Treatment of obstructive sleep apnea in high risk pregnancy: a multicenter randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) during pregnancy is a risk factor for preeclampsia possibly through a link to placental physiology. This study evaluates the efficacy of continuous positive airway pressure (CPAP) on the modulation of blood pressure and the reduction in preeclampsia in women with high-risk pregnancy and OSA. METHODS: A multicenter open-label, randomized controlled trial comparing CPAP treatment versus usual antenatal care was conducted in three academic hospitals in Bangkok, Thailand. Participants included singleton pregnant women aged older than 18 years with any high-risk condition (i.e., chronic hypertension, obesity, history of preeclampsia or gestational diabetes in the previous pregnancy, or diabetes), and OSA (respiratory disturbance index 5-29.99 events/hour by polysomnography), who presented either in the first trimester (gestational age, GA 0-16 weeks) or subsequently developed OSA during the 2nd trimester (GA 24-28 weeks). The primary endpoint was blood pressure during antenatal care. Secondary endpoints included the incidence of preeclampsia. An intention-to-treat analysis was performed with additional per-protocol and counterfactual analyses for handling of nonadherence. RESULTS: Of 340 participants, 96.5% were recruited during the first trimester. Thirty participants were later excluded leaving 153 and 157 participants in the CPAP and usual-care groups for the modified-intention-to-treat analysis. CPAP adherence rate was 32.7% with average use of 2.5 h/night. Overall, CPAP treatment significantly lowered diastolic blood pressure (DBP) by - 2.2 mmHg [95% CI (- 3.9, - 0.4), p = 0.014], representing approximately - 0.5 mmHg per hour of CPAP use [95%CI (- 0.89, - 0.10), p = 0.013]. CPAP treatment also altered the blood pressure trajectory by continuously lowering DBP throughout pregnancy with mean differences (95% CI) of - 3.09 (- 5.34, - 0.93), - 3.49 (- 5.67, - 1.31) and - 3.03 (- 5.20, - 0.85) mmHg at GA 18-20, 24-28, and 32-34 weeks, respectively compared to 0-16 weeks. Preeclampsia rate was 13.1% (20/153 participants) in the CPAP and 22.3% (35/157 participants) in the usual-care group with a risk difference (95% CI) of - 9% (- 18%, - 1%, p-value = 0.032) and a number-needed-to-treat (95% CI) of 11 (1, 21). CONCLUSIONS: CPAP treatment in women with even mild-to-moderate OSA and high-risk pregnancy demonstrated reductions in both DBP and the incidence of preeclampsia. CPAP treatment also demonstrated a sustained reduction in DBP throughout gestation. Trial registration ClinicalTrial.GovNCT03356106, retrospectively registered November 29, 2017.

Determinants of Wake Pco2 and Increases in Wake Pco2 over Time in Patients with Obstructive Sleep Apnea.

RATIONALE: The progression from obesity and obstructive sleep apnea to obesity with hypoventilation and daytime hypercapnia may relate to features of sleep-disordered breathing events that affect loading and unloading of carbon dioxide. OBJECTIVES: To determine whether the wake Pco2 increases over time in untreated obstructive sleep apnea, and whether that increase is explained by changes in sleep-disordered breathing event duration, interevent duration, or postevent ventilation amplitude. METHODS: We selected 14 adults who had two polysomnographic studies more than 1 year apart because of untreated or suboptimally treated moderate to severe obstructive sleep apnea. Demographic and polysomnographic data were reviewed for both sets of studies, including the evening wake end-tidal CO2, the ratio of mean event to mean interevent duration (subsuming apneas and hypopneas), and the ratio of mean post- to preevent breath amplitude. MEASUREMENT AND MAIN RESULTS: The mean (SD) wake end-tidal Pco2 increased between studies from 35.9 (4.2) to 39.5 (3.9) mm Hg (P < 0.005). The wake end-tidal CO2 correlated inversely with the post- to pre-event breath amplitude and positively with the ratio of mean event to mean interevent duration and with body mass index. However, those three variables were not significantly changed between the two studies. The wake end-tidal CO2 did not correlate with the apnea-hypopnea index or age. There was a significant increase in bicarbonate level between studies (median, 24.0-26.5 mmol/L; P = 0.01). CONCLUSIONS: In our study cohort, wake end-tidal CO2 correlated with body mass index and features of sleep apnea that influence the balance of loading and unloading of CO2. However, those features remained fixed over time, even as the wake Pco2 and bicarbonate levels increased with untreated sleep apnea.