Milk-borne epidermal growth factor modulates bilirubin levels in neonatal rats

Objectives: Breast milk jaundice (BMJ) is commonly of undetermined etiology. Recently, it has been shown that the degree of BMJ was associated with the increased levels of milk-borne EGF (Epidermal Growth Factor). The aim of the present study was to test the effects of enteral administration of EGF on the development of hyperbilirubinemia in neonatal rats. Methods: Pups were divided into three groups: Group 1; artificially fed with formula, Group 2; artificially fed with formula supplemented with 500 ng/ml rat EGF, Group 3; fed by their mothers. Hyperbilirubinemia was induced by an intraperitoneal injection of unconjugated bilirubin suspension once daily for 5 consecutive days. Bilirubin levels, length of ideal villi, and EGF-R expression in the intestine was determined at postnatal day 6. Results: In the groups of 2 and 3, serum bilirubin levels were significantly higher when compared to animals in the group 1. There was no significant difference in terms of serum bilirubin levels between the Group 2 and Group 3. Length of ileal villi was significantly longer in the Group 2 and Group 3 than the Group 1 animals. The pattern of EGF-R expression in the Group 2 was similar to that seen in Group 3 animals. In contrast, animals given formula without EGF had markedly decreased expression of the EGF-R. Conclusion: Results suggest that EGF supplementation in newborn rats leads to a significant increase in intestinal mucosal proliferation and a significant decrease in bilirubin elimination. These data suggest that EGF possibly increases intestinal bilirubin absorption and may have a role in development of breast milk jaundice. Further studies are needed to confirm this hypothesis.