Dynamic cerebral autoregulation and endothelial dysfunction in preeclampsia

Abstract

Background: Preeclampsia affects approximately 1 in 20 pregnant women and may cause severe morbidity and mortality in both mother and fetus. The pathophysiology remains partly unclear, and the clinical course is highly variable. Reliable tools to predict organ dysfunction are currently lacking. Aim: The overarching aim of this thesis was to investigate whether autoregulation index, angiogenic markers, and glycocalyx degradation products may serve as predictors and indicators of organ dysfunction in preeclampsia, at the time of diagnosis, in the early postpartum period, and 1 year postpartum. Method: We assessed cerebral autoregulation in normotensive pregnancies, preeclampsia, and eclampsia, using transcranial Doppler and non-invasive continuous blood pressure monitoring to calculate the autoregulatory index. In normotensive pregnancies and preeclampsia, we investigated whether plasma concentrations of the glycocalyx degradation products syndecan-1, hyaluronic acid, and thrombomodulin correlated with disease severity, using blood samples collected at inclusion and information on organ dysfunction. We examined whether plasma levels of angiogenic markers and glycocalyx degradation products could predict subsequent organ dysfunction in women with preeclampsia. Blood samples were collected at diagnosis, and clinical outcomes were monitored. Results: Cerebral autoregulation was found to be enhanced in normotensive pregnancies but depressed in preeclampsia. No differences were observed between preeclampsia with and without organ dysfunction. One year postpartum, autoregulation was comparable across groups. Cerebral autoregulation was depressed in eclampsia in the early postpartum period. Syndecan-1 levels were equal regardless of disease and disease severity. Hyaluronic acid was increased in preeclampsia but did not correlate with extent of organ dysfunction. Thrombomodulin levels were elevated in preeclampsia and even more so in cases with multiple organ dysfunctions. None of the glycocalyx markers reliably predicted overall organ dysfunction, though hyaluronic acid predicted thrombocytopenia and liver injury. sFlt-1 concentrations predicted thrombocytopenia, liver, and kidney injury, while PlGF and the sFlt-1/PlGF ratio showed limited predictive value. Conclusion: Cerebral autoregulation is depressed in preeclampsia and eclampsia, underscoring the importance of blood pressure management to prevent cerebral complications. Although sFlt-1 dysregulation and glycocalyx degradation appear involved in preeclampsia pathophysiology, their utility in predicting organ dysfunction in women with a preeclampsia diagnosis is limited.