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1.  Markers of Sleep-Disordered Breathing and Prediabetes in US Adults 
Background. Prediabetes is a preclinical stage in the hyperglycemia continuum where subjects are at increased risk of developing diabetes. Several studies reported a positive association between markers of sleep-disordered breathing (SDB) and diabetes. However, few studies investigated the relationship between SDB markers and prediabetes. Methods. We examined 5,685 participants ≥20 years from the National Health and Nutrition Examination Survey (NHANES) 2005–2008. The exposure of interest was SDB markers including sleep duration, snoring, snorting, and daytime sleepiness. The outcome was prediabetes (n = 2058), among subjects free of diabetes. Results. SDB markers were associated with prediabetes. Compared to those without any sleep disturbance, the multivariable odds ratio (OR) (95% confidence interval (CI)) of prediabetes among those with three or more SDB markers was 1.69 (1.28–2.22). In subgroup analyses, the association between SDB markers and prediabetes was stronger among women (OR (95% CI) = 2.09 (1.36–3.23) when compared to men (1.52 (1.00–2.35)) and was present among non-Hispanic whites (2.66 (1.92–3.69)) and Mexican Americans (1.99 (1.13–3.48)), but not among non-Hispanic blacks (1.10 (0.70–1.73)). Conclusion. SDB markers were associated with prediabetes. This association was stronger in women and was present mainly in non-Hispanic whites and Mexican Americans.
doi:10.1155/2012/902324
PMCID: PMC3398596  PMID: 22829819
2.  Sleepiness, Quality of Life, and Sleep Maintenance in REM versus non-REM Sleep-disordered Breathing 
Rationale: The impact of REM-predominant sleep-disordered breathing (SDB) on sleepiness, quality of life (QOL), and sleep maintenance is uncertain.
Objective: To evaluate the association of SDB during REM sleep with daytime sleepiness, health-related QOL, and difficulty maintaining sleep, in comparison to their association with SDB during non-REM sleep in a community-based cohort.
Methods: Cross-sectional analysis of 5,649 Sleep Heart Health Study participants (mean age 62.5 [SD = 10.9], 52.6% women, 22.6% ethnic minorities). SDB during REM and non-REM sleep was quantified using polysomnographically derived apnea-hypopnea index in REM (AHIREM) and non-REM (AHINREM) sleep. Sleepiness, sleep maintenance, and QOL were respectively quantified using the Epworth Sleepiness Scale (ESS), the Sleep Heart Health Study Sleep Habit Questionnaire, and the physical and mental composites scales of the Medical Outcomes Study Short Form (SF)-36.
Measurements and Main Results: AHIREM was not associated with the ESS scores or the physical and mental components scales scores of the SF-36 after adjusting for demographics, body mass index, and AHINREM. AHIREM was not associated with frequent difficulty maintaining sleep or early awakening from sleep. AHINREM was associated with the ESS score (β = 0.25; 95% confidence interval [CI], 0.16 to 0.34) and the physical (β = −0.12; 95% CI, −0.42 to −0.01) and mental (β = −0.20; 95% CI, −0.20 to −0.01) components scores of the SF-36 adjusting for demographics, body mass index, and AHIREM.
Conclusions: In a community-based sample of middle-aged and older adults, REM-predominant SDB is not independently associated with daytime sleepiness, impaired health-related QOL, or self-reported sleep disruption.
doi:10.1164/rccm.200908-1304OC
PMCID: PMC3269234  PMID: 20093641
epidemiology; sleep apnea syndromes; sleep, REM; hypersomnia
3.  Glucose intolerance and gestational diabetes risk in relation to sleep duration and snoring during pregnancy: a pilot study 
BMC Women's Health  2010;10:17.
Background
Insufficient sleep and poor sleep quality, considered endemic in modern society, are associated with obesity, impaired glucose tolerance and diabetes. Little, however, is known about the consequences of insufficient sleep and poor sleep quality during pregnancy on glucose tolerance and gestational diabetes.
Methods
A cohort of 1,290 women was interviewed during early pregnancy. We collected information about sleep duration and snoring during early pregnancy. Results from screening and diagnostic testing for gestational diabetes mellitus (GDM) were abstracted from medical records. Generalized linear models were fitted to derive relative risk (RR) and 95% confidence intervals (95% CIs) of GDM associated with sleep duration and snoring, respectively.
Results
After adjusting for maternal age and race/ethnicity, GDM risk was increased among women sleeping ≤ 4 hours compared with those sleeping 9 hours per night (RR = 5.56; 95% CI 1.31-23.69). The corresponding RR for lean women (<25 kg/m2) was 3.23 (95% CI 0.34-30.41) and 9.83 (95% CI 1.12-86.32) for overweight women (≥ 25 kg/m2). Overall, snoring was associated with a 1.86-fold increased risk of GDM (RR = 1.86; 95% CI 0.88-3.94). The risk of GDM was particularly elevated among overweight women who snored. Compared with lean women who did not snore, those who were overweight and snored had a 6.9-fold increased risk of GDM (95% CI 2.87-16.6).
Conclusions
These preliminary findings suggest associations of short sleep duration and snoring with glucose intolerance and GDM. Though consistent with studies of men and non-pregnant women, larger studies that include objective measures of sleep duration, quality and apnea are needed to obtain more precise estimates of observed associations.
doi:10.1186/1472-6874-10-17
PMCID: PMC2885310  PMID: 20470416
4.  Incidence and Remission of Sleep Disordered Breathing and Related Symptoms in 6-17 Year Old Children-the Tucson Children's Assessment of Sleep Apnea Study (TuCASA) 
The Journal of pediatrics  2010;157(1):57-61.
Objective
To determine the incidence and remission of sleep disordered breathing in adolescent children.
Study design
319 children completed two home polysomnograms approximately 5 years apart. Sleep disordered breathing (SDB) was determined to be present if a child had a respiratory disturbance index ≥ 1 event per hour associated with a ≥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. BMI percentiles were calculated using CDC childhood growth charts 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 (OR=3.93, p=.008, CI= 1.41-10.90). Children with Prevalent SDB were more likely to be boys (OR=2.48, p=.006) and had a greater increase in BMI percentile change (OR 1.01, p=.034). Children with Prevalent SDB also had 3.41 greater odds of developing 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 developed obesity. These risks are similar to those observed in adults.
doi:10.1016/j.jpeds.2010.01.033
PMCID: PMC2886190  PMID: 20304429
5.  Polysomnography in Patients With Obstructive Sleep Apnea 
Executive Summary
Objective
The objective of this health technology policy assessment was to evaluate the clinical utility and cost-effectiveness of sleep studies in Ontario.
Clinical Need: Target Population and Condition
Sleep disorders are common and obstructive sleep apnea (OSA) is the predominant type. Obstructive sleep apnea is the repetitive complete obstruction (apnea) or partial obstruction (hypopnea) of the collapsible part of the upper airway during sleep. The syndrome is associated with excessive daytime sleepiness or chronic fatigue. Several studies have shown that OSA is associated with hypertension, stroke, and other cardiovascular disorders; many researchers believe that these cardiovascular disorders are consequences of OSA. This has generated increasing interest in recent years in sleep studies.
The Technology Being Reviewed
There is no ‘gold standard’ for the diagnosis of OSA, which makes it difficult to calibrate any test for diagnosis. Traditionally, polysomnography (PSG) in an attended setting (sleep laboratory) has been used as a reference standard for the diagnosis of OSA. Polysomnography measures several sleep variables, one of which is the apnea-hypopnea index (AHI) or respiratory disturbance index (RDI). The AHI is defined as the sum of apneas and hypopneas per hour of sleep; apnea is defined as the absence of airflow for ≥ 10 seconds; and hypopnea is defined as reduction in respiratory effort with ≥ 4% oxygen desaturation. The RDI is defined as the sum of apneas, hypopneas, and abnormal respiratory events per hour of sleep. Often the two terms are used interchangeably. The AHI has been widely used to diagnose OSA, although with different cut-off levels, the basis for which are often unclear or arbitrarily determined. Generally, an AHI of more than five events per hour of sleep is considered abnormal and the patient is considered to have a sleep disorder. An abnormal AHI accompanied by excessive daytime sleepiness is the hallmark for OSA diagnosis. For patients diagnosed with OSA, continuous positive airway pressure (CPAP) therapy is the treatment of choice. Polysomnography may also used for titrating CPAP to individual needs.
In January 2005, the College of Physicians and Surgeons of Ontario published the second edition of Independent Health Facilities: Clinical Practice Parameters and Facility Standards: Sleep Medicine, commonly known as “The Sleep Book.” The Sleep Book states that OSA is the most common primary respiratory sleep disorder and a full overnight sleep study is considered the current standard test for individuals in whom OSA is suspected (based on clinical signs and symptoms), particularly if CPAP or surgical therapy is being considered.
Polysomnography in a sleep laboratory is time-consuming and expensive. With the evolution of technology, portable devices have emerged that measure more or less the same sleep variables in sleep laboratories as in the home. Newer CPAP devices also have auto-titration features and can record sleep variables including AHI. These devices, if equally accurate, may reduce the dependency on sleep laboratories for the diagnosis of OSA and the titration of CPAP, and thus may be more cost-effective.
Difficulties arise, however, when trying to assess and compare the diagnostic efficacy of in-home PSG versus in-lab. The AHI measured from portable devices in-home is the sum of apneas and hypopneas per hour of time in bed, rather than of sleep, and the absolute diagnostic efficacy of in-lab PSG is unknown. To compare in-home PSG with in-lab PSG, several researchers have used correlation coefficients or sensitivity and specificity, while others have used Bland-Altman plots or receiver operating characteristics (ROC) curves. All these approaches, however, have potential pitfalls. Correlation coefficients do not measure agreement; sensitivity and specificity are not helpful when the true disease status is unknown; and Bland-Altman plots measure agreement (but are helpful when the range of clinical equivalence is known). Lastly, receiver operating characteristics curves are generated using logistic regression with the true disease status as the dependent variable and test values as the independent variable. Thus, each value of the test is used as a cut-point to measure sensitivity and specificity, which are then plotted on an x-y plane. The cut-point that maximizes both sensitivity and specificity is chosen as the cut-off level to discriminate between disease and no-disease states. In the absence of a gold standard to determine the true disease status, ROC curves are of minimal value.
At the request of the Ontario Health Technology Advisory Committee (OHTAC), MAS has thus reviewed the literature on PSG published over the last two years to examine new developments.
Methods
Review Strategy
There is a large body of literature on sleep studies and several reviews have been conducted. Two large cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study, are the main sources of evidence on sleep literature.
To examine new developments on PSG published in the past two years, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Database of Systematic Reviews and Cochrane CENTRAL, INAHTA, and websites of other health technology assessment agencies were searched. Any study that reported results of in-home or in-lab PSG was included. All articles that reported findings from the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study were also reviewed.
Diffusion of Sleep Laboratories
To estimate the diffusion of sleep laboratories, a list of sleep laboratories licensed under the Independent Health Facility Act was obtained. The annual number of sleep studies per 100,000 individuals in Ontario from 2000 to 2004 was also estimated using administrative databases.
Summary of Findings
Literature Review
A total of 315 articles were identified that were published in the past two years; 227 were excluded after reviewing titles and abstracts. A total of 59 articles were identified that reported findings of the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study.
Prevalence
Based on cross-sectional data from the Wisconsin Sleep Cohort Study of 602 men and women aged 30 to 60 years, it is estimated that the prevalence of sleep-disordered breathing is 9% in women and 24% in men, on the basis of more than five AHI events per hour of sleep. Among the women with sleep disorder breathing, 22.6% had daytime sleepiness and among the men, 15.5% had daytime sleepiness. Based on this, the prevalence of OSA in the middle-aged adult population is estimated to be 2% in women and 4% in men.
Snoring is present in 94% of OSA patients, but not all snorers have OSA. Women report daytime sleepiness less often compared with their male counterparts (of similar age, body mass index [BMI], and AHI). Prevalence of OSA tends to be higher in older age groups compared with younger age groups.
Diagnostic Value of Polysomnography
It is believed that PSG in the sleep laboratory is more accurate than in-home PSG. In the absence of a gold standard, however, claims of accuracy cannot be substantiated. In general, there is poor correlation between PSG variables and clinical variables. A variety of cut-off points of AHI (> 5, > 10, and > 15) are arbitrarily used to diagnose and categorize severity of OSA, though the clinical importance of these cut-off points has not been determined.
Recently, a study of the use of a therapeutic trial of CPAP to diagnose OSA was reported. The authors studied habitual snorers with daytime sleepiness in the absence of other medical or psychiatric disorders. Using PSG as the reference standard, the authors calculated the sensitivity of this test to be 80% and its specificity to be 97%. Further, they concluded that PSG could be avoided in 46% of this population.
Obstructive Sleep Apnea and Obesity
Obstructive sleep apnea is strongly associated with obesity. Obese individuals (BMI >30 kg/m2) are at higher risk for OSA compared with non-obese individuals and up to 75% of OSA patients are obese. It is hypothesized that obese individuals have large deposits of fat in the neck that cause the upper airway to collapse in the supine position during sleep. The observations reported from several studies support the hypothesis that AHIs (or RDIs) are significantly reduced with weight loss in obese individuals.
Obstructive Sleep Apnea and Cardiovascular Diseases
Associations have been shown between OSA and comorbidities such as diabetes mellitus and hypertension, which are known risk factors for myocardial infarction and stroke. Patients with more severe forms of OSA (based on AHI) report poorer quality of life and increased health care utilization compared with patients with milder forms of OSA. From animal models, it is hypothesized that sleep fragmentation results in glucose intolerance and hypertension. There is, however, no evidence from prospective studies in humans to establish a causal link between OSA and hypertension or diabetes mellitus. It is also not clear that the associations between OSA and other diseases are independent of obesity; in most of these studies, patients with higher values of AHI had higher values of BMI compared with patients with lower AHI values.
A recent meta-analysis of bariatric surgery has shown that weight loss in obese individuals (mean BMI = 46.8 kg/m2; range = 32.30–68.80) significantly improved their health profile. Diabetes was resolved in 76.8% of patients, hypertension was resolved in 61.7% of patients, hyperlipidemia improved in 70% of patients, and OSA resolved in 85.7% of patients. This suggests that obesity leads to OSA, diabetes, and hypertension, rather than OSA independently causing diabetes and hypertension.
Health Technology Assessments, Guidelines, and Recommendations
In April 2005, the Centers for Medicare and Medicaid Services (CMS) in the United States published its decision and review regarding in-home and in-lab sleep studies for the diagnosis and treatment of OSA with CPAP. In order to cover CPAP, CMS requires that a diagnosis of OSA be established using PSG in a sleep laboratory. After reviewing the literature, CMS concluded that the evidence was not adequate to determine that unattended portable sleep study was reasonable and necessary in the diagnosis of OSA.
In May 2005, the Canadian Coordinating Office of Health Technology Assessment (CCOHTA) published a review of guidelines for referral of patients to sleep laboratories. The review included 37 guidelines and associated reviews that covered 18 applications of sleep laboratory studies. The CCOHTA reported that the level of evidence for many applications was of limited quality, that some cited studies were not relevant to the recommendations made, that many recommendations reflect consensus positions only, and that there was a need for more good quality studies of many sleep laboratory applications.
Diffusion
As of the time of writing, there are 97 licensed sleep laboratories in Ontario. In 2000, the number of sleep studies performed in Ontario was 376/100,000 people. There was a steady rise in sleep studies in the following years such that in 2004, 769 sleep studies per 100,000 people were performed, for a total of 96,134 sleep studies. Based on prevalence estimates of the Wisconsin Sleep Cohort Study, it was estimated that 927,105 people aged 30 to 60 years have sleep-disordered breathing. Thus, there may be a 10-fold rise in the rate of sleep tests in the next few years.
Economic Analysis
In 2004, approximately 96,000 sleep studies were conducted in Ontario at a total cost of ~$47 million (Cdn). Since obesity is associated with sleep disordered breathing, MAS compared the costs of sleep studies to the cost of bariatric surgery. The cost of bariatric surgery is $17,350 per patient. In 2004, Ontario spent $4.7 million per year for 270 patients to undergo bariatric surgery in the province, and $8.2 million for 225 patients to seek out-of-country treatment. Using a Markov model, it was concluded that shifting costs from sleep studies to bariatric surgery would benefit more patients with OSA and may also prevent health consequences related to diabetes, hypertension, and hyperlipidemia. It is estimated that the annual cost of treating comorbid conditions in morbidly obese patients often exceeds $10,000 per patient. Thus, the downstream cost savings could be substantial.
Considerations for Policy Development
Weight loss is associated with a decrease in OSA severity. Treating and preventing obesity would also substantially reduce the economic burden associated with diabetes, hypertension, hyperlipidemia, and OSA. Promotion of healthy weights may be achieved by a multisectorial approach as recommended by the Chief Medical Officer of Health for Ontario. Bariatric surgery has the potential to help morbidly obese individuals (BMI > 35 kg/m2 with an accompanying comorbid condition, or BMI > 40 kg/m2) lose weight. In January 2005, MAS completed an assessment of bariatric surgery, based on which OHTAC recommended an improvement in access to these surgeries for morbidly obese patients in Ontario.
Habitual snorers with excessive daytime sleepiness have a high pretest probability of having OSA. These patients could be offered a therapeutic trial of CPAP to diagnose OSA, rather than a PSG. A majority of these patients are also obese and may benefit from weight loss. Individualized weight loss programs should, therefore, be offered and patients who are morbidly obese should be offered bariatric surgery.
That said, and in view of the still evolving understanding of the causes, consequences and optimal treatment of OSA, further research is warranted to identify which patients should be screened for OSA.
PMCID: PMC3379160  PMID: 23074483
6.  A postal survey of maternal sleep in late pregnancy 
Background
Sleep disturbances in late pregnancy are common. This study aimed to survey sleep problems in third trimester pregnant women and to compare sleep in the pre-pregnancy period with the third trimester.
Methods
Third-trimester women (n=650) were sent a postal survey containing questions relating to sleep experience, including perceived sleep quality, sleep difficulties, night waking, sleep environment, snoring, daytime tiredness and daytime napping. Time periods reported on were before pregnancy and in the last week.
Results
Respondents numbered 244 (38%). Before pregnancy, the mean reported duration of night-time sleep was 8.1 (SD 1.1) hours; in the last week this had decreased to 7.5 (SD 1.8) hours (p<.0001). Only 29% rated their sleep quality in the last week as very good or fairly good, compared with 82% rating their sleep this way before the pregnancy. The main reasons for sleeping difficulties were discomfort (67%) and pain (36%). Snoring increased significantly over the course of the pregnancy, with 37% reporting snoring often or every night in the last week. Those with a pre-pregnancy body mass index of greater than 25 were significantly more likely to snore (p=.01). Only 4% of women had an abnormal Epworth Sleepiness Scale score (i.e. >10) prior to pregnancy, whereas in the last week 33% scored in the abnormal range. Likewise, 5% had regularly napped during the daytime before pregnancy, compared with 41% in the last week.
Conclusions
Sleep problems are common in women in late pregnancy, and increase markedly compared with before pregnancy.
doi:10.1186/1471-2393-12-144
PMCID: PMC3541269  PMID: 23228137
Pregnancy; Sleep disturbances; Sleep quality; Snoring; Daytime sleepiness
7.  Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study 
PLoS Medicine  2009;6(8):e1000132.
In a cohort of 6,441 volunteers followed over an average of 8.2 years, Naresh Punjabi and colleagues find sleep-disordered breathing to be independently associated with mortality and identify predictive characteristics.
Background
Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older.
Methods and Findings
We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: ≥30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80–1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality.
Conclusions
Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 1 in 10 women and 1 in 4 men have a chronic condition called sleep-disordered breathing although most are unaware of their problem. Sleep-disordered breathing, which is commonest in middle-aged and elderly people, is characterized by numerous, brief (10 second or so) interruptions of breathing during sleep. These interruptions, which usually occur when relaxation of the upper airway muscles decreases airflow, lower the level of oxygen in the blood and, as a result, affected individuals are frequently aroused from deep sleep as they struggle to breathe. Symptoms of sleep-disordered breathing include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. Affected people can also use special devices to prevent them sleeping on their backs, but for severe sleep-disordered breathing, doctors often recommend continuous positive airway pressure (CPAP), a machine that pressurizes the upper airway through a face mask to keep it open.
Why Was This Study Done?
Sleep-disordered breathing is a serious condition. It is associated with several adverse health conditions including coronary artery disease (narrowing of the blood vessels that supply the heart, a condition that can cause a heart attack) and daytime sleepiness that can affect an individual's driving ability. In addition, several clinic- and community-based studies suggest that sleep-disordered sleeping may increase a person's risk of dying. However, because these studies have been small and have often failed to allow for other conditions and characteristics that affect an individual's risk of dying (“confounding factors”), they provide inconsistent or incomplete information about the potential association between sleep-disordered breathing and the risk of death. In this prospective cohort study (part of the Sleep Heart Health Study, which is researching the effects of sleep-disordered breathing on cardiovascular health), the researchers examine whether sleep-disordered breathing is associated with all-cause mortality (death from any cause) in a large community sample of adults. A prospective cohort study is one in which a group of participants is enrolled and then followed forward in time (in this case for several years) to see what happens to them.
What Did the Researchers Do and Find?
At enrollment, the study participants—more than 6,000 people aged 40 years or older, none of whom were being treated for sleep-disordered breathing—had a health examination. Their night-time breathing, sleep patterns, and blood oxygen levels were also assessed and these data used to calculate each participant's apnea-hypopnea index (AHI)—the number of apneas and hypopneas per hour. During the study follow-up period, 1,047 participants died. Compared to participants without sleep-disordered sleeping, participants with severe sleep-disordered breathing (an AHI of ≥30) were about one and a half times as likely to die from any cause after adjustment for potential confounding factors. People with milder sleep-disordered breathing did not have a statistically significant increased risk of dying. After dividing the participants into subgroups according to their age and sex, men aged 40–70 years with severe sleep-disordered breathing had a statistically increased risk of dying from any cause (twice the risk of men of a similar age without sleep-disordered breathing). Finally, death from coronary artery disease was also associated with sleep-disordered breathing in men but not in women.
What Do These Findings Mean?
These findings indicate that sleep-disordered breathing is associated with an increased risk of all-cause mortality, particularly in men aged 40–70 years, even after allowing for known confounding factors. They also suggest that the increased risk of death is specifically associated with coronary artery disease although further studies are needed to confirm this finding because it was based on the analysis of a small subgroup of study participants. Although this study is much larger than previous investigations into the association between sleep-disordered breathing and all-cause mortality, it has several limitations including its reliance on a single night's measurements for the diagnosis of sleep-disordered breathing. Nevertheless, these findings suggest that clinical trials should now be started to assess whether treatment can reduce the increased risk of death that seems to be associated with this common disorder.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000132.
The US National Heart Lung and Blood Institute has information (including a video) about sleep-disordered breathing (sleep apnea) (in English and Spanish)
The UK National Heath Service also provides information for patients about sleep apnea
MedlinePlus provides links to further information and advice about sleep-disordered breathing (in English and Spanish)
More information on the Sleep Heart Health Study is available
doi:10.1371/journal.pmed.1000132
PMCID: PMC2722083  PMID: 19688045
8.  Habitual snoring and depressive symptoms during pregnancy 
Background
Depression is frequently observed in patients with untreated sleep-disordered breathing (SDB) in the general population. Pregnant women are particularly vulnerable since pregnancy increases the risk of both SDB and depressive symptoms. However, no study has investigated whether SDB symptoms prior to or in early pregnancy are associated with such mood problems.
Methods
A retrospective chart review of pregnant women. Women were included if they attended prenatal clinics between June 2007 and July 2010, were ≥18 years old, pregnant with a single fetus, and had been screened for habitual snoring as well as depressive symptoms using the Edinburgh Postnatal Depression Scales (EPDS).
Results
In total, 362 women were included and 32.3% reported habitual snoring. Twenty-nine percent of women had an EPDS score ≥10. Significantly more snoring women, compared to non-snorers, had an EPDS score ≥10 (42.7% vs. 22.9%, p < 0.001) despite the mean EPDS values not reaching statistical significance (6.1 ± 4.9 vs. 5.4 ± 5.0, p = 0.2). In a logistic regression model controlling for parity, the presence of pre-pregnancy obesity, presence of a partner, sleep quality, African American race, maternal educational level, pre-eclampsia, and diabetes, snoring was independently associated with a prenatal EPDS score ≥10 (O.R. 2.0, 95%CI 1.13-3.46; p = 0.023).
Conclusion
Maternal snoring may be a risk factor for prenatal depressive symptoms. Further investigation of the temporal relationship between maternal snoring and depressive symptoms is warranted.
doi:10.1186/1471-2393-13-113
PMCID: PMC3660222  PMID: 23679132
Pregnancy; Snoring; Sleep quality; Depressive symptoms; EPDS
9.  Elevated Serum C-Reactive Protein and Markers of Sleep Disordered Breathing 
Background. Previous studies indicated sleep-disordered breathing (SDB) is associated with cardiovascular disease (CVD). Systemic inflammation is recognized as a risk factor for CVD. Studies examining SDB and inflammation are limited. Methods. We studied sleep duration, snoring, snorting, and daytime sleepiness, and an additive SDB score. The main outcome was a C-reactive protein (CRP) of >1 mg/dL. Results. Snoring, snorting, daytime sleepiness, and sleeping >7 or <7 hours, and the additive score were significantly associated with high CRP. The additive score was not associated in men but moderately associated in women in a multivariable model adjusting for age, gender, race/ethnicity, education, smoking, hypertension, alcohol intake, physical activity, body mass index, depression, diabetes, hypertension, and total cholesterol (P-interaction  = 0.42). For race/ethnicity, the association was strongest in Mexican Americans/others, modest in Non-Hispanic whites, and absent in Non-Hispanic blacks (P-interaction  = 0.07). Conclusions. The association between SDB and high CRP was present mainly in women and Mexican Americans, implying SDB has a residual, independent association with inflammation after controlling for lifestyle and metabolic risk factors like BMI, physical activity, depression, diabetes, and cholesterol.
doi:10.1155/2012/914593
PMCID: PMC3303542  PMID: 22518315
10.  Clinical Screening of School Children for Polysomnography to Detect Sleep-Disordered Breathing—the Tucson Children’s Assessment of Sleep Apnea Study (TuCASA) 
Study Objectives
This report describes the associations, specificities, sensitivities, and positive likelihood ratios of clinical symptoms to a finding of sleep-disordered breathing (SDB) on polysomnography in children.
Methods
Four hundred eighty unattended home polysomnograms were completed in a community-based cohort of children 6 to 11 years of age (50% boys, 42.3% Hispanic, and 52.9% between the ages of 6 and 8 years). SDB was present if the child had a respiratory disturbance index of ≥ 1 event per hour.
Measurements and Results
Boys were twice as likely as girls to have SDB (p<.01); however, witnessed apnea, ethnicity, age, obesity, and air-way size (based on clinical evaluation) were not significantly different between those with SDB and without SDB. The sensitivity of any individual or combined clinical symptoms was poor, with male sex (60%) and snoring (29.5%) having the greatest proportion of SDB children. However, high specificities for snoring (89.5%), excessive daytime sleepiness (86.3%), and learning problems (95.9%) were noted. Combinations of symptoms such as snoring+male sex (95.1%), snoring+excessive daytime sleepiness (97.0%), and snoring+learning problems (98.9%) had specificities approaching 1. Positive likelihood ratios for snoring (2.8), learning (2.8), and symptoms combined with snoring such as snoring+male sex(3.9), snoring+learning problems (4.0), and snoring+excessive daytime sleepiness (2.9) were observed.
Conclusions
Snoring, excessive daytime sleepiness, and learning problems are each highly specific, but not sensitive, for SDB in 6- to 11-year old children. However, specificities and positive likelihood ratios for the combination of some of these symptoms is sufficiently high to suggest that some children may not require a polysomnogram for the diagnosis of SDB.
PMCID: PMC1307497  PMID: 16429591
Sleep; children; sleep-disordered breathing; sleep apnea; respiratory disturbance index
11.  Primary Prevention of Gestational Diabetes Mellitus and Large-for-Gestational-Age Newborns by Lifestyle Counseling: A Cluster-Randomized Controlled Trial 
PLoS Medicine  2011;8(5):e1001036.
In a cluster-randomized trial, Riitta Luoto and colleagues find that counseling on diet and activity can reduce the birthweight of babies born to women at risk of developing gestational diabetes mellitus (GDM), but fail to find an effect on GDM.
Background
Our objective was to examine whether gestational diabetes mellitus (GDM) or newborns' high birthweight can be prevented by lifestyle counseling in pregnant women at high risk of GDM.
Method and Findings
We conducted a cluster-randomized trial, the NELLI study, in 14 municipalities in Finland, where 2,271 women were screened by oral glucose tolerance test (OGTT) at 8–12 wk gestation. Euglycemic (n = 399) women with at least one GDM risk factor (body mass index [BMI] ≥25 kg/m2, glucose intolerance or newborn's macrosomia (≥4,500 g) in any earlier pregnancy, family history of diabetes, age ≥40 y) were included. The intervention included individual intensified counseling on physical activity and diet and weight gain at five antenatal visits. Primary outcomes were incidence of GDM as assessed by OGTT (maternal outcome) and newborns' birthweight adjusted for gestational age (neonatal outcome). Secondary outcomes were maternal weight gain and the need for insulin treatment during pregnancy. Adherence to the intervention was evaluated on the basis of changes in physical activity (weekly metabolic equivalent task (MET) minutes) and diet (intake of total fat, saturated and polyunsaturated fatty acids, saccharose, and fiber). Multilevel analyses took into account cluster, maternity clinic, and nurse level influences in addition to age, education, parity, and prepregnancy BMI. 15.8% (34/216) of women in the intervention group and 12.4% (22/179) in the usual care group developed GDM (absolute effect size 1.36, 95% confidence interval [CI] 0.71–2.62, p = 0.36). Neonatal birthweight was lower in the intervention than in the usual care group (absolute effect size −133 g, 95% CI −231 to −35, p = 0.008) as was proportion of large-for-gestational-age (LGA) newborns (26/216, 12.1% versus 34/179, 19.7%, p = 0.042). Women in the intervention group increased their intake of dietary fiber (adjusted coefficient 1.83, 95% CI 0.30–3.25, p = 0.023) and polyunsaturated fatty acids (adjusted coefficient 0.37, 95% CI 0.16–0.57, p<0.001), decreased their intake of saturated fatty acids (adjusted coefficient −0.63, 95% CI −1.12 to −0.15, p = 0.01) and intake of saccharose (adjusted coefficient −0.83, 95% CI −1.55 to −0.11, p  =  0.023), and had a tendency to a smaller decrease in MET minutes/week for at least moderate intensity activity (adjusted coefficient 91, 95% CI −37 to 219, p = 0.17) than women in the usual care group. In subgroup analysis, adherent women in the intervention group (n = 55/229) had decreased risk of GDM (27.3% versus 33.0%, p = 0.43) and LGA newborns (7.3% versus 19.5%, p = 0.03) compared to women in the usual care group.
Conclusions
The intervention was effective in controlling birthweight of the newborns, but failed to have an effect on maternal GDM.
Trial registration
Current Controlled Trials ISRCTN33885819
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Gestational diabetes mellitus (GDM) is diabetes that is first diagnosed during pregnancy. Like other types of diabetes, it is characterized by high levels of sugar (glucose) in the blood. Blood-sugar levels are normally controlled by insulin, a hormone that the pancreas releases when blood-sugar levels rise after meals. Hormonal changes during pregnancy and the baby's growth demands increase a pregnant woman's insulin needs and, if her pancreas cannot make enough insulin, GDM develops. Risk factors for GDM, which occurs in 2%–14% of pregnant women, include a high body-mass index (a measure of body fat), excessive weight gain or low physical activity during pregnancy, high dietary intake of polyunsaturated fats, glucose intolerance (an indicator of diabetes) or the birth of a large baby in a previous pregnancy, and a family history of diabetes. GDM is associated with an increased rate of cesarean sections, induced deliveries, birth complications, and large-for-gestational-age (LGA) babies (gestation is the time during which the baby develops within the mother). GDM, which can often be controlled by diet and exercise, usually disappears after pregnancy but increases a woman's subsequent risk of developing diabetes.
Why Was This Study Done?
Although lifestyle changes can be used to control GDM, it is not known whether similar changes can prevent GDM developing (“primary prevention”). In this cluster-randomized controlled trial, the researchers investigate whether individual intensified counseling on physical activity, diet, and weight gain integrated into routine maternity care visits can prevent the development of GDM and the occurrence of LGA babies among newborns. In a cluster-randomized controlled trial, groups of patients rather than individual patients are randomly assigned to receive alternative interventions, and the outcomes in different “clusters” are compared. In this trial, each cluster is a municipality in the Pirkanmaa region of Finland.
What Did the Researchers Do and Find?
The researchers enrolled 399 women, each of whom had a normal blood glucose level at 8–12 weeks gestation but at least one risk factor for GDM. Women in the intervention municipalities received intensified counseling on physical activity at 8–12 weeks' gestation, dietary counseling at 16–18 weeks' gestation, and further physical activity and dietary counseling at each subsequent antenatal visits. Women in the control municipalities received some dietary but little physical activity counseling as part of their usual care. 23.3% and 20.2% of women in the intervention and usual care groups, respectively, developed GDM, a nonstatistically significant difference (that is, a difference that could have occurred by chance). However, the average birthweight and the proportion of LGA babies were both significantly lower in the intervention group than in the usual care group. Food frequency questionnaires completed by the women indicated that, on average, those in the intervention group increased their intake of dietary fiber and polyunsaturated fatty acids and decreased their intake of saturated fatty acids and sucrose as instructed during counseling, The amount of moderate physical activity also tended to decrease less as pregnancy proceeded in the intervention group than in usual care group. Finally, compared to the usual care group, significantly fewer of the 24% of women in the intervention group who actually met dietary and physical activity targets (“adherent” women) developed GDM.
What Do These Findings Mean?
These findings indicate that intensified counseling on diet and physical activity is effective in controlling the birthweight of babies born to women at risk of developing GDM and encourages at least some of them to alter their lifestyle. However, the findings fail to show that the intervention reduces the risk of GDM because of the limited power of the study. The power of a study—the probability that it will achieve a statistically significant result—depends on the study's size and on the likely effect size of the intervention. Before starting this study, the researchers calculated that they would need 420 participants to see a statistically significant difference between the groups if their intervention reduced GDM incidence by 40%. This estimated effect size was probably optimistic and therefore the study lacked power. Nevertheless, the analyses performed among adherent women suggest that lifestyle changes might be a way to prevent GDM and so larger studies should now be undertaken to test this potential primary prevention intervention.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001036.
The US National Institute of Diabetes and Digestive and Kidney Diseases provides information for patients on diabetes and on gestational diabetes (in English and Spanish)
The UK National Health Service Choices website also provides information for patients on diabetes and on gestational diabetes, including links to other useful resources
The MedlinePlus Encyclopedia has pages on diabetes and on gestational diabetes; MedlinePlus provides links to additional resources on diabetes and on gestational diabetes (in English and Spanish)
More information on this trial of primary prevention of GDM is available
doi:10.1371/journal.pmed.1001036
PMCID: PMC3096610  PMID: 21610860
12.  Objectively-measured sleep duration and hyperglycemia in pregnancy 
Sleep medicine  2013;15(1):51-55.
Objective
Our primary purpose was to assess the impact of objectively-measured nighttime sleep duration on gestational glucose tolerance. We additionally examined associations of objectively-measured daytime sleep duration and nap frequency on maternal glycemic control.
Methods
63 urban, low-income, pregnant women wore wrist actigraphs for an average of 6 full days in mid-pregnancy prior to screening for hyperglycemia using the 1-hour oral glucose tolerance test (OGTT). Correlations of nighttime and daytime sleep durations with 1-hour OGTT values were analyzed. Multivariable logistic regression was used to evaluate independent associations between sleep parameters and hyperglycemia, defined as 1-hour OGTT values ≥ 130 mg/dL.
Results
Mean nighttime sleep duration was 6.9 ± 0.9 hours which was inversely correlated with 1-hour OGTT values (r = −0.28, p = 0.03). Shorter nighttime sleep was associated with hyperglycemia, even after controlling for age and body mass index (adjusted OR: 0.2; 95% CI: 0.1, 0.8). There were no associations of daytime sleep duration and nap frequency with 1-hour OGTT values or hyperglycemia.
Conclusions
Using objective measures of maternal sleep time, we found that women with shorter nighttime sleep durations had an increased risk of gestational hyperglycemia. Larger prospective studies are needed to confirm our negative daytime sleep findings.
doi:10.1016/j.sleep.2013.07.018
PMCID: PMC3947268  PMID: 24239498
Sleep duration; Actigraphy; Pregnancy; Hyperglycemia; Gestational diabetes
13.  Sleep-Disordered Breathing and Gestational Diabetes Mellitus 
Diabetes Care  2013;36(10):3353-3360.
OBJECTIVE
Recently, sleep-disordered breathing (SDB) has been reported to be associated with the development of gestational diabetes mellitus (GDM). Accordingly, as this is emergent area of research that has significant clinical relevance, the objective of this meta-analysis is to examine the relationship between SDB with GDM.
RESEARCH DESIGN AND METHODS
We searched several electronic databases for all of the studies published before January 2013 and reviewed references of published articles. Meta-analytic procedures were used to estimate the unadjusted and BMI-adjusted odds ratios (ORs) using a random effects model. Significant values, weighted effect sizes, and 95% CIs were calculated, and tests of homogeneity of variance were performed.
RESULTS
Results from nine independent studies with a total of 9,795 pregnant women showed that SDB was significantly associated with an increased risk of GDM. Women with SDB had a more than threefold increased risk of GDM, with a pooled BMI-adjusted OR 3.06 (95% CI 1.89–4.96).
CONCLUSIONS
These findings demonstrate a significant association between SDB and GDM that is evident even after considered confounding by obesity. This meta-analysis indicates a need to evaluate the role of early recognition and treatment of SDB early during pregnancy.
doi:10.2337/dc13-0778
PMCID: PMC3781575  PMID: 24065843
14.  Consequences of Gestational Diabetes in an Urban Hospital in Viet Nam: A Prospective Cohort Study 
PLoS Medicine  2012;9(7):e1001272.
Jane Hirst and colleagues determined the prevalence and outcome of gestational diabetes mellitus in urban Vietnam and found that choice of criteria greatly affected prevalence, and has implications for the ability of the health system to cope with the number of cases.
Background
Gestational diabetes mellitus (GDM) is increasing and is a risk for type 2 diabetes. Evidence supporting screening comes mostly from high-income countries. We aimed to determine prevalence and outcomes in urban Viet Nam. We compared the proposed International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criterion, requiring one positive value on the 75-g glucose tolerance test, to the 2010 American Diabetes Association (ADA) criterion, requiring two positive values.
Methods and Findings
We conducted a prospective cohort study in Ho Chi Minh City, Viet Nam. Study participants were 2,772 women undergoing routine prenatal care who underwent a 75-g glucose tolerance test and interview around 28 (range 24–32) wk. GDM diagnosed by the ADA criterion was treated by local protocol. Women with GDM by the IADPSG criterion but not the ADA criterion were termed “borderline” and received standard care. 2,702 women (97.5% of cohort) were followed until discharge after delivery. GDM was diagnosed in 164 participants (6.1%) by the ADA criterion, 550 (20.3%) by the IADPSG criterion. Mean body mass index was 20.45 kg/m2 in women with out GDM, 21.10 in women with borderline GDM, and 21.81 in women with GDM, p<0.001. Women with GDM and borderline GDM were more likely to deliver preterm, with adjusted odds ratios (aORs) of 1.49 (95% CI 1.16–1.91) and 1.52 (1.03–2.24), respectively. They were more likely to have clinical neonatal hypoglycaemia, aORs of 4.94 (3.41–7.14) and 3.34 (1.41–7.89), respectively. For large for gestational age, the aORs were 1.16 (0.93–1.45) and 1.31 (0.96–1.79), respectively. There was no significant difference in large for gestational age, death, severe birth trauma, or maternal morbidity between the groups. Women with GDM underwent more labour inductions, aOR 1.51 (1.08–2.11).
Conclusions
Choice of criterion greatly affects GDM prevalence in Viet Nam. Women with GDM by the IADPSG criterion were at risk of preterm delivery and neonatal hypoglycaemia, although this criterion resulted in 20% of pregnant women being positive for GDM. The ability to cope with such a large number of cases and prevent associated adverse outcomes needs to be demonstrated before recommending widespread screening.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Gestational diabetes mellitus (GDM) is diabetes that is first diagnosed during pregnancy. Like other types of diabetes, it is characterized by high levels of sugar (glucose) in the blood. Blood-sugar levels are usually controlled by insulin, which is made by the pancreas. Hormonal changes during pregnancy and the baby's growth demands increase a pregnant woman's insulin needs, and if her pancreas cannot make enough insulin, GDM develops, usually in mid-pregnancy. Risk factors for GDM include a high body mass index (a measure of body fat), excessive weight gain or lack of physical activity during pregnancy, and glucose intolerance (an indicator of diabetes that is measured using the “oral glucose tolerance test”). GDM increases the risk of premature delivery, induced delivery, and having a large-for-gestational-age baby (gestation is the time during which the baby develops within the mother). It also increases the baby's risk of having low blood sugar (neonatal hypoglycemia). GDM, which can often be controlled by exercise and diet, usually disappears after pregnancy but increases the risk of diabetes developing later in both mother and baby.
Why Was This Study Done?
The prevalence (occurrence) of diabetes is increasing rapidly, particularly in low/middleincome countries as they become more affluent. Because GDM increases the subsequent risk of diabetes, some experts believe that screening for GDM should be included in prenatal care as part of diabetes preventative strategies. However, most of the evidence supporting GDM screening comes from high-income countries, so in this prospective cohort study (a study that analyses associations between the baseline characteristics of a group of patients and outcomes), the researchers investigate the prevalence of GDM (diagnosed using the oral glucose tolerance test) and the consequences of GDM among women attending an urban hospital in Viet Nam, a low/middle-income country. An oral glucose tolerance test measures a patient's blood-sugar level after an overnight fast, and one and two hours after consuming a sugary drink. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) and the American Diabetes Association (ADA) guidelines state, respectively, that one and two of these blood-sugar measurements must be abnormally high for a diagnosis of GDM. In this study, the researchers use both guidelines to diagnose GDM.
What Did the Researchers Do and Find?
Nearly 3,000 women who attended the hospital for routine prenatal care had a glucose tolerance test at around 28 weeks' gestation and were followed until discharge after delivery. Women who had GDM diagnosed by the ADA criterion were referred for dietary advice and glucose monitoring. Those diagnosed by the IADPSG criterion only were described as having “borderline” GDM and received standard prenatal care. GDM was diagnosed in 6.1% and 20.3% of the women using the ADA and IADPSG criteria, respectively. After allowing for other factors that might have affected outcomes, compared to women without GDM, women with GDM or borderline GDM were more likely to deliver prematurely, and their babies were more likely to have neonatal hypoglycemia. Also, women with GDM (but not borderline GDM) were more likely to have their labor induced than women without GDM.
What Do These Findings Mean?
These findings show that the criterion used to diagnose GDM markedly affected the prevalence of GDM among pregnant women attending this Vietnamese hospital—the use of the IADPSG criterion more than tripled the prevalence of GDM and meant that a fifth of the study participants were diagnosed as having GDM. Importantly, the findings also show that GDM diagnosed using the IADPSG criterion was associated with an increased risk of preterm delivery and neonatal hypoglycemia. Although these findings may not be generalizable to other settings within Viet Nam or to other countries, they highlight the need to demonstrate that sufficient resources are available to cope with an increased GDM burden before recommending widespread screening using the IADPSG criterion. Moreover, because the long-term significance of GDM diagnosed using the IADPSG criterion is not known, all the potential benefits and harms and the costs of screening and treating GDM in low-income settings need to be further investigated before any recommendation for “universal” GDM screening is made.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10. 1371/journal.pmed.1001272.
The US National Institute of Diabetes and Digestive and Kidney Diseases provides information for patients on diabetes and on gestational diabetes (in English and Spanish)
The UK National Health Service Choices website also provides information for patients about diabetes and about gestational diabetes, including links to other useful resources
The American Diabetes Association also provides detailed information for patients and professionals about all aspects of diabetes, including gestational diabetes (in English and Spanish)
The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) 2010 recommendations on the diagnosis and classification of gestational diabetes are available
The charity Diabetes UK provides detailed information for patients and carers, including information on gestational diabetes; its blog includes a personal story about gestational diabetes, and its website includes a selection of other stories from people with diabetes; the charity Healthtalkonline also has an interview describing a personal experience of gestational diabetes
MedlinePlus provides links to additional resources on diabetes and on gestational diabetes (in English and Spanish)
doi:10.1371/journal.pmed.1001272
PMCID: PMC3404117  PMID: 22911157
15.  Sleep Outcomes in Children with Hemifacial Microsomia and Controls: A Follow-Up Study 
Pediatrics  2009;124(2):e313-e321.
Objective
Children with craniofacial anomalies are at high risk of sleep-disordered breathing (SDB), yet its prevalence among children with craniofacial conditions is not known. Children with a relatively common congenital craniofacial condition, hemifacial microsomia (HFM), are likely particularly vulnerable to SDB due to underdevelopment of the mandible and oropharynx. Nevertheless, most children with HFM are not referred for sleep studies. We hypothesized that sleep outcomes would be worse in children with HFM versus controls.
Methods
We conducted a follow-up study among 124 cases and 349 controls who previously participated in a study of HFM risk factors. Cases were eligible if diagnosed by a craniofacial specialist at one of 25 participating centers. Controls were matched to cases by pediatric practice and age at interview. Parents completed the Pediatric Sleep Questionnaire (PSQ) regarding symptoms of SDB and sleep habits. Regression models were adjusted for region, age, sex, race/ethnicity and maternal education.
Results
Snoring was more commonly reported for children with HFM (29%) than controls (17%) [adjusted odds ratio (adjOR)=1.9, 95% confidence interval (CI) 1.1–3.2]. Compared with controls, children with HFM more often had symptoms consistent with SDB (adjOR=2.8, CI 1.5–5.1). On average, cases’ parents reported 1.9 times as many symptoms on the PSQ breathing scale (CI 1.4–2.7), and 1.3 times more symptoms on the PSQ sleepiness scale (CI 0.9–1.8) than did controls’ parents, with little difference on the PSQ behavior scale. Parents of children with HFM reported 1.4 times more night awakenings than did controls’ parents (CI 0.9–2.2). There was no association for sleep-onset latency or time in bed.
Conclusions
Children with HFM experienced more snoring and other symptoms of SDB than controls. Pediatricians should be aware of the increased vulnerability for SDB among children with mandibular or external ear underdevelopment or asymmetry, and should refer to a sleep specialist as needed.
doi:10.1542/peds.2008-3488
PMCID: PMC2739665  PMID: 19651569
Hemifacial microsomia; Oculoauriculovertebral syndrome; Goldenhar syndrome; Craniofacial abnormalities; Sleep; Sleep-disordered breathing; Snoring; Child; Epidemiology
16.  Risk of sleep-disordered breathing in Parkinson’s disease 
Objective
The objective of this study is to assess the risk of sleep-disordered breathing (SDB) in patients with Parkinson’s disease (PD) in a cross-sectional survey of PD subjects and controls in a university-based movement disorders clinic.
Methods
One hundred thirty-four consecutive PD subjects and 94 control subjects without prior diagnosis of SDB were assessed. Participants were assessed with clinical history, Unified Parkinson’s Disease Rating Scale, Geriatric Depression Scale, Berlin Questionnaire to classify SDB risk, Epworth Sleepiness Scale, Parkinson’s Disease Sleep Scale, and SF-36 to examine quality of life. The presence of risk for SDB was assessed by the Berlin Questionnaire.
Results
High risk for SDB was apparent in 66 (49.3%) of the PD patients and 32 (34.8%) of the controls. After adjustment for age, gender, and body mass index (BMI), PD subjects in comparison to controls showed higher risk for SBD (odds ratio=2.81; 95% confidence interval, 1.36–5.82). Quality of life (physical component score) was significantly diminished in PD patients at high risk for SDB. PD severity did not correlate well with SDB risk. PD patients at high risk for SDB had higher BMIs and Epworth scores.
Conclusions
PD patients have features suggesting increased risk for SDB. This frequently undiagnosed sleep disorder may have a substantial impact on quality of life of PD patients.
doi:10.1007/s11325-010-0362-3
PMCID: PMC2978748  PMID: 20473719
Sleep-disordered breathing; Obstructive sleep apnea; Parkinson’s disease; Berlin questionnaire; Sleepiness; Depression; Quality of life
17.  Excessive daytime sleepiness among rural residents in Saskatchewan 
Obstructive sleep apnea and its sequelae are emerging public health issues in North America, and symptoms are often under-recognized or under-reported. Although several patient factors have been identified, limited data regarding the prevalence of and predictors for excessive daytime sleepiness in rural or remote populations area available. Accordingly, this study used Epworth Sleepiness Scale scores to evaluate daytime sleepiness in a large rural population participating in the Saskatchewan Rural Health Study.
BACKGROUND:
Obstructive sleep apnea (OSA) is a common diagnosis in clinical practice. Excessive daytime sleepiness may be a warning for possible OSA.
OBJECTIVES:
To assess the prevalence of excessive daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS) in a rural community population; potential risk factors for OSA were also assessed.
METHODS:
In 2010, a baseline respiratory health questionnaire within the Saskatchewan Rural Health Study was mailed to 11,982 households in Saskatchewan. A total of 7597 adults within the 4624 (42%) respondent households completed the ESS questionnaire. Participants were categorized according to normal or high (>10) ESS scores. Data obtained included respiratory symptoms, doctor-diagnosed sleep apnea, snoring, hypertension, smoking and demographics. Body mass index was calculated. Multivariable logistic regression analysis examined associations between high ESS scores and possible risk factors. Generalized estimating equations accounted for the two-tiered sampling procedure of the study design.
RESULTS:
The mean age of respondents was 55.0 years and 49.2% were male. The prevalence of ESS>10 and ‘doctor diagnosed’ OSA were 15.9% and 6.0%, respectively. Approximately 23% of respondents reported loud snoring and 30% had a body mass index >30 kg/m2. Of those with ‘doctor-diagnosed’ OSA, 37.7% reported ESS>10 (P<0.0001) and 47.7% reported loud snoring (P<0.0001). Risk of having an ESS>10 score increased with age, male sex, obesity, lower socioeconomic status, marriage, loud snoring and doctor-diagnosed sinus trouble.
CONCLUSIONS:
High levels of excessive daytime sleepiness in this particular rural population are common and men >55 years of age are at highest risk. Examination of reasons for residual sleepiness and snoring in persons with and without sleep apnea is warranted.
PMCID: PMC4173890  PMID: 24791255
Epworth Sleepiness Scale; Farm; Nonfarm; Obesity; Rural; Sleep apnea; Snoring; Socioeconomic
18.  Markers of Sleep-Disordered Breathing and Metabolic Syndrome in a Multiethnic Sample of US Adults: Results from the National Health and Nutrition Examination Survey 2005–2008 
Previous studies have documented an association between markers of sleep-disordered breathing (SDB) and metabolic syndrome. However, it is not clear if there are gender or ethnic differences in this association. We examined 6,122 participants aged ≥20 years from the National Health and Nutrition Examination Survey 2005–08. Metabolic syndrome was defined as the presence of ≥3 of the following components: (1) abdominal obesity, (2) elevated blood triglycerides, (3) low HDL cholesterol, (4) high BP, and (5) hyperglycemia. SDB severity was defined based on an additive summary score including sleep duration, snoring, snorting, and daytime sleepiness. We found that short sleep duration, snoring, snorting, daytime sleepiness and the summary SDB score were significantly associated with metabolic syndrome independent of potential confounders. Compared to those without any sleep disturbance, the multivariable odds ratio (OR) (95% confidence interval [CI]) of metabolic syndrome among those with three or more sleep disturbances was 3.92 (2.98–5.16). In subgroup analyses, this association was consistently present among men and women and all race-ethnic groups. In summary, SDB was independently associated with metabolic syndrome in a nationally representative sample of US adults.
doi:10.1155/2012/630802
PMCID: PMC3347463  PMID: 22577590
19.  A survey of parentally reported sleep health disorders in estonian 8–9 year old children 
BMC Pediatrics  2013;13:200.
Background
Pediatric sleep research is rather new in Estonia. There has not been a comprehensive study of age specific sleep disorders in Estonian children. The aim of this study was to investigate sleep disorders in a sample of Estonian second grade children.
We hypothesized that:
• Children with low BMI are as susceptible to SDB as are children with high BMI.
• Under weight children are susceptible to residual SDB after adenotonsillectomy.
• Parasomnias present with SDB in children.
• Excessive day time sleepiness is a significant symptom which leads parents to suspect sleep disorders in their child.
Methods
A retrospective questionnaire based survey was used to analyze factors influencing sleep, parasomnias, daytime sleepiness, and sleep disordered breathing (SDB). 1065 Pediatric Sleep Questionnaire (PSQ) packets were distributed by post to randomly selected parents of second grade students; 703 (66%) subjects were included in the study group; each parent/guardian participant had one second grade child. Descriptive statistics were used to compare characteristics of SDB symptomatic and healthy children. We used logistic regression to analyze factors influencing sleep and parasomnias in relation to SDB severity. Odds ratios (OR) and 95% CI were used to estimate relative risk.
Results
Parents of children with SDB complaints seem to pay attention to sleep disorders especially when a child is suffering from excessive day time sleepiness. Parasomnias are present simultaneously with SDB and tend to worsen in relation to more severe SDB complaints. Many underweight children have SDB symptoms after adenotonsillectomy.
Conclusion
SDB symptoms are found in both overweight and underweight children. Both groups should be observed, especially in terms of the current focus on overweight children. Careful follow up after SDB treatment is necessary in case of under and overweight children. Parental suspicions regarding SDB are noticeably higher in cases of excessive daytime sleepiness in their children.
doi:10.1186/1471-2431-13-200
PMCID: PMC4235015  PMID: 24304942
Sleep disordered breathing; Children; Sleep health; BMI; Parasomnia
20.  SLEEP-DISORDERED BREATHING AND DAYTIME NAPPING ARE ASSOCIATED WITH MATERNAL HYPERGLYCAEMIA 
Sleep & breathing = Schlaf & Atmung  2013;17(3):1093-1102.
Objectives
Sleep disturbances in pregnancy may impair glucose mechanism. This study aimed to examine associations of sleep-disordered breathing, sleep and nap-duration with one-hour glucose challenge test (GCT) levels in pregnant women after controlling for known risk factors for gestational diabetes.
Methods
This is a case-control study of 104 pregnant women. All women underwent full polysomnography and a glucose challenge test (GCT), and completed the Multivariable Apnoea Prediction and Pittsburgh Sleep Quality Indexes. The primary outcome was maternal hyperglycaemia measured by GCT. Bivariate and multivariable logistic regression analyses were performed.
Results
Over 13% subjects reported habitual snoring in the first trimester. Only 9.3% women with normoglycaemia (GCT<135) were habitual snorers, whereas 45.5% women with hyperglycaemia-(GCT≥135) had habitual snoring (p<0.001). Sleep-disordered breathing symptoms (loud snoring, snorting/gasping and apnoeas), (odds ratio (OR) 2.85; 95% confidence interval (CI) 1.50–5.41; p=0.001) and total nap-duration (OR 1.48; 95% CI 0.96–2.28; p=0.08) were associated with hyperglycaemia. After adjusting for confounders, sleep-disordered breathing symptoms (OR 3.37; 95% CI, 1.44–8.32; p=0.005) and nap-duration (OR 1.64; 95% CI, 1.00–2.681.02; p=0.05) continued to be associated with hyperglycaemia. However, the primary exposure measure, the apnea/hypopnea index in the first-trimester was not significantly associated with hyperglycaemia (OR 1.03; 95% CI 0.83–1.28; p=0.77).
Conclusions
Sleep-disordered breathing symptoms and nap duration are associated with hyperglycaemia. Sleep-duration was not associated with hyperglycaemia. Research is needed concerning whether women with sleep-disordered breathing and/or daytime napping are at risk for gestational diabetes.
doi:10.1007/s11325-013-0809-4
PMCID: PMC3696035  PMID: 23354511
Apnoea symptom score; gestational diabetes; glucose dysregulation; sleep duration; snoring; hyperglycaemia
21.  Modification of the Epworth Sleepiness Scale in Central China 
Quality of Life Research  2011;20(10):1721-1726.
Purpose
The well-known excessive daytime sleepiness (EDS) assessment, Epworth Sleepiness Scale (ESS), is not consistently qualified for patients with diverse living habits. This study is aimed to build a modified ESS (mESS) and then to verify its feasibility in the assessment of EDS for patients with suspected sleep-disordered breathing (SDB) in central China.
Methods
A Ten-item Sleepiness Questionnaire (10-ISQ) was built by adding two backup items to the original ESS. Then the 10-ISQ was administered to 122 patients in central China with suspected SDB [among them, 119 cases met the minimal diagnostic criteria for obstructive sleep apnea by sleep study, e.g., apnea and hypopnea index (AHI) ≥ 5 h−1] and 117 healthy central Chinese volunteers without SDB. Multivariate exploratory techniques were used for item validation. The unreliable item in the original ESS was replaced by the eligible backup item, thus a modified ESS (mESS) was built, and then verified.
Results
Item 8 proved to be the only unreliable item in central Chinese patients, with the least factor loading on the main factor and the lowest item-total correlation both in the 10-ISQ and in the original ESS, deletion of it would increase the Cronbach’s alpha (from 0.86 to 0.87 in the 10-ISQ; from 0.83 to 0.85 in the original ESS). The mESS was subsequently built by replacing item 8 in the original ESS with item 10 in the 10-ISQ. Verification with patients’ responses revealed that the mESS was a single-factor questionnaire with good internal consistency (Cronbach’s alpha = 0.86). The sum score of the mESS not only correlated with AHI (P < 0.01) but was also able to discriminate the severity of obstructive apnea (P < 0.01). Nasal CPAP treatment for severe OSA reduced the score significantly (P < 0.001). The performance of the mESS was poor in evaluating normal subjects.
Conclusion
The mESS improves the validity of ESS for our patients. Therefore, it is justified to use it instead of the original one in assessment of EDS for patients with SDB in central China.
doi:10.1007/s11136-011-9898-3
PMCID: PMC3220816  PMID: 21484529
Epworth Sleepiness Scale; Excessive daytime sleepiness; Sleep-disordered breathing
22.  Association between maternal sleep practices and risk of late stillbirth: a case-control study 
Objectives To determine whether snoring, sleep position, and other sleep practices in pregnant women are associated with risk of late stillbirth.
Design Prospective population based case-control study.
Setting Auckland, New Zealand
Participants Cases: 155 women with a singleton late stillbirth (≥28 weeks’ gestation) without congenital abnormality born between July 2006 and June 2009 and booked to deliver in Auckland. Controls: 310 women with single ongoing pregnancies and gestation matched to that at which the stillbirth occurred. Multivariable logistic regression adjusted for known confounding factors.
Main outcome measure Maternal snoring, daytime sleepiness (measured with the Epworth sleepiness scale), and sleep position at the time of going to sleep and on waking (left side, right side, back, and other).
Results The prevalence of late stillbirth in this study was 3.09/1000 births. No relation was found between snoring or daytime sleepiness and risk of late stillbirth. However, women who slept on their back or on their right side on the previous night (before stillbirth or interview) were more likely to experience a late stillbirth compared with women who slept on their left side (adjusted odds ratio for back sleeping 2.54 (95% CI 1.04 to 6.18), and for right side sleeping 1.74 (0.98 to 3.01)). The absolute risk of late stillbirth for women who went to sleep on their left was 1.96/1000 and was 3.93/1000 for women who did not go to sleep on their left. Women who got up to go to the toilet once or less on the last night were more likely to experience a late stillbirth compared with women who got up more frequently (adjusted odds ratio 2.28 (1.40 to 3.71)). Women who regularly slept during the day in the previous month were also more likely to experience a late stillbirth than those who did not (2.04 (1.26 to 3.27)).
Conclusions This is the first study to report maternal sleep related practices as risk factors for stillbirth, and these findings require urgent confirmation in further studies.
doi:10.1136/bmj.d3403
PMCID: PMC3114953  PMID: 21673002
23.  The Role of Serotonin in Sleep Disordered Breathing Associated with Parkinson Disease: A Correlative [11C]DASB PET Imaging Study 
PLoS ONE  2012;7(7):e40166.
Sleep dysfunction and excessive daytime sleepiness are common in Parkinson disease (PD). Several studies suggest that PD patients exhibit high prevalence of sleep-disordered breathing (SDB). PD has a complex profile of neurochemical deficits in which abnormalities of different neurotransmitter systems may play significant and differing roles in the development of non-motor features. In the present study, we investigated whether SDB in PD is related to serotoninergic neuron degeneration. We used a cross-sectional design to assess the correlation between SDB and measures of caudal brainstem serotonin neuron integrity. Fifty one PD participants with mean disease duration of 6.0 (SD 3.7) years and mean age of 63.9 (SD 6.2) years were studied. We measured caudal brainstem serotoninergic innervation with [11C]DASB positron emission tomography (PET) imaging and striatal dopaminergic innervation with [11C]DTBZ PET imaging. SDB was assessed with polysomnography (PSG) and sleepiness with multiple sleep latency tests. Greater than half of participants exhibited PSG evidence of significant SDB; 12 participants had normal PSGs, 6 had mild SDB, 20 had moderate SDB, and 13 had severe SDB. We found no association between severity of SDB and caudal brainstem serotoninergic innervation in PD participants. Striatal dopaminergic denervation did not correlate with severity of SDB. We did find significant correlations between measures of motor function impairment and sleep quantity and quality in PD. Neither serotoninergic nor dopaminergic neuron degeneration is likely to play a major role in SDB observed in PD patients.
doi:10.1371/journal.pone.0040166
PMCID: PMC3390329  PMID: 22792235
24.  Interaction between Sleep-Disordered Breathing and Acute Ischemic Stroke 
Background and Purpose
Sleep-disordered breathing (SDB) is suggested to be strongly associated with ischemic strokes. Risk factors, stroke subtypes, stroke lesion distribution, and the outcome of SDB in stroke patients remain unclear in Korea.
Methods
We prospectively studied 293 patients (159 men, 134 women; age 68.4±10.5) with acute ischemic stroke. Cardiovascular risk factors, stroke severity, sleep-related stroke onset, distribution of stroke lesions, and 3-month score on the modified Rankin Scale (mRS) were assessed. Stroke severity was assessed by the US National Institutes of Health Stroke Scale (NIHSS) and the mRS. The apnea-hypopnea index (AHI) was determined 6.3±2.2 days after stroke onset with the Apnea Link portable sleep apnea monitoring device.
Results
The prevalence of SDB (defined as an AHI of ≥10) was 63.1% (111 men, 74 women). Those in the SDB group were older, had higher NIHSS and mRS scores, greater bulbar weakness, and a higher incidence of sleep-associated stroke onset. Among risk-factor profiles, alcohol consumption and atrial fibrillation were significantly related to SDB. The stroke outcome was worse in patients with SDB than in those without SDB. The lesion location and specific stroke syndrome were not correlated with SDB.
Conclusions
SDB is very common in acute cerebral infarction. Different risk-factor profiles and sleep-related stroke onsets suggest SDB as a cause of ischemic stroke. The higher NIHSS score and greater bulbar involvement in the SDB group seem to show the influence of ischemic stroke on the increased SDB prevalence.
doi:10.3988/jcn.2013.9.1.9
PMCID: PMC3543913  PMID: 23346154
sleep-disordered breathing; acute cerebral infarction; prevalence
25.  Predictors of sleep disordered breathing in obese adults who are chronic short sleepers 
Sleep Medicine  2012;13(5):484-489.
Background
Sleep disordered breathing (SDB) is more common in obese adults, but not all obese adults have SDB. The aim of these analyses was to determine what predicted SDB in a sample of obese adults.
Methods
We conducted cross-sectional analysis of 139 obese men and women aged 18–50 years who are chronic short sleepers. Habitual sleep duration and sleep efficiency were estimated using 2 weeks of wrist actigraphy. Respiratory Disturbance Index (RDI) was assessed by a portable screening device. SDB was defined as RDI≥15 events/hour. Subjective sleep quality, sleepiness, and sociodemographic characteristics were evaluated by questionnaires.
Results
Increased sleep duration from actigraphy was associated with reduced odds of SDB (OR 0.44 per hour, p=.043). Neither subjective sleep quality nor sleepiness was associated with SDB. Male sex, older age, and increased waist circumference were associated with increased odds of SDB.
Conclusions
In this sample of obese adults, subjective measures of sleep quality and sleepiness were not indicators of SDB. These results suggest that in obese patients, physicians should not rely on subjective measures to determine who should be referred for a clinical sleep study. A wider use of portable apnea screening devices should be considered in non symptomatic, Non-Hispanic white males.
doi:10.1016/j.sleep.2011.11.009
PMCID: PMC3323698  PMID: 22326831
sleep-disordered breathing; obese; actigraphy; subjective sleep quality; sleepiness; apnea

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