSA, APOE ε4 was found in 16 of 146 children (p < 0.0002). Furthermore, 16 of 74 children with OSA and cognitive scores <85% had the APOE ε4 allele compared with 3 of 72 children with OSA with abnormal cognitive scores (p < 0.002). Conclusions: APOE ε4 allele is more frequent in children with obstructive sleep apnea and particularly in those who develop neurocognitive deficits, suggesting that the APOE ε4 allele is associated with not only increased odds of having sleep-disordered breathing, but also with an increased risk for neurocognitive dysfunction.

The effect of stimulants on sleep characteristics in children with attention deficit/hyperactivity disorder

OBJECTIVE To investigate the effects of stimulant medications on subjective and objective sleep characteristics of children with attention deficit/hyperactivity disorder (ADHD) compared with control children. METHODS An observational study in the sleep clinic and the community. Children with characteristics of ADHD, both stimulant-medicated (n=53), and non-medicated (n=34), together with control children (n=53) completed a sleep habits questionnaire prior to undergoing full overnight polysomnographic assessment. RESULTS Medicated and non-medicated ADHD subjects were reported to have more sleep disturbances compared with controls. Both groups of ADHD children also demonstrated decreased REM sleep percentage compared with controls (P=0.006 for ADHDmed; P=0.02 for ADHDnon). However, the use of stimulant medication (n=53) was not associated with differences in subjective sleep quality or objective sleep measures, compared to ADHD children not taking any medication (n=34; P=n.s.). CONCLUSIONS Despite the high prevalence of reported sleep disturbance in children with ADHD, stimulant medication appears to have minimal effects on subjective and objective sleep characteristics in children with reported ADHD.

Increased Morning Brain Natriuretic Peptide Levels in Children With Nocturnal Enuresis and Sleep- Disordered Breathing: A Community-Based Study

INTRODUCTION. Habitual snoring and obstructive sleep apnea have been associated with bed-wetting in children, and effective obstructive sleep apnea treatment may improve enuresis. OBJECTIVES. The purpose of this work was to assess whether habitual snoring is associated with increased incidence of enuresis and whether severity of obstructive sleep apnea correlates with enuretic frequency and to evaluate brain natriuretic peptide levels. METHODS. Parental surveys of 5- to 7-year-old children were reviewed for habitual snoring and enuresis. Enuresis was also assessed in a cohort of 378 children with habitual snoring undergoing overnight polysomnographic evaluation, and brain natriuretic peptide plasma levels were determined in 20 children with obstructive sleep apnea, 20 with habitual snoring without obstructive sleep apnea, and 20 nonsnoring children, matched for enuresis. RESULTS. There were 17646 surveys completed (50.6% boys; 18.3% black). A total of 1976 (11.2%) of these children were habitual snoring (53% boys; 25.2% black). A total of 531 habitual snoring children also had enuresis (26.9%), with a predominant representation of boys (472 boys [87.5%]). Among the 15670 nonsnoring children, enuresis was reported in 1821 children (11.6%), of whom 88.8% were boys. However, enuresis among 378 children with habitual snoring did not correlate with the magnitude of sleep respiratory disturbances. Indeed, enuresis was reported in 33 of 149 children with obstructive sleep apnea (obstructive apnea hypopnea index: >2 per hour of total sleep time; 53% boys) as compared with 36 habitual snoring children with enuresis (62% boys) and obstructive apnea hypopnea index <2 per hour of total sleep time. Brain natriuretic peptide levels were elevated among children with enuresis and were marginally increased among children with obstructive sleep apnea. CONCLUSIONS. Habitual snoring is associated with increased prevalence of enuresis, and brain natriuretic peptide levels are increased in enuretic children with further increases with obstructive sleep apnea. However, the prevalence of enuresis is not modified by severity of sleep disturbance. Even mild increases in sleep pressure because of habitual snoring may raise the arousal threshold and promote enuresis, particularly among prone children, that is, those with elevated brain natriuretic peptide levels.

Sleep in children with psychiatric disorders

Although the exact nature of sleep disturbances present in children with psychiatric disorders has not been studied extensively, it is apparent that children with significant emotional and behavioral problems are more likely to experience sleep difficulties. Children with sleep-related issues that are limited to bedtime can be managed effectively with specific cognitive-behavioral interventions. Children with more pervasive anxiety (eg, PTSD or OCD, mood disorders such as major depression or bipolar disorder, or neurodevelopmental disabilities such as autism) require a more exhaustive evaluation, and most of them also need sleep problems to be managed by sleep professionals using combinations of psychotherapeutic and pharmacologic approaches.

Normal Sleep in Children and Adolescents

This article reviews the normal development of sleep in infants, children, and adolescents, with specific focus on both the subjective and objective aspects of sleep. Notably, sleep duration decreases substantially from infancy through adolescence with increased consolidation of sleep to the nighttime period only. Sleep architecture exhibits developmental changes with decreases in slow-wave sleep and increases in stage 2 sleep from childhood through adolescence. Although the development of sleep is a dramatic and relatively rapid process during the first decades of life, changes in sleep continue across the life span.

Clinical and Parental Assessment of Sleep in Children with Attention-Deficit/Hyperactivity Disorder Referred to a Pediatric Sleep Medicine Center

Frequently reported sleep problems in children with attention deficit-hyperactivity disorder (ADHD) referred to a pediatric sleep medicine center were assessed and compared with objective sleep assessments. A retrospective review of 97 children with ADHD (mean age of 8.3 ± 3.0 years) was conducted. Polysomnography in 69 children revealed periodic limb movement disorder (PLMD) in 36% and sleep-disordered breathing in 7%, while actigraphy uncovered substantial variability in sleep schedules of 16 patients. Although parental subjective sleep complaints were verified by objective sleep assessments in a small proportion of cases, PLMD and night-to-night variability in sleep patterns were common.

Infant-Feeding Methods and Childhood Sleep-Disordered Breathing

OBJECTIVE. Childhood sleep-disordered breathing has an adverse impact on cognitive development, behavior, quality of life, and use of health care resources. Early viral infections and other immune-mediated responses may contribute to development of the chronic inflammation of the upper airway and hypertrophic upper airway lymphadenoid tissues underlying childhood sleep-disordered breathing. Breastfeeding provides immunologic protection against such early exposures. Therefore, we sought to explore whether sleep-disordered breathing severity would differ for children who were breastfed as infants. METHODS. The parents or guardians of 196 habitually snoring children (mean ± SD: 6.7 ± 2.9 years old) who were undergoing overnight polysomnography at Kosair Childrens Hospital Sleep Medicine and Apnea Center completed a retrospective survey on the method(s) used to feed the child as an infant. RESULTS. Among habitually snoring children, those who were fed breast milk for at least 2 months had significantly reduced sleep-disordered breathing severity on every measure assessed, including apnea-hypopnea index, oxyhemoglobin desaturation nadir, and respiratory arousal index. Breastfeeding for longer than 5 months did not contribute additional benefits. CONCLUSIONS. Our findings support the notion that breastfeeding may provide long-term protection against the severity of childhood sleep-disordered breathing. Future research should explore mechanism(s) whereby infant-feeding methods may affect the pathophysiology of development of childhood sleep-disordered breathing.

Plasma IGF-1 levels and cognitive dysfunction in children with obstructive sleep apnea

BACKGROUND Pediatric OSA is associated with substantial morbidity in cognitive function. However, for any given OSA severity level, altered cognitive performance may or may not be present. Since IGF-1 is neuroprotective, we hypothesized that higher systemic IGF-1 levels may identify children at lower susceptibility for cognitive morbidity. METHODS Consecutive habitually snoring and non-snoring children ages 5-7 years were recruited from the community, and underwent overnight polysomnography, and neurocognitive testing and a blood draw the next morning. Snoring children were divided into OSA or no OSA, and OSA children were further subdivided into those with >=2 abnormal cognitive subtests and into those with normal cognitive scores. Plasma levels of IGF-1 were also measured using ELISA. RESULTS Among snoring children without OSA, circulating IGF-1 was 910 +/- 110 pg/mL compared with 1070 +/- 240 pg/mL in those with OSA (p<0.01). However, IGF-1 was 540 +/- 70 pg/mL in children with OSA and cognitive deficits, compared to 1370 +/- 170 microg/L in children with OSA and normal cognitive scores (p<0.001). CONCLUSIONS IGF-1 levels are higher in children with OSA, particularly in those who do not manifest neurocognitive deficits, suggesting that the magnitude of the IGF-1 response elicited by OSA may play a significant protective role against the neurocognitive dysfunction associated with OSA.