James William Gaynor

Individuals with congenital heart disease are living well into adulthood, resulting in a growing population at risk for neurocognitive and psychosocial challenges. Numerous studies have described these risks in childhood, but significant gaps remain in our understanding of how those challenges evolve across stages of adulthood and how to optimally integrate neurocognitive and psychosocial care for adults with congenital heart disease. A multidisciplinary group of experts and patient partners assembled in April 2024 in Atlanta, GA, forming 3 working groups: (1) Genetics and Brain Health, (2) Characterizing Neuropsychological and Psychological Outcomes, and (3) Neuropsychological and Psychosocial Interventions. Current knowledge was reviewed, knowledge gaps were identified, and recommendations to address these gaps were formulated. Five critical questions regarding the characterization of neuropsychological and psychological outcomes of adults with congenital heart disease were prioritized for discussion: which neurocognitive and psychosocial domains should be prioritized in research and clinical care, what are the trajectories of neurocognitive and psychosocial functioning over the lifespan, how should neurocognitive and psychosocial screening be deployed, what should neurocognitive and psychosocial assessments include, and how do we make comprehensive neurocognitive and psychosocial care a reality. Although many gaps in knowledge were identified, particularly around characterizing neurocognitive trajectories throughout adulthood, there is substantial evidence of increased risk for poor psychosocial outcomes among adults with with congenital heart disease. Clinical and research advances must progress in tandem to address these risks. Specific recommendations for advancing this field over the next decade are offered.

BACKGROUND: Neurodevelopmental and functional impairments are among the most consequential morbidities for survivors of hypoplastic left heart syndrome after staged single ventricle surgical palliation. The SVRIII trial (Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type) enrolled adolescents, who were randomized to different surgical shunt types at the time of Norwood procedure as neonates, for multifaceted in-person evaluation. This study reports their neurodevelopmental outcomes. METHODS: Transplant-free survivors from SVRIII were invited to complete an in-person comprehensive neurodevelopmental evaluation in early adolescence. Outcomes across domains of cognition, academics, learning, memory, and attention, as well as social, emotional, behavioral, adaptive, and executive function, were compared with those of normative populations. Associations with demographic and medical covariates, including Norwood shunt type, were also assessed. RESULTS: Among 549 participants enrolled in the SVR trial (Single Ventricle Reconstruction), 200 of the 237 SVRIII participants (84%) completed a neurodevelopmental evaluation at a mean age of 11 years (range, 10 to 14 years). SVRIII participants who did versus did not undergo evaluation were more likely to be male (63% versus 51%), to be White (87% versus 76%), and to have a higher Childhood Opportunity Index score (61±26 versus 46±39). Full-scale intelligence quotient (88±18) was significantly lower than in the normative population, with 39% >1 and 15% >2 SD below the normative mean. Similar patterns were seen for reading (38% >1 SD and 16% >2 SD below the normative mean) and math (38% >1 SD and 19% >2 SD below the normative mean) scores. Attention, executive functioning, social development, visual memory, and adaptive functioning were all more impaired than in the normative population. Measures of socioeconomic status, number of medical complications, and requirement for a gastrostomy tube were each independent predictors of neurodevelopment, with socioeconomic status the most consistently significant factor across models. Group differences by shunt type were inconsistent across neurodevelopmental domains without a clear benefit of one surgical strategy. CONCLUSIONS: In early adolescence, transplant-free survivors of surgical palliation for hypoplastic left heart syndrome show concerning impairments across all domains of neurodevelopment. The distribution of affected outcomes is broad and associated with demographic, medical, and, most frequently, socioeconomic factors. Our findings support recommendations for neurodevelopmental evaluation during adolescence to guide individualized interventions to promote educational success and psychosocial well-being. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02455531.

Background: Advances in procurement techniques have enabled use of hearts obtained via donation after circulatory death (DCD), expanding the donor pool; however, the impact of DCD heart transplant on outcomes in children is not well described. We aim to characterize waitlist survival and outcomes in pediatric heart transplant candidates listed for donation after brain death (DBD) versus DCD hearts. Methods: The United Network for Organ Sharing database was queried for patients aged P =0.01). No patients in the status 1B/2 DCD subgroup died while waitlisted. There were no differences in 1‐year posttransplant survival. Conclusions: Among candidates for pediatric heart transplant listed as status 1B/2, patients listed for DCD hearts in addition to DBD hearts have shorter waitlist duration, improved transplant rates, lower waitlist mortality rates, and comparable survival to patients listed for DBD hearts alone.

Prenatal maternal mental health and social determinants of health may influence pregnancy, child hospitalisation, and child neurodevelopmental outcomes in critical congential heart disease (CHD). We examined 189 mother–child dyads of children born with CHD who underwent neonatal cardiac surgery and completed neurodevelopmental assessment between the ages 13 and 29 months. We used latent profile analysis to identify distinct maternal groups based on prenatal maternal mental health screening scores and individual- and neighbourhood-level social determinants of health factors. We examined the association between maternal groups with their child’s gestational age, birth weight, hospital length of stay (HLOS), and neurodevelopment. Latent profile analysis identified two distinct groups: high-risk (n = 46) and low-risk (n = 143). Mothers in the high-risk group had higher mental health screening scores, lower age, higher social vulnerability, lower education, and were more likely to have Medicaid insurance and represent a minority group than mothers in the low-risk group. The high-risk group had children with lower gestational age and weight at birth, longer HLOS, and lower cognitive, language, and motor scales than children in the low-risk group (p < 0.05). Sensitivity analysis in mother–infant dyads without foetal extracardiac conditions found that significant relationships persisted in the high-risk group, with lower gestational age and lower language scale scores than the low-risk group (p < 0.05). Children of mothers with adverse prenatal maternal mental health and social determinants of health risks had significantly worse pregnancy and child outcomes. Interventions are critically needed to address maternal mental health and social determinants of health risks beginning in the prenatal period.

Background: We lack early biomarkers for predicting neurodevelopment (ND) outcomes in children with congenital heart disease (CHD). Placentas of fetuses with CHD have abnormalities, including unbalanced fetal/placental weight ratios (F/P). Although DNA methylation profiles have revealed insights into the maternal-fetal environment (MFE), it is unknown if DNA methylation correlates to normalized F/P weight ratio groups and how these differences relate to ND outcomes. Methods: We prospectively recruited a cohort of pregnant women carrying a fetus with CHD. A subset of the cohort had DNA methylation performed on either umbilical cord blood or postnatal blood (45 full-term neonates). We calculated normalized F/P weight ratios, focusing on three normalized F/P ratio groups for analysis. We calculated differential methylation signals in eight ND disabilities-associated gene sets. Normalized F/P ratios were compared to 18-month Bayley Scales of Infant Development-III scores (BSID-III). Results: Unbiased gene ontology enrichment analysis of differentially methylated regions revealed enrichment for brain development-related pathways. Although there were no significant differences between normalized F/P weight ratio groups and BSID-III, disease-associated gene set pathway analysis revealed significant methylation differences between the most severely unbalanced F/P weight ratio and normal F/P weight ratio groups. Conclusion: Gene ontology enrichment analysis of differential methylation regions revealed significant differences between normalized F/P weight ratio groups in neurogenesis genes. Furthermore, our data identified methylation differences between unbalanced and balanced normalized F/P weight ratio groups in gene pathways associated with ND dysfunction common in the aging CHD population suggesting converging pathways for ND disorders that should be investigated further.