Identifying Novel Biomarkers To Predict Risk Of Excessive Blood Loss At Delivery

Principal Investigators

Abstract: Maternal blood loss is a normal component of childbirth in our species, due in large part to the way our placentas work. The human placenta produces highly invasive cells that penetrate and remodel maternal vessels. However, the effectiveness of invasive processes varies, sometimes leading to complications. For example, pre-eclampsia (PE), a gestational hypertensive disorder that affects 3-5% of pregnancies in the United States, is characterized by insufficient transformation of the uterine spiral arteries, impairing their ability to accommodate increased blood flow to the placenta and the fetus. The vessels remain constricted, blood flow to the fetus is reduced, and therefore maternal blood pressure increases due to increased impedance of blood through the placenta. Less is known about what happens when too many vessels are remodeled too deeply and too aggressively, and to what degree this could predict blood loss.

Examining underlying mechanisms of blood loss is critical because postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide, accounting for 25% of maternal deaths. PPH is treatable with blood transfusions and drugs that promote uterine contractility, but many women in low-resource contexts may not have access to these treatments. Unfortunately, there are no assays currently available that will predict excessive blood loss in a clinically useful time frame. Our central hypothesis is that blood loss at delivery is caused in part by processes of placental cell invasion and inflammation that can lead to overly aggressive remodeling of maternal blood vessels, rendering them less able to control the flow of blood to the placenta. We will measure placental biomarkers in maternal blood early in pregnancy when invasion and remodeling of maternal vessels by placental cells is greatest. We will also implement quantitative ultrasound (QUS) techniques to image the interface between the placenta and the uterine wall in order to determine if tissue remodeling is a) detectable and b) predictive of blood loss at delivery.

Our short-term goal is to test whether the hypothesized relationship between degrees of blood loss and mechanisms of aggressive placental invasion and vascular remodeling is supported by our proposed biomarkers and measurements. Our long-term goal is twofold: 1) to better understand the role trophoblast invasion during placentation plays in the pathophysiology of postpartum hemorrhage and 2) to apply our results to the development of a low-cost diagnostic kit that would allow women and their health-care providers to make better-informed choices for prenatal care and risk prevention, particularly in low-resource contexts.

Internal Research Support Program (IRSP)