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（如先兆子痫）有关。该项目的目的是了解OSA与胎盘组织病理学和功能异常的关系，反映在与先兆子痫发展相关的胎盘分泌标志物的改变中，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，该项目计划招募有OSA风险的妇女，通过家庭睡眠呼吸暂停测试对她们进行筛查，并招募OSA阳性诊断的妇女参加该项目。在入组时，女性将进行基线临床风险评估和循环标志物测量。然后，这些妇女将随机接受气道正压通气治疗（非妊娠人群中接受的OSA治疗）或鼻贴（安慰剂）。本项目中使用的骨灰盒随机化方法将优化两组中OSA严重程度分布相似的机会。两组中的妇女将接受强化培训和频繁监测依从性，气道正压通气组远程，鼻贴组通过电话和监测需要补充。循环标志物和血压测量将在妊娠中期和晚期重复进行，并在两组中进行比较。由于睡眠质量可能是结局的潜在混杂因素，因此将在孕早期和孕晚期使用问卷和体动记录进行睡眠质量评估。在分娩时，将收集女性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记物，并证明这些标记物的来源是胎盘而不是其他组织。了解OSA和先兆子痫之间的联系机制将有助于识别处于不良结局（如先兆子痫）风险中的女性。这些知识将用于为预防和治疗一种疾病的重点战略铺平道路，这种疾病代表着巨大的经济负担，是母亲及其子女长期心血管和代谢结果的前兆。

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.