Children’s Hospital of Philadelphia Researchers Secure Funding to Explore Progesterone Therapy Response Mechanisms in Fetuses with Hypoplastic Left Heart Syndrome (HLHS)

A research team in the Cardiac Center at Children’s Hospital of Philadelphia (CHOP) in collaboration with Boston Children’s Hospital and the Perelman School of Medicine at the University of Pennsylvania was awarded a $660,000 grant over three years by Additional Ventures through its Single Ventricle Research Fund to accelerate research and develop therapies for fetuses with hypoplastic left heart syndrome (HLHS).

There are currently no treatments available during pregnancy to improve the health or survival of babies with HLHS, leaving families without options to reduce the risks before birth. However, a prior CHOP study showed that treatment of pregnant women with progesterone, a hormone important for brain development, lowered the risk of death for infants with HLHS from 20% to 7%. Researchers found the results promising and are seeking to better understand why progesterone was beneficial to design the best treatments for HLHS. 

Led by J. William Gaynor, MD, a surgeon in the Cardiac Center at CHOP, the research team – including 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 -- will build on the prior study’s foundation. They proposed metabolomic, transcriptomic, and genetic studies using placenta, maternal/cord blood, and exome sequencing to identify mechanisms underlying 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. 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,” said Gaynor.  “These results will teach us about the role of progesterone during pregnancy, which will help us to identify new potential prenatal therapies for HLHS.”

The research will focus on determining if alterations in placental progesterone metabolism are mechanistically associated with HLHS fetal and post-natal outcomes. The study will also evaluate the impact of common genetic variation on gestational age (GA) at birth, birthweight, and placental weight and efficiency in fetal congenital heart disease (CHD). Additionally, the team will identify transcriptional and cellular impacts of vaginal progesterone therapy.

The researchers hope their findings will help transform the paradigm for treating HLHS, allowing clinicians to take potentially lifesaving steps before a baby is born.