Prenatal structural brain abnormalities in fetuses with congenital heart diseases confirmed with post-mortem examinations: a retrospective study in cases of fetal death

Congenital heart diseases (CHD) are gross structural abnormalities of the heart or intrathoracic great vessels that are actually or potentially of functional significance. CHD are among the main causes of prenatal and neonatal morbidity and mortality. With an estimated incidence of approximately 8-12 cases per 1,000 live births, CHD are among the most common congenital anomalies. Neurodevelopmental impairment is increasingly recognized as the most common morbidity in CHD and spans deficits in motor function, cognition, language, executive function, visual-spatial skills, and behavioral and psychosocial outcomes. The development of brain abnormalities, even in the absence of chromosomal/dysmorphic conditions, supports the theory that these abnormalities could develop following other mechanisms linked to an altered cardiac fetal embryogenesis. In previous studies, structural abnormalities have been found in 28% of CHD fetuses with fetal brain MRI examinations. These structural brain anomalies were not associated with the severity of the cardiac lesion and occurred in both cyanotic and acyanotic CHD. Thus, brain abnormalities in fetal development may arise from direct mechanisms associated with altered cardiac embryogenesis, such as compromised circulation and oxygenation caused by complex CHD. These direct effects can disrupt the normal development of the brain, leading to structural and functional abnormalities. Additionally, indirect mechanisms, which are not yet fully understood, may also play a significant role. We built this study to bridge the knowledge gap between prenatal diagnosis and postmortem confirmation, providing a more comprehensive understanding of the association between CHD and brain anomalies. We explored the role of genetic abnormalities, detected by comparative genomic hybridization (CGH) array, in contributing to the observed cerebral anomalies in the presence of confirmed CHD cases. Our aim was to enhance our understanding of the interplay between cardiac and cerebral development in fetuses with CHD, to improve prenatal counseling, to guide clinical management, and to inform decisions regarding the continuation of pregnancy in cases of fetal CHD malformations.