1

Introduction

Congenital heart disease (CHD) is a wide category of structural and functional heart abnormalities present at birth. Cardiac anomalies include defects in the cardiac muscle, septa, valves, arteries, or veins. CHD is among the most common types of birth defects, with a prevalence of 1 % [ , ]. Examples of CHD include atrial septal defect, ventricular septal defect, tetralogy of Fallot, transposition of the great arteries, and hypoplastic left heart syndrome. The effects and severity of illness secondary to these cardiac abnormalities depend on the associated hemodynamic characteristics and ability of the heart to pump oxygenated blood effectively to vital organs, including the developing brain.

Previous studies have established clinically relevant correlations between CHD, variation in pediatric brain development, and increased risk of adverse neurodevelopmental outcomes. The degree of impact on early childhood development is multifaceted and varies with the structural changes, etiologic genetic syndromes, surgical risk factors, and social determinants of health [ ]. Risk factors for atypical or delayed development include ineffective circulation and decreased oxygenation, which may delay a child’s physical (gross and fine motor) and cognitive development [ ]. Frequent hospitalizations, medical procedures, and physical limitations associated with the diagnosis and treatment of CHD may markedly affect emotional and psychosocial development [ , ]. Prior research has established a direct correlation between surgical treatment and duration of hospitalizations with the risk of developing neurodevelopmental delay [ , , ].

In response to the established risk of developing neurodevelopmental disability associated with CHD, developmental screening and assessment are recommended for all children with CHD [ ]. Developmental screening uses standardized tools and questionnaires to quickly identify children who are at risk of developmental delay. Abnormal screening results may prompt referral for developmental evaluation, which involves comprehensive testing conducted by professionals such as psychologists and other developmental specialists. In addition to identifying children at risk for developmental deficits, developmental evaluation aims to diagnose specific delays so that early treatment may be initiated. Early intervention for developmental delay may improve long-term outcomes [ , ].

The purpose of this article is to review neurodevelopmental outcomes associated with CHD, including risk factors, genetic syndromes, and developmental screening and evaluation in pediatric patients with CHD.

2

Neurodevelopmental outcomes across the lifespan

Neurodevelopmental disabilities may be observed across the lifespan of individuals with CHD in various domains, including motor, language, cognitive, and academic abilities. As 90 % of children with CHD survive to adulthood, CHD has an impact on the child’s developmental trajectory and adult cognitive and functional abilities [ , ]. Developmental delay may be identified during infancy and early childhood in patients with CHD [ ]. Delays in one or multiple domains range in prevalence from 22 % to 75 % of children with CHD, depending on the specific developmental domain and age at assessment [ , ]. In early childhood, defined as the period from birth to age three years, motor deficits may be identified at an increased rate in patients with CHD [ ]. Through late childhood and into adolescence, lower performance on cognitive and executive function measures indicate lower than average functioning in these domains for individuals with CHD compared with same-aged peers. Cognitive deficits are greatest in children who have hypoplastic left heart syndrome compared with other cardiac defects [ ]. Children with CHD have 1.24-fold greater risk of having academic difficulty in mathematics or reading compared with peers [ ]. Children with CHD are 50 % more likely to receive special education services than children without heart defects, and a study of one urban area over two decades showed that CHD was associated with a higher prevalence of special education categories for intellectual disability, sensory impairment, other health impairment, marked developmental delay, and specific learning disability [ ].

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Risk factors for neurodevelopmental disabilities associated with congenital heart disease

4

Genetic syndromes associated with congenital heart disease and neurodevelopmental disabilities

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Developmental screening of pediatric patients with congenital heart disease

Developmental screening entails use of a standardized tool to identify a recognized risk of abnormal development. The American Academy of Pediatrics recommends that primary care providers perform developmental screening for all children [ ]. Developmental screening is distinct from developmental surveillance, which is the identification of children who may be at risk for developmental delays but without the use of a standardized tool or risk stratification. Developmental screening also is distinct from developmental evaluation, which is a complex process that uses a standardized tool or battery of instruments to diagnose specific developmental disorders and guide recommended interventions. Screening does not provide a diagnosis but helps to identify patients who may have a problem [ ].

According to an algorithm developed by the American Academy of Pediatrics, all children receive general developmental screening at the 9-, 18-, and 30-month visits and autism-specific screening at the 18- and 24-month visits [ ]. In addition, developmental screening is appropriate at any time that caregivers, professionals, or others raise concerns about development. Positive screening results are followed by medical and developmental evaluation [ ].

Children with CHD are at increased risk of having various types of developmental delays and disorders. Therefore, all children with CHD receive surveillance and screening as recommended by the American Academy of Pediatrics [ , ]. The American Heart Association also published a scientific statement in 2012 and an updated, expanded version in 2024 about evaluation and treatment of children with CHD to optimize neurodevelopmental outcomes [ , ].

The 2012 American Heart Association scientific statement drew from the algorithm for developmental surveillance and screening that was published by the American Academy of Pediatrics in 2006 [ ]. The American Heart Association scientific statements reiterate the importance of developmental surveillance and screening for children with CHD because of their increased risk of having developmental delay and disorders. The 2024 statement provided criteria for stratifying children with CHD into three risk categories for developmental delay and disorders: (1) risk category 1, patients who had cardiac surgery with cardiopulmonary bypass during infancy; (2) risk category 2, patients with chronic cyanosis who did not have cardiac surgery with cardiopulmonary bypass during infancy; and (3) risk category 3, patients with increased neurodevelopmental risk who did not have infant cardiac surgery with cardiopulmonary bypass and were not chronically cyanotic [ ]. The 2024 statement included an algorithm for referral, evaluation, and treatment of patients at high risk (Fig. 3 in [ ]). The American Heart Association guidelines recommend that children with CHD who are at low risk of having developmental delay or disorders receive developmental screening according to the 2020 recommendations from the American Academy of Pediatrics [ , ]. The American Heart Association recommends that children with CHD who are at high risk of having developmental delay or disorders be referred for developmental evaluation and monitored regularly, bypassing the need for regular screening [ ].

A useful screening tool is reliable, valid, sensitive, and specific and may be completed and scored efficiently [ ]. Selection of a screening tool is determined by the age and developmental level of the child because instruments may be valid only for specific ages or developmental levels. Screening tools typically are questionnaires completed by caregivers or direct assessments performed by clinicians.

General developmental screening tests address multiple developmental domains, whereas other screening tests may focus on specific conditions such as autism or developmental domains such as language [ ]. General developmental screening tests that may be completed by caregivers include the Ages and Stages Questionnaires (ASQ); Parents’ Evaluation of Developmental Status-Revised (PEDS-R); Parents’ Evaluation of Developmental Status: Developmental Milestones (PEDS:DM); and Survey of Well-being of Young Children (SWYC) [ ]. Direct screening tools that are administered by trained professionals include the Bayley Scales of Infant and Toddler Development screening test, Brigance Early Childhood Screening Assessments, and Battelle Developmental Inventory (BDI). Studies assessing the utility of particular screening tools in children with CHD are limited. However, the ASQ was evaluated and may be useful in screening for neurodevelopmental disorders in children with CHD [ , ].

Autism screening is recommended for all children aged 18 to 24 months [ ]. Multiple factors may increase the risk of developing autism in children with CHD, including the presence of genetic syndromes and brain injury from oxygen deprivation [ ]. Instruments commonly used to screen for autism that are completed by caregivers include the Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F), Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist (CSBS DP-ITC), and Social Communication Questionnaire (SCQ) [ , ]. Direc, clinician-administered screening tools include the Screening Tool for Autism in Toddlers and Young Children (STAT) and Rapid Interactive Screening Test for Autism in Toddlers (RITA-T) [ ].

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Developmental evaluation of pediatric patients with congenital heart disease

Developmental evaluation with standardized testing and rating scales by a qualified professional is recommended by the American Heart Association for children with CHD who are at high risk of neurodevelopmental sequelae [ ]. The Cardiac Neurodevelopmental Outcome Collaborative published recommended age-based standardized tests for patients with CHD, including children up to age 5 years and school-aged individuals [ , ]. Domains evaluated in children aged 1 to 5 years may include cognition, growth, language development, motor skills, self-regulation, adaptive skills, autism, social-emotional functioning, attention-behavior, executive function, school readiness, and primary caregiver mental health. For children and adolescents aged 5 to 18 years, domains evaluated may vary with age and include components of intelligence, academic abilities, attention and executive function, memory, fine motor skills, adaptive behavior, emotional and behavioral functioning, and social skills. Evaluations for the psychosocial effects of CHD are important components of evaluation [ ]. Furthermore, individualized developmental evaluation may be unique to the specific problems and needs of the patient [ ]. The American Heart Association has acknowledged the limitations of standardized tests in culturally and racially diverse populations [ ].

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Clinical practice in cardiac neurodevelopmental programs

Clinical practice in cardiac developmental centers is highly varied across the United States, and variations in practice at cardiac neurodevelopmental follow-up programs have been documented by the Cardiac Neurodevelopmental Outcome Collaborative [ ]. The timing and schedule of neurodevelopmental evaluation may be highly varied, with most resources used for evaluation of children between birth and age 5 years. Most cardiac developmental clinics are multidisciplinary, with most mental and behavioral health diagnoses being made by a psychologist or developmental pediatrician. Furthermore, there is wide variation in specific standardized tests and scales used, with the most frequently used evaluations being the Bayley Scales of Infant and Toddler Development (Bayley-III) from birth to age 3 years and Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) and parent-completed Adaptive Behavior Assessment System (ABAS-3) up to and including age 5 years. Routine neonatal brain imaging during hospitalization after cardiac surgery is completed in less than 25 % of patients, and most neonatal developmental testing is performed with clinical tests only.

A recent study comparing national guidelines to single-center use of referral for developmental evaluation or intervention indicated that most patients with CHD in a single-center were not referred for neurodevelopmental services and evaluation [ ]. In addition, neurodevelopmental evaluation attendance may be a barrier to identification of developmental and behavioral diagnoses because only 7.8 % to 54.3 % of patients in cardiac centers attend developmental evaluation [ ]. Therefore, initiatives to standardize evaluation in clinical practice and increase attendance may provide opportunities for future improvement.

The need for early therapeutic intervention for high-risk pediatric patients with CHD supports early referral [ , ]. In high-risk pediatric patients with CHD requiring cardiac surgery, 67 % of patients who underwent developmental evaluation received early intervention services within the first year after birth [ ]. An additional single-center study indicated that approximately one-third of high-risk patients with CHD may require therapeutic intervention referral at the first developmental evaluation [ ]. More than 40 % of patients are referred for ancillary medical services, including additional medical subspecialist and audiology referrals, during the initial evaluation [ ]. In high-risk school-aged children and adolescents, developmental evaluation may improve access to academic services, an individualized education plan, small group academic instruction, and instructional supports [ ]. Further research is needed to evaluate referrals resulting from developmental evaluations in these high-risk patients and the response to developmental interventions.

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Conclusion

Research on neurodevelopmental outcomes in CHD patients supports the need for early identification of developmental disabilities. The effects of CHD on neurodevelopment are multifactorial and include intrinsic and extrinsic factors. The study of neurodevelopmental outcomes of pediatric patients with CHD has continued to expand our knowledge about risk factors, neuroprotective factors, and neuropsychological profiles. This knowledge may enable the implementation of effective strategies that may optimize outcomes in affected individuals.

Developmental surveillance and screening are essential to identify children with CHD who are at risk of having adverse neurodevelopmental outcomes. Surveillance and screening are recommended for all children with CHD, regardless of severity. Children who present with positive screening tests or other signs of developmental problems require prompt referral to a developmental specialist for comprehensive evaluation and early intervention.

The evidence included in this review is limited by the high variability in screening, evaluation, and intervention guidelines for developmental delay in children with CHD. Referral for early therapeutic intervention may not be used consistently because of the lack of standardized methods. Further improvements are needed in standardized methods and access to developmental screening and evaluation for pediatric CHD patients.

Declaration of Generative AI and AI-assisted technologies in the writing process

AI was not used in preparation of this manuscript.

Funding

Editorial support was provided by the Dean’s Office, University of South Alabama , Frederick P. Whiddon College of Medicine .

CRediT authorship contribution statement

Kahlea Haladwala: Writing – review & editing, Writing – original draft. Edwin Boyer: Writing – review & editing, Writing – original draft. Ginger Llivina: Writing – review & editing, Writing – original draft. Stephanie Anderson: Writing – review & editing, Writing – original draft. Induja Gajendran: Writing – review & editing. Sara Shank: Writing – review & editing, Writing – original draft.