Beyond Survival: Focus on Improving Neurodevelopmental Outcomes For Patients with Congenital Heart Disease
Lindsey Loveland MD, James DiNardo MD, Viviane Nasr MD, Susan Nicolson MD
Congenital heart disease “is the most common birth defect, with an estimated prevalence of 9 per 1,000 live births and affects all racial, ethnic, and socioeconomic groups.”1 As a result of advancements in medical and surgical care, >90% of patients with CHD survive to adulthood. We are fortunate to have Drs. Lindsey Loveland, James DiNardo, Viviane Nasr, and Susan Nicolson on the PAAD’s executive council to review articles on the perioperative management of these patients. Today’s PAAD should also serve as a reminder that there is a critical shortage of (pediatric) anesthesiologists who are trained in the perioperative management of CHD patients. For those of you who are early in your professional training, this (wo)manpower crisis should be seen as an opportunity to train in this subspecialty. You will be amongst the most sought after and most respected members of our profession. Myron Yaster MD
Before reading today’s PAAD, an American Heart Association scientific statement1, some basic definitions from the article are needed:
^ Neurodevelopmental is used to denote the acquisition, development, and execution of cognitive, academic, motor, language, neuropsychological, adaptive, social-emotional, behavioral, and psychiatric functioning during the developmental period
* Developmental delay denotes that a child is not developing or achieving skills according to the expected time frames. Developmental disorder refers to a mental or physical impairment or combination of the two that results in substantial functional limitations in major life activities
# Complex CHD –congenital cardiac lesions that necessitate cardiac surgery within the 1st year of life for survival
Original article: An American Heart Association Scientific Statement
Sood E, Newburger JW, Anixt JS, Cassidy AR, Jackson JL, Jonas RA, Lisanti AJ, Lopez KN, Peyvandi S, Marino BS; American Heart Association Council on Lifelong Congenital Heart Disease and Heart Health in the Young and the Council on Cardiovascular and Stroke Nursing. Neurodevelopmental Outcomes for Individuals With Congenital Heart Disease: Updates in Neuroprotection, Risk-Stratification, Evaluation, and Management: A Scientific Statement From the American Heart Association. Circulation. 2024 Feb 22. doi: 10.1161/CIR.0000000000001211. Epub ahead of print. PMID: 38385268.
Over the last decade, research has advanced knowledge of neurodevelopmental^ outcomes in individuals with congenital heart disease (CHD). Factors that increase risk such as genetic predisposition, fetal, perinatal and perioperative factors, socioeconomic disadvantage and parental psychological distress have all been explored. In addition, neuroprotective strategies in patients with CHD undergoing cardiac surgery have been scrutinized. This update to the 2012 American Heart Association Scientific Statement2 is intended to inform practitioners caring for patients with CHD of the current state of knowledge of neurodevelopmental outcomes in this high-risk population. Best practices for risk stratification, neuroprotection, evaluation and management of developmental delays and disorders* are delineated. Because pediatric cardiac and pediatric anesthesiologists and intensivists care deeply about the outcomes of their patients this update is essential reading.
While not every individual with CHD will experience a developmental delay or disorder, these deficits rank among the most enduring and impactful adverse outcomes faced by individuals with CHD. The extent of the problem is broad. There are measurably worse outcomes in intellectual functioning, academic achievement, motor, speech, and language skills, neuropsychologic outcomes, adaptive social emotional and behavioral functioning, psychiatric outcomes, and health related quality of life (HRQOL) in many patients with CHD.
For example, IQ is lower on average among individuals with CHD, even in those without a genetic syndrome, with the deficiency being 1-2 points for patients with atrial or ventricular septal defects, and 12 points for those with HLHS.3 There is a 25% higher risk of substandard academic outcomes and as compared to children without CHD, 50% are more likely to require special education services.4 On standardized parent and teacher ratings, children with CHD have a 4-times greater risk of impairment for attention and 2-times greater risk for impairment of executive function. Twenty-five percent of children and adolescents with complex CHD# exhibit internalizing (anxiety or depression) or externalizing (aggression, hyperactivity) behavior problems.5 Children with CHD score lower than controls on measures of social cognition, perhaps contributing to lower rate of marriage or significant relationships as adults. The relative risk of autism spectrum disorder (ASD) appears higher in individuals with CHD with one study finding that children with CHD are twice as likely to develop ASD.
Adults with CHD have lower average educational attainment which has downstream consequences on employment and economic self-sufficiency.6 A population-based study demonstrated an increased risk of early onset dementia for adults with any form of CHD and with risk increasing in patients with more complex forms of CHD.
“To aid in risk stratification of this large and growing patient population, today’s scientific statement proposes 3 categories of individuals with congenital heart disease at high risk for developmental delay or disorder according to current scientific evidence (Figure 1).”1
Figure 1 outlines the updated risk categories for developmental delay or disorder in the CHD cohort
Category 1: Individuals Who Had Cardiac Surgery With Cardiopulmonary Bypass as Infants.
The use of cardiopulmonary bypass (CPB) to repair congenital cardiac lesions results in a hyperinflammatory response, an increased risk of emboli to the brain and hypoperfusion resulting in ischemia/reperfusion injury. Several aspects of CPB management affect perfusion of the developing brain such as the degree and duration of cooling, total CPB time, and the use of antegrade cerebral perfusion and deep hypothermic circulatory arrest (DHCA). The impact of DHCA on neurodevelopmental outcomes is nonlinear, and the “safe” duration threshold depends on multiple factors. While intraoperative management of CPB is important it likely contributes less variance to neurodevelopmental outcomes than patient-specific and preoperative factors, perioperative hemodynamic instability and postoperative morbidities.
Category 2: Individuals With Chronic Cyanosis Who Did Not have Cardiac Surgery in Infancy
Although these individuals avoid some of the inherent risk associated with infant heart surgery, they are at increased risk for developmental delay due to chronic hypoxemia. The impact of chronic hypoxemia on neurodevelopmental outcomes is likely multifactorial.
Category 3: Individuals With Increased Neurodevelopmental Risk (Not Represented in Category 1 or 2)
Patients who had an intervention or hospitalization secondary to CHD in childhood and have 1 or more factors known to increase neurodevelopmental risk are included in this category (see figure 2). Many factors that increase the risk of neurodevelopmental delay or disorder are prevalent within the CHD population. This new category is intended to identify people for whom CHD may have significantly contributed to their risk of developmental delay or disorder.
The last 12 years have led to significantly improved understanding of the factors that increase the risk of neurodevelopmental delay or disorder in children with CHD (figure 2). The established risk factors explain only about 1/3 of the variance in the outcomes for individual with CHD. Recently factors such as the effect of altered cardiovascular physiology on in utero brain blood flow and development, abnormal placental development, the timing of initial cardiac surgery relative to date of birth, prolonged or repeated anesthetic exposure, exposure to neurotoxic chemicals, and multiple interventions with associated adverse events have all been identified as potentially significant contributors to the development of neurodevelopmental delay or disorder.
While the authors have described the broad range of poorer neurobehavioral outcomes for children with CHD and have updated risk stratification for who will develop these consequences and they have suggested strategies as to how to best protect those at risk. Multiple strategies were identified, but as pediatric anesthesiologists and intensivists, there are a few that deserve our particular attention. These include prenatal diagnosis to allow for immediate post-partum PGE therapy and planning for full term delivery. While early neonatal surgery may be of benefit to brain health performance of a good technical operation that minimizes the deleterious effects of CPB cannot be underestimated. Post-operative neuroprotective strategies such as family centered developmental care similar to that routinely deployed in NICUs, support to families as primary care givers, and rehabilitative services should all be implemented. Transition from hospital to home should be encouraged following early discharge planning, needs assessment, and comprehensive care coordination. Risk stratification should occur before hospital discharge with early referral of individuals at high risk for developmental delay or disorder to appropriate service providers. Children should have age-based evaluations with early intervention services from birth to age 3, special education preschool services starting at age 3, combined with clinic based neurodevelopmental services and family-based interventions.
In short, children with CHD are at increased risk for poorer neurobehavioral outcomes in each of the domains measured due to the complex interaction of myriad factors. Increased survival among high-risk patients has resulted in a growing population with developmental delay and disorders and a greater need for societal resources to assist these patients in achieving a high quality of life. It is important to remember that while tremendous progress has been made in improving survival in patients with CHD, neurodevelopmental outcomes have not meaningfully improved concomitantly with survival. Continued focus on improving neurodevelopmental outcomes is paramount. Survival with a quality of life comparable to patients without CHD remains the goal.
What do you think? Send your thoughts and comments to Myron who will post in a Friday reader response.
References
1. Sood E, Newburger JW, Anixt JS, et al. Neurodevelopmental Outcomes for Individuals With Congenital Heart Disease: Updates in Neuroprotection, Risk-Stratification, Evaluation, and Management: A Scientific Statement From the American Heart Association. Circulation 2024 (In eng). DOI: 10.1161/cir.0000000000001211.
2. Marino BS, Lipkin PH, Newburger JW, et al. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation 2012;126(9):1143-72. (In eng). DOI: 10.1161/CIR.0b013e318265ee8a.
3. Feldmann M, Bataillard C, Ehrler M, et al. Cognitive and Executive Function in Congenital Heart Disease: A Meta-analysis. Pediatrics 2021;148(4) (In eng). DOI: 10.1542/peds.2021-050875.
4. Riehle-Colarusso T, Autry A, Razzaghi H, et al. Congenital Heart Defects and Receipt of Special Education Services. Pediatrics 2015;136(3):496-504. (In eng). DOI: 10.1542/peds.2015-0259.
5. Abda A, Bolduc ME, Tsimicalis A, Rennick J, Vatcher D, Brossard-Racine M. Psychosocial Outcomes of Children and Adolescents With Severe Congenital Heart Defect: A Systematic Review and Meta-Analysis. Journal of pediatric psychology 2019;44(4):463-477. (In eng). DOI: 10.1093/jpepsy/jsy085.
6. Cohen S, Earing MG. Neurocognitive Impairment and Its Long-term Impact on Adults With Congenital Heart Disease. Prog Cardiovasc Dis 2018;61(3-4):287-293. (In eng). DOI: 10.1016/j.pcad.2018.08.002.