ObjectiveTo evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio in physicians’ decision making in pregnant women with signs and symptoms of preeclampsia in routine clinical practice.MethodsA multicenter, prospective, open, non-interventional study enrolled pregnant women presenting with preeclampsia signs and symptoms in several European perinatal care centers. Before the soluble fms-like tyrosine kinase 1/placental growth factor ratio result was known, physicians documented intended clinical procedures using an iPad® application (data locked/time stamped). After the result was available, clinical decisions were confirmed or revised and documented. An independent adjudication committee evaluated the appropriateness of decisions based on maternal/fetal outcomes. Clinician decision making with regard to hospitalization was the primary outcome.ResultsIn 16.9% of mothers (20/118) the hospitalization decision was changed after knowledge of the ratio. In 13 women (11.0%), the initial decision to hospitalize was changed to no hospitalization. In seven women (5.9%) the revised decision was hospitalization. All revised decisions were considered appropriate by the panel of adjudicators (McNemar test; p < 0.0001).ConclusionsThe use of the soluble fms-like tyrosine kinase 1/placental growth factor test influenced clinical decision making towards appropriate hospitalization in a considerable proportion of women with suspected preeclampsia. This is the first study to demonstrate the impact of angiogenic biomarkers on decision making in a routine clinical practice.

During pregnancy, substantial alterations in cerebral plasticity, vascular remodeling and neuronal growth occur in the maternal brain. We investigated whether concentrations of selected neurodiagnostic biomarkers in the cerebrospinal fluid of women with preeclampsia/HELLP syndrome differ from those in healthy controls using enzyme-linked immunosorbent assay technique. We found that tau protein concentrations (p = 0.016) and phospho-tau/tau ratio (p < 0.001) in cerebrospinal fluid were significantly lower in 39 preeclamptic women compared to 44 healthy controls during third trimester of pregnancy. Beta-amyloid(1-40)/(1-42) ratio was significantly higher in HELLP syndrome than in severe preeclampsia (8.49 + 2.73 vs. 4.71 + 1.65; p = 0.007). We conclude that betaamyloid(1-40)/(1-42) ratio in cerebrospinal fluid can discriminate severe preeclampsia and HELLP syndrome. High beta-amyloid peptide and low tau protein concentrations are associated with impaired development of the materno-feto-placental unit and correlate with placental dysfunction. During pregnancy, the invasion of trophoblast cells into maternal tissue of the uterus and the conversion of spiral arteries into wide sinusoids with low resistance and high flow are paramount for normal placental development 1. In preeclampsia (PE) placental development is impaired by defective deep placentation, platelet and thrombin activation, intravascular inflammation, endothelial dysfunction and imbalanced angiogenesis 2. Altered expression of proteins comes along with excess of antiangiogenic substances such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) and decreased levels of proangiogenic substances like placental growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) 3. Ciampa et al. observed in 13 patients with PE altered concentrations of proteins related to signaling pathways important for vascular remodeling, inflammation, and neuronal growth 4. Recent studies have shown that PE shares pathophysiologic features with recognized misfolding disorders and aggregation of proteins 4-8. There are several dysregulated proteins in PE but it is not clear whether aggregated proteins induce defective trophoblast invasion 4. D'Souza et al. reported that neurotrophic factors influence the development of the materno-feto-placental unit during pregnancy 9. Altered blood-brain barrier and impaired cerebral autoregulation may affect erebral blood flow in the maternal brain 10. Aggregated beta-amyloid peptides were observed in PE as well as in Alzheimer's disease 7. The presence of beta-amyloid aggregates in placentas of women with PE and intrauterine growth restriction (IUGR) further supports the notion that this condition goes with protein conformational disorders 6,11. Moreover, it was observed that short peptides occupying the self-recognition sites of beta-amyloid inhibit beta-amyloid aggregation 8. The aim of this study was to determine whether CSF concentrations of beta-amyloid peptides and tau protein differ between women with PE...

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