New Study Explores Placental Malperfusion's Impact on Fetal Health and Development in Congenital Heart Disease

Children's Hospital of Philadelphia study highlights the role of genetic and developmental pathways on fetal health and outcomes in congenital heart disease

PHILADELPHIA, Nov. 3, 2025 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) discovered that placental malperfusion (PMP), a condition that disrupts blood flow in the placenta, is common in fetuses with congenital heart disease (CHD) and is linked to poor fetal growth, longer hospital stays and potentially increased mortality. Published today in theJournal of the American College of Cardiology, the study, led by Rebecca Josowitz MD, PhD, also highlights that genetic changes in key pathways for placental and cardiac development may underlie PMP in CHD.

An adverse maternal-fetal environment, and especially abnormal placental development, is associated with an elevated risk of CHD development and adverse outcomes. Fetuses with CHD often have mothers experiencing higher rates of clinical PMP conditions like preeclampsia. Despite current understanding of the link between PMP and CHD, researchers are delving deeper to better understand how PMP exacerbates negative outcomes in fetuses with CHD and to investigate its mechanisms.

The retrospective study marks the first research paper from the Cardiac Center to utilize data from CHOP's Birth Defects Biorepository. The Biorepository offers a sustainable resource for research into birth defect causes and outcomes, providing genomic and phenotypic datasets to enhance understanding of long-term outcomes and personalized medicine. It is one of the rare biorepositories to routinely collect and bank placental tissue.

In the study, researchers reviewed data from 299 CHD fetuses, comparing those with PMP to those without the condition. They found PMP in 51% of these fetuses. Non-syndromic fetuses with PMP had lower birth weight, shorter length and smaller head circumference compared to those without PMP.

The findings also revealed that PMP is associated with longer hospitalization and a trend towards increased mortality in CHD. CHD fetuses with PMP more often carry harmful de novo variants – spontaneous genetic changes not inherited from parents – that affect crucial placental and cardiac developmental pathways.

"Our study shows the importance of the prenatal environment in both short- and long-term outcomes in CHD. Understanding the genetic and developmental pathways responsible for the development of PMP could allow us to design therapies to improve placental function, ultimately improving fetal health and outcomes, particularly in cases of CHD," said Rebecca Josowitz, MD, PhD, the study's lead author and attending physician in the Cardiac Center at CHOP. "This is crucial for early diagnosis, personalized medicine and improved outcomes."

Research is ongoing to determine which types of CHD might be most susceptible to the effects of PMP, and whether the mechanisms of PMP may differ by CHD type. Dr. Josowitz sees these insights as a foundation for driving research into new therapies to improve the prenatal environment in CHD, enhancing care and improving long-term outcomes.

The work was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR001878), National Human Genome Research Institute (R01HG013355) and the National Heart Lung and Blood Institute (T32 HL007915-25).

Josowitz et al. "Placental Malperfusion is Associated with Adverse Outcomes in Congenital Heart Disease and With Genetic Variants in Placental Developmental Pathways." JACC. November 3, 2025. DOI: 10.1016/j.jacc.2025.07.069.

About Children's Hospital of Philadelphia: 
A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey. CHOP also operates the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia, the Behavioral Health and Crisis Center (including a 24/7 Crisis Response Center) and the Center for Advanced Behavioral Healthcare, a mental health outpatient facility. Its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu. 

Contact: Natalie Solimeo
Children's Hospital of Philadelphia
267-426-6246
[email protected]

SOURCE Children's Hospital of Philadelphia