INSULIN-LIKE GROWTH-FACTORS AND THEIR BINDING-PROTEINS IN THE TERM AND PRETERM HUMAN FETUS AND NEONATE WITH NORMAL AND EXTREMES OF INTRAUTERINE GROWTH

Insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and insulin are believed to be important in the regulation of fetal and n eonatal growth. We previously reported that the profiles of IGFBPs in fetal cord serum (FCS) were dependent on the growth/metabolic status o f the fetus. The goals of the current study were to examine the IGF sy stem in FCS from term fetuses with normal growth, those with intrauter ine growth retardation (IUGR), and those who were large for gestationa l age (LGA) and in FCS from normal weight preterm (25-37 weeks) and te rm fetuses in the neonatal period from the day of birth (day 0) until 7 days of age (day 7). Western ligand blotting (WLB) of term FCS revea led IGFBPs with mol wt of 43 and 38 kilodaltons (kDa; IGFBP-3), 34 kDa (IGFBP-2), 28 kDa (IGFBP-1 and glycosylated IGFBP-4), and 24 kDa (IGF BP-4). In IUGR FCS, there was a 50% decrease in IGFBP-3 detected by WL B, which was shown not to be due to an IGFBP-3 protease in IUGR sera. In LGA FCS, IGFBP-3 levels were elevated 2-fold by densitometric analy sis of ligand blots. In normal term FCS, the following levels (+/- SE) were present: IGF-I, 76 +/- 16;IGF-II, 401 +/- 38;IGFBP-3, 700 +/- 11 2;IGFBP-1, 77 +/- 10 ng/mL; and insulin, 3.8 +/- 1.6 mu U/mL. In IUGR FCS, IGF-I, IGF-II, and IGFBP-3 were significantly reduced, and IGFBP- 1 was 7-fold higher than in FCS from normal weight fetuses. In LGA FCS , IGF-I, insulin, and IGFBP-3 were significantly increased, whereas IG FBP-1 was significantly decreased. During the neonatal period, IGF-I l evels on day 0 were 4-fold higher in FCS from term (38-40 weeks) compa red to preterm (25-31 weeks) newborns. FCS IGF-II levels did not chang e significantly on day 0 between 25-40 weeks gestation. In the first 7 days of postnatal life, IGF-I levels were unchanged in preterm newbor ns, whereas in term neonates, IGF-I levels decreased precipitously on day 1, remained low during the first 3 days of life, and returned to b irth levels by the end of the first week. In contrast, IGF-II and IGFB P-3 levels did not significantly change during the first week of life in preterm or term newborns. Different IGFBP and insulin-like peptide levels in fetuses with normal compared to extremes of intrauterine gro wth and changes in IGF-I levels in the third trimester and the neonata l period suggest roles for the IGF system in the somatic growth and de velopment of the human fetus and neonate.