FETAL NUTRIENT UPTAKE AND METABOLISM AND REGULATION OF FETAL GROWTH IN IUGR.

 FETAL NUTRIENT UPTAKE AND METABOLISM AND REGULATION OF FETAL GROWTH  In IUGR .

1. Glucose Uptake, Metabolism:

First, relative fetal hypoglycemia is an important and natural compensatory mechanism that helps to maintain the maternal-to-fetal glucose concentration gradient and thus the transport of glucose across the placenta to the fetus.

Despite this compensation, fetal hypoglycemia limits tissue glucose uptake directly by diminished mass action and indirectly by limiting fetal insulin secretion and thus the effect of insulin to promote tissue glucose uptake by skeletal muscle, heart, adipose tissue, and liver.

Reduced glucose supply alone decreases fetal growth rate and oxygen consumption rate (metabolic rate) proportionally.

Insulin also normally suppresses hepatic glucose production and release, and it acts as an anabolic hormone that increases net protein balance by inhibiting protein breakdown. Thus, a decrease in fetal plasma insulin concentration initially may allow fetal glucose production to take place, thereby providing glucose for both fetal and placental needs, but subsequently, combined with hypoglycemia, results in increased protein breakdown and decreased protein accretion.

Circulating concentrations and tissue-specific expression of growth factors such as IGF-I also are decreased during fetal hypoglycemia, which may contribute to increased fetal protein breakdown and decreased rates of fetal growth.

Thus, fetal hypoglycemia in response to a decrease in maternal glucose supply acts to maintain fetal glucose supply, but it also leads to lower anabolic hormone concentrations, which limit the rate of fetal growth, thereby decreasing fetal nutrient needs.

2. Fetal Amino Acid Metabolism:

The placenta contains a large variety of amino acid transporters that use energy to actively concentrate amino acids in the trophoblast, which, followed by diffusion into the fetal plasma, produces higher concentrations than in the maternal plasma. With small placentas, fetal amino acid supply is reduced, as are fetal amino acid concentrations, fetal protein synthesis, fetal protein and nitrogen balance, and, ultimately, fetal growth rate.

A consistent feature in human IUGR pregnancies is reduced placental transfer of certain essential amino acids.

Furthermore, the severity of IUGR correlates with the severity of decreased amino acid transfer.

Reduced energy supply to the placenta also reduces amino acid transport to the fetus. This is especially the case for oxygen deficit, either from primary hypoxemia or from reduced uteroplacental blood flow, and glucose deficit from chronic maternal and fetal hypoglycemia. Of course, hypoxemia and hypoglycemia could reduce fetal growth independently of reduced amino acid transport, for example, by limiting anabolic hormone and growth factor production or by decreasing energy supply, both of which are necessary to produce protein synthesis and to limit protein breakdown in fetal tissues.

Clearly, amino acid and energy deficits will affect the growth rate of the fetus at earlier stages of gestation, when fetal growth normally is much more rapid than at term.