Fetal and Amniotic Insulin-Like Growth Factor-I Supplements Improve Growth Rate in Intrauterine Growth Restriction Fetal Sheep

Abstract

To date, there is no known prenatal treatment for intrauterine growth restriction (IUGR). IGF-I is an important regulator of fetal growth and circulating IGF-I concentrations are reduced in IUGR fetuses. We investigated whether any of three different methods of fetal IGF-I administration would reverse IUGR in sheep. Animals were randomized into five groups: control ( n = 17), IUGR + saline ( SAL, n = 17), IUGR + iv IGF-I (IGF-IV, n = 14), IUGR + intraamniotic IGF-I ( IGF-AF, n = 14), or IUGR + intraamniotic IGF- I with nutrients ( IGF-NUT, n = 16). Weekly IGF- I dose was 360 mu g in each treatment group. IUGR was induced by placental embolization between 93 and 99 d and treatment was from 100 - 128 d gestation (term = 147 d). Embolization caused asymmetrical IUGR with reduced fetal growth rates and body and organ weights, but increased brain to liver weight ratio, at post mortem. Embolized fetuses were also hypoxemic and hypoglycemic and had reduced circulating IGF-I and insulin concentrations. IGF-AF and IGF-IV significantly increased fetal growth rates, but only IGF-AF significantly increased fetal liver weight, compared with saline-treated fetuses. Fetal weights and brain to liver weight ratios in all IGF-I-treated fetuses were intermediate between the control and SAL groups. Addition of nutrients reduced the effects of amniotic IGF-I treatment and increased fetal hemoglobin and lactate concentrations. Treatments did not change fetal plasma IGF-I and insulin concentrations. This is the first report of an intrauterine treatment significantly increasing fetal growth rate in established IUGR. Amniotic IGF-I administration may provide the basis for a clinically applicable prenatal treatment for the IUGR fetus.