Estonian researchers are leading a translational research project in reproductive biomedicine with the aim of developing a quick blood test to predict, and consequently prevent complications at a very early stage of pregnancy.
The development of the prognostic test is part of a large study called Happy Pregnancy. Although the project came to its formal end in August 2015, the "real" investigation of the study materials is only beginning now, according to Professor Maris Laan, coordinator of the Happy Pregnancy study in Estonia. “We have collected biological samples and clinical-epidemiological data from thousands of women and right now we are trying to get new funding to continue with analysing this unique resource,” she said.
A cohort of more than 2,500 pregnant women, as well as more than 4,000 participants who form the study groups of infertile male and female patients, and fertile controls, makes it one of the biggest studies of its kind in Europe. However, its significance lies rather in its comprehensiveness. While most studies in reproductive biomedicine focus on a narrow specialty such as andrology, gynaecology or genetics, the Happy Pregnancy project combines the complementary expertise of all these areas and creates synergies in research on reproductive health, its genetic determinants in men and women, and the development of diagnostic tools for the timely monitoring of a pregnancy’s course.
One of the study’s aims is to test and evaluate the clinical relevance of novel DNA polymorphisms discovered by the research group, and to translate these genetic tests into routine application in molecular diagnostics, as well as analyse their pharmacogenetic potential in reproductive medicine. In parallel, the project team investigates the clinical prognostic value of novel as well as previously suggested maternal blood serum biomarkers in pregnancy complications. The ultimate goal is to develop a multi-marker test of these biomarkers for daily usage in clinics, available for all future mothers. To put it simply, Laan and her peers are monitoring the gestational health of mothers in the longer run, while trying to find new ways to predict pregnancy complications earlier and more precisely.
This abovementioned multi-marker test is the most tangible part of the study so far, as the team will soon complete the pilot phase of the test’s technological development. “The idea is to introduce a test for determining women’s risk to develop pregnancy complications such as preeclampsia (a disorder of pregnancy characterised by high blood pressure and renal failure) as early as possible,” Laan said.
This type of test would have a major effect on the society, as preeclampsia affects about 3–5 percent of pregnant women. It’s a serious disease with long-term consequences both for the offspring and mother. “So far we have not had a prognostic test with high specificity, sensitivity and early long-term predictive value. Today, preeclampsia is often discovered only when the first symptoms appear. Early prediction is expected to lead to improved clinical guidelines and options for timely management and prevention,” Laan explains. Although preeclampsia has thus far been the first clinical focus, predictive tests for other complications such as gestational diabetes or preterm birth are in the ‘waiting list’ to be included in the development pipeline.
In addition to the development of diagnostic/prognostic tests, the longitudinal monitoring of maternal health and its effectors during the pregnancy is a vital part of the study. “We need to look at how pregnancy and experienced gestational complications affect both the mother and child in the long run during a person’s entire life, not only at the time of pregnancy. What is more, we need to look at the effects of lifestyle, environment and genetics in all this,” Laan said. She gave an example of a recent study, where British researchers found that a mother’s intake of Paracetamol leads to impairing the programming of the reproductive physiology of an unborn male baby.
Studying the effects of pregnancy on a mother’s health is a new direction in pregnancy studies across the world. Yet, according to Laan, it is vital. “If a mother has suffered from preeclampsia, she has a higher risk of cardiovascular diseases (CVD) and other metabolic disorders in later years. We aim to clarify whether a complicated pregnancy is the causative factor for increased CVD risk or whether some people are more susceptible to both conditions, i.e., impaired cardiovascular health in pregnancy and after the menopause due to the inability to cope with changes in metabolism,” she described. In current clinical practice, pregnancy complications are handled upon making a diagnosis, but there is no systematic postpartum monitoring of maternal health. Laan hopes that if the risks, diseases and their consequences are better established, patients with complicated pregnancies may get more clinical attention. “When a patient suffers from a heart attack, we have precise rehabilitation instructions that the general practitioner should pursue in the following years. The same system could be applied to women after pregnancy complications.”
Additionally, the collected Happy Pregnancy research material enables to investigate genetic determinants behind male and female infertility, and those which increase the risk of pregnancy complications. The availability of these molecular diagnostic tools is expected to have an impact on the overall quality of maternal and foetal medicine.
Overall, Laan is excited about the results and discoveries made so far and still to be achieved. However, she is worried about keeping the study alive. Estonian research relies mostly on temporary project-based funding that comes to an end at the project deadline. “Right now we’re trying to find long-term funding sources, especially as when it comes to pregnancy studies, longitudinal research is the keyword. In order to collect data on the health outcomes revealed at later life, we need to analyse the same mothers and babies again during the future decades, but this requires a sustainable funding resource.” Yet, at least for now, she remains optimistic.
This article was first published on Research in Estonia website.
Editor: M. Oll