Updates on Pre-eclampsia

I am going to present updates on pre-eclampsia . We’ll start by reviewing epidemiological data and then turning to new insights on pathophysiology followed by guidelines on clinical management and perspectives in prevention. With regards to epidemiology, the incidence rate of PE worldwide ranges from 2-17 cases per 100 deliveries. However, databases are not available for all countries. If we concentrate on the data from the United States and Europe, it can be seen that they are very similar, in fact the incidence rate is between 2.6 and 5.3 for the States and between 2.5. and 6.5 in Europe. As we all know as obstetricians, PE is one of the most serious complications encountered during pregnancy and according to UK statistics , PE and eclampsia are number 2 among the causes of direct maternal death, accounting for 13.6 % of all maternal deaths The most frequent complication of severe PE according to our data is HELLP Syndrome, followed by abruptio placenta, disseminated intravascular coagulation, acute renal failure, eclampsia. and pulmonary edema. With regard to the fetus in our series of PE, we registered more than 37% of pre-term deliveries before 28 weeks, 46% FGR and 5% of perinatal mortality Moving on to pathophysiology, the clinical manifestations of the disease are the results of a complex series of chain of events, starting from a defective recognition of the trophoblast by decidual immune cells and immune activation causing , an abnormal trophoblastic invasion of the spiral arteries and an excessive inflammatory response, which in turn are responsible for placental ischemia , oxidative stress and release of proinflammatory cytokines causing systemic endothethial cell dysfunction associated with platelet and clotting system activation and vasoconstriction. (And of course, pre-existing medical conditions, such as obesity, insulin resistance, hyperglycemia, hyperlipedemia, chronic hypertension, thrombophilia, renal disease ,SLE , favour some of these pathophysiological events.) With regards to apoptosis it is known that this process occurs through two broad pathways: the intrinsic pathway also known as the mitochondrial pathway which can be triggered by any stimuli that causes oxidative stress and mytochondrial disturbances and/or DNA damage and the extrinsic pathway also known as the death receptor pathway, through which apoptosis is induced by the ligand binding of death receptors. One of the most important ligand death receptor system is the FAS ligand –FAS. The FAS-ligand induces apoptosis by binding to FAS ,its cognate receptor. And the FAS Ligand is expressed in somatic cells in areas of immune privilege such as the trophoblastic cell and the binding of FAS ligand to FAS expressed on T-lymphocytes leads to the recruitment of FAS -associated death domain forming a complex which can bind to initiator caspases thereby leading to apoptosis. We found that the 670 G Fas gene variant, which is associated with a decreased FAS production in activated T-lymphocytes, is significantly more frequent in Pre- eclamptic women than in normal pregnant subjects. This finding may explain why under normal conditions normal Fas expression on avtivated T-lymphocytes may allow interaction with Fas ligand expressed on trophoblasts. Therefore, the induction of apoptosis in these T-cells makes them unable to recognize and destroy the cytotrophoblasts invading the myometrial spiral arteries. On the contrary, in preeclampsia the lower expression of Fas on activated T lymphocytes decreases the possible interaction with Fas ligand on trophoblasts. As a consequence T lymphocytes undergo a reduced apoptosis and are therefore able to destroy the trophoblasts.