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Background: Brain magnetic resonance imaging (MRI) of infants with congenital heart disease (CHD) shows brain immaturity assessed via a cortical-based semi-quantitative score. Our primary aim was to develop an infant paralimbic-related subcortical-based semi-quantitative dysmaturation score, termed brain dysplasia score (BDS), to detect abnormalities in CHD infants compared to healthy controls and secondarily to predict clinical outcomes. We also validated our BDS in a preclinical mouse model of hypoplastic left heart syndrome. Methods: A paralimbic-related subcortical BDS, derived from structural MRIs of infants with CHD, was compared to healthy controls and correlated with clinical risk factors, regional cerebral volumes, feeding, and 18-month neurodevelopmental outcomes. The BDS was validated in a known CHD mouse model named Ohia with two disease-causing genes, Sap130 and Pchda9. To relate clinical findings, RNA-Seq was completed on Ohia animals. Findings: BDS showed high incidence of paralimbic-related subcortical abnormalities (including olfactory, cerebellar, and hippocampal abnormalities) in CHD infants (n = 215) compared to healthy controls (n = 92). BDS correlated with reduced cortical maturation, developmental delay, poor language and feeding outcomes, and increased length of stay. Ohia animals (n = 63) showed similar BDS findings, and RNA-Seq analysis showed altered neurodevelopmental and feeding pathways. Sap130 mutants correlated with a more severe BDS, whereas Pcdha9 correlated with a milder phenotype. Conclusions: Our BDS is sensitive to dysmaturational differences between CHD and healthy controls and predictive of poor outcomes. A similar spectrum of paralimbic and subcortical abnormalities exists between human and Ohia mutants, suggesting a common genetic mechanistic etiology. [ABSTRACT FROM AUTHOR]

Background: The US Pediatric Heart Allocation Policy (PHAP) was revised in March 2016, with the goal of reducing waitlist mortality. We evaluated the hypothesis that these changes, which increased status exceptions, have worsened racial disparities in waitlist outcomes. Methods: Children in the Pediatric Heart Transplant Study database listed for first heart transplant from January 2012 – June 2020 were included and stratified by listing before (Era 1) or after (Era 2) the PHAP revision. Results: A total of 4,089 children were listed during the study period. Compared with white children (n = 2648), non‐white children (n = 1441) were more likely to have an underlying diagnosis of cardiomyopathy in both eras. Waitlist mortality was similar in white and non‐white children in Era 1, but comparatively worse for non‐white children in Era 2. In multivariable analysis controlling for diagnosis, age, and severity markers, non‐white children had a significantly higher waitlist mortality only in Era 2 (Era 1: sHR 1.22 [95%CI 0.90 – 1.66] vs. Era 2: sHR 1.57 [95%CI 1.17 – 2.10]). Conclusions: Widening racial disparities in waitlist mortality may be an unintended consequence of the 2016 PHAP revision. Additional analyses may inform the degree to which this policy vs. unrelated changes in care differentially contribute to these disparities. [ABSTRACT FROM AUTHOR]