Placental role in mediating adverse outcomes in obstructive sleep apnea

描述(由申请人提供)：阻塞性睡眠呼吸暂停(OSA)与胎盘介导的结局有关，如先兆子痫。本项目的目的是了解OSA与胎盘组织病理学和功能异常的关系，反映在胎盘分泌标志物的变化上，这些标志物与子痫前期的发展有关，并评估OSA治疗对胎盘形态和功能的影响。为了实现这些目标，该项目计划招募OSA高危女性，通过家庭睡眠呼吸暂停测试对她们进行筛查，并招募那些被诊断为OSA阳性的人参与这一项目。在登记时，妇女将接受基线临床风险评估和循环标志物的测量。然后，这些妇女将被随机分成两组，分别接受正压治疗(非妊娠人群接受的阻塞性睡眠呼吸暂停治疗)或鼻带(安慰剂)。本项目中使用的骨灰盒随机化方法将优化两组OSA严重程度分布相似的机会。两组中的妇女都将接受强化培训和经常监测依从性，远程监测呼吸道正压组，并通过电话和监测鼻带组的补药需求。在孕中期和孕晚期重复循环标志物和血压测量，并对两组进行比较。由于睡眠质量可能是结果的潜在混杂因素，因此将在怀孕的第一和第三个三个月通过问卷和活动记录仪进行睡眠质量评估。在分娩时，妇女将收集她们的胎盘进行显微组织检查和染色，以识别胎盘组织中相同的循环标志物，并证明这些标志物的来源是胎盘而不是其他组织。了解阻塞性睡眠呼吸暂停综合征和先兆子痫之间的联系机制，将有助于确定面临先兆子痫等不良后果风险的妇女的努力。这些知识将被用来为预防和治疗这种疾病的重点战略铺平道路，这种疾病是一种巨大的经济负担，是母亲及其子女长期心血管和新陈代谢结果的先兆。

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) has been linked to placenta-mediated outcomes such as preeclampsia. The aims of this project are to understand the association of OSA with abnormalities in placental histopathology and function, reflected in alterations in placenta-secreted markers that have been linked to the development of preeclampsia, and to evaluate the effect that treatment of OSA will have on placental morphology and function. To meet these aims, the project plans to recruit women at risk for OSA, screen them with home sleep apnea testing and enroll those with a positive diagnosis of OSA to participate in this project. At enrollment women will have baseline clinical risk assessment and measurement of circulating markers. These women will then be randomized to receive positive airway pressure therapy (accepted therapy for OSA in the non-pregnant population) or nasal strips (placebo). The urn randomization method utilized in this project will optimize the chance of having a similar distribution of OSA severity in the two groups. Women in both groups will receive intensive training and frequent monitoring of compliance, remotely for positive airway pressure group, and by phone calls and monitoring of need for refills in the nasal strips group. Circulating markers and blood pressure measurements will be repeated in the second and third trimester and compared in both groups. Sleep quality assessment with questionnaires and actigraphy will be performed in the first and third trimester since sleep quality may be a potential confounder of outcomes. At the time of delivery, women will have their placentas collected for microscopic tissue examination and for staining that will identify th same circulating markers in placental tissue and to demonstrate that the source of these markers is the placenta rather than other tissues. Understanding the mechanisms linking OSA and preeclampsia will facilitate efforts to identify women at risk for adverse outcomes such as preeclampsia. Such knowledge will be used to pave the way for focused strategies in prevention and treatment of a disorder that represents a substantial financial burden and is the precursor of long- term cardiovascular and metabolic outcomes in both mothers and their children.