What congenital heart diseases are associated with Autism Spectrum Disorder (ASD)?

Congenital Heart Diseases Associated with Autism Spectrum Disorder

Children with congenital heart disease are approximately twice as likely to develop autism spectrum disorder compared to children without congenital heart disease, with atrial septal defects and ventricular septal defects showing the strongest associations. 1, 2

Overall Risk Magnitude

• Children with any form of congenital heart disease have approximately 2-fold increased risk of developing autism spectrum disorder compared to the general population 1
• The prevalence of autism spectrum disorder in children with congenital heart disease is higher than the estimated 9 per 1000 (or 1 per 110) prevalence in the general pediatric population 1
• This elevated risk persists across multiple congenital heart disease subtypes, though specific lesions carry differential risk 2, 3

Specific Congenital Heart Lesions with Highest ASD Risk

Atrial septal defects (ASD) and ventricular septal defects (VSD) are the two specific congenital heart lesions most strongly associated with increased autism spectrum disorder risk. 2

Atrial Septal Defects

• Children with atrial septal defects have 1.72-fold increased odds of developing autism spectrum disorder (95% CI 1.07-2.74) after adjusting for genetic syndromes, maternal age, gestational diabetes, short gestation, newborn epilepsy, birth asphyxia, and low birth weight 2
• This association holds across all ASD subtypes including secundum, primum, and sinus venosus defects 2

Ventricular Septal Defects

• Children with ventricular septal defects have 1.65-fold increased odds of developing autism spectrum disorder (95% CI 1.21-2.25) after controlling for confounding variables 2
• This represents the most common congenital heart defect at birth (3.0-3.5 per 1000 live births) and carries significant autism risk 2

Complex Congenital Heart Disease and Higher Risk

Children with complex congenital heart disease requiring neonatal or infant open heart surgery face particularly elevated autism spectrum disorder risk and warrant heightened surveillance. 1

• Transposition of the great arteries (TGA) is associated with social impairments including deficits in "theory of mind" domains 1
• Children with single-ventricle heart disease and those undergoing the Norwood/stage 1 or arterial switch operations show early adaptive skills deficits that may herald autism spectrum disorder 1
• Tetralogy of Fallot with ventricular septal defect repair carries risk for both autism spectrum disorder and ADHD comorbidity 4

Genetic Syndromes with Dual CHD-ASD Risk

Deletion 22q11 syndrome (DiGeorge/velocardiofacial syndrome) carries exceptionally high autism spectrum disorder risk (20-40%) in addition to its congenital heart disease associations. 1

• This syndrome commonly presents with conotruncal heart defects including ventricular septal defects, tetralogy of Fallot, and interrupted aortic arch 1
• Down syndrome is associated with atrioventricular septal defects (including primum ASD) and carries developmental delay risk, though autism spectrum disorder prevalence data are less specific 1

Risk Factors Beyond Cardiac Anatomy

Several medical and perinatal factors compound autism spectrum disorder risk in children with congenital heart disease:

• Surgical factors: Delayed sternal closure following cardiac surgery increases autism spectrum disorder risk 3
• Prematurity: Late-preterm infants (34-36 weeks) with congenital heart disease face compounded developmental delay and autism spectrum disorder risk 1
• Genetic findings: Any positive genetic testing result in a child with congenital heart disease elevates autism spectrum disorder risk 3
• Chronic hypoxemia: Cyanotic congenital heart disease not requiring neonatal surgery still carries developmental risk through chronic hypoxemia 1

Clinical Screening Recommendations

All children with congenital heart disease should undergo autism spectrum disorder screening at 18 and 24 months during well-child visits, with heightened surveillance for those with complex lesions or requiring neonatal cardiac surgery. 1

• Standard autism spectrum disorder screening tools should be applied at 18 and 24 months as per American Academy of Pediatrics guidelines 1
• Children with complex congenital heart disease (requiring neonatal open heart surgery, cyanotic lesions, or those with comorbidities) warrant more intensive developmental monitoring 1
• Any child failing autism spectrum disorder screening requires referral for comprehensive diagnostic evaluation 1
• Periodic reevaluation should occur at 12-24 months, 3-5 years, and 11-12 years of age for high-risk congenital heart disease patients 1

Underlying Biological Mechanisms

• Emerging evidence suggests shared ciliary biology pathways between autism spectrum disorder and congenital heart disease genes, with disruption of primary cilia formation representing a common mechanism 5
• Seven specific genes (CEP290, CHD4, KMT2E, NSD1, OFD1, RFX3, and TAOK1) involved in both ciliary function and cardiac development may explain the comorbidity 5
• Social cognition deficits in children with complex congenital heart disease may reflect shared neurodevelopmental vulnerabilities with autism spectrum disorder 1