Fetal therapy with rhIGF-1 in a rabbit model of intrauterine growth retardation

Background Intrauterine growth retardation (IUGR) may, in part, be due to a deficiency of insulinlike growth factor-1 (IGF-1). The objectives, of this study were to determine the relationship between fetal serum IGF-I levels and fetal and placental size in a rabbit model of IUGR and to compare two t echniques of selective, exogenous IGF-1 administration (transamniotic and b ranch uterine arterial catheter infusion) to growth-retarded fetuses in ute ro. Materials and Methods. Pregnant rabbits (n = 6) had their fetuses harvested near term (31 days) for fetal and placental weighing and serum collection. Growth-retarded fetuses were selectively infused for 7 days with recombina nt human IGF-1 (rhIGF-1; 1,440 ng/ day) either through a transamniotic cath eter (n = 8) or via an adjacent uterine arterial branch catheter (n = 6). O pposite horn runts were sham catheterized, but not infused, at term, the fe tal runt pairs and their placentas were harvested and weighed, and their se rum was collected. The correlation between fetal and placental weight and e ndogenous serum IGF-1 was calculated (Pearson coefficient, r), while paired t-tests were used to compare the means between the IGF-1-infused and contr ol groups. Results. There was a significant correlation between fetal (r = 0.4230; P = 0.022) and placental weight (r 0.4166; P = 0.025) and endogenous serum lev els of IGF-I. Transamniotic infusion of rhIGF-1 was associated with an incr ease in serum IGF-I level (254 +/- 79 vs 351 +/- 101 ng/ml, P = 0.04) and p lacental weight (5.4 +/- 2.3 vs 7.1 +/- 3.2 g, P = 0.005), and with a trend toward increased fetal weight between matched fetal runt pairs. Fetal mort ality in the uterine arterial catheterized group was 76%, and there was no significant difference in fetal or placental weight or IGF-1 levels between infused and noninfused survivors. Conclusions. Endogenous fetal serum levels correlate with fetal and placent al size in the rabbit IUGR model. Transamniotic administration of rhIGF-1 s ignificantly increases serum IGF-1 levels and placental weight of fetal run ts, while uterine vessel catheterization results in prohibitive fetal morta lity and does not increase fetal or placental growth or IGF-1 levels. (C) 2 001 Academic Press.