What patient-specific factor places a newborn with hypoplastic left heart syndrome (HLHS) at the highest risk for neurodevelopmental disability at 1 year of age?

Patient-Specific Factors Affecting Neurodevelopmental Outcomes in HLHS

The presence of a genetic syndrome is the patient-specific factor that places a newborn with hypoplastic left heart syndrome (HLHS) at the highest risk for neurodevelopmental disability at 1 year of age, based on Calderon et al. (Front Pediatr 2022).

Risk Factors for Neurodevelopmental Disability in HLHS

Children with HLHS are at high risk for neurodevelopmental disabilities due to multiple factors:

Genetic Factors

• Genetic disorders or syndromes may be found in up to 30% of pediatric patients with CHD and significantly impact neurodevelopmental outcomes 1
• Multivariate analyses have shown that the presence of a genetic syndrome has significant negative effects on neurodevelopmental outcomes at 1 year of age 2
• Chromosomal defects are particularly unfavorable, with early risk of death doubled and 10-year survival significantly reduced (25±9% vs 54±2%) 3

Perinatal Factors

• Younger gestational age and the need for preoperative intubation have significant negative effects on neurodevelopmental outcomes 2
• Premature infants (less than 37 weeks), especially those born weighing less than 1500g, are at increased risk for developmental delay 1
• Lower birth weight and gestational age are associated with developmental disorders in the complex CHD population 1

Neurological Factors

• Significant abnormalities on neuroimaging or microcephaly are associated with neurodevelopmental disabilities 1
• Perioperative seizures related to CHD surgery are linked to increased risk for worse neurodevelopmental outcomes 1
• Alterations in cerebral blood flow in fetuses with complex CHD and impaired volumetric brain growth in third-trimester fetuses with CHD contribute to developmental issues 1

Surgical and Hospital Factors

• Prolonged hospitalization (postoperative length of stay >2 weeks) is associated with poorer outcomes 1
• A longer hospital stay is significantly associated with lower verbal, performance, and full-scale IQ scores 4
• History of mechanical support (ECMO or VAD use) increases risk for developmental disorders 1

Neurodevelopmental Profile in HLHS at 1 Year

• At 1 year of age, there is a significant incidence of neurodevelopmental disabilities in children with HLHS 2
• Motor scores are particularly concerning, with a median Psychomotor Development Index score of 73, and 48% of patients having scores <70 (2 SDs below the general population mean) 2
• The median Mental Development Index score is typically around 90, with approximately 11% having scores <70 2
• Neuromuscular examination results are abnormal or suspect in approximately 65% of patients at 1 year 2

Clinical Implications

• Early identification of genetic syndromes is crucial for risk stratification and intervention planning 1
• Children with HLHS should be categorized as high-risk for developmental disorders based on American Heart Association guidelines 1
• Regular neurodevelopmental surveillance, screening, and evaluation are essential for these patients 1
• Early intervention services should be considered for all HLHS patients, particularly those with genetic syndromes 1
• The medical home model should coordinate comprehensive care for these children with special health care needs 1

Important Considerations

• Jacobsen syndrome (11q23 deletion) is associated with HLHS and intellectual disability in 97% of cases 1
• Turner syndrome accounts for the majority of chromosomal defects in HLHS population (79%) and significantly impacts survival 3
• Quality-of-life outcomes must be considered when management options for children with HLHS are evaluated 5
• Neurodevelopmental deficits remain prevalent among school-aged children with HLHS, regardless of surgical approach 4