Background: Term newborns with congenital heart disease (CHD) show delayed brain development as early as the third trimester, especially in single-ventricle physiology (SVP). Mechanisms causing delayed brain development in CHD are uncertain but may include impaired fetal brain blood flow. Our objective was to determine if cardiac anatomy associated with obstruction to antegrade flow in the ascending aorta is predictive of delayed brain development as measured by diffusion tensor imaging and magnetic resonance spectroscopic (MRS) imaging. Methods: Echocardiograms from 36 term newborns with SVP were reviewed for the presence of aortic atresia and the diameter of the ascending aorta. Quantitative magnetic resonance imaging parameters measuring brain microstructural (fractional anisotropy (FA) and average diffusivity (Dav)) or metabolic development (N-acetylaspartate (NAA) and lactate/choline (Lac/Cho)) were recorded. Results: Increasing NAA/Cho and white matter (WM) FA, and decreasing Dav and Lac/Cho characterize normal brain development. Consistent with the hypothesis that delayed brain development is related to impaired brain perfusion, smaller ascending aortic diameter and aortic atresia were associated with higher Dav and lower WM FA. Echocardiogram variables were not associated with brain metabolic measures.Conclusions:These observations support the hypothesis that obstruction to fetal cerebral blood flow impairs brain microstructural development.