Queen of Hearts-study
Although the Queen of Hearts study initially started as a large consortium study, aiming to detect early stages of heart failure in women, it developed quickly and became a large research line. Now the Queen of Hearts study includes several studies with two major objectives: reducing cardiovascular disease and hypertensive pregnancy disorders (small for gestational age infancies, preeclampsia, HELLP-Syndrome) with 25% the next 25 years.
Objective 1: To decrease the risk of cardiovascular disease in women by25% over the next 25 years. This can be achieved only if we recognized pregnancy as women specific biological stress test. Nowadays, 1 out of 4 women dies due to cardiovascular disease. Queen of Hearts researchers are developing early detection tools to assess which women are at increased risk for cardiovascular disease early in life to assure early preventive measures, before the disease evolves. regnancy is used as an important risk indicator in the study.
Objective 2: To decrease the risk of hypertensive pregnancy disorders by 25% over the next 25 years. Hypertensive pregnancy disorders (small for gestational age babies, preeclampsia, HELLP-Syndrome) are the major causes of maternal and fetal morbidity and mortality. Every year, 76.000 women and 500.000 babies die due to these hypertensive pregnancy disorders. Queen of Hearts researchers are working on studies for early detection and prevention of hypertensive pregnancy disorders.
Women who have suffered from preeclampsia are at higher risk for cardiovascular disease and stroke earlier in life compared to those who have had a healthy pregnancy. Up to a quarter of women with a clinical history of preeclampsia also report psychological and cognitive complaints, such as trouble finding the right words, and reduced concentration and memory capabilities. These effects are measurable up to years after the complicated pregnancy as shown by several neuropsychological studies.
On the one hand, these complaints are similar to those experienced by people with cerebral small vessel disease and a dysfunctional microvasculature might be the underlying cause in former preeclamptic women. On the other hand, the symptoms and cognitive impairments after preeclampsia resemble those seen in post-traumatic stress disorder (PTSD). Preeclamptic women are not uncommonly facing traumatic events, such as preterm termination of their pregnancy, NICU admission or loss of their child. PTSD is associated with altered functional brain activity and reduced volumes of the regions within the limbic system.
The DECONNECT-study aims find evidence for PTSD and to evaluate the role of microvascular dysfunction in the brain and heart of former preeclamptic women through Magnetic Resonance Imaging and neuropsychological testing.
Early Vascular Adjustments Trial
Paradoxical fetal and maternal results of studies have led to inconsistent use of antihypertensive drugs, or no treatment at all in the case of mild to moderate gestational hypertension in the Netherlands. However, none of the previous studies has considered the individual underlying maternal circulatory state or the contemplated blood pressure response to class of antihypertensive medication prescribed. Antihypertensive drugs should be regarded as correctors of the hemodynamic state rather than solely reducers of blood pressure. Hypertension may result from a high cardiac output, low vascular resistance state, or a low cardiac output, high vascular resistance profile, the latter being associated with early onset preeclampsia and impaired fetal growth. Stepwise chosen beta-blockade is expected to effectively treat hypertension with a high cardiac output but might be counterproductive and even contribute to impaired fetal growth in high vascular resistance hypertension in which reduction of vascular resistance by calcium-channel blockers or centrally acting sympatholytic drugs seems to be more effective. In the Early Vascular Adjustments – trial, women with mild to moderate gestational hypertension are prescribed hemodynamically guided antihypertensive therapy, and prevalence of progression to severe hypertension and/or preeclampsia is compared to a control group of women with no-pharmaceutical treatment of mild to moderate gestational hypertension.
Researcher: Eva Mulder
OVIDE: the role of natural killer cells in unexplained recurrent pregnancy loss
Patients with recurrent pregnancy loss endure enormous feelings of despair and grief trying to become pregnant. As 50% of cases cannot be explained by current clinical investigations, they are also in desperate need for answers. Since a complex immunological interplay of maternal and fetal factors is key to maintain pregnancy and avoid rejection of the conceptus, the immune system is also of great importance. Of all immune cells, natural killer cells are believed to play a crucial role during the first trimester of pregnancy in the uterus. Here, they don’t seem to live up to their name as killers of diseased cells, but, rather help to create a pregnancy-favourable environment. To investigate their exact role in unexplained recurrent pregnancy loss we study natural killer cell phenotype and function, both systemically in peripheral blood and locally in menstrual blood, and link this to clinical features to predict pregnancy outcome. Since physical activity has been shown to affect important parameters that improve pregnancy outcome, and natural killer cells are the most responsive cells of the immune system to physical activity, we investigate the influence of exercise on natural killer cells in-vivo and in-vitro. In this way, we hope to provide further insight in the role and function of natural killer cells and provide new perspectives on treatment possibilities for patients with unexplained recurrent pregnancy loss.
Researcher: Denise Habets
Placenta ULtraSound Evaluation study
A successful pregnancy outcome is dependent on normal placental development during early gestation. An abnormal placental function can lead to pregnancy complications (pre-eclampsia and intrauterine growth restriction). The golden standard for identifying placental dysfunction is postpartum patho-histological analysis, however this is behind time to affect clinical decision making in endangered gestation. Therefore, a screening method for defective placenta development antedating complicated pregnancies during early gestation, may timely indicate those at risk and possibly still susceptible for preventive outcome-improving interventions. Aim of this study is to investigate of placenta ultrasound is related to placenta pathology and can be used as a predictor for complicated pregnancies.
Researcher: Veronique Schiffer
The Glycocalyx Layer as a marker of Obstetrical Well-being
During pregnancy, several cardiovascular adaptations in the female body occur to ensure adequate blood flow to the fetus. If the cardiovascular system fails to adapt sufficiently, pregnancy complications such as preeclampsia could develop.
The GLOW study is a research project that uses the endothelial glycocalyx to measure vascular adaptation during pregnancy. The endothelial glycocalyx is the most inner layer of blood vessels and can be visualized non-invasively using a light-emitting camera which is placed sublingually.
Previous studies have shown that the glycocalyx is damaged in women who are diagnosed with preeclampsia. The aim of this study is to map changes in glycocalyx thickness during pregnancy and investigate if there are differences in thickness between women with high and low-risk pregnancies. Measurements are performed several times during and after pregnancy.
Researcher: Astrid Bruekers