Placental role in mediating adverse outcomes in obstructive sleep apnea

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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.