PR001745 (Project)

Description:Monochorionic-diamniotic twin pregnancies comprise 70% of identical twin pregnancies and are susceptible to unique complications arising from a single placenta shared by two fetuses. Twin-twin transfusion syndrome (TTTS) is a constellation of disturbances caused by unequal blood flow within the shared placenta giving rise to a major hemodynamic imbalance between the twins. If untreated, it leads to fetal cardiac failure and death. Here, we applied TTTS as a model to uncover fetal metabolic adaptations to cardiovascular stress. We compared untargeted mass spectrometry-based metabolomic analyses of amniotic fluid samples from a cohort of severe TTTS cases showing sonographic evidence of increased afterload and heart failure vs. uncomplicated singleton controls. Amniotic fluid metabolites demonstrated footprints of changes in fatty acid, glucose, and steroid hormone metabolism in TTTS. Among TTTS cases, unsupervised principal component analysis revealed two distinct clusters of disease defined by levels of glucose metabolites, amino acids, urea, and redox status. Our results suggest that the human fetal heart can adapt to hemodynamic stress by modulating its glucose metabolism. Furthermore, we have uncovered heterogeneity among cases of severe TTTS suggesting potential differences in the ability of individual fetuses to respond to cardiovascular stress.