The effect of mild hypothermia on insulin-like growth factors after severe asphyxia in the preterm fetal sheep

OBJECTIVES: Persistent reductions in insulin-like growth factor I (IGF-I) levels in the preterm infant are strongly associated with increased risk of retinopathy and other complications, and may result from exposure to severe hypoxia. The effects of a potential new treatment for hypoxic-ischemic encephalopathy, cerebral hypothermia, on the responses of the IGF axis to hypoxia are unknown. The aim of this study was to examine the effects of prenatal asphyxia and cerebral hypothermia on changes in IGF-I and -II, IGF-binding protein 1 (IGFBP-1), and insulin levels. METHODS: Fetal sheep at 0.7 of gestation underwent either sham asphyxia and sham cooling (n = 7), asphyxia induced by 25 minutes of complete umbilical cord occlusion alone (n = 8), or asphyxia and head cooling (n = 8, extradural temperature 29.5 +/- 2.6C [vs 39.4 +/- 0.3C; P <.05]). Fetuses were studied for 3 days post-insult, during which time fetal blood samples were taken for endocrine measurements. RESULTS: There were no IGF axis changes during occlusion. Plasma IGF-I levels significantly decreased between 6 hours and 48 hours after asphyxia and IGF-II levels by 10 hours, in both asphyxia groups. IGFBP-1 rose from 4 hours, reaching a peak at 10 hours and returning Q to control values by 48 hours in the normothermia group, and by 24 hours in the hypothermia group. Insulin levels decreased between 2 hours and 10 hours after asphyxia in both asphyxia groups, and subsequently normalized. CONCLUSIONS: This study demonstrates for the first time that transient asphyxia in the preterm sheep fetus is associated with a significant decrease in IGF-II as well as IGF-I during recovery, and that these responses arc not altered by mild systemic hypothermia. Copyright (c) 2005 by the Society for Gynecologic Investigation.