Adherence and efficacy of mandibular advancement splint treatment of sleep-disordered breathing during pregnancy: a pilot study.

PURPOSE: Sleep-disordered breathing (SDB) is common in pregnancy and is associated with adverse health consequences for both mother and child. Mandibular advancement splints (MAS) have been shown to improve sleep quality, daytime sleepiness and snoring in non-pregnant women. The effectiveness of MAS for treating SDB in pregnancy is unknown. This pilot study aimed to evaluate the efficacy and adherence to MAS in pregnant women with SDB. METHODS: Women with mild-moderate SDB (apnea-hypopnea index (AHI) 10-29/h) on level 2 polysomnography (PSG) performed at 22.0 ± 5.5 weeks' gestation were treated with a MAS during pregnancy to 6 months postpartum. An embedded micro-recorder measured adherence. PSG was repeated while on titrated treatment, and off treatment in the postpartum period. RESULTS: Among 17 women completing the study, MAS was worn ≥ 4 h/night for 57.5 ± 36.7% of nights during the antepartum period. While using MAS, nightly snoring time decreased from 25.9 ± 24.5% at baseline to 6.4 ± 7.8% when treated during pregnancy (p = .003). AHI decreased from 17.6 ± 5.1 to 12.9 ± 6.3 (p = .02) and fell by ≥ 30% and below 15/h in 60% of participants. During the postpartum period, MAS was used for ≥ 4 h/night on 24.8 ± 27.9% of nights. Moreover, the mean AHI off MAS was 17.9 ± 13.1; 88% of women had persistent SDB (AHI ≥ 10). CONCLUSIONS: In this cohort, treatment efficacy and objective adherence were variable. Device use was less frequent in the postpartum period even though a substantial number of women had persistent SDB after delivery. Clinical trial registered with  www. CLINICALTRIALS: gov number: NCT03138291.

Sleep-disordered breathing in high-risk pregnancies is associated with elevated arterial stiffness and increased risk for preeclampsia.

BACKGROUND: Impaired vascular function is a central feature of pathologic processes preceding the onset of preeclampsia. Arterial stiffness, a composite indicator of vascular health and an important vascular biomarker, has been found to be increased throughout pregnancy in those who develop preeclampsia and at the time of preeclampsia diagnosis. Although sleep-disordered breathing in pregnancy has been associated with increased risk for preeclampsia, it is unknown if sleep-disordered breathing is associated with elevated arterial stiffness in pregnancy. OBJECTIVE: This prospective observational cohort study aimed to evaluate arterial stiffness in pregnant women, with and without sleep-disordered breathing and assess the interaction between arterial stiffness, sleep-disordered breathing, and preeclampsia risk. STUDY DESIGN: Women with high-risk singleton pregnancies were enrolled at 10 to 13 weeks' gestation and completed the Epworth Sleepiness Score, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaires at each trimester. Sleep-disordered breathing was defined as loud snoring or witnessed apneas (≥3 times per week). Central arterial stiffness (carotid-femoral pulse wave velocity, the gold standard measure of arterial stiffness), peripheral arterial stiffness (carotid-radial pulse wave velocity), wave reflection (augmentation index, time to wave reflection), and hemodynamics (central blood pressures, pulse pressure amplification) were assessed noninvasively using applanation tonometry at recruitment and every 4 weeks from recruitment until delivery. RESULTS: High-risk pregnant women (n=181) were included in the study. Women with sleep-disordered breathing (n=41; 23%) had increased carotid-femoral pulse wave velocity throughout gestation independent of blood pressure and body mass index (P=.042). Differences observed in other vascular measures were not maintained after adjustment for confounders. Excessive daytime sleepiness, defined by Epworth Sleepiness Score >10, was associated with increased carotid-femoral pulse wave velocity only in women with sleep-disordered breathing (Pinteraction=.001). Midgestation (first or second trimester) sleep-disordered breathing was associated with an odds ratio of 3.4 (0.9-12.9) for preeclampsia, which increased to 5.7 (1.1-26.0) in women with sleep-disordered breathing and hypersomnolence, whereas late (third-trimester) sleep-disordered breathing was associated with an odds ratio of 8.2 (1.5-39.5) for preeclampsia. CONCLUSION: High-risk pregnant women with midgestational sleep-disordered breathing had greater arterial stiffness throughout gestation than those without. Sleep-disordered breathing at any time during pregnancy was also associated with increased preeclampsia risk, and this effect was amplified by hypersomnolence.

Scoring heart rate increases as a surrogate arousal marker on portable monitor studies for obstructive sleep apnea: Impact on diagnostic accuracy and clinical decision-making.

Cortical arousal-related hypopneas are not scored on type 3 home devices, which therefore limits their diagnostic accuracy for obstructive sleep apnea. The objective of this study was to evaluate whether scoring heart rate accelerations as surrogate markers of arousal improves type 3 portable monitor diagnostic agreement compared with polysomnography and improves therapeutic decision-making. We prospectively recruited patients evaluated for obstructive sleep apnea to undergo in-laboratory simultaneous full polysomnography + type 3 portable monitoring. Hypopnea events were scored on portable monitor studies with and without autonomic scoring, which was defined as an associated increase in pulse oximetry-derived heart rate ≥6 beats per min (autonomic hypopnea). Portable monitor diagnostic agreement compared with polysomnography with and without autonomic hypopnea scoring was assessed. We also evaluated whether reporting autonomic hypopnea scoring improves portable monitor clinical treatment decision agreement after four physicians reviewed clinical data and sleep study results (polysomnography, portable monitor with autonomic hypopnea, portable monitor without autonomic hypopnea). Eighty-two participants completed simultaneous polysomnography and in-laboratory portable monitor studies. Scoring autonomic hypopnea resulted in a decreased mean difference between in-laboratory portable monitor respiratory event index and polysomnography apnea-hypopnea index in Bland-Altman analysis (mean difference 14.6 per hr without versus 6.1 per hr with autonomic hypopnea scoring [p ˂ 0.01]), and increased intraclass correlation from 0.769 to 0.844. Inclusion of autonomic hypopnea scoring resulted in better accuracy between portable monitor and polysomnography expert's treatment decisions, and ultimately resulted in 24% fewer additional polysomnographies requested. The addition of pulse oximetry heart rate increases for autonomic hypopnea scoring during portable monitor resulted in better diagnostic agreement, improved clinical decision-making and reduced additional polysomnography testing.

Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline.

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.

Accuracy of portable devices in sleep apnea using oximetry-derived heart rate increases as a surrogate arousal marker.

PURPOSE: Type 3 home study (HS) monitors do not detect cortical arousal-related hypopneas and may therefore underestimate the polysomnography (PSG)-based apnea-hypopnea index (AHI). Our aim was to test the hypothesis that scoring hypopneas using heart rate accelerations as a surrogate marker for cortical arousal (autonomic hypopnea; AnH) improves the accuracy of HS for OSA diagnosis, using PSG AHI as the diagnostic gold standard. METHODS: We retrospectively identified patients referred for OSA who underwent complete PSG following an initial inconclusive HS. Respiratory events were scored using AASM research (Chicago) criteria with additional HS scoring for AnH, defined as hypopneas based on flow criteria associated with an increase in pulse oximetry-derived heart rate ≥ 6 beats/min. RESULTS: A total of 178 patients met inclusion criteria, with mean (±SD) HS AHI = 4.4 ± 4.2/h, which increased to 8.5 ± 5.3/h with AnH scoring. The hypopnea arousal index on subsequent PSG was 7.6 ± 7.7/h, with total AHI 15.6 ± 11.9/h. Bland-Altman analysis showed improved agreement between HS and PSG AHI (mean difference 11.2/h (95%CI 33.6, - 11.1) without vs. 7.2/h (95%CI 29.6, - 15.4) with AnH scoring). Overall diagnostic accuracy was improved with AnH scoring as reflected by an increased area under the receiver-operating characteristic curve for AHI thresholds of 10 and 15 events/h. CONCLUSIONS: In this retrospective analysis, the diagnostic accuracy of type 3 HS was improved by the inclusion of hypopnea-associated heart rate increases as a surrogate marker of arousal. Prospective studies are warranted to evaluate the impact of AnH scoring on clinical decision-making and patient outcomes.

Maternal sleep-disordered breathing and the risk of delivering small for gestational age infants: a prospective cohort study.

OBJECTIVE: It is unclear whether objectively measured maternal sleep-disordered breathing (SDB) leads to poor fetal outcomes. In this study, we prospectively assessed whether polysomnography-based diagnosis of SDB in the third trimester is associated with the delivery of small for gestational age (SGA) infants. STUDY DESIGN: Participants were recruited from a multicentre pregnancy cohort study. Eligible participants were evaluated for SDB based on symptoms (snoring and/or witnessed apnoeas assessed using the Pittsburgh Sleep Quality Index questionnaire) and in-home complete polysomnography in the third trimester. SGA was defined as <10th centile using customised birthweight centiles adjusted for maternal parity, prepregnancy body mass index (BMI), ethnicity, gestational age and infant sex. RESULTS: Of the 234 pregnant participants who completed a sleep study, 82% were Caucasian, with mean (SD) age of 31 (4.3) years and a prepregnancy BMI of 23 (4) kg/m(2). The delivery of SGA infants occurred in 27 (12%) of the study participants. The symptoms of SDB had poor overall sensitivity and specificity for diagnosing SDB identified by polysomnography. Symptoms of SDB in the third trimester demonstrated a potential association with delivering an SGA infant, however this did not reach statistical significance (OR 2.36 (95% CI 0.85 to 6.54, p=0.10)). However, the odds of delivering an SGA infant were significantly increased with polysomnography-based diagnosis of maternal SDB (using apnoea-hypopnoea index cut-off of 10, OR 2.65 (95% CI 1.15 to 6.10, p=0.02)). CONCLUSIONS: Objectively measured SDB in the third trimester is significantly associated with the delivery of SGA infants.

Eight Hours of Nightly Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Improves Glucose Metabolism in Patients with Prediabetes. A Randomized Controlled Trial.

RATIONALE: Although obstructive sleep apnea (OSA) is associated with impaired glucose tolerance and diabetes, it remains unclear whether OSA treatment with continuous positive airway pressure (CPAP) has metabolic benefits. OBJECTIVES: To determine the effect of 8-hour nightly CPAP treatment on glucose metabolism in individuals with prediabetes and OSA. METHODS: In a randomized controlled parallel group study, 39 participants were randomly assigned to receive either 8-hour nightly CPAP (n = 26) or oral placebo (n = 13). Sleep was polysomnographically recorded in the laboratory on each night. CPAP adherence was ensured by continuous supervision. Participants continued their daily routine activities outside the laboratory. Glucose metabolism was assessed at baseline and after 2 weeks of assigned treatment using both the oral and intravenous glucose tolerance tests. The primary outcome was the overall glucose response as quantified by the area under the curve for glucose during 2-hour oral glucose tolerance testing. Secondary outcomes included fasting and 2-hour glucose and insulin, the area under the curves for insulin and insulin secretion, norepinephrine, insulin sensitivity, acute insulin response to glucose, and 24-hour blood pressure. MEASUREMENTS AND MAIN RESULTS: The overall glucose response was reduced (treatment difference: -1,276.9 [mg/dl] · min [95% confidence interval, -2,392.4 to -161.5]; P = 0.03) and insulin sensitivity was improved (treatment difference: 0.77 [mU/L](-1) · min(-1) [95% confidence interval, 0.03-1.52]; P = 0.04) with CPAP as compared with placebo. Additionally, norepinephrine levels and 24-hour blood pressure were reduced with CPAP as compared with placebo. CONCLUSIONS: In patients with prediabetes, 8-hour nightly CPAP treatment for 2 weeks improves glucose metabolism compared with placebo. Thus, CPAP treatment may be beneficial for metabolic risk reduction. Clinical trial registered with www.clinicaltrials.gov (NCT 01156116).

Maternal sleep-disordered breathing and adverse pregnancy outcomes: a systematic review and metaanalysis.

OBJECTIVE: Symptoms of sleep-disordered breathing (SDB) are increased in pregnancy compared to the nongravid state. Maternal SDB may be associated with adverse pregnancy outcomes, but this is still under investigation. We performed a systematic literature review, and where feasible, a metaanalysis, to evaluate whether women with SDB in pregnancy have a higher risk of specific adverse pregnancy outcomes compared with women without SDB. STUDY DESIGN: Original studies published until June 2012 evaluating the association between gestational hypertension/preeclampsia, gestational diabetes, low birthweight infants, and maternal SDB, defined either by symptoms or the reference standard polysomnography, were identified from PubMed, EMBASE, and Web of Science. Data were extracted on study design and outcome estimates. When appropriate, effect estimates from each study were pooled using a random-effects model. RESULTS: Of the 4386 studies identified, 31 met the defined criteria. Twenty-one studies, all observational in design, reported dichotomous outcomes; 9 of these adjusted for potential confounders. Maternal SDB was significantly associated with gestational hypertension/preeclampsia (pooled adjusted odds ratio [aOR], 2.34; 95% confidence interval [CI], 1.60-3.09; 5 studies), and gestational diabetes (pooled aOR, 1.86; 95% CI, 1.30-2.42; 5 studies). CONCLUSION: Based on published observational studies to date, maternal SDB is associated with an increased risk of gestational hypertension and gestational diabetes after adjusting for potential confounders. However, large-scale, prospective cohort, and interventional studies are needed to further elucidate the relationship between maternal SDB and adverse pregnancy outcomes.

Positive Airway Pressure Treatment of Obstructive Sleep Apnea-Hypopnea in Hypertensive Disorders of Pregnancy: A Pilot Randomized Proof-of-Concept Clinical Trial.

Rationale: Maternal obstructive sleep apnea-hypopnea (OSAH) is associated with hypertensive disorders of pregnancy (HDP). OSAH treatment with positive airway pressure (PAP) in the general population lowers blood pressure (BP). However, there are limited data on the effects of PAP therapy in maternal OSAH. Objectives: Our primary objective was to assess the feasibility of recruitment to a pilot randomized trial and adherence to PAP therapy for OSAH in women with HDP. Secondary objectives included assessment of PAP effects on 24-h BP, arterial stiffness, and maternal and fetal outcomes. Methods: Women with singleton pregnancies at ⩾12 weeks' gestation and hypertension underwent home level 2 polysomnography; those with mild to moderate OSAH (apnea-hypopnea index ⩾ 5 events/h; women with severe OSAH with apnea-hypopnea index > 30 events/h and oxygen desaturation index > 30 were excluded) were randomized to either PAP or nasal dilator strip (NDS; control) therapy. After PAP education, adherence was monitored online with episodic phone or in-person support by research personnel. Twenty-four-hour BP and arterial stiffness were assessed at baseline and before delivery. Maternal and fetal outcomes were also recorded. Results: Of 105 potentially eligible participants, 67 agreed to undergo screening for OSAH over 38 months; 48 women meeting OSAH inclusion criteria were randomized to PAP (n = 27) or NDS (n = 21) therapy. Of these, 14 PAP (52%) and 13 NDS (62%) participants completed all predelivery measurements, with lack of completion due to urgent delivery (19% in the PAP group, 14% in the NDS group), PAP intolerance at initiation (19%), or other factors. Mean PAP use was 3.1 ± 2.5 h/night, with use ⩾4 h/night on 38.4 ± 33.7% of nights during 9.6 ± 4.0 weeks of treatment. BP was controlled within the target range in most participants. There were no differences in mean change in 24-hour BP or arterial stiffness measurements or in adverse maternal and fetal outcomes between the PAP and NDS groups in either intention-to-treat or per-protocol analyses. Conclusions: PAP adherence was suboptimal in this HDP cohort despite education and troubleshooting. Further work is required to identify optimal OSAH treatment strategies during pregnancy. Clinical trial registered with www.clinicaltrials.gov (NCT03309826).

Strategies to Assess the Effect of Continuous Positive Airway Pressure on Long-Term Clinically Important Outcomes among Patients with Symptomatic Obstructive Sleep Apnea: An Official American Thoracic Society Workshop Report.

Continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA). Although CPAP improves symptoms (e.g., daytime sleepiness), there is a lack of high-quality evidence that CPAP prevents many long-term outcomes, including cognitive impairment, myocardial infarction, and stroke. Observational studies suggest that patients with symptoms may be particularly likely to experience these preventive benefits with CPAP, but ethical and practical concerns limited the participation of such patients in prior long-term randomized trials. As a result, there is uncertainty about the full benefits of CPAP, and resolving this uncertainty is a key priority for the field. This workshop assembled clinicians, researchers, ethicists, and patients to identify strategies to understand the causal effects of CPAP on long-term clinically important outcomes among patients with symptomatic OSA. Quasi-experimental designs can provide valuable information and are less time and resource intensive than trials. Under specific conditions and assumptions, quasi-experimental studies may be able to provide causal estimates of CPAP's effectiveness from generalizable observational cohorts. However, randomized trials represent the most reliable approach to understanding the causal effects of CPAP among patients with symptoms. Randomized trials of CPAP can ethically include patients with symptomatic OSA, as long as there is outcome-specific equipoise, adequate informed consent, and a plan to maximize safety while minimizing harm (e.g., monitoring for pathologic sleepiness). Furthermore, multiple strategies exist to ensure the generalizability and practicality of future randomized trials of CPAP. These strategies include reducing the burden of trial procedures, improving patient-centeredness, and engaging historically excluded and underserved populations.

Prevalence, clinical features, and CPAP adherence in REM-related sleep-disordered breathing: a cross-sectional analysis of a large clinical population.

PURPOSE: Due to inconsistent definitions used in the literature, the prevalence of rapid eye movement (REM)-related sleep-disordered breathing (SDB) has been quite variable and its clinical significance remains unclear. This study aimed to compare the prevalence of and clinical characteristics between various criteria for defining REM-related SDB. We also investigated how frequently CPAP therapy was recommended in patients with REM-related SDB and if they had lower CPAP adherence compared to non-stage-specific SDB. METHODS: In this cross-sectional study, we evaluated 1,019 consecutive adults referred for a polysomnogram for suspicion of SDB. The prevalence of REM-related SDB was calculated based on "traditional criteria" commonly reported in the literature and a "strict criteria" that minimized the contribution of SDB during non-REM sleep. RESULTS: The prevalence of REM-related SDB ranged from 13.5% to 36.7%. There were no clinically significant differences between the strict definition and the traditional definition of REM-related SDB. REM-related SDB was more prevalent in women, younger individuals and African Americans. Compared to non-stage-specific obstructive sleep apnea (OSA), patients with REM-related SDB were equally symptomatic and hypersomnolent. CPAP titration was recommended in 88% of patients with REM-related SDB vs. 94% of patients with non-stage-specific OSA (p < 0.001). There was no significant difference in CPAP adherence between the two groups. CONCLUSIONS: Regardless of how REM-related SDB is defined, it was highly prevalent in our large clinical cohort. Compared to non-stage-specific OSA, these patients were equally hypersomnolent and adherent to CPAP therapy despite having overall significantly milder OSA. Further research is needed to better establish whether these patients will derive any benefit from long-term CPAP therapy.

Persistence and prevalence of sleep-disordered breathing after delivery: A scoping review of longitudinal and cross-sectional studies.

While emerging literature has shown that sleep-disordered breathing (SDB) in pregnancy occurs in up to ∼30% of women by the third trimester, it is less clear if SDB persists after delivery. In this scoping review, our main objectives were to summarize the evidence on SDB with respect to 1) its persistence from pregnancy to after delivery and 2) its prevalence after delivery. Searches in Medline (PubMed), Web of Science, and Scopus until February 2022 were performed. Of the 1591 studies initially identified, 13 studies met the eligibility criteria. Nine were longitudinal studies from pregnancy to postpartum and four were cross-sectional studies of postpartum only. Our review demonstrated that over half (53-65%) of women had persistent SDB after delivery, but that the overall severity of SDB improved. The prevalence of snoring was reduced by two-fold (62% vs 29%) from pregnancy to after delivery. In addition, the overall prevalence of SDB using objective sleep studies was ∼24% (range 13-83%) after delivery. Changes in body weight from pregnancy to postpartum did not reliably predict persistent SDB across studies, but increased postpartum weight was associated with a greater risk of having persistent SDB after delivery.

Effect of Maternal Obstructive Sleep Apnea-Hypopnea on 24-Hour Blood Pressure, Nocturnal Blood Pressure Dipping and Arterial Stiffness in Hypertensive Disorders of Pregnancy.

Rationale: Maternal obstructive sleep apnea-hypopnea (OSAH) is associated with hypertensive disorders of pregnancy (HDP). Attenuation of the normal nocturnal blood pressure (BP) decline (non-dipping) is associated with adverse pregnancy outcomes. OSAH is associated with nocturnal non-dipping in the general population, but this has not been studied in pregnancy. We therefore analyzed baseline data from an ongoing RCT (NCT03309826) assessing the impact of OSAH treatment on HDP outcomes, to evaluate the relationship of OSAH to 24-h BP profile, in particular nocturnal BP dipping, and measures of arterial stiffness. Methods: Women with a singleton pregnancy and HDP underwent level II polysomnography. Patients with OSAH (apnea-hypopnea index (AHI) ≥ 5 events/h) then underwent 24-h ambulatory BP monitoring and arterial stiffness measurements (applanation tonometry, SphygmoCor). Positive dipping was defined as nocturnal systolic blood pressure (SBP) dip ≥ 10%. The relationships between measures of OSAH severity, measures of BP and arterial stiffness were evaluated using linear regression analyses. Results: We studied 51 HDP participants (36.5 ± 4.9 years, BMI 36.9 ± 8.6 kg/m2) with OSAH with mean AHI 27.7 ± 26.4 events/h at 25.0 ± 4.9 weeks' gestation. We found no significant relationships between AHI or other OSA severity measures and mean 24-h BP values, although BP was generally well-controlled. Most women were SBP non-dippers (78.4%). AHI showed a significant inverse correlation with % SBP dipping following adjustment for age, BMI, parity, gestational age, and BP medications (ß = -0.11, p = 0.02). Significant inverse correlations were also observed between AHI and DBP (ß = -0.16, p = 0.01) and MAP (ß = -0.13, p = 0.02) % dipping. Oxygen desaturation index and sleep time below SaO2 90% were also inversely correlated with % dipping. Moreover, a significant positive correlation was observed between carotid-femoral pulse wave velocity (cfPWV) and REM AHI (ß = 0.02, p = 0.04) in unadjusted but not adjusted analysis. Conclusion: Blood pressure non-dipping was observed in a majority of women with HDP and OSAH. There were significant inverse relationships between OSAH severity measures and nocturnal % dipping. Increased arterial stiffness was associated with increasing severity of OSAH during REM sleep in unadjusted although not adjusted analysis. These findings suggest that OSAH may represent a therapeutic target to improve BP profile and vascular risk in HDP.

Maternal Sleep-Disordered Breathing in Pregnancy and Increased Nocturnal Glucose Levels in Women with Gestational Diabetes Mellitus.

BACKGROUND: Women with hyperglycemia during pregnancy are at high risk for adverse perinatal outcomes. Maternal sleep-disordered breathing (SDB) during pregnancy is common and is a risk factor for gestational diabetes mellitus (GDM). However, the relationship between SDB severity and glucose control is unknown. RESEARCH QUESTION: Is there an association between SDB severity and glucose levels as assessed by continuous glucose monitoring in GDM? STUDY DESIGN AND METHODS: Women with GDM underwent sleep recordings and 72-hour continuous glucose monitoring. Linear mixed models were used to estimate the association of the apnea-hypopnea index (AHI), rapid eye movement (REM)-AHI, and non-REM-AHI with mean glucose levels during nighttime (two periods: 11 pm to 3 am and 3 am to 6 am), daytime (8 am to 9 pm), and 24-hours. Models were adjusted for BMI and antihyperglycemic medications. RESULTS: In 65 participants who were 35 ± 5 (mean ± SD) years of age with BMI of 33 ± 7 kg/m2, 31% were undergoing insulin and/or metformin therapy. A ten-unit increase in AHI was associated with elevated nocturnal glucose levels (11 pm to 3 am: 0.20 mmol/L [95% CI, 0.04-0.40]) with persistent elevations into the morning (8 am: 0.26 mmol/L [95% CI, 0.08-0.4]) when adjusted for BMI and medications. REM-AHI was also associated with higher nocturnal and morning glucose levels, whereas non-REM was not. AHI was not associated with either mean daytime or 24-hour glucose levels. INTERPRETATION: Greater severity of SDB was associated with higher nocturnal and morning glucose levels in women with GDM.

Optimal Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Reduces Daytime Resting Heart Rate in Prediabetes: A Randomized Controlled Study.

Background It has been widely recognized that obstructive sleep apnea (OSA) is linked to cardiovascular disease. Yet, randomized controlled studies failed to demonstrate a clear cardiovascular benefit from OSA treatment, mainly because of poor adherence to continuous positive airway pressure (CPAP). To date, no prior study has assessed the effect of CPAP treatment on daytime resting heart rate, a strong predictor of adverse cardiovascular outcomes and mortality. Methods and Results We conducted a randomized controlled study in 39 participants with OSA and prediabetes, who received either in-laboratory all-night (ie, optimal) CPAP or an oral placebo for 2 weeks. During daytime, participants continued daily activities outside the laboratory. Resting heart rate was continuously assessed over 19 consecutive days and nights using an ambulatory device consisting of a single-lead ECG and triaxis accelerometer. Compared with placebo, CPAP reduced daytime resting heart rate (treatment difference, -4.1 beats/min; 95% CI, -6.5 to -1.7 beats/min; P=0.002). The magnitude of reduction in daytime resting heart rate after treatment significantly correlated with the magnitude of decrease in plasma norepinephrine, a marker of sympathetic activity (r=0.44; P=0.02), and the magnitude of decrease in OSA severity (ie, apnea-hypopnea index [r=0.48; P=0.005], oxygen desaturation index [r=0.50; P=0.003], and microarousal index [r=0.57; P<0.001]). Conclusions This proof-of-concept randomized controlled study demonstrates, for the first time, that CPAP treatment, when optimally used at night, reduces resting heart rate during the day, and therefore has positive cardiovascular carry over effects. These findings suggest that better identification and treatment of OSA may have important clinical implications for cardiovascular disease prevention. Registration URL: https:/// www.clini​caltr​ials.gov; Unique identifier: NCT01156116.

Maternal Sleep-Disordered Breathing.

Emerging literature suggests that sleep-disordered breathing (SDB) worsens over the course of pregnancy and is associated with adverse maternal and fetal outcomes. Earlier studies, using mainly snoring as a surrogate marker for SDB, have shown an increase in the prevalence of SDB during pregnancy compared with that in the pregravid state. More recently, prospective observational studies in which the investigators ascertained SDB by using complete polysomnography have shown a prevalence ranging from approximately 17% to 45% in the third trimester. Pregnancy itself can be associated with daytime hypersomnolence, so complaints of increasing fatigue and sleepiness during pregnancy are not specific for SDB. Moreover, snoring in isolation also has relatively poor sensitivity and specificity as a screening tool for diagnosing maternal SDB. The indications for screening for SDB during routine obstetric prenatal visits are still unclear, but observational studies indicate that maternal SDB is linked with the development of adverse pregnancy outcomes, such as gestational hypertension and gestational diabetes mellitus. Some studies also have identified a relationship between maternal SDB and the delivery of infants who are small for gestational age. Aside from a few small interventional studies of CPAP in pregnant patients with gestational hypertension, little currently is known about whether treatment of SDB during pregnancy improves clinical outcomes for the mother and/or baby. Additional current knowledge gaps include elucidating underlying mechanisms of maternal SDB, determining optimal treatment strategies, and understanding the trajectory of SDB after delivery.