In fetuses with complex type of congenital heart disease (CHD), impaired brain growth and brain development starts in utero. A complex interplay between heart, brain, and placenta takes place within the second and third trimester of pregnancy. Altered fetal cardiovascular hemodynamics due to the type of CHD leads to an altered cerebral and placental perfusion, both factors contributing to maturational delay of body and brain development. Impaired cerebral perfusion, oxygenation, and nutritive energy supply affects brain growth and leads to brain developmental delay of 3-4 weeks until birth. Comparable to the altered brain development in pre-terms, pathogenic mechanisms lead to an encephalopathy of CHD on a micro- and macrostructural level. After birth palliative or corrective cardiac surgery is needed, which further contributes to the brain maturational delay with consequences on the neurodevelopmental outcome.