PROJECT SUMMARY/ABSTRACT Preeclampsia (PEC) affects 1 in 20 pregnancies and is a leading cause of severe maternal morbidity and mortality. Life-threatening neurological complications of PEC include intracerebral hemorrhage, cerebral edema, cerebral vasospasm, and ischemic stroke. Most maternal deaths due to PEC-associated cerebrovascular complications occur postpartum. Despite this, clinical research has primarily focused on antepartum blood pressure (BP) treatment, rather than postpartum. Current BP management guidelines for postpartum patients recommend absolute thresholds for treatment, without accounting for factors such as degree or rapidity of change from patients’ baseline BP. Clinicians urgently need better methods to 1) identify individuals at risk for these devastating postpartum complications, and 2) guide BP management using personalized, precise targets optimized for brain protection. Normal brain function requires constant cerebral blood flow (CBF). Cerebral arterioles respond actively in response to fluctuations in BP, protecting the brain from acute injury due to hypo- or hyper-perfusion, a phenomenon known as cerebral autoregulation. Changes in cerebral autoregulation contribute to the pathophysiology of postpartum cerebrovascular complications. In individuals with impaired autoregulation, targeting BP parameters to optimize cerebral perfusion could help reduce the risk of ischemia, elevated intracranial pressure, cerebral edema and intracerebral hemorrhage. Near-infrared spectroscopy (NIRS) is a non-invasive bedside monitoring modality that measures brain tissue oxygenation as a proxy for CBF. The use of NIRS-based autoregulation-guided BP targets improves clinical outcomes in neurologically injured patients. We propose to apply this novel approach to the management of postpartum PEC (within 6 weeks of delivery) in a single-center, Phase II clinical trial, PROMIS (PROtecting Maternal brains from Injury and Stroke). We will use NIRS monitoring to calculate personalized limits of cerebral autoregulation in 20 individuals with postpartum preeclampsia with severe features (Aim 1); and pilot the use of autoregulation-guided BP goals for postpartum preeclampsia with severe features in an additional 20 individuals (Aim 2). We hypothesize that: 1) standard guideline-based BP management for postpartum PEC over 24 hours will result in ≥ 10% of time during which BP exceeds personalized upper or lower limits of autoregulation; 2) more time with BP outside personalized limits of autoregulation will be associated with a) increased neurological symptoms and b) objective evidence of cerebral hypo- or hyper-perfusion by NIRS; and 3) targeted BP management using autoregulation-guided goals will result in fewer neurological symptoms and less time spent outside limits of autoregulation, compared with patients treated according to current guidelines. This novel, high-risk, high-reward trial will be the first early phase interventional neuro-obstetric trial aimed at preventing postpartum maternal death and disability due to neurological causes.

PROJECT NARRATIVE Acute neurological complications, including intracerebral hemorrhage, cerebral edema, cerebral vasospasm, and ischemic stroke, are a leading cause of postpartum severe maternal morbidity and mortality in individuals with preeclampsia. We propose to apply a novel, non-invasive neuromonitoring approach to the management of BP in postpartum preeclampsia in a single-center, Phase II clinical trial, PROMIS (PROtecting Maternal brains from Injury and Stroke). We will use near-infrared spectroscopy monitoring to calculate personalized limits of cerebral autoregulation in 20 individuals with postpartum preeclampsia with severe features (Aim 1); and pilot the use of autoregulation-guided BP goals for treatment of postpartum preeclampsia with severe features in an additional 20 individuals with (Aim 2).