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 neonatal growth. We previously reported that the profiles of IGFBPs in fetal cord serum (FCS) were dependent on the growth/metabolic status of the fetus. The goals of the current study were to examine the IGF system in FCS from term fetuses with normal growth, those with intrauterine growth retardation (IUGR), and those who were large for gestational age (LGA) and in FCS from normal weight preterm (25-37 weeks) and term 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 revealed 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 (IGFBP-4). In IUGR FCS, there was a 50% decrease in IGFBP-3 detected by WLB, 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 analysis of ligand blots. In normal term FCS, the following levels (±SE) were present: IGF-I, 76 ± 16; IGF-II, 401 ± 38; IGFBP-3, 700 ± 112; IGFBP-1, 77 ± 10 ng/mL; and insulin, 3.8 ± 1.6 μU/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 IGFBP-1 was significantly decreased. During the neonatal period, IGF-I levels on day 0 were 4-fold higher in FCS from term (38-40 weeks) compared to preterm (25-31 weeks) newborns. FCS IGF-II levels did not change significantly on day 0 between 25-40 weeks gestation. In the first 7 days of postnatal life, IGF-I levels were unchanged in preterm newborns, whereas in term neonates, IGF-I levels decreased precipitously on day 1, remained low during the first 3 days of life, and returned to birth levels by the end of the first week. In contrast, IGF-II and IGFBP-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 growth and changes in IGF-I levels in the third trimester and the neonatal period suggest roles for the IGF system in the somatic growth and development of the human fetus and neonate.