JACC Basic Transl Sci. 2025 Apr 23:101251. doi: 10.1016/j.jacbts.2025.01.022. Online ahead of print.
PMID: 40272355 DOI: 10.1016/j.jacbts.2025.01.022
Abstract
Congenital heart disease (CHD) is the primary cause of birth defects, affecting 9 per 1,000 live births. Up to 50% of them will develop neurodevelopmental disorders, two-thirds of which being unexplained by postnatal risk factors. Recent advances suggest a triangular relationship between the placenta and the fetal heart and brain in CHD, consistent with the Developmental Origins of Health and Disease hypothesis, ie, the in utero programming of early and later-in-life noncommunicable cardiometabolic and mental diseases. The current review provides comprehensive evidence of placental, cardiac, and cerebral tissues interactions, and details how placental dysregulation may affect vasculogenesis, angiogenesis and neural tube closure, hemodynamics, energy supply, endocrine function, and epigenetic regulation of the developing heart and brain. Future studies should include placental research, since identifying placental biomarkers would allow early identification of CHD infants at higher risk for neurodevelopmental disorders, leading to targeted preventive personalized interventions.
Keywords: fetal development; placenta-heart-brain axis; placental dysfunction.