Amy Storfer-Isser

Variation of C-Reactive Protein Levels in Adolescents Association With Sleep-Disordered Breathing and Sleep Duration

Background—There is increasing evidence that sleep-disordered breathing (SDB) is an independent risk factor for cardiovascular disease (CVD) in adults. C-reactive protein (CRP), a marker of systemic inflammation, is an important predictor of future cardiovascular events. The goal of this study was to quantify the associations of SDB, sleep duration, and CRP in adolescents to better understand the role of SDB in CVD risk. Methods and Results—Adolescents (n=143; age, 13 to 18 years; 36% black; 50% female) with a wide range of SDB severity underwent polysomnography and measurement of high-sensitivity CRP. SDB was quantified with the apnea hypopnea index (AHI) and oxygen desaturation measures. Sleep duration was estimated from 7-day actigraphy. The independent and dose-response associations of SDB with CRP were addressed through linear mixed-effects models. Forty-eight percent were overweight or obese, and 12% had SDB (AHI ≥5). CRP levels varied with increasing body mass index and SDB. After adjustment for body mass index, age, sex, and race, mean CRP levels were 0.50, 0.43, 0.97, and 1.66 mg/L for SDB severity levels of AHI <1, 1 to 4.9, 5 to 14.9, and ≥15, respectively (P=0.0049, AHI ≥15 versus <1). Adjusted mean CRP levels demonstrated a dose response with SDB above a threshold AHI of 5. This association was partially explained by overnight hypoxemia and less so by sleep duration. Conclusions—In adolescents free of known CVD, an AHI ≥5 is associated with increasing levels of CRP, suggesting that pediatric SDB may confer additional CVD risk beyond that of obesity.

Sleep Quality and Elevated Blood Pressure in Adolescents

Background— We assessed whether insufficient sleep is associated with prehypertension in healthy adolescents. Methods and Results— We undertook a cross-sectional analysis of 238 adolescents, all without sleep apnea or severe comorbidities. Participants underwent multiple-day wrist actigraphy at home to provide objective estimates of sleep patterns. In a clinical research facility, overnight polysomnography, anthropometry, and 9 blood pressure measurements over 2 days were made. Exposures were actigraphy-defined low weekday sleep efficiency, an objective measure of sleep quality (low sleep efficiency ≤85%), and short sleep duration (≤6.5 hours). The main outcome was prehypertension (≥90th percentile for age, sex, and height), with systolic and diastolic blood pressures as continuous measures as secondary outcomes. Prehypertension, low sleep efficiency, and short sleep duration occurred in 14%, 26%, and 11% of the sample, respectively. In unadjusted analyses, the odds of prehypertension increased 4.5-fold (95% CI, 2.1 to 9.7) in adolescents with low sleep efficiency and 2.8-fold (95% CI, 1.1 to 7.3) in those with short sleep. In analyses adjusted for sex, body mass index percentile, and socioeconomic status, the odds of prehypertension increased 3.5-fold (95% CI, 1.5. 8.0) for low sleep efficiency and 2.5-fold (95% CI, 0.9 to 6.9) for short sleep. Adjusted analyses showed that adolescents with low sleep efficiency had on average a 4.0±1.2-mm Hg higher systolic blood pressure than other children (P<0.01). Conclusions— Poor sleep quality is associated with prehypertension in healthy adolescents. Associations are not explained by socioeconomic status, obesity, sleep apnea, or known comorbidities, suggesting that inadequate sleep quality is associated with elevated blood pressure.

Triggering of Nocturnal Arrhythmias by Sleep-Disordered Breathing Events

OBJECTIVES This study sought to evaluate respiratory disturbances as potential triggers for arrhythmia in patients with sleep-disordered breathing (SDB). BACKGROUND SDB is associated with an increased risk of atrial fibrillation and nonsustained ventricular tachycardia (NSVT) as well as a predilection for sudden cardiac death during nocturnal sleeping hours. However, prior research has not established whether respiratory disturbances operate as triggers for nocturnal arrhythmias. METHODS Overnight polysomnograms from the Sleep Heart Health Study (n = 2,816) were screened for paroxysmal atrial fibrillation and NSVT. We used the case-crossover design to determine whether apneas and/or hypopneas are temporally associated with episodes of paroxysmal atrial fibrillation or NSVT. For each arrhythmia, 3 periods of sinus rhythm were identified as control intervals. Polysomnograms were examined for the presence of respiratory disturbances, oxygen desaturations, and cortical arousals within a 90-s hazard period preceding each arrhythmia or control period. RESULTS Fifty-seven participants with a wide range of SDB contributed 62 arrhythmias (76% NSVT). The odds of an arrhythmia after a respiratory disturbance were nearly 18 times (odds ratio: 17.5; 95% confidence interval: 5.3 to 58.4) the odds of an arrhythmia occurring after normal breathing. The absolute rate of arrhythmia associated with respiratory disturbances was low (1 excess arrhythmia per 40,000 respiratory disturbances). Neither hypoxia nor electroencephalogram-defined arousals alone increased arrhythmia risk. CONCLUSIONS Although the absolute arrhythmia rate is low, the relative risk of paroxysmal atrial fibrillation and NSVT during sleep is markedly increased shortly after a respiratory disturbance. These results support a direct temporal link between SDB events and the development of these arrhythmias.

Associations of Executive Function with Sleepiness and Sleep Duration in Adolescents

BACKGROUND. Sleep deprivation and sleepiness are associated with poorer school performance, impaired neurobehavioral functioning, and behavioral problems. OBJECTIVE. To determine if adolescents with high levels of sleepiness or short sleep duration have impaired executive functioning. METHODS. Ours was a cross-sectional analysis of data from 236 healthy adolescents in a community-based cohort study. Sleepiness was measured by using a modified version of the Epworth Sleepiness Scale. Participants underwent 5- to 7-day wrist actigraphy at home before overnight polysomnography. Exposure variables were excessive sleepiness (Epworth Sleepiness Scale ≥ 11) and weekday mean sleep duration. The main outcome measures were the global executive composite scale from the Behavior Rating Inventory of Executive Function and the tower test-total achievement score from the Delis-Kaplan Executive Functioning System. RESULTS. Participants (N = 236) were 13.7 ± 0.8 years of age, and 52.1% were boys. Mean weekday sleep duration was 7.70 ± 1.03 hours; 11% slept <6.5 hours on average on weekdays, and 26% reported excessive sleepiness. In unadjusted analyses, sleepy adolescents had poorer executive functioning on the Behavior Rating Inventory of Executive Function global executive composite scale and the Delis-Kaplan Executive Functioning System tower test-total achievement. Analyses adjusted for potential confounders resulted in a modest attenuation of the association with the Behavior Rating Inventory of Executive Function and a larger attenuation for the Delis-Kaplan Executive Functioning System. Caregiver education modified the association between sleepiness and the Behavior Rating Inventory of Executive Function outcomes. Among sleepy adolescents, those with less-educated caregivers had greater impairment on the Behavior Rating Inventory of Executive Function global executive composite scale. Sleep duration was not significantly associated with executive functioning outcomes. CONCLUSIONS. Decrements in selected executive function scales are associated with subjective sleepiness, but not sleep duration, in adolescents. The association between sleepiness and executive functioning is strongest among adolescents with primary caregivers who have lower levels of education, suggesting an increased susceptibility. Pediatricians and public health officials should consider sleepiness as a potentially important contributor to adolescent functioning.

Persistence of Maternal Depressive Symptoms throughout the Early Years of Childhood

AIMS The purpose of these analyses was to examine the persistence and predictors of elevated depressive symptoms in 884 women over their childrens preschool years. RESULTS Depressive symptoms in women with young children are surprisingly consistent throughout their childrens preschool years. Of the 82.6% of women without elevated depressive symptoms at the initial assessment (study child was 11-42 months of age), 82.4% remained without symptoms over two follow-up assessments. Of 17.4% of women with elevated symptoms at baseline, 35.6% had elevated symptoms at one of the two follow-ups, and 27.4% had elevated symptoms at both follow-ups. Persistently elevated depressive symptoms were related to low education, high levels of anxiety, high parenting distress, and low levels of emotional support at baseline. CONCLUSIONS Women who report symptoms of depression when their children are young are highly likely to continue to report such symptoms. These results support the need to screen for elevated depressive symptoms at varying intervals depending on prior screening results and for screening in locations where women most at risk routinely visit, such as well-child clinics. Further, these results point to the need for a system to identify and manage this common treatable condition because these elevated symptoms continue throughout their childrens preschool years for a substantial portion of women.

Prenatal and Neonatal Risk Factors for Sleep Disordered Breathing in School-Aged Children Born Preterm

OBJECTIVES Previously published data from the Cleveland Childrens Sleep and Health Study demonstrated that preterm infants are especially vulnerable both to sleep disordered breathing (SDB) and its neurocognitive sequelae at age 8 to 11 years. In this analysis, we aimed to identify the components of the neonatal medical history associated with childhood SDB among children born prematurely. STUDY DESIGN This analysis focuses on the 383 children in the population-based cohort from the Cleveland Childrens Sleep and Health Study who were born <37 weeks gestational age and who had technically acceptable sleep studies performed at ages 8 to 11 years (92% of all preterm children). Logistic regression was used to evaluate the associations between candidate perinatal and neonatal risk factors and the presence of childhood SDB by sleep study. RESULTS Twenty-eight preterm children (7.3%) met the definition for SDB at age 8 to 11 years. Having a single mother and mild maternal preeclampsia were strongly associated with SDB in unadjusted and race-adjusted models. Unadjusted analyses also identified xanthine use and cardiopulmonary resuscitation or intubation in the delivery room as potential risk-factors for SDB. We did not find a significant link between traditional markers of severity of neonatal illness-such as gestational age, birth weight, intraventricular hemorrhage, bronchopulmonary dysplasia, or duration of ventilation-and childhood SDB at school age. CONCLUSIONS These results represent a first step in identifying prenatal and neonatal characteristics that place preterm infants at higher risk for childhood SDB. The strong association between mild preeclampsia and childhood SDB underscores the importance of research aimed at understanding in utero risk factors for neurorespiratory development.

Sleep disordered breathing is associated with asthma severity in children

OBJECTIVE To examine the relationships among obesity, sleep-disordered breathing (SDB, defined as intermittent nocturnal hypoxia and habitual snoring), and asthma severity in children. We hypothesized that obesity and SDB are associated with severe asthma at a 1- year follow-up. STUDY DESIGN Children aged 4-18 years were recruited sequentially from a specialty asthma clinic and underwent physiological, anthropometric, and biochemical assessment at enrollment. Asthma severity was determined after 1 year of follow-up and guideline-based treatment, using a composite measure of level of controller medication, symptom burden, and health care utilization. Multivariate logistic regression was used to examine adjusted associations of SDB and obesity with asthma severity at 12-month follow-up. RESULTS Among 108 subjects (mean age, 9.1±3.4 years; 45.4% African-American; 67.6% male), obesity and SDB were common, affecting 42.6% and 29.6% of subjects, respectively. After adjusting for obesity, race, and sex, children with SDB had a 3.62-fold increased odds of having severe asthma at follow-up (95% CI, 1.26-10.40). Obesity was not associated with asthma severity. CONCLUSION SDB is a modifiable risk factor for severe asthma after 1 year of specialty asthma care. Further studies are needed to determine whether treating SDB improves asthma morbidity.

Relationship of Sleep Parameters, Child Psychological Functioning, and Parenting Stress to Obesity Status Among Preadolescent Children

Objective: Insufficient sleep may be a significant contributing factor to the increase in pediatric obesity and thus may also contribute to adult obesity and chronic illness. Previous research has been based on large survey studies with consideration of demographics and lifestyle factors (e.g., snacking and TV watching) but not of child psychological/behavioral functioning and parenting factors. Method: This study investigated the relationship of sleep duration to obesity status in 819 children ages 8 to 11 years old, with consideration of demographics, clinical elevations in child psychological/behavioral functioning, and parenting stress. Results: In unadjusted and adjusted analyses, parent-reported child sleep duration was significantly associated with the odds of obesity with an increase of 41% for each 1-hour reduction in sleep duration. In addition to sleep duration, only median neighborhood income was significantly related to obesity status. Indices of child psychological/behavioral functioning and parenting stress were associated with sleep duration but not with obesity, and adjusting for these behavioral and parenting characteristics did not appreciably alter the relationship between sleep duration and obesity status. Exploratory gender-specific analyses found that mean sleep duration was significantly associated with the odds of obesity for boys but not for girls. Conclusions: These results show that the relationship of shorter sleep duration to a greater likelihood of being obese persists even after adjusting for potential confounders of child psychological/behavioral functioning and parenting stress. Gender-specific associations are similar to findings reported in samples that include adolescents.

A randomized trial comparing two approaches to weight loss: differences in weight loss maintenance.

This study compared treatment outcomes for a new weight loss program that emphasized reducing unhealthy relationships with food, body image dissatisfaction, and internalized weight bias (New Perspectives) to a weight loss program that emphasizes environmental modification and habit formation and disruption (Transforming Your Life). Fifty-nine overweight and obese adults (body mass index ≥ 27 kg/m2) were randomly assigned to either a 12-week New Perspectives or Transforming Your Life intervention. Despite equivalent outcomes at the end of treatment, the Transforming Your Life participants were significantly more effective at maintaining their weight loss than New Perspectives participants during the 6-month no-treatment follow-up period.

Relation Between Sleep Duration and BMI Varies by Age and Sex in Youth Age 8–19

The objectives of this study were to (i) compare the strength of associations between sleep duration and body mass index (BMI) in middle childhood, and early and late adolescence; (ii) determine whether sleep duration in middle childhood predicts BMI in early or late adolescence; and (iii) examine the consistency of these associations by sex.