164 Insulin-Like Growth Factors and Their Binding Proteins in Early Milk from Mothers of Preterm and Term Infants and Thei Biological Relevance

Abstract

Background: Breast fed preterm infants often show a better neurological outcome than formula-fed. The benefit of human milk is partly ascribed to it's content of the growth promoting insulin-like growth factors (IGFs). The aim of this study was to investigate, whether the content of IGFs und Their binding proteins (IGFBPs) is higher in human milk from mothers of preterm infants than of term infants and to test their biological relevance.Methods: In a prospective study we investigated the concentrations of IGF-I, IGF-II and their binding proteins IGFBP-2 and IGFBP-3 in human milk from mothers of 30 preterm infants (<31 SSW) and of 19 term infants (>37 SSW) at day 7 and 21 after birth by means of an RIA, and the protein content of human milk by the Bichinonic acid (BCA) method. We analyzed the specific proteolysis of IGFBP-2 in human milk and the stability of 125I-IGF-I and 125IGFBP-2 in the presence of gastric juice from neonates.Results: Mean concentrations (±SD) of IGF-I(2,8 ± 0,2 vs. 2,3 ± 0,1 ng/ml), IGF-II (12,0 ± 0,4 vs. 12,2 ± 0,5 ng/ml) and IGFBP-3 (100,0 ± 5,1 vs. 80,0 ± 5,8 ng/ml) did not differ in human milk of preterm versus term infants on day 7. The content of IGFBP-2 (3144 ± 172 vs. 2428 ± 188 ng/ml) was higher in preterm human milk (p<0,05). IGF-I, IGF-II and IGFBP-2 did slightly change until day 21. IGFBP-3 decreased from day 7 to day 21 by 41%/ 27% in human milk of preterm/ term infants (p<0,05). The protein content in human milk of preterm infants was on day 7 (2,5 ± 0,1 g/dl) higher than on day 21 (p<0,05). On day 21 the protein content was equal to term infants (1,9 ± 0,1 g/dl). Preterm human milk contained about 42% more IGFBP-2- fragments of 14 und 25 kDa (p< 0,05). Incubation with gastric juice led to a complete digestion of 125IGFBP-2 and a partial digestion of 125I-IGF-II, while complexation with each other protected IGF-II and IGFBP-2 from cleavage.Conclusion: We suggest that IGF-II and IGFBP-2 play a role in the nutrition of preterm infants. Both are found in a constant level in human milk and IGF-2 showed a higher concentration in preterm than in term human milk for the first 3 weeks. IGFBP-2/IGF-II-complexes can partly pass the stomach and may exert their promotive effects in the intestine. Taken together it can be concluded that preterm infants profits best from breast milk of it's own mother.