Fetal metabolic adaptations to cardiovascular stress in twin-twin transfusion syndrome
Jacqueline G. Parchem,
Huihui Fan,
Lovepreet K. Mann,
Qiuying Chen,
Jong H. Won,
Steven S. Gross,
Zhongming Zhao,
Heinrich Taegtmeyer,
Ramesha Papanna
Affiliations
Jacqueline G. Parchem
Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal-Fetal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; Corresponding author
Huihui Fan
Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Lovepreet K. Mann
Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal-Fetal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; The Fetal Center at Children’s Memorial Hermann Hospital, Houston, TX, USA
Qiuying Chen
Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA
Jong H. Won
Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal-Fetal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Steven S. Gross
Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA
Zhongming Zhao
Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA
Heinrich Taegtmeyer
Department of Internal Medicine, Division of Cardiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Ramesha Papanna
Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal-Fetal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; The Fetal Center at Children’s Memorial Hermann Hospital, Houston, TX, USA; Corresponding author
Summary: Monochorionic-diamniotic twin pregnancies 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. Here, we applied TTTS as a model to uncover fetal metabolic adaptations to cardiovascular stress. We compared untargeted metabolomic analyses of amniotic fluid samples from severe TTTS cases vs. singleton controls. Amniotic fluid metabolites demonstrated alterations 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 and identify potential differences in the ability of individual fetuses to respond to cardiovascular stress.
