Researchers at Tel Aviv University were able to decipher 25 markers that make it possible to predict with 85% accuracy whether a woman is prone to preeclampsia. Dr. Noam Shomron: "The findings form the basis for the development of a simple blood test to predict preeclampsia at an early stage of pregnancy"
A study led by Dr. Noam Shomron and Prof. Moshe Hod from Tel Aviv University's School of Medicine, revealed for the first time molecular markers in the blood of women at the beginning of pregnancy, and the future of having preeclampsia. The biological markers, discovered through new generation genetic sequencing technology and advanced computational methods, may allow early diagnosis with a high degree of certainty, followed by preventive treatment, which will completely prevent the onset of the disease.
The research was carried out at Tel Aviv University by doctoral student Liron Yaffe, in collaboration with Prof. Moshe Hod, Director of the Research Institute for Perinatal Medicine at Beilinson Hospital and President of the European Association for Maternal and Fetal Medicine and with other hospitals in England, Russia, Italy and Spain. The article was published on Wednesday, 21.2.18, in the journal scientific report Of the group Nature.
"Up to 8 percent of pregnant women may suffer from preeclampsia during the second or third trimester of their pregnancy," explains Dr. Shumron. "This is a serious disease that endangers the health, and sometimes even the lives, of the mother and the fetus. It is not known what causes it, but there is a proven and simple preventive treatment for it: administration of low-dose aspirin - starting from the 16th week at the latest, until the end of the pregnancy." As of today, the preventive treatment is given to pregnant women who are considered to be at risk of developing preeclampsia, according to their doctors' assessments. But in the absence of a clear and unequivocal biological marker for early diagnosis, the prediction is based on general criteria, such as previous pregnancies, the patient's feelings, blood pressure or sophisticated ultrasound tests combined with blood biochemistry tests with insufficient diagnostic sensitivity. The new research is designed to enable early diagnosis with a much higher level of certainty.
Tests in the first trimester
"In our work, we sought to find a molecular marker that appears in the woman's blood already in the first trimester of pregnancy - when she still does not suffer from any symptoms, and predicts the appearance of preeclampsia later on," says Dr. Shumron. To this end, the researchers followed thousands of pregnant women, and took blood samples from all of them in the 12th week of their pregnancy. Later (after the end of the pregnancies) they focused on 75 samples: 35 samples from women who later suffered from preeclampsia, and about 40 samples from a control group - women who ended their pregnancy in complete health. From all of them, the researchers extracted RNA molecules - about 20 million molecules from each sample.
"Many researchers all over the world are engaged in reading the DNA of the fetus, but very few are looking for solutions based on the RNA - the same genetic material that brings the DNA to expression," says Dr. Shumron. "In my lab we decided to focus specifically on RNA, with the aim of opening a new window to preeclampsia, and also to other diseases related to pregnancy." The researchers exposed the RNA molecules to the 'new generation genetic sequencing' technology, and Liron Yaffe - a computational biologist by training, applied advanced computational means of 'machine learning' to locate the exact differences between the RNA of the women who fell ill later in pregnancy, and that of The healthy women. In total, 25 specific RNA molecules were found (out of 20 million, as mentioned) that can be used as clinical markers: their configuration in the blood sample indicates - with an efficiency of 85% - if that woman will suffer from poisoning in a more advanced stage of her pregnancy.
"Our findings form the basis for the development of a simple blood test to predict preeclampsia," concludes Dr. Shomron. "But they also have another importance: they prove that RNA molecules can be used as molecular markers already at an early stage of pregnancy. In doing so, they join a global trend, which seeks to advance the pregnancy tests to the first trimester - in contrast to the situation today, when most tests are performed in the third trimester. The advance of the tests will allow doctors to prevent damage to the mother and the fetus, and if necessary to start preventive treatment as early as possible, something that will significantly improve the health of the mother and the fetus.
Prof. Moshe Hod, a key partner in our research, is one of the leaders of the trend in Israel and the world, and even recently established a first trimester clinic at Beilinson Hospital. Today in our laboratory we are looking for RNA markers also for gestational diabetes - a disease many times more common than preeclampsia, which can cause significant damage to the baby for the rest of its life."
Prof. Moshe Hod, Director of the Research Institute for Perinatal Medicine in Bilinson and President of the European Association for Maternal and Fetal Medicine, currently leads the Maternal and Fetal Health Committee of the International Association of Gynecology and Obstetrics (FIGO) whose main goal is to foster the trend towards predicting future pregnancy complications already in the first trimester of pregnancy. According to him, "It is important to understand that the complications of pregnancy cause a disruption in the processes of the normal development of the fetus and affect all its future diseases starting from childhood, adolescence and adulthood." That is, it is important to transfer the weight of the tests and diagnosis to the first trimester of pregnancy in order to prevent the appearance of pregnancy complications such as gestational diabetes, preeclampsia, early labor and fetal growth disorders in the advanced stages of pregnancy." Hood points out that there is currently progress in finding modern technologies, based on innovative genetics (micro RNA) as in this research work, as well as microbiome, metabolome (markers in the mother's blood - proteins and metabolites) and others.
Hod concludes: "These technologies will allow us in the future to make very early predictions from the very first stages of pregnancy and to take preventative action to avoid complications. This is the future of obstetrics.
