Effect of epidermal growth factor infusion on fetal rabbit intrauterine growth retardation and small intestinal development.

BACKGROUND/PURPOSE: Intrauterine growth retardation (IUGR) infants have impaired gastrointestinal function with resultant feeding difficulties and predisposition to necrotizing enterocolitis. Supplemented amniotic fluid swallowed by the developing fetus is a potential prenatal treatment for IUGR. Rabbits have naturally occurring IUGR fetuses based on uterine position. To determine intestinal response to epidermal growth factor (EGF) infusion, this rabbit model of IUGR was studied.

METHODS

Eight pregnant rabbits underwent placement of intraamniotic catheters into 2 normal and 2 IUGR fetuses per mother on gestational day 24 of a 31-day gestation. Miniosmotic pumps infused either EGF (about 300 microg/kg/d) or control solution forming 4 study groups (EGF-Favored [Fav] v. Cont-Fav; EGF-IUGR v. Cont-IUGR). On gestational day 31, the fetal gastrointestinal tracts were harvested for analysis. Intestinal epithelial cell proliferation was studied by 5-bromo-2-deoxyuridine (BrdU) incorporation, villus heights were measured, and EGF mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR). Statistical analysis was performed using Students' t test.

RESULTS

Fetal survival rate was 87%. EGF-IUGR fetal weights were increased compared with Cont-IUGR fetuses. EGF infusion significantly increased IUGR fetal small intestinal villus height and BrdU-positive small intestinal (SI) crypt cells, all approaching Cont-Fav levels. EGF mRNA was expressed throughout the gastrointestinal tract.

CONCLUSIONS

Supplemental amniotic EGF normalizes fetal weight and intestinal proliferation in the IUGR fetal rabbit. The inclusion of EGF in supplemental amniotic feeding solutions is supported.