Impact of Primary Graft Dysfunction on Neurodevelopmental Outcomes in Pediatric Heart Transplant Recipients

Background: Primary graft dysfunction (PGD) remains one of the leading causes of early mortality after pediatric heart transplant (HT). While neurodevelopmental impacts of congenital heart disease (CHD) are well-characterized, the effect of PGD on long-term neurodevelopmental outcomes in pediatric HT recipients remains unknown. We sought to determine the association between PGD and neurodevelopmental outcomes in this population. Methods: We performed a retrospective cohort study using the United Network for Organ Sharing (UNOS) database. All pediatric (age <18 years) isolated heart transplant recipients from 2010-2025 were included. The most recent pre- and post-transplant neurodevelopmental outcomes including cognitive delay, motor development, academic progress, and function status (stratified by age) were compared between PGD (n=434) and non-PGD groups (n=6956). Results: PGD patients had significantly worse pre-transplant functional status and motor development. Post-transplant, PGD was associated with worse motor development (18.8% vs. 13.0% definite motor delay; p=0.01) and functional status in younger children (39.5% vs. 57.8% able to keep up with peers; p<0.001). Post-transplant stroke occurred 3.5 times more frequently in PGD patients (11.5% vs. 3.3%; p<0.001). Cognitive development (p=0.94) and academic progress (p=0.09) did not differ significantly. Thirty-day (7.8% vs. 1.9%) and 1-year mortality (20.3% vs. 6.4%) were significantly higher in PGD patients (both p<0.001). Conclusions: This is the first study to characterize neurodevelopmental outcomes in pediatric patients undergoing HT with PGD. PGD is associated with significantly worse motor development and functional status independent of pre-transplant baseline. There is a 3.5-fold higher stroke rate providing a plausible neurological mechanism. The findings support targeted developmental surveillance recommendations and early intervention for this high-risk population.