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

doi:10.1016/j.isci.2023.107424

Fetal metabolic adaptations to cardiovascular stress in twin-twin transfusion syndrome

iScience. 2023 Jul 20;26(8):107424. doi: 10.1016/j.isci.2023.107424. eCollection 2023 Aug 18.

Authors

Jacqueline G Parchem¹, Huihui Fan^{2

3}, Lovepreet K Mann^{1

4}, Qiuying Chen⁵, Jong H Won¹, Steven S Gross⁵, Zhongming Zhao², Heinrich Taegtmeyer⁶, Ramesha Papanna^{1

4}

Affiliations

¹ 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.
² Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.
³ Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁴ The Fetal Center at Children's Memorial Hermann Hospital, Houston, TX, USA.
⁵ Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.
⁶ Department of Internal Medicine, Division of Cardiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Abstract

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.

Keywords: Biology of human development; Cardiovascular medicine; Developmental anatomy; Health sciences.