Intrauterine growth restriction is associated with increased perinatal morbidity and mortality and with increased risk of adult diseases such as diabetes, hypertension, and coronary artery disease. Impaired growth may persist during childhood despite optimum nutrition. Although a poorly growing fetus can be relatively easily identified by obstetric ultrasound, the therapeutic options are limited. Thus, sustained poor growth in utero frequently results in the fetus being delivered, with the attendant morbidity and mortality of preterm birth. Further, preterm birth is itself associated with hypertension, diabetes and insulin resistance, ischemic heart disease and stroke in later life. It is unclear whether intervention early in postnatal life can ameliorate these increased risks. For example, accelerated postnatal growth may increase the long-term risks associated with reduced size at birth. Therefore, attempting to reverse IUGR in utero may represent the optimum approach. In developed nations, IUGR typically is caused by placental insufficiency, resulting in a reduced fetal nutrient supply. Thus, clinical attempts to improve fetal growth by maternal supplementation with protein or oxygen were unsuccessful. Attempts to increase placental blood flow with sildenafil citrate in IUGR ovine pregnancies resulted in adverse outcome, and supplementation of pregnant women carrying severely IUGR fetuses with L-arginine had no effect on fetal growth. Therefore, a treatment that bypasses the placenta may provide the most promising approach. Insulin-like 
growth factor-1 is the primary endocrine regulator of fetal growth in late gestation. Birth weight is positively associated with IGF-1 concentrations in umbilical cord blood, and circulating fetal IGF-1 concentrations are lower in IUGR pregnancies. Acute high-dose intravenous IGF-1 infusion has anabolic effects on fetal sheep, stimulating substrate uptake and inhibiting protein breakdown. However, while continuous vascular access to the fetus is not practicable in IUGR treatment, the amniotic fluid compartment is routinely accessed in clinical practice. IGF-1 administered into the amniotic fluid in sheep is swallowed and taken up across the fetal gut to circulate Albaspidin-AA intact in the fetus. Further, Ginsenoside-Ro administration of low dose intra-amniotic IGF-1 thrice weekly increases growth of ovine fetuses with IUGR induced by placental embolization. However, for intraamniotic IGF-1 treatment to be clinically useful, a less frequent administration is required. In addition, circulating fetal concentrations of IGF-1 following treatment were either unaltered or actually decreased, with down-regulation of fetal hepatic igf1 mRNA levels. These data suggest that the increased fetal growth after intra-amniotic IGF-1 is unlikely to be mediated directly by circulating IGF-1. One possible mechanism is via effects on placental nutrient transport. Glucose is transported across the placenta by facilitated diffusion, mediated by glucose transporters. SLC2A1 and SLC2A3 are the major glucose transporter isoforms in the placenta of ruminants and rodents, with SLC2A4 also described in humans and rats. In contrast, amino acids are transported across the placenta by active transport mediated by numerous different amino acid transporters, many of which have several isoforms. Recent studies have suggested that changes in placental amino acid transport, possibly mediated by altered activity of mammalian target of rapamycin, precede growth restriction and may therefore directly contribute to decreased fetal growth. IGF-1 is known to alter activity and/or expression of nutrient transporters in different placental preparations.