Two researchers awarded Fall 2023 seed funding
The Dunlevie Maternal-Fetal Medicine Center for Discovery, Innovation and Clinical Impact has a mission to empower an arc of discovery and implementation in maternal-fetal science. Aligned with this mission, the Center continues to provide seed-funding in the spring and fall. Today, we are excited to announce the recipients of the Fall 2023 seed grants: Andrea Henkel, MD, MS, and Kristy Red-Horse, PhD.
Director of Research Anna Girsen, MD, PhD, shares, “It was wonderful to see applications from a variety of researchers who are interested in advancing the science of maternal-fetal medicine. The study designs spanned from basic science experiments to clinical trials and population health analyses thus demonstrating the arch of discovery we are empowering as a center.”
Continue reading to learn more about the funded projects.
Andrea Henkel, MD, MS
The proposal “Cabergoline for lactation inhibition after early second-trimester abortion or pregnancy loss (eLISTA): A randomized controlled trial” from Clinical Assistant Professor of Obstetrics and Gynecology Dr. Henkel was selected because validating the routine use of cabergoline for lactation inhibition has the potential to improve maternal outcomes and overall patient experience after pregnancy loss or termination.
Breast engorgement and milk leakage are common following second-trimester perinatal loss and abortion and can cause both physical pain and emotional distress. Dopamine agonists, such as cabergoline, have previously been shown to be effective in lactation inhibition for third-trimester fetal/neonatal loss or those with contraindications to breastfeeding. Dr. Henkel’s recent work demonstrated that compared to a placebo, a single dose of cabergoline was effective in preventing breast symptoms after abortion or loss between 18-28 weeks.
As lactogenesis starts as early as 16 weeks gestation, Dr. Henkel hopes to determine the efficacy of cabergoline earlier in the second trimester, 16-20 weeks. Her team will conduct a double-blinded, placebo-controlled, gestational-age stratified superiority trial of those undergoing abortion or intrauterine fetal demise between 16- and 20-weeks gestation at Stanford Medicine and Planned Parenthood Mar Monte. Participants will be randomized to either cabergoline (1 mg) or placebo the day of procedure, and will complete a survey to assess symptoms, using the validated Bristol Breast Symptoms Inventory, and side-effects at baseline and on Day 2, 4, 7, and 14 after the procedure. The primary outcome is breast symptoms on Day 4 based on term lactation physiology. Secondary outcomes include satisfaction, acceptability, and side effects.
Kristy Red-Horse, PhD
Dr. Red-Horse, Associate Professor of Biology, submitted the proposal “Creating a 3D atlas of placental perfusion over gestation,” which was selected because of the exceptional study design and demonstrated capability of Dr. Red-Horse and the team to develop a 3D-atlas of human placental perfusion over gestation. Review committee felt that creation of this atlas will significantly advance the understanding of maternal-fetal interface and placental physiology.
During pregnancy, many physiologic changes occur to support a successful pregnancy, including remodeling of the maternal vasculature. Uterine arteries, veins and lymphatic vessels must reorganize to perfuse an entirely new organ — the placenta — and provide enough nutrition by the third trimester to support a growing fetus. These vascular changes are carefully orchestrated; however, owing to the uniquely invasive nature of human placentation, many details of this process remain inadequately understood. For example, to what extent do fetal trophoblasts, which invade maternal blood vessels, invade by migrating against arterial blood flow (i.e., intravasation) or by entering vasculature from the uterine stroma (i.e., extravasation)? How is each vasculature subtypes remodeled over pregnancy, and how heterogeneous is this process among vessels of the same subtype? How does trophoblast invasion impact blood flow in the uterus and the placenta?
Thoroughly answering these questions requires the mapping of trophoblast invasion of uterine blood vessels in three dimensions (3D). To do so, Dr. Red-Horse’s team will image immunolabeled human placental samples using whole mount imaging. Her lab has advanced the use of tissue clearing and light sheet microscopy for difficult-to-image whole organs like the heart. Using multiple human samples collected across gestation from 6 weeks to term, she hopes to elucidate the interplay between maternal and fetal cells in the context of vascular perfusion. This 3D atlas of human placentation will not only serve to expand our understanding of a currently opaque process, but understanding these questions in normal placentation are key to understanding what goes wrong in disease settings where the placenta is insufficiently perfused such as preeclampsia or intrauterine growth restriction.
We are looking forward to sharing updates about these funded projects and hope that you will keep an eye out for the Center’s future funding opportunities.