Late gestation maternal undernutrition increases cardiac output in fetuses using cardiac MRI (CMR): Implications of fetal glucose infusion

Introduction: Preclinical studies suggest there is an association between poor maternal nutrition in late pregnancy and remodelling of the fetal heart (Darby, J Physiol, 2018) and reduced cardiac function in adulthood (Kuo, J Physiol, 2017; Muralimanoharan, JMCC,2017). It is not known if this change of cardiac function is present in the fetus or develops in postnatal life.

Methods: Pregnant Merino single bearing ewes were assigned by minimisation to control (C; n=14;100% metabolizable energy requirement (MER)), late gestation maternal undernutrition (LGUN; n=10; 50% MER), or LGUN + fetal glucose infusion (LGUN+G; n=6; ~9ml 50% dextrose over 24h) one day after fetal surgery (109-112d), in which the fetal femoral artery was catheterized. At 138-140d, ewes were anesthetized and underwent CMR using the femoral arterial line for cardiac gating. Fetal cardiac and phase-contrast (PC) CMR acquisitions were analyzed to measure ejection fraction (EF) and combined ventricular output (CVO). Data were analysed by one-way ANOVA with a Bonferroni correction (P<0.05; mean±SEM).

Results: 19/30 CMR acquisitions had suitable quality for post-processing (C=9, LGUN=5, LGUN+G=5). Fetal glucose infusion restored the LGUN induced decrease in fetal weight (4.90±0.15C,4.22±0.23LGUN&4.92±0.23LGUN+G kg; P=0.0284) but had no effect on glucose levels (0.80±0.03C,0.63±0.02LGUN &0.67±0.02LGUN+G mmol/L;P<0.001. LGUN fetuses had a higher LV- and RV-EF compared with control, but this was normalised by fetal glucose infusion. LGUN fetuses had higher CVO compared with control, but this also was normalised by fetal glucose infusion (Figure 1).

Conclusion: Increased EF and CVO may be an early life compensatory response to maternal undernutrition in order to support fetal development. However, this response may become pathological as the life course progresses. This finding is in keeping with data on growth restricted human fetuses and children, with increased fetal cardiac output and decompensation manifesting in reduced cardiac function (Zhu, AJOG, 2016;Crispi, Circulation, 2010;Kuo, J Physiol, 2017).