Our Research

BACKGROUND: Thrombotic events, including acute ischemic stroke, are more common in individuals with congenital heart disease (CHD). Whether common thrombophilia variants contribute to thrombotic risk in this population remains unclear. We evaluated whether prothrombin G20210A (F2 c.97G>A) and factor V Leiden (F5 c.1601G>A; p.Arg534Gln) are associated with thrombotic events in CHD.

METHODS: Participants in the Pediatric Cardiac Genomics Consortium with exome sequencing and electronic medical record data were identified. Individuals were stratified by prothrombin G20210A and factor V Leiden genotypes, ventricular physiology, and antithrombotic therapy. The primary outcome was the presence of International Classification of Diseases (ICD) or Phecodes (phenotype codes) for thrombotic events.

RESULTS: Among 4008 participants (median age, 11.4 [interquartile range, 5.1-17.9] years; 44.4% boys), thrombotic events occurred in 737 (18%), including 93 (13%) with acute ischemic stroke. Compared with the Genome Aggregation Database, the CHD cohort had a lower prevalence of heterozygous prothrombin G20210A and factor V Leiden variants. Variant prevalence did not differ between participants with and without thrombotic events. Single-ventricle CHD was associated with higher thrombosis frequency than biventricular CHD (35% versus 16%, P≤0.0001), without differences in variant prevalence.

CONCLUSIONS: In this multicenter CHD cohort, prothrombin G20210A and factor V Leiden were not significantly associated with thrombotic outcomes, supporting recommendations against routine screening. Given low variant prevalence, the study was powered to exclude only large associations. Reduced variant frequency suggests survivorship bias beginning in fetal life. Larger integrated clinical-genomic studies are needed to refine thrombotic risk stratification in CHD.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03347214.

BACKGROUND: Congenital heart disease (CHD) affects about 1% of births and is linked to differences in thinking and learning. Understanding how birth, genetic, clinical, and environmental factors together explain cognitive variability can inform monitoring and care. This study builds a multivariate model predicting cognition across multiple domains in adolescents and young adults with CHD.

METHODS: We studied 89 adolescents and young adults (AYAs; mean age 16 years) with CHD who completed structural and diffusion MRI and fifteen neurocognitive tests across seven domains. Using an enhanced forward-inclusion and backward-elimination strategy with cross-validation, we built multivariate models incorporating biological, socioeconomic, clinical, genetic, and brain imaging features. Performance was evaluated using Pearson correlation (r) between observed and inferred scores, mean absolute error (MAE), and inverse inferability score (IIS).

RESULTS: Here we show that models infer scores with moderate accuracy (r = 0.245-0.648; MAE = 1.6-12.0 points; mean MAE = 6.3). Highest correlations include Digit Span (r = 0.65; p < 0.001), Verbal Comprehension Index (r = 0.594; p < 0.001), and Matrix Reasoning (r = 0.574; p < 0.001). Domain ranking by IIS shows the best (lowest) scores for general intelligence (0.0886), followed by working memory (0.7100), and a higher (worse) score for perceptual reasoning (1.9199).

CONCLUSIONS: A multivariate approach combining brain imaging with genetic, clinical, and environmental factors provides clinically meaningful inference of individual cognitive performance in AYAs with CHD. These findings suggest complementary roles of brain, genetic, and contextual factors in shaping cognitive variability and motivate validation in larger cohorts.

With improvement in medical and surgical care, the number of adults with congenital heart disease (CHD) is soaring. Adults with CHD commonly have impairments in brain health. However, significant gaps in knowledge remain regarding the relevant types and prevalence of neurologic and psychiatric risk and their associated risk factors. We sought to review current evidence, identify gaps in knowledge, and develop key next steps to improve scientific understanding and clinical care. Three working groups-Genetics and Brain Health, Characterizing Neuropsychological and Psychological Outcomes, and Neuropsychological and Psychosocial Interventions-were composed of multidisciplinary experts in relevant clinical and research domains, as well as adults with CHD. Each group identified 5 key knowledge gaps and associated next investigations needed to address those gaps. For Genetics and Brain Health, 5 key knowledge gaps were identified: lack of a standardized neuroimaging protocol for adults with CHD, need to understand neuroradiological-pathological-neuropsychological correlates, role of gene-environment interactions, what can be learned from brain health risk models from other groups, and how existing multimodal approaches influence risk and neuroresilience. Adults with CHD can benefit from routine assessment of brain health, as well as increased clinical and basic research into the underlying factors that contribute to risk and neuroresilience for neurologic and psychiatric sequalae. Multidisciplinary collaborative efforts that incorporate adults with CHD across the research cycle are essential for all key next steps.

OBJECTIVE: Optimize use of rapid genomic sequencing (rGS) in a level IV NICU.

STUDY DESIGN: We designed interventions to improve patient identification, ordering processes, and provider education for rGS in our level IV NICU. We measured the percentage of infants eligible for rGS by internal criteria who had rGS sent, diagnostic yield of rGS (balancing measure), and days from genetics consult to rGS result (balancing measure).

RESULT: Our study included 560 infants undergoing genetics evaluation. The percentage of eligible infants who had rGS sent significantly increased from 37% pre-intervention (January 2019-March 2021) to 54% post-intervention (April 2021-September 2024) (p < 0.001). Diagnostic yield of rGS remained stable (32% vs 34%). Time from genetics consult to rGS result significantly decreased from median 32 to 27 days (p = 0.04).

CONCLUSION: Our quality improvement initiative increased rGS use with stable diagnostic yield and decreased time to rGS result for critically ill infants with suspected genetic disorders.

Congenital heart disease (CHD) is the most common major birth defect, affecting nearly 1% of live-born infants. There is a high prevalence of CHD among premature neonates, with prematurity and low birth weight compounding the risks associated with CHD and leading to increased morbidity and mortality. Despite advances in diagnosis, surgery, and intensive care, outcomes for preterm infants with CHD remain guarded, particularly in the earliest gestational age groups. These infants face heightened risks of neonatal decompensation, cardiac arrest, and early mortality, but also long-term complications including neurodevelopmental impairment. The interplay between maternal-fetal factors, perinatal environment, and the complex physiology of both prematurity and CHD underscores the need for multidisciplinary care. Prenatal diagnosis, careful delivery planning, specialized postnatal management, and tailored surgical timing are critical to optimizing outcomes. Neonatal and cardiac intensivists, cardiologists, surgeons, anesthesiologists, and allied professionals must collaborate closely to address diverse challenges including hemodynamic instability, respiratory support, nutrition, neuroprotection, and social disparities. This review synthesizes current evidence on the epidemiology, pathophysiology, and management of neonates with CHD with a focus on prematurity. We highlight evolving models of interdisciplinary care and outline priorities for research. A physiology-based, team-oriented approach is essential to improve both survival and long-term quality of life for this vulnerable population. What is Known: • CHD is the most common birth defect and a leading cause of neonatal morbidity and mortality. • Prematurity and low birthweight worsen outcomes, with complications and surgical risk inversely related to gestational age. What is New: • Pregnancies with CHD carry up to a threefold higher risk of preterm delivery. • Outcomes reflect maternal-fetal and neonatal factors, highlighting the need for tailored timing, evaluation, and surgical strategies, with a key role for multidisciplinary care.