Mk Bauer

FETAL GROWTH AND PLACENTAL FUNCTION

Fetal growth is largely determined by the availability of nutrients to the fetus. The fetus is at the end of a supply line that ensures delivery of nutrients from the maternal/uterine circulation to the fetus via the placenta. However, this supply line can not be regarded as a linear relationship. Maternal undernutrition will not only reduce global nutrient availability but will also influence the maternal and fetal somatotrophic axis. Both endocrine systems react in a very similar way to limited substrate supply. The hormones of the fetal somatotrophic axis, and in particular insulin-like growth factor (IGF)-1, are important regulators of fetal growth. Placental function is pivotal to materno-fetal nutrient and metabolite transfer. Placental function in turn, is heavily influenced by the maternal and fetal growth hormone (GH)-IGF-1 system. The placenta itself is also an active endocrine organ and it produces a large number of hormones including GH and IGF-1 as well their corresponding receptors. Thus the placenta can no longer be considered merely a passive conduit for fetal nutrition. Rather, it is actively involved in the integration of nutritional and endocrine signals from the maternal and fetal somatotrophic axes.

Metabolic consequences of intrauterine growth retardation

This review focuses on intrauterine growth retardation (IUGR) occurring spontaneously and without a defined infective, toxic or genetic cause. Such fetal growth retardation is generally thought to be a consequence of inadequate provision of nutritional substrates across the placenta.

Effects of intrauterine growth restriction and intraamniotic insulin-like growth factor-I treatment on blood and amniotic fluid concentrations and on fetal gut uptake of amino acids in late-gestation ovine fetuses.

Objectives To investigate, in the late-gestation ovine fetus: 1) amino acid concentrations in blood and amniotic fluid, 2) the effects of intrauterine growth restriction (IUGR) induced by placental embolization on these concentrations, 3) fetal gut uptake of glutamine in healthy and IUGR fetuses, and 4) the effects of intraamniotic insulin-like growth factor-I (IGF-1) treatment on these parameters. Methods Fetuses were randomly assigned to control (n = 9), IUGR + saline (n = 9), or IUGR + IGF-1 (n = 11) groups. IUGR was induced by uteroplacental embolization from 114 to 119 days (term = 145 days). IUGR fetuses received daily intraamniotic injections of saline or IGF-1 (20 &mgr;g/d) from 120 to 130 days. Results Baseline amino acid concentration was higher in fetal blood than amniotic fluid for all essential amino acids except lysine and histidine, but was lower for serine, alanine, and methylhistidine. Embolization reduced total amino acid concentration in blood and amniotic fluid by approximately 15%. Concentrations were reduced for serine, glutamine, and methylhistidine in blood and for serine in amniotic fluid, but were increased for glycine, alanine, and asparagine in blood and for alanine in amniotic fluid. Glutamine was taken up by the fetal gut (glutamine:oxygen quotient of 0.65) and citrulline was released by the gut. IGF-1 treatment did not alter amino acid concentration in blood or amniotic fluid, but reduced gut uptake of glutamine from blood and the gut glutamine:oxygen quotient by 15%. Citrulline release was unchanged. Conclusions These data suggest that amniotic fluid amino acids are not simply filtered from fetal blood and may provide an important pool of nutrients for the fetus. They demonstrate for the first time that glutamine is taken up by the fetal gut. IGF-1 treatment may promote gut utilization of amino acids from the amniotic fluid pool.

A chronic low dose infusion of insulin-like growth factor I alters placental function but does not affect fetal growth.

Knowledge of the anabolic effects of insulin-like growth factor I (IGF-I) on fetal growth and feto-placental metabolism are derived from studies using large doses of IGF-I. Low doses of enteral IGF-I have trophic effects on the fetal gut, but there are no data on the effects of systemic low doses of IGF-I on fetal growth and feto-placental metabolism. We therefore compared the effects of a chronic infusion of low dose IGF-I (50 microg day(-1), n = 7) with vehicle-infused controls (n = 7) on fetal growth, metabolism and placental transfer capacity in the chronically instrumented late gestation ovine fetus (121-132 days of gestation; term = 145 days). Insulin-like growth factor I infusion did not affect fetal growth or the size of individual organs, including liver, spleen and bone. Placental morphology was altered, and placental clearances of 3-O-[methyl-3H]D-glucose (a non-metabolizable glucose analogue) and [methyl(14C)]aminoisobutyric acid (a non-metabolizable analogue of amino acids utilizing the system A transporter), were reduced in IGF-I-treated fetuses (P < 0.05 v. control). However, fetal and placental metabolite uptake was not significantly different between groups. We conclude that, despite altering placental transfer capacity and morphology, a chronic low dose infusion of IGF-I does not alter fetal growth or metabolism.

Antenatal therapy for intrauterine growth retardation

Currently, there is no effective antenatal therapy for intrauterine growth retardation (IUGR). Although the IUGR fetus is undernourished in utero and there have been many attempts to treat IUGR with nutritional supplements, most studies have been poorly controlled, and there is no evidence to date that nutrient supplements can reverse the process of IUGR once it is established. Nutrient supplementation is also potentially risky and a combination of nutrients is likely to be needed. Alternative approaches to antenatal therapy for IUGR that show promise include fetal growth hormone and insulin‐like growth factor I treatment to improve fetal growth. Fetal and maternal hormone supplements may also prove useful in IUGR by improving placental function and thus fetal substrate supply. Fetal enteral supplementation by the administration of growth factors and/or nutrients into the amniotic fluid may also prove effective and clinically feasible. It seems likely that combinations of these approaches will be required before effective therapy can be devised for the IUGR fetus in utero. □ Amniotic fluid, fetus, growth, growth hormone, growth retardation, insulin‐like growth factor I, nutrition, therapy