**6.3 PAPP-A**

*Prediction of Maternal and Fetal Syndrome of Preeclampsia*

**26**

**6.2 sFlt-1/PlGF ratio**

*endothelial dysfunction.*

**Figure 2.**

of preeclampsia [55].

ing and monitoring PE [56].

Researches show that sFlt-1 is an antiangiogenic molecule and therefore seems to be involved importantly in the pathogenesis of preeclampsia. High levels of circulatings sFlt-1 in early pregnancy are associated with the later commencement of preeclampsia. An in vitro research shows that sFlt-1 inhibits tube formation of endothelial cells from human umbilical vein. In essential cytotrophoblast cell culture, sFlt-1 production and mRNA expression are related inversely to oxygen saturation. A twofold elevation in the level of sFlt-1 was also observed when normal villous explants were exposed to a hypoxic state (1% oxygen), compared with physiologic exposure to 5% oxygen. Therefore, it is reasonable that the hypoxic placenta releases an excess of sFlt-1 into the maternal circulation, which induces maternal endothelial dysfunction and clinical symptoms of preeclampsia. There is also a tendency that an excess of sFlt-1 production can trigger events in the pathogenesis

*An excessive production of sFlt-1 is known in patients with preeclampsia. As an antagonist, it binds with high affinity to free PIGF in maternal serum. Thereby, proangiogenic effects by binding of PIGF to membranous sFlt-1 receptors (a vascular endothelial growth factor) are inhibited and are thought to be responsible for* 

Especially, the sFlt-1/PlGF ratio connects to the clinical condition of the disease,

differentiates between healthy and preeclamptic pregnancies, and gives a shortterm prediction of disease development. Consequently, the estimation of sFlt-1 and PlGF was measured in clinical routine as a reliable and meaningful tool in examin-

Research on antiangiogenesis factors such as sFlt-1 failed to convince as the exclusive marker for the prediction of preeclampsia in the first trimester [51]. Verlohren et al. showed that the combination of angiogenesis and antiangiogenesis factors, at least in the second and third trimesters, may offer the possibility of a risk classification by an sFlt-1/PlGF ratio. It was found that patients with preeclampsia

Pregnancy-associated plasma protein A (PAPP-A), an insulin-like growth factorbinding protein protease, is secreted by the syncytiotrophoblast. As part of the first-trimester screening, it has long been used in risk calculation for chromosomal abnormalities. We could show that patients with decreased levels of PAPP-A in maternal blood during the first trimester develop preeclampsia [54], especially an early-onset preeclampsia as revealed also by others [34, 59, 60, 74].
