The blood protein test for early detection of preeclampsia

Prof. Ron Gonen, Deputy Director of the Department of Women and Obstetrics and Director of the Department of Maternity and Delivery Rooms at the Bnei Zion Medical Center, in Haifa, explains how to identify preeclampsia and act against it, following the unfortunate event this week in which a Rambam mother died a few hours after giving birth to twins

Prof. Ron Gonen

Preeclampsia usually appears towards the end of pregnancy, but its roots lie in the first months of pregnancy, at the time when the placental implantation process takes place in the mother's womb. Identifying early signs of preeclampsia gives the opportunity to offer women who are at high risk of the onset of the disease, a variety of treatments that can prevent its appearance or reduce its severity

A new scientific study conducted in Israel tested the early prediction ability of preeclampsia using a protein in the woman's blood, known as PP13. This protein is unique to the placenta and reaches the pregnant mother's blood through the bloodstream. Preeclampsia develops in about 5% of pregnancies and is a serious complication that endangers the health of the mother and the fetus. The signs of the disease are expressed in high blood pressure, increased secretion of protein in the urine and sometimes also damage to the function of the liver, kidneys and the coagulation system. In addition, there may be a disturbance in the functioning of the placenta, a condition that may harm the growth and development of the fetus and may lead to fetal distress, the birth of low-weight and premature babies, with all the risks and complications arising from this. The disease usually appears towards the end of pregnancy, but its roots lie in the first months of pregnancy, at the time when the placental implantation process takes place in the mother's womb. As of today, no treatment has been found that can completely prevent preeclampsia and only childbirth stops the disease. Childbirth is a good solution when the complication appears at the end of pregnancy and the fetus is already ripe for life outside the womb, but it may endanger the health of the baby and even cause its death, when the doctors are forced to induce premature birth. This is why scientists and doctors all over the world are trying to find a way to predict preeclampsia early. Early detection will not only allow these women to be referred to high-risk pregnancy clinics for careful monitoring and optimal treatment, which can improve pregnancy outcomes, but also to offer those women preventive treatment with low-dose aspirin, calcium supplements and folic acid, measures that scientific studies have proven to be able to reduce the rate of the disease and reduce its severity. To date, dozens of markers have been proposed and studied, some of them better and some less good, but the disadvantage of all of them is that the detection is done in advanced stages of pregnancy, at a time when the ability to prevent the disease is already limited. As with other serious diseases, also with preeclampsia, early detection and early initiation of preventive treatment increases the chance of preventing the disease or at least reducing its severity.

In the study, conducted by a team of researchers from the Bnei Zion Medical Center and the Technion's Faculty of Medicine and the start-up company Diagnostic Technologies in Yokneam, and which lasted for about two years, over 1,200 pregnant women who were treated as part of Maccabi Health Services throughout the State of Israel took part. For these women, the PP13 protein level in the blood was tested. The results of the study showed that low levels of PP13 protein in the second month of pregnancy identify about 80% of women who may develop preeclampsia in more advanced stages of pregnancy, i.e. towards the end. The detection involves misidentifying 15% of women who, despite low PP13 values, will not develop preeclampsia. In previous studies published, among others, by Prof. Kypros Nicolaides, the researchers showed that it is possible to minimize the number of women mistakenly identified as having a high risk of suffering from preeclampsia, using a Doppler test, a test of the blood flow in the uterine arteries using ultrasound. In a study conducted in Israel, it was found that the misidentification can be reduced even without the Doppler tests, which is a test that requires expensive equipment, high skill of the tester and therefore a high cost. The researchers from Israel found that in women who did not develop preeclampsia, the PP13 protein level remained low even in the second trimester of pregnancy, while in women who developed the disease later, the PP13 protein level increased from the first to the second and third trimesters. This finding, discovered for the first time by the researchers from Israel, makes it possible to develop the test for the slope of a change in the 13PP level. When the slope is very steep, it reinforces the results of the first test, while when the slope is flat, the warning was wrong and the woman is not expected to develop preeclampsia. So, if a second blood test is performed, at week 16-20, only for those women who were found to have a low level of PP13 in the first trimester of pregnancy, the rate of incorrect prediction can be reduced from 15% to 6%.

The Israeli study joins previous studies conducted in Great Britain, the United States, Germany and South America, which indicate that the PP13 protein test in the blood in the first trimester of pregnancy, which was developed in Israel in the laboratories of the start-up company Diagnostic Technologies, is the earliest means available today for the early prediction of preeclampsia. The uniqueness of the Israeli research is that it provides an easy and simple way to confirm or deny the results of the preliminary test and increase the accuracy of the prediction through the subsequent tests.

This innovative approach, according to which it is possible to increase the accuracy ofPrediction of preeclampsia by monitoring the change in PP13 level in repeated blood tests during pregnancy, and thereby enable very early identification of women who are at high risk of preeclampsia, attracted the attention of the editor-in-chief of the prestigious British journal of obstetrics and gynecology British Journal of Obstetrics and Gynecology in which the study was published, who crowned the article as the editor's choice - - the highest rank awarded to research published in this journal.

In the editorial of the same journal, the editor-in-chief, Prof. Philip Steer, writes that "the research data proves that the PP13 test is of significant importance in the early prediction of preeclampsia, since the test allows the identification of 80% of the women who will have complications." Carrying out a follow-up test only for women who were found to be at risk based on the first test, is a new biostatistical approach, which makes it possible to focus attention on those women who are at high risk, and has important consequences for the women being tested and for reducing the costs of the test for the health system.

The Israeli research shows that today there is a possibility, which did not exist before, to identify women who are at an increased risk of developing preeclampsia. The results of the study also provide guidelines for performing the test in Israel. Pregnant women can perform the blood test for PP13 in week 6-10 (second month) of pregnancy at one of foreign laboratory branches throughout the country. Women who are identified in the first trimester of pregnancy as having a high risk of preeclampsia are referred for consideration of treatment and are invited to perform a second or even a third test, if necessary, at no additional charge. The additional tests can confirm or rule out the existence of the risk factor to a large extent and direct the follow-up.

The author is the deputy director of the women's and obstetrics department and director of the obstetrics and delivery rooms department at the Bnei Zion Medical Center in Haifa, he was the main researcher in the Israeli study and serves as a medical consultant to the start-up company Diagnostic Technologies.

* This article is based on a scientific study published in the December issue of the British Journal of Obstetrics and Gynecology