The Sooner, the Better: Neuroprotective Strategies in Fetuses With Congenital Heart Disease

Congenital heart disease (CHD) is the most frequent congenital malformation at birth and is associated with neurodevelopmental impairments. Alterations in cardiovascular physiology can lead to reduced cerebral blood perfusion and oxygenation, which negatively affects brain growth and maturation. Advanced imaging studies indicate that these aberrations in brain development can manifest as early as in utero, resulting from the inability of the fetal circulatory system to meet the increased metabolic demands of the brain. Fetal brain dysmaturation increases the susceptibility to postnatal brain injury and is related to adverse long-term neurodevelopmental outcomes throughout childhood. This emphasizes the potential for effective prenatal neuroprotective strategies in fetuses with CHD, as optimization of their intrauterine environment may prevent irreversible neurological damage and minimize long-term neurodevelopmental comorbidities. This review provides a comprehensive overview of prenatal neuroprotective strategies in fetuses with critical CHD, including in utero therapeutic interventions, prenatal surgical cardiac interventions, and modifiable prenatal and perinatal risk factors.