Placenta-specific proteins released into maternal blood as biomarkers of placental function

Placenta related pregnancy complications, like fetal growth restriction and preeclampsia (PE) are relatively common and associated with severe short term and long term complications for mother and child. Fetal growth restriction is associated with stillbirth, neonatal death, encephalopathy and cerebral palsy. Preeclampsia is associated with severe neonatal and maternal morbidity, stillbirth and preterm birth. Children born after growth restriction or preeclampsia are at increased risk of developing adult diseases like diabetes, adiposity and cardiovascular disease. Currently, there are no well-established biomarkers to predict and monitor placental function or the risk of PE and fetal growth restriction. The inaccessibility of the human placenta prior to delivery constitutes a major roadblock in order to achieve this goal. One reason that the biomarkers for fetal growth restriction and PE have proven insufficient is that it has been unknown if the placenta is a source of the substances (i.e. the substances are placenta-specific). The present project will use a novel placental sampling method called 4-vessel sampling, enabling detection of substances secreted from the placenta. Furthermore, previous research to establish biomarkers has focused only on one single out of a multitude of substances. Rather, we will use a novel platform for analyses of 5000 proteins that will identify new possible biomarkers of placental function. Our ultimate aim is to develop a blood test for biomarkers of the functional state of the placenta and thus better predict the risk of PE and fetal growth restriction.

The National Institutes of Health state that the placenta is the least understood human organ. There are no valid minimally invasive tests to monitor placental function or to predict placenta related pregnancy complications, like intrauterine growth restriction (IUGR) and preeclampsia (PE). IUGR and PE are common, they are associated with severe short term and long term complications for mother and child, and placental dysfunction plays a central role in the pathogenesis. IUGR is associated with stillbirth, neonatal death, encephalopathy and cerebral palsy. PE is associated with severe neonatal and maternal morbidity, stillbirth and preterm birth. Children born after IUGR or PE are at increased risk of developing adult diseases like diabetes, adiposity and cardiovascular disease. Current ultrasound methods only detect IUGR cases where the fetus already has severe malnutrition and deficient oxygen supply. Similarly, there are no biomarkers to predict and monitor PE. To be clinically useful, minimally invasive approaches to monitor placental function in real time are required. The inaccessibility of the human placenta prior to delivery constitutes a major roadblock to achieve this goal. One reason that the biomarkers for IUGR and PE have proven insufficient is that it has been unknown if the placenta is a source of the substances (i.e. the substances are placenta-specific). The present protocol offers a solution to this problem. A second reason for previous failures is that the tests have been based on one single out of a multitude of risk factors. By the advent of systems biology, broader profiles of biochemical parameters can be tested. Exploring protein profiles in the context of placental function is rational. Our ultimate aim is to develop biomarkers of the functional state of the placenta, by an unprecedented combination of our novel sampling method to detect compounds released from the placenta with state-of-the-art proteomics technology.