Glucose Metabolism Is Elevated and Vascular Resistance and Maternofetal Transfer Is Normal in Perfused Placental Cotyledons from Severely Growth-Restricted Fetuses

Abstract

We hypothesized that placental resistance was elevated and transfer reduced in cotyledons from intrauterine growth-restricted (IUGR) fetuses. We perfused 10 cotyledons from term, normally grown fetuses, six from preterm, normally grown fetuses with normal umbilical arterial end-diastolic velocities (EDV), and six from preterm IUGR fetuses (<3rd centile) with absent or reversed umbilical arterial EDV. Perfused cotyledons were pressure-fixed, and villi were observed by scanning electron microscopy. The groups did not differ in fetoplacental resistance at baseline; neither did they differ in the change in resistance that followed the administration of nitroglycerin or angiotensin II. The increase in resistance during hypoxia was similar in the two preterm groups but greater in the term than in the preterm normally grown group (p < 0.05). Groups did not differ in net maternofetal transfer of oxygen or glucose, or in clearance of aminoisobutyric acid or antipyrine. However, glucose consumption was doubled in cotyledons of preterm IUGR versus preterm normally grown fetuses (p < 0.05). Terminal villi of perfused cotyledons from preterm IUGR fetuses displayed less terminal villous branching and budding than preterm controls, as anticipated from previous work. IUGR fetuses with absent or reversed umbilical arterial EDV in vivo may have high placental resistance due to a vasoconstrictive rather than anatomic abnormality and an elevated placental glucose consumption that may impair glucose transfer.

The Herbal Medicine Tokishakuyakusan Increases Fetal Blood Glucose Concentrations and Growth Hormone Levels and Improves Intrauterine Growth Retardation Induced by Nω-Nitro-L-arginine Methyl Ester

“…Hypoglycemia in small-forgestational-age fetus may be related to reduced supply and transfer of glucose across the placenta (23). The increase in the baseline consumption in IUGR placenta has also been reported (24). Although the effect of L-NAME infusion on fetal blood glucose has been scarcely investigated, the present data that L-NAME treatment decreased fetal blood glucose concentration is in good agreement with the above findings.…”

Placental glucose transporter 3 (GLUT3) is up-regulated in human pregnancies complicated by late-onset intrauterine growth restriction

“…Increased GLUT3 within late-term IUGR CTB could plausibly lead to a reversal of transplacental glucose flux resulting in transport from the fetus into the placental tissue, as has been described with maternal hypoglycemia [47]. More likely, increased GLUT3 within late-term IUGR CTB helps supply an excess consumption of glucose by the placenta itself, leading to a decreased rate of transplacental transport to the fetus [29, 30]. …”

“…However in the human, the fetus affected by IUGR demonstrates hypoglycemia, the magnitude of which is correlated to the severity of growth restriction [27] and magnitude of decreased blood flow [28]. It is thus widely believed that in conditions of fetal hypoxia leading to IUGR, it is an excess consumption of glucose by the placenta that is responsible for a decreased rate of transplacental transport to the fetus [29, 30]. …”

Correlation of placental pathology with prenatal ultrasound findings

“…The UA Doppler indices change rapidly following experimental occlusion of maternal uteroplacental flow, demonstrating that the mechanism must act rapidly and be reversible 36. Finally, perfusion of cotyledons from normal and IUGR pregnancies after delivery also shows that the high placental flow resistance is due to vasoconstriction of stem vessels 38. This dynamic relationship between the two circulations has a physiological function, allowing matching of uteroplacental and fetoplacental flows, to minimise flow mismatch 39 40.…”