Three researchers awarded seed funding through the Center

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 announced a seed-funding opportunity for researchers at Stanford working on projects that advance maternal-fetal medicine science. Today, we are excited to announce the recipients of the Fall 2022 seed grants: Yair Blumenfeld, MD, Alexander Butwick, MBBS, FRCA, MS, and Anca Pasca, MD.

Director of Research Anna Girsen, MD, PhD shares, “We had such a high-quality application pool for this inaugural seed grant cycle, and are very excited to fund these three impactful research projects thanks to the funds provided by our generous donors. The Center will have a seed grant call now twice a year – in the spring and in the fall – and we welcome proposals for work advancing the science of maternal-fetal medicine again in early 2023.”

Continue reading to learn more about the funded projects.

Yair Blumenfeld, MD

Director of the Fetal Therapy and Professor of Obstetrics and Gynecology, Dr. Blumenfeld’s proposal, “Assessment of a novel fetal LUTO shunt (the “Vortex shunt”) using a validated fetal lamb model for obstructive uropathies,” was selected as it addresses an important need in fetal medicine and has the prospect of improving long term bladder outcomes among infants with lower urinary tract obstruction (LUTO).

Fetal lower urinary tract obstruction (LUTO) occurs in 2 to 3 cases per 10,000 births due to an obstruction of the fetal bladder outlet. Severe LUTO leads to a markedly enlarged fetal bladder, dilated kidneys due to backward flow of fetal urine, renal injury, and absence of amniotic fluid. Without in-utero therapy, LUTO is associated with up to 80% mortality rate, mostly due to lung injury incompatible with life. In survivors, there is a significant risk of progressing to end-stage renal disease before or soon after birth.  Because the diagnosis can be made prenatally by ultrasound and because of the severity of the condition, fetal vesico-amniotic shunting (VAS) is used to treat severe LUTO cases. Existing VAS shunts have high dislodgement risks and paired with the invasive nature of VAS and associated complications, VAS is usually reserved for the most severe LUTO cases. In addition, VAS has been shown to decrease neonatal mortality but has not been shown to improve renal impairment in survivors. Given these deficiencies, Dr. Blumenfeld and others recently developed a novel fetal VAS, the “Vortex” shunt, which has improved technical specifications compared to the existing shunts.  After the initial bench-top testing, the next step is to study the feasibility of deploying the novel Vortex shunt in the LUTO animal model. Dr. Blumenfeld has established a collaboration with a research group in Leuven, Belgium, which under the leadership of Professor Jan Deprest, recently developed and validated a surgical sheep LUTO model. With the support of the Dunlevie Center, the team is able to further develop and optimize the one-way valve component of the “Vortex” shunt, arguably the most unique aspect of the shunt, and assess its efficacy on bladder and renal function in the sheep LUTO model. This is an important first step towards a future clinical efficacy study and reducing neonatal morbidity and mortality.

Also on Dr. Blumenfeld’s research team is Kunj Sheth, MD (Pediatric Urology), Enrico Danzer, MD (Pediatric Surgery), Eric Johnson, MS (Engineering), and James Wall, MD (Pediatric Surgery).

Alexander Butwick, MBBS, FRCA, MS

Professor of Anesthesiology, Perioperative and Pain Medicine, Dr. Butwick’s proposal, “Understanding Hospital-Level Variation in the Quality of Epidural Labor Analgesia among Patients Intending Vaginal Delivery: Quantitative and Qualitative Analyses” was selected because the project addresses the understudied but important issue of variability in hospital rates of epidural analgesia and complications, and what drives this variability.

Childbirth pain can be the most excruciating pain a pregnant patient endures in their lifetime. Level 1 evidence indicates that epidural analgesia is the most effective means of treating patients’ childbirth pain. However, complications from epidural analgesia, including post-dural puncture headache (PDPH) and epidural abscess, impact >11,000 US pregnant individuals annually.. These complications can potentially result in devastating long-term morbidity for patients, including chronic headache and permanent neurological deficit. The overarching goal of Dr. Butwick’s project is to develop quality improvement strategies that optimize the delivery of high-quality epidural analgesia for pregnant patients intending vaginal delivery in U.S. hospitals. With support from the Dunlevie Center seed funding, his team will evaluate variation in risk-standardized rates of epidural analgesia and complications in California hospitals by analyzing maternal discharge and vital statistics datasets provided by California Maternal Quality Care Collaborative at Stanford. He will also perform a pilot qualitative study involving informant interviews with front-line staff and clinician leads at 2 outlier hospitals (1 hospital with a very high rate and 1 hospital with a very low rate of epidural complications) to identify hospital unit characteristics potentially associated with hospital-level complication rates. These findings will provide critical preliminary data for future research that will examine the individual and combined effects of patient-level, provider-level, and hospital-organizational factors that influence hospital quality of care for patients receiving epidural analgesia.

Supporting Dr. Butwick is research data analyst Nan Guo, PhD, MS.

Anca Pasca, MD

Assistant Professor of Pediatrics, Dr. Pasca’s proposal, “Identification of neuroprotective compounds for hypoxic brain injury using high-throughput screening platforms in cortical organoids” was selected for its potential to find neuroprotective compounds that could be used in keeping the developing brain safe from hypoxic brain injury before and during labor and delivery.

Hypoxic stress during the fetal period of development of the human cerebral cortex is strongly associated with neurodevelopmental impairments. The exact cellular and molecular mechanisms by which hypoxia-induced stress leads to abnormal development of the human cerebral cortex and increased risk for neuropsychiatric diseases remain poorly defined. Dr. Pasca’s project aims to identify neuroprotective compounds for hypoxic brain injury using an in vitro high-throughput screening platform her team developed, using brain organoids derived from human-induced pluripotent stem cells. To address these limitations, Dr. Pasca has developed and implemented technology to reliably capture in vitro human corticogenesis in tridimensional (3D) cultures derived from stem cells, called region-specific cortical organoids. To study hypoxic brain injury, her team has recently developed the first in vitro human cellular model of hypoxic brain injury of prematurity and identified cell-specific vulnerability of cortical intermediate progenitors, a population of cells considered to contribute to the unique complexity of the human cerebral cortex compared to rodents. Dr. Pasca found that under hypoxic conditions, these cells differentiate into neurons, thus prematurely depleting the pool of progenitors. Her cellular models offer an unprecedented opportunity for (i) screening for potential neuroprotective therapies and (ii) understanding fetal and neonatal brain injury at a molecular and cellular level by providing access to previously inaccessible aspects of human brain development.

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.