Thinking Outside the “Flow-Mediated” Box: An Analysis of Aortic Dilation in 100 Fetuses with Tetralogy of Fallot Compared to Matched Controls

Abstract

Background: Aortic dilation in tetralogy of Fallot (TOF) is primarily attributed to increased aortic flow in utero. An alternative hypothesis is abnormal neural crest cell migration, with unequal septation of the truncus arteriosus resulting in a larger aorta and inherently hypoplastic pulmonary artery (PA). If so, we hypothesize the aorta to PA ratio (Ao:PA) in TOF is stable throughout gestation, and the total sum of dimensions of the great arteries is similar to controls. Methods: We performed a single-center retrospective study of all fetuses with TOF (2014-2020) and gestational age-matched controls. We compared sums of diameters, circumferences, and cross-sectional areas of the aorta and PA and evaluated the Ao:PA across gestation in TOF with pulmonary stenosis (TOF-PS) and atresia (TOF-PA). We analyzed data with two-tailed t-tests and Pearson's correlation. Results: There were 100 fetuses with TOF (36% TOF-PA) with median gestational age of 31 weeks [IQR 26.5, 34.4] and median maternal age of 34 years [IQR 30, 37]. There were no differences in sums of great artery dimensions between TOF-PS and controls. In TOF-PA, sums were significantly lower than controls. The Ao:PA was stable throughout gestation. Conclusions: The aorta in fetal TOF is large but grows proportionally throughout gestation, with a sum of great artery dimensions similar to controls. TOF-PA appears to be distinct from TOF-PS (with overall smaller dimensions), and is a group that warrants further investigation. In conclusion, our findings do not support the flow-mediated model of aortic dilation in TOF, and instead suggest an intrinsic developmental mechanism.