Congenital heart disease through a neuropsychological lens of analysis: introduction to a special issue of Child Neuropsychology

With an estimated prevalence of approximately 9 per 1,000 live births, congenital heart disease (CHD) is the most common congenital anomaly (Van Der Linde et al., 2011). Investigators first began writing about the neurodevelopmental consequences of CHD in the 1960s (Linde et al., 1967; Silbert et al., 1969). However, at that time, survival remained limited to non-existent for many children with CHD; and while children with cyanotic forms of CHD were included in some studies, samples were small and represented only a limited segment of the broader CHD population. This began to change in the 1980s. Fueled by dramatic breakthroughs in cardiac surgical techniques, survival rates started to increase. Pioneering surgeons showed for the first time that the arterial switch operation could be successfully performed in neonates with transposition of the great arteries (TGA), and that the Norwood procedure could sustain the lives of children born with hypoplastic left heart syndrome (HLHS), a condition previously considered universally fatal. Advances such as these were unfathomable even a few decades earlier.

On the heels of these monumental advances came a slowly dawning realization that it was no longer sufficient to focus our scientific efforts solely on mortality and medical morbidity in children with CHD; that it was also critically important to attend to quality of life and its neurodevelopmental and psychosocial underpinnings.

In the 40+ years since then, our understanding of development within the context of CHD has grown exponentially. A PubMed search for “congenital heart disease AND (neurodevelopment OR neuropsychology)” conducted at the time of writing (April 2023) yielded nearly 500 results, >65% of which were published in the past 5 years alone. In 2012, around the same time the American Heart Association and American Academy of Pediatrics released a landmark scientific statement calling for periodic neurodevelopmental surveillance, screening, and evaluation of children with complex CHD (Marino et al., 2012), the Cardiac Neurodevelopmental Outcome Collaborative (CNOC) held its first meeting and incorporated shortly thereafter, bringing together professionals and families united by the common goal of optimizing neurodevelopmental outcomes for every individual affected by CHD (Marino et al., 2020). Today, systematic neurodevelopmental monitoring and follow-up are considered the standard-of-care for children with complex CHD, endorsed by CNOC, and implemented by more than 50 dedicated cardiac neurodevelopmental programs across North America and Europe, as well as countless others worldwide (Ilardi et al., 2020; Marino et al., 2012; Miller et al., 2020; Ware et al., 2020).

While it is now well established that complex CHD poses a serious threat to neurodevelopmental and psychosocial outcomes across the lifespan, there is still much that we do not know about CHD and its impact on the developing brain. For all our progress, we still cannot distinguish a priori and with confidence which children will thrive, and which will struggle. Modifiable risk factors remain stubbornly elusive, as do effective modes of intervention. And like society in general, there are marked disparities in outcomes for individuals with CHD, driven predominantly by racial, cultural, linguistic, and sociodemographic factors. Those most in need of high-quality neurodevelopmental and psychosocial support are also the least likely to get it.

Recognizing these knowledge gaps, as well as the need for greater clarity moving forward, the National Heart, Lung, and Blood Institute (NHLBI) of the United States National Institutes of Health (NIH) funded several CNOC-sponsored working groups, each focused on a crucial domain related to neurodevelopmental and psychosocial outcomes in CHD and tasked with proposing a research agenda specific to that domain for the next decade (Sood et al., 2021). Among the many notable ideas put forward, there was a strong and unequivocal call to reconsider how outcomes are conceptualized, and to diversify our methodology and measurement strategies accordingly. This included a better understanding of symptom networks and dimensions that go beyond traditional diagnostic categories; which neurodevelopmental factors have the most meaningful impact on daily life; how neurological factors impact these outcomes; how change occurs longitudinally across the developmental trajectory; and how we can address health disparities more effectively (Sanz et al., 2021). Also highlighted was the need to develop effective intervention strategies across the lifespan, with an eye toward not only mitigating existing neurodevelopmental and psychosocial morbidities but also taking meaningful steps toward preventing them in the first place (Cassidy et al., 2021).

The eight papers presented in this Special Issue begin to answer these urgent calls to action. The first three research papers, submitted by investigators in the United States, Switzerland, and France, highlight novel, clinically informative approaches to characterizing key features of neurodevelopmental phenotypes in CHD. To start, Ilardi and colleagues (2022) show that parent income and education account for roughly six times more of the variance in IQ and academic achievement outcomes than medical/surgical factors. These findings highlight the need for neuropsychologists to appreciate a broader ecology of risk and resilience among individuals with CHD, from intra-personal to social-environmental systems, and their relevance within the context of clinical assessment. With time, they may also help us achieve more appropriate risk stratification and more appropriate allocation of resources toward those families most in need. Next, Jassal and colleagues (2022) report on attention and executive function outcomes, as well as broader neuropsychological, psychosocial, and adaptive skills outcomes, among children and adolescents with single-ventricle cardiac disease who have undergone the Fontan procedure. Once again demonstrating the salience of the broader sociodemographic context, these investigators also identify attention/executive function skills as significant predictors of both academic and adaptive skill outcomes within a CHD patient population that is recognized as being among the highest risk for neurodevelopmental impairment. Last, and in a similarly clinically relevant fashion, Ehrler, Bellinger, and colleagues (2023) move beyond typical diagnostic constructs and examine social cognition independent of autism spectrum disorder diagnosis. Within their sample of children and adolescents with varied CHD subtypes, 39% were rated by their parents as having social/behavioral difficulties, the overwhelming majority (95%) of whom were also rated as struggling with executive function and/or anxiety. Their findings call attention to the elevated risk of social issues experienced by children with CHD – even among those who do not meet diagnostic criteria for autism – and underscore the importance of holistic and integrative psychological/neuropsychological interventions for the CHD population.

The next three papers, which come from investigators in Switzerland and Canada, explore novel applications of three different neuroimaging techniques and their respective utility for highlighting and understanding the neurodevelopmental consequences of CHD across development. First, Ehrler, Brugger, and colleagues (2022) examine white matter microstructure among children, adolescents, and young adults with varied types of CHD, finding similar changes in fractional anisotropy (a measure of white matter microstructural integrity) across age groups, perhaps suggesting relative stability in the degree of white matter microstructural alterations over time. This study also provides evidence of associations between white matter microstructural integrity and performance-based executive function impairments, which not only demonstrates the importance of ongoing neuropsychological follow-up across the lifespan but also points to the need for early neuroprotective interventions and their potential to improve executive function outcomes perhaps years or even decades down the line. The next two papers use novel functional imaging techniques to map neural networks and connectivity. Fourdain and colleagues (2023) use functional near-infrared spectroscopy (fNIRS) to explore alterations in functional connectivity and cortical functional organization among 4-month-old infants who have undergone surgery for CHD. Their paper offers first known evidence of widespread alterations in post-operative functional connectivity among neonates with CHD, most (although not all) of which were found to be reduced relative to controls, and particularly involving frontal brain regions which are recognized as providing an important substrate for executive function. Though preliminary and pending further replication in larger samples, this study showcases fNIRS as a portable, relatively lower cost, and motion-tolerant imaging technique that can be used effectively in infancy (and beyond) to examine changes in brain development, and potentially how these may predict behavioral and cognitive outcomes. Last, Wehrle and colleagues (2022) use sleep slow wave activity, recorded via electroencephalogram (EEG), to chart the functional neural network organization of working memory in children with complex CHD and healthy controls. Finding a consistent pattern of strong associations over prefrontal and fronto-parietal brain regions long recognized for their role in working memory, the authors conclude that CHD does not seem to fundamentally alter working memory network organization – a finding which is particularly interesting considering that working memory test scores were, in fact, lower on average among children with CHD in their study. This study also showcases sleep EEG as a novel technique with the potential to be useful in mapping neural network organization as a baseline, and perhaps also as an endpoint following treatment/intervention.

Finally, the issue contains two review papers, one topical and the other conceptual, that frame CHD as a truly lifespan neurodevelopmental condition. In the first, Sanz and colleagues (2023) provide an overview of the neurological and neurodevelopmental implications of CHD, beginning prenatally and extending throughout infancy, childhood, adolescence, and adulthood – with a particular focus on identifying key points of intervention to support positive outcomes. Further exploring the prenatal period as a pivotal time of both risk and opportunity, Cassidy and Neumann (2023) then conclude with a developmental origin of health and disease-inspired call for pediatric neuropsychology to harness its full potential as a source of primary prevention for families affected by a CHD diagnosis.

This Special Issue of Child Neuropsychology represents an important first: to our knowledge, it is the first time a major peer-reviewed journal has devoted an entire issue to the neuropsychological implications of CHD. A neuropsychological lens of analysis has proven highly consequential in the history of cardiac neurodevelopmental research, and it is truly an honor to showcase some of the latest work in this area here. We also deeply appreciate and are constantly inspired by the rapid growth of cardiac neurodevelopmental research, as well as by the compassion and ingenuity of the clinicians, scientists, patients, and caregivers driving the field forward; this issue is dedicated to them.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.