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.

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).

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.

Prevalence of obstructive sleep apnea-hypopnea in severe versus moderate asthma.

BACKGROUND: Previous studies have suggested a link between obstructive sleep apnea and poor asthma control, which may be mediated through airway inflammation, obesity, and other mechanisms. OBJECTIVE: To test the hypothesis that the prevalence and severity of sleep apnea is greater among patients with severe compared with moderate asthma and controls without asthma. METHODS: Complete overnight home polysomnography was performed in 26 patients with severe asthma consecutively recruited to a difficult asthma program, 26 patients with moderate asthma, and 26 controls without asthma of similar age and body mass index. Flow rates and Juniper asthma control and quality of life questionnaires were also obtained. RESULTS: Obstructive sleep apnea-hypopnea, defined by an Apnea-Hypopnea Index > or = 15 events/h of sleep scored using Chicago criteria, was present in 23 of 26 (88%) patients with severe asthma, 15 of 26 (58%) patients with moderate asthma, and 8 of 26 (31%) controls without asthma (chi(2): P < .001). Using the more restrictive scoring criteria applied in the Wisconsin cohort study, Apnea-Hypopnea Index > or = 5/h was present in 50% (severe), 23% (moderate), and 12% (control) of subjects (P = .007). Mean nocturnal arterial oxygen saturation was significantly lower in patients with severe asthma versus controls, and apnea-hypopnea severity measures were significantly worse for both asthmatic groups compared with controls. Among subjects with asthma, no significant correlations were identified between the severity of sleep-disordered breathing and asthma severity or control measures (FEV(1), Juniper scores). CONCLUSIONS: Obstructive sleep apnea-hypopnea was significantly more prevalent among patients with severe compared with moderate asthma, and more prevalent for both asthma groups than controls without asthma. These observations suggest potential pathophysiologic interactions between obstructive sleep apnea-hypopnea and asthma severity and control.

A Pilot Randomized-Controlled Trial on the Effect of CPAP Treatment on Glycemic Control in Gestational Diabetes: Study Design and Methods.

Background: Gestational diabetes (GDM) is associated with adverse short- and long-term maternal and fetal outcomes. Observational data support a link between sleep-disordered breathing (SDB) during pregnancy and GDM. However, it is unknown whether treatment of SDB with continuous positive airway pressure (CPAP) improves glucose control in this patient population. In addition, CPAP adherence and feasibility as a treatment option in pregnancy is unknown. This pilot randomized, controlled trial aims to primarily determine the feasibility of CPAP treatment in pregnant women with SDB and GDM. This study is also investigating the effect of SDB treatment on 24-h glucose profiles as an exploratory outcome. Objectives: To describe the study methodology in this ongoing study of pregnant women with GDM and SDB. Patients and Methods: Pregnant women with GDM and SDB defined by apnea-hypopnea index (AHI) ≥10 (Chicago Scoring Criteria) on level 2 polysomnography are randomized to either auto titrating CPAP (experimental group) or a nasal dilator strip (control group) until delivery. The primary outcome, objectively-assessed adherence to CPAP, is measured over the course of the treatment period using device-specific software. Recruitment and retention rates will be calculated to assess the feasibility for planning future trials. Twenty-four hour glucose profiles are measured over a 72-h period using the continuous glucose monitoring (CGM) system, before and after the intervention. Conclusion: The results of this study will be highly informative to determine whether CPAP is a feasible treatment for pregnant women with GDM and SDB, a specialized population at risk for substantial comorbidity. The trial results will ultimately be useful in planning future SDB treatment trials in pregnancy and GDM. The study is registered on clinicaltrials.gov (NCT02245659).