Maternal late gestation undernutrition in sheep is associated with increased ductus venosus shunting and reduced cerebral oxygen consumption

Placental restriction and models of maternal hypoxia result in fetal growth restriction (FGR) with fetal circulatory redistribution, including increased ductus venosus shunting and brain sparing. In contrast, there are limited reports on the effects of fetal nutrient restriction on circulatory redistribution, with data on acute hypoglycaemic challenges or end-organ weights following chronic nutrient restriction. Fetal cardiovascular magnetic resonance (CMR) was employed to define fetal haemodynamics in utero following 25 days of maternal late gestation undernutrition (LGUN). Control ewes received 100% metabolizable energy requirements (MER), whereas LGUN and LGUN + intrafetal glucose supplementation (LGUN + G) ewes received 50% of MER. Fetal CMR was conducted after the dietary regime, and fetal liver was collected the following day. All fetuses were normoxaemic, whereas mean gestational fetal plasma glucose concentrations were lower in both LGUN and LGUN + G fetuses compared to control. There was a negative relationship between relative brain weight and fetal plasma glucose concentration. Biventricular ejection fraction and ductus venosus shunting were increased in LGUN compared to control but were normalized in LGUN + G. Relative left liver lobe weight demonstrated a negative linear relationship with fetal glucose, whereas right-lobe weight revealed a positive relationship. Cerebral oxygen delivery was lower in LGUN compared to control, whereas cerebral oxygen consumption (VO₂) was diminished in both LGUN and LGUN + G compared to control. Cerebral VO₂ correlated positively with fetal glucose. Although intrafetal glucose infusion did not normalize fetal glucose, cardiovascular changes were normalized, providing support for the role of glucose in mediating aspects of FGR physiology in normoxaemic but hypoglycaemic fetuses of LGUN ewes. KEY POINTS: Maternal late gestation undernutrition (LGUN) can lead to fetal growth restriction (FGR) independent of fetal hypoxaemia, but detailed characterization of fetal haemodynamics in utero is lacking. There was a negative relationship between relative brain weight and fetal plasma glucose concentration. LGUN increased fetal ventricular ejection fraction and ductus venosus shunting, both of which were normalized in LGUN fetuses that received intrafetal glucose infusion (LGUN + G). Relationships between left liver lobe sparing and cerebral oxygen consumption (VO₂) and fetal glucose concentrations were observed. Cerebral VO₂ was diminished in both LGUN and LGUN + G compared to control. This study is the first to comprehensively characterize fetal haemodynamics and oxygen consumption in the setting of LGUN and fetal normoxaemia, suggesting the role of fetal plasma glucose concentration in mediating aspects of FGR physiology.