Differential changes in insulin-like growth factors and their binding proteins following asphyxia in the preterm fetal sheep.

1. The purpose of this study was to examine the changes in circulating concentrations of insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-2 and insulin following asphyxia in utero. 2. Fetal sheep at 90-93 days gestation underwent either sham occlusion (n = 7) or asphyxia (n = 6) induced by complete umbilical cord occlusion for 30 min. Fetal blood samples were taken before occlusion and 4, 6, 24, 48 and 72 h post-occlusion. 3. During the early phase of recovery there was a substantial fall (80 %) in circulating plasma IGF-I concentrations by 6 h post-asphyxia (P < 0.001). This was associated with a rapid rise in IGFBP-1 (P < 0.001), but no change in IGF-II or IGFBP-2. Insulin was significantly reduced at 4 h (P < 0.001) and glucose slightly elevated (P < 0.05), but insulin values returned to baseline by 6 h. Between 24 and 72 h of recovery, IGF-I gradually increased, IGFBP-1 returned to control values, and there was an increase in IGFBP-2 after 24 h (P < 0.05) and in IGF-II by 72 h (P < 0.05) after asphyxia. 4. These data demonstrate a differential effect of asphyxia on the IGF axis of the premature fetal sheep. A key finding was the large fall in circulating IGF-I, but not IGF-II, during the early phase of recovery. IGF-I bioavailability was, in part, regulated by IGFBP-1, but maximal changes in IGF-I and IGFBP-1 were independent of plasma insulin and glucose.5. The impact of this substantial change in circulating IGF-I on the fetus is unknown. It may facilitate metabolic requirements by promoting catabolism. Alternatively, as IGFs play a role in wound repair, the acute changes in IGF-I and IGFBP-1 may reflect transport of IGF-I from the circulatory pool to injured tissues to promote wound repair.