Maximizing health and functional outcomes for children and adolescents with congenital heart disease and Trisomy 21: What are we still missing?

Up to 50% of infants with Trisomy 21 (T21) also have congenital heart disease (HD), with the most frequent cardiac anomalies including atrioventricular septal defects, ventricular septal defects, or atrial septal defects.¹ Both T21 and congenital HD independently impact health, functional status, and quality of life, but evidence specific to individuals living with both conditions is limited. This American Heart Association (AHA) Scientific Statement is an important step forward, as it summarizes relevant considerations for both T21 and congenital HD, outlines gaps in knowledge about those with concurrent T21 and congenital HD, discusses potential interactions between the two diagnoses, and offers suggestions for research and clinical areas of focus. Throughout, the statement maintains a focus on equitable, family-centered developmental care to optimize the health and quality of life of those living with T21 and congenital HD.

How does cardiac management differ in the context of T21 and congenital HD?

The authors of the scientific statement note that management of the cardiac condition is largely similar with or without a co-occurring T21 diagnosis, with a few key considerations. Individuals with T21 are at increased risk for pulmonary hypertension from birth, in part related to intrinsic differences in alveolarization and pulmonary vascularization.^2,3 This condition can be exacerbated by pulmonary overcirculation secondary to residual lesions from the cardiac defect, and can impact surgical/interventional treatment type and timing. Given a lack of screening or treatment guidelines for pulmonary hypertension that are specific to individuals with T21, the authors suggest close pulmonary hypertension monitoring throughout the lifespan, along with future research to improve our understanding of pulmonary hypertension mechanisms, biomarkers, and treatments in this population.

The statement addresses additional important issues related to management of particularly critical situations in congenital HD for individuals with T21; specifically, single ventricle physiology and end-stage heart failure necessitating transplant. Children with single ventricle forms of congenital HD are typically treated with a series of palliative surgical or catheter-based interventions. The authors note that T21 appears to increase the risk for in-hospital mortality in both stage I and Fontan palliations, and highlight questions about the optimal treatment strategy for these children.⁴ Similarly, there are ethical and physiological uncertainties surrounding heart transplantation for individuals with coexisting congenital HD and T21, with T21 considered a contraindication for heart transplant at the majority of United States centers and little existing research to inform decision-making. While one small, multicenter, retrospective case series demonstrated similar outcomes for pediatric transplant patients with and without T21,⁵ it is likely that this sample may have exhibited selection bias and generalizability is unknown. While the National Down Syndrome Society specifically opposes discrimination in organ transplant for individuals with T21,⁶ addressing the evidence gap in this area is challenging, as resources are limited⁷ and the patient population is small. It is clear that clinical guidelines are urgently needed to minimize provider- and site-specific variation in referral for heart transplant,⁸ and to facilitate ethical, equitable care for individuals with T21 and congenital HD.

How do co-occurring conditions impact individuals with T21 and congenital HD?

Individuals with T21 often experience co-occurring physical conditions involving multiple body systems, including gastrointestinal, respiratory, endocrine, hematologic/oncologic, and neurologic challenges. The scientific statement helpfully summarizes common co-occurring diagnoses and highlights implications for management in the context of congenital HD.

For example, infants with T21 are at high risk for feeding and swallowing dysfunction, which can contribute to poor weight gain, nutritional deficiencies, and aspiration. Problems with growth can be of heightened concern in the context of congenital HD as malnutrition has been associated with poor surgical⁹ and neurodevelopmental¹⁰ outcomes. Extended need for tube feeding adds substantial stress to family caregivers, who are managing their child's already complex medical needs.¹¹ Aspiration secondary to feeding and swallowing dysfunction may exacerbate pulmonary hypertension or contribute to respiratory infection, adding further strain to cardiopulmonary imbalance.

Neurodevelopment for infants with congenital HD has received increased attention in recent years, including a previously published AHA scientific statement outlining best practices for management of developmental delays and disorders in this population.¹² Up to 50% of children with critical forms of congenital HD experience at least some form of developmental delay, and these neurodevelopmental challenges can be exacerbated by co-occurring genetic or chromosomal anomalies such as T21.

Several psychiatric disorders including autism spectrum disorder, attention-deficit/hyperactivity disorder, depression, and anxiety are more prevalent in individuals with congenital HD. Multifactorial fetal (e.g., altered cerebral perfusion), genetic, clinical (e.g., developmentally toxic hospital setting), social, and environmental factors may contribute to the etiology of these disorders in the context of congenital HD.^13,14 T21 has also been linked to higher risk for psychiatric conditions (e.g., autism spectrum disorder), but the authors of this statement emphasize that screening tools for psychiatric or mood disorders may not be suitable for individuals with T21, and highlight an almost complete lack of evidence on neurodevelopmental, behavioral, and psychological health that includes participants with both congenital HD and T21. This uncertainty extends to research on functional outcomes (e.g., daily living activities), and it is also unclear how neurodevelopmental, psychological, and functional challenges may impact quality of life for those with congenital HD and T21. This scientific statement underscores a striking knowledge gap in this area, and serves as a call to action for further investigation – for example, to identify genetic mediators of psychiatric disorders for children with both T21 and congenital HD; and to develop screening tools with sensitivity to diagnose mental health disorders in this specific population.

Given these knowledge gaps, this statement emphasizes the critical importance of specialist evaluation and supportive, family-centered intervention beginning in early childhood and continuing throughout the lifespan for individuals with T21 and congenital HD. As there are no published guidelines for neurodevelopmental care specific to this population, the authors suggest using guidelines for both congenital HD¹² and T21,¹⁵ and assessing the greatest needs of each individual. Both cardiac neurodevelopmental follow-up clinics and T21-focused follow-up clinics exist, and it will be important for future research to determine the optimal medical home for these individuals.

The importance of family-centered care and the medical home

This scientific statement is particularly beneficial in that it outlines a clear framework for family-centered, developmentally supportive care for individuals with T21 and congenital HD. The authors ground their clinical guidance in national standards for care coordination for children and youth with special healthcare needs¹⁶ and propose an intentional, multidisciplinary approach focused on care coordination and communication, the importance of a medical home, equity and inclusivity, and transition planning. Transition from pediatric to adult care can have unique challenges in this group,¹⁷ who may have varied medical complexity and intellectual disability; thus, future clinical and research focus is needed to identify effective models to support care transition for adolescents with T21 and congenital HD.

Future directions and conclusions

One of the strongest contributions of this scientific statement is the clear delineation of clinical directions and research priorities to deepen our understanding of the ways in which T21 and congenital HD interact, and to improve care for individuals with both diagnoses. For example, the authors highlight a need to examine heart transplant outcomes to determine whether individuals with T21 can be viable candidates for transplant, and to answer the question of whether heart transplant or Fontan palliation provide better outcomes for children with single ventricle physiology and T21. Improved non-pharmacological and pharmacological treatment options for pulmonary hypertension could help optimize health and improve survival. Screening tools that can identify mental health conditions in children with T21 are needed to support targeted, individualized neurodevelopmental care throughout the lifespan. Strategies to effectively support the transition from pediatric to adult care will be critical in addressing the medical complexity and risk for loss to follow-up in this patient population. In sum, this scientific statement provides a comprehensive summary of current evidence and offers suggestions to guide care and improve health and functional outcomes for children and adolescents with T21 and congenital HD.