The brain in congenital heart disease: from fetus through childhood

Abstract

The human brain develops rapidly during gestation and early infancy. The complex developmental processes occurring during this critical period are susceptible to injurious events, including those associated with critical congenital heart disease. Neurological developmental problems are a major complication in survivors of early life open-heart surgery for critical congenital heart disease (CHD). This thesis describes fetal and neonatal brain development under the changed cardiovascular physiology in critical congenital heart disease, brain injuries occurring before and after neonatal open-heart surgery and its relationship with neurocognitive functioning in childhood. Furthermore, biomarkers and risk factors of suboptimal early life brain development in infants with critical congenital heart disease are investigated. Brain immaturity and acquired brain injury coexist in neonates with critical CHD. Brain immaturity at a microstructural and structural level is the result of reduced antenatal brain growth under the changed cardiovascular physiology of critical CHD. After birth, acute fluctuations in cerebral blood flow and oxygen delivery can result in (hypoxic-)ischemic brain injury. Brain injury is a common comorbidity in infants with critical CHD, with an incidence of ~65% across clinical cohorts and distinct predictors related to different practice approaches for multifocal and focal ischemic brain injury. Low cardiac output syndrome and cardiac interventions are the main risk factors for neonatal ischemic brain injury. Neonates with single ventricle physiology are at a higher risk of brain immaturity and ischemic brain injury than neonates with biventricular critical cardiac defects. Abnormal brain activity after birth or after open-heart surgery is associated with brain injury and has the potential to identify neonates with the highest risk of brain injury at an early stage. Brain immaturity and neonatal ischemic brain injury contribute to the range of subsequent neurodevelopmental problems in children with critical CHD. This thesis shows that neonates undergoing open-heart surgery for critical congenital heart disease have a high risk of aberrant brain development and acquired brain injury, with consequences for subsequent long-term neurodevelopment. This thesis confirms that the high rate of brain injury in infants with critical CHD is a clinical concern. Reducing the cumulative burden of brain injury and improving functional outcomes should be a priority for both research and clinical care in the growing CHD population. Brain imaging protocols and neurodevelopmental follow-up programs implemented in standard clinical care for individuals with critical CHD under uniform guidelines are required to improve functional outcomes. Risk- and prognostic stratification models for brain development and functional outcomes in individuals with critical CHD are necessary for early identification and individualized treatment.