A research team at the Cardiac Center of Children’s Hospital of Philadelphia (CHOP), in collaboration with Boston Children’s Hospital and the Perelman School of Medicine at the University of Pennsylvania, has been awarded a $660,000 grant over three years. The funding is provided by Additional Ventures through its Single Ventricle Research Fund. This grant aims to accelerate research and develop therapies for fetuses diagnosed with hypoplastic left heart syndrome (HLHS).
Currently, there are no available treatments during pregnancy to improve the health or survival rates of babies with HLHS, leaving families without prenatal options to mitigate risks. A previous study conducted by CHOP indicated that treating pregnant women with progesterone, a hormone crucial for brain development, reduced the risk of death in infants with HLHS from 20% to 7%. The promising results have prompted researchers to further investigate why progesterone proved beneficial and how it can be used to design effective treatments for HLHS.
The research project is led by J. William Gaynor, MD, a surgeon at CHOP’s Cardiac Center. The team includes Lauren Anton, PhD, Research Assistant Professor of Obstetrics and Gynecology at Penn Medicine, and Sarah Morton, MD, PhD, Assistant Professor of Pediatrics at Harvard Medical School. They plan to conduct metabolomic, transcriptomic, and genetic studies using placenta samples, maternal/cord blood, and exome sequencing to uncover mechanisms behind the response to progesterone therapy in fetuses with HLHS.
“We will study placental, maternal, and fetal samples collected during our recent study to investigate how progesterone may improve placental function and thus survival in fetal HLHS,” said Gaynor. “We will determine how progesterone treatment altered placental cells and will also test whether the infants who had the most benefit from progesterone had a different response compared to those who did not have a benefit.”
The focus of this research is on determining if changes in placental progesterone metabolism are linked mechanistically with fetal and post-natal outcomes in HLHS cases. Additionally, the study will evaluate common genetic variations’ impact on gestational age at birth as well as birthweight and placental weight efficiency in fetal congenital heart disease (CHD). The team also aims to identify transcriptional and cellular impacts of vaginal progesterone therapy.
Researchers hope their findings will transform treatment paradigms for HLHS by enabling clinicians to take potentially lifesaving steps before birth.
