Maternal and Fetal Hemodynamics in the Setting of Undernutrition Characterized by Cardiovascular Magnetic Resonance

Abstract

This thesis describes a set of experiments that aimed to characterize maternal, fetal, and placental hemodynamics in the setting of maternal undernutrition using cardiovascular magnetic resonance (CMR) in sheep. The application of fetal CMR to assess fetal ventricular volumes and function was validated to establish the methodology. Our CMR results with respect to late gestational fetal sheep cardiac parameters were in keeping with prior descriptions in terms of ventricular wall thickness and ejection fractions obtained using other techniques. In combination with MRI techniques previously established by our group, including cine phase-contrast vessel flow quantification and magnetic resonance oximetry, maternal-placental hemodynamics were characterized in the setting of late gestation undernutrition (LGUN). Maternal hemodynamic adaptations were observed in response to LGUN, with redirection of peripheral blood flow to the uteroplacental circulation and preservation of uterine oxygen consumption. Associations were found between the degree of these adaptations and the change in maternal weight, hinting at relationships between maternal metabolism and maternal cardiovascular physiology in pregnancy. LGUN resulted in normoxemic fetuses, regardless of glycemic state, and the cardiovascular data collectively indicated increased fetal sympathetic activation, evidenced by increased myocardial contractility and ductus venosus (DV) shunting. Fetal plasma glucose concentrations were negatively correlated with relative brain weight, DV shunting, and hepatic expression of insulin-like growth factor (IGF)-2, the primary mediator of fetal growth. These findings collectively suggest the presence of fetal brain-sparing physiology at the expense of nutrient delivery to the fetal liver during maternal LGUN, despite the absence of fetal hypoxemia, providing further insight into pathophysiology of fetal intrauterine growth restriction.