Translating Cardiac Development Insights to Non-Invasive Prenatal Intervention ― Maternal Administration for Neural Crest-Related Congenital Heart Disease ―

ongenital heart disease (CHD) affects ~1% of newborns and remains a leading cause of infant morbidity and mortality.1 Cardiac outflow tract (OFT) malformations, in particular, impose substantial lifelong burden despite major advances in pediatric cardiology and surgery. 1 In many patients, repair requires a highly invasive intervention during the neonatal period, and outcomes can be constrained by residual lesions and the limited availability of autologous tissues suitable for reconstruction.2,3 These clinical realities motivate efforts to identify modifiable prenatal factors that are mechanistically linked to early morphogenesis and could complement postnatal care by reducing disease risk or attenuating phenotypic severity.Heart formation depends on coordinated morphogenetic programs that assemble and remodel cardiac structures within a narrow embryonic time window.4-6 In humans, the sensitive period for cardiovascular development is generally recognized as weeks 3-8 of embryonic development (Figure).4-6 During this period, cardiac neural crest cells (cNCCs) play central roles in OFT septation and great-vessel patterning, and impaired cNCC deployment is a hallmark of conotruncal malformations.7 In 22q11.2deletion syndrome (22q11DS), disruption of pharyngeal arch development can secondarily affect cNCC migration and differentiation, producing characteristic OFT and aortic arch abnormalities.