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[Preprint]. 2026 Apr 2:2026.03.30.26349794. [Version 1] doi: 10.64898/2026.03.30.26349794

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

Jorge A Monserrate-Marrero, Mario Castro Medina, Brian Feingold, Manuel Giraldo Grueso, Kisten Rose-Felker, Richard Tang, Kei Kobayashi, Carlos Diaz-Castrillon, Katie McIntyre, Luciana Da Fonseca Da Silva, Jose P Da Silva, Victor O Morell, Laura Seese
PMCID: PMC13060432  PMID: 41959789

Abstract

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.

Full Text

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