Pre-eclampsia

Preeclampsia (old name: EPH- eclampsia, Spätgestose or Schwangerschaftsintoxikation ) denotes a hypertensive disorder in pregnancy ( pregnancy-induced hypertension ). In rare cases, it occurs only up to 14 days after delivery. Characterized preeclampsia traditionally by the prognostic trend-setting keynotes hypertension ( high blood pressure) and proteinuria (protein in the urine). Edema ( water retention ) alone does not affect the prognosis of mother and child. From these three cardinal symptoms, there is also the common name today EPH- eclampsia: Edema (English ) for edema, proteinuria and hypertension for hypertension.

Symptoms

Besides the already mentioned three cardinal symptoms (edema, proteinuria and hypertension ) sufferers report dizziness and headaches, dizziness, visual disturbances such as blurred vision, nausea and vomiting. The doctor can tell a hyperreflexia ( exaggerated reflexes ).

In addition, it comes in 20 % of cases of liver involvement and thus an increase in liver enzymes (transaminases, alkaline phosphatase and bilirubin), which can be detected by laboratory tests.

In a study in mice pre-eclampsia symptoms were simulated by inducing a lack of catechol-O- methyltransferase ( COMT).

Epidemiology

Pre-eclampsia develops in about 5 to 7 percent of all pregnancies in Western Europe. In 70 % of these cases there is a pre-eclampsia, in 30% of a previously passed, undiagnosed hypertension. More commonly affected are first-time mothers and women over 35 years. Other risk factors include the occurrence of pre-eclampsia in a previous pregnancy, multiple pregnancies, pre-existing hypertension, obesity and diabetes mellitus. Several studies indicate that periodontal disease may increase the risk of severe pre-eclampsia.

Etiology

The causes of preeclampsia are not currently clear. Discussed an impaired implantation of the trophoblast, which leads to an undesirable development of the arterial vessels in the placenta. Also, disorders in the prostaglandin metabolism appear to play a role. A bacterial or viral origin, however, is unlikely. A study by the University of Pittsburgh shows that a vitamin D deficiency in early pregnancy favored the emergence of the disease. A number of recent studies suggest, however, appear to be most likely a central involvement of blood pressure - regulating ( endothelial ) substances.

Changes in the kidney

Signaling molecules that are released from the altered placental be accessed through the bloodstream to the kidneys and lead to renal characteristic changes that are responsible for the main symptoms of toxemia.

The renal corpuscles ( glomeruli ) are enlarged, the lumina of capillary loops are closed due to swelling of endothelial and mesangial cells. The swelling of endothelial cells, also referred to as endotheliosis. The number of endothelial cells is not increased. This affects only the specific fenestrated endothelium of the renal corpuscle, the endothelial cells of the arterioles are not changed. The cause of eclampsia is probably a local Gefäßkonstriktionen of medium caliber arteries to the capillaries ( stasis, edema). In the immunofluorescent deposits of fibrin are detectable immune complexes lacking. This can lead to thrombosis of the renal vessels come ( thrombotic microangiopathy ). In electron microscopy, the window of the endothelial cells are missing. Endothelial cells and mesangial cells are so swollen by accumulation of fluid and lipids that Kapillarlichtungen are gone. The capillary lining cells ( podocytes ), however, are not changed ( pictures below ).

The closure of Kapillarlichtungen leads to a decrease in glomerular filtration rate and thus deterioration of renal function, water retention and high blood pressure. The cause of proteinuria has not yet been clarified. In other kidney diseases, proteinuria is usually due to changes in podocytes, whereas the podocytes appear not changed during preeclampsia.

In the healthy kidney, the podocyte constantly produce the growth factor vascular endothelial growth factor ( VEGF). This growth factor is a prerequisite for a proper function of endothelial cells, especially for the formation of the characteristic window. In the absence of VEGF, the endothelial cells of the renal corpuscle lose the windows and swell. In the blood of patients with toxemia of high concentrations of a soluble VEGF receptor are detectable before onset of symptoms, referred to as soluble fms -like sVEGFR1 or tyrosine kinase ( sFlt1 ). sFlt1 is produced in the placenta, enters the blood stream into the kidney, binds to VEGF in the glomeruli and inhibits its activity.

Endoglin, another protein that is elevated in pre-eclampsia, also leads to endothelial swelling, but does not cause proteinuria. In animal experiments, the simultaneous administration of endoglin and sFlt1 to very serious diseases.

Diagnostics

In cases of suspected pre-eclampsia - the pregnant woman reported dizziness and headache, drowsiness, blurred vision, nausea and vomiting - must be necessarily admitted to the hospital the victim. The diagnosis should be done first several blood pressure measurements. The excretion of protein in the urine ( proteinuria) should be measured, this should be carried out for the diagnosis not using urine test strips, as well as pregnant women physiologically enhances the excretion of proteins, but with a 24 - hour urine collection. The urine test strips can be used to monitor the progress. Although the diagnostic edema have lost their importance, they can be used by means of weight measurement for rough follow-up.

From pre-eclampsia occurs when an in pregnancy new onset blood pressure of 140 /90 ( or an increase of more than 30 /15) and thus induced by pregnancy hypertension is present and in the urine of the last 24 hours, more than 300 mg of protein per day then measured and proteinuria is confirmed.

A report by the National Institute of Child Health and Human Development of the United States, according to a research team at Richard Levine now found in Bethesda, a test method for the early detection of pre-eclampsia. The researchers had once again made ​​the blood samples of the participants of the "Calcium for Preeclampsia Prevention " study. There, before the preventive effect of calcium had been worked out effectively as not significant. They noticed in the re- analysis that the Endoglinwert increases already two to three months before the clinical onset of pre-eclampsia. They subsequently published a case-control study in the New England Journal of Medicine, showing that in the blood of pregnant women, an increase of certain proteins is detectable already weeks before the first symptoms. This allows pre-eclampsia diagnosed using serum markers. In women with preeclampsia, there are changes in serum levels of PlGF ( placental growth factor) and sFlt -1 (soluble fms -like tyrosine kinase -1, and VEGF receptor -1). Moreover can be limited prior to the onset of clinical symptoms due to the detection of the PlGF and / or sFlt -1 concentrations in the blood of a normal pregnancy associated with pre-eclampsia of pregnancy. In a normal pregnancy, the pro- angiogenic factor PlGF increases during the first two trimesters and decreases towards the end of pregnancy. In contrast, the anti-angiogenic factor sFlt- 1 during the early and middle stages of pregnancy remains the same, and then displays to the end of pregnancy, a steady increase. In women who develop pre-eclampsia, increased sFlt -1 levels and lower PlGF concentrations were found than in normal term pregnancies. Recent studies have shown that the determination of PlGF higher sensitivity aufwie as the quotient of sFlt1/PlGF. Also, in pre-eclampsia placental endoglin, a member of the TGF- β family, upregulated and released as soluble endoglin in the bloodstream of the mother. In severe cases of preeclampsia showed an increased concentration of soluble endoglin.

In summary it can be said that the possibilities for the diagnosis of pre-eclampsia, the date on clinical symptoms, proteinuria determination ( at least 24 hours) and artery based uterine Doppler sonography in by the rapid immunological determination of PlGF and sFlt -1 concentrations blood of the mother can be significantly improved.

Therapy

Since the cause of the disease is still unclear, one should be careful with the treatment of the symptoms. In particular, the attempt to combat edema with low-salt diet or even drainage treatments, usually leads to the deterioration of the health status of pregnant women and to a threatening condition of the fetus, which can then often saved only by an immediate emergency C-section.

An uncontrolled drug lowering blood pressure can lead to a deficiency of the fetus and should therefore not be - for the protection of pregnant women - at constant values ​​over 170/110 mmHg done. However, the blood pressure should not be reduced below 140/90 so as not to greatly reduce the " need for high-pressure " of the child and thus not to endanger the child. By special preparations, however, can - by dilation of the uterine vessels - on the one hand an effective, necessary for the mother's blood pressure reduction can be achieved and at the same time the child's care be ensured. Due to the protein loss through the proteinuria enough protein must be supplied through the diet.

In severe cases, can be expected with the occurrence of seizures ( eclampsia → ).

It is compulsory for the regular monitoring of the fetal heart actions with the Cardiotokogramm (CTG ) and regular growth and, where appropriate, the child Doppler checks to diagnose a chronic placental insufficiency in time. In extreme cases, a premature termination of pregnancy is essential to prevent eclampsia, which can be life-threatening for both the child and the mother.

Preventive measures

According to an American study, which was conducted from 1996 to 2000 to 2291 pregnant women, the consumption of chocolate may reduce the risk of pre-eclampsia in pregnant women. The number of women with relevant symptoms was there a direct negative depending on the level of theobromine contained in chocolate in serum.

Course

The history of pre-eclampsia is progressive and difficult to predict. Each diagnosed pre-eclampsia requires hospitalization and close medical supervision. As severe complications of preeclampsia eclampsia or HELLP syndrome may occur. Basically, a careful risk assessment, consideration of risks for both mother and the unborn child must be made. By lowering blood pressure alone can not prevent an aggravation.

Forecast

The risk of preterm birth and life-threatening blood pressure derailment of the mother increases with the severity of pre-eclampsia. Therefore, the control and possible control of blood pressure and the measurement of excreted protein in urine as part of prenatal care is very important. Early detection of pre-eclampsia is possible since 2009 by means of a blood test.

The symptoms are formed after birth ( whether these are spontaneous or forced to enter ) back. Late damage to the child have become rare nowadays.