IGF‐I, IGF‐II, free IGF‐I and IGFBP‐1, ‐2 and ‐3 levels in venous cord blood: relationship to birthweight, length and gestational age in healthy newborns

Abstract

The insulin‐like growth factors (IGF‐I and IGF‐II) and their binding proteins (IGFBPs) have been implicated in regulating fetal growth and development. The aim of this study was to determine whether fetal IGFs correlate with auxologic data at birth and/or gestational age. Venous cord blood was obtained from 138 healthy newborns immediately after birth and clinical data were recorded using a standardized data sheet. For the determination of IGF‐I and IGF‐II, IGFBP‐blocked radioimmunoassays were used. A coated‐tube immunoradiometric assay was applied for the measurement of free IGF‐I. IGFBP‐1, ‐2, and ‐3 were measured using specific radioimmunoassays. IGF‐I levels were 61 ± 21 ng ml‐1, median 61 ng ml‐1, range 19‐114ng ml‐1: IGF‐II levels were 466 ± 80ng ml‐1, median 457 ng ml‐1, range 311–701 ng ml‐1; free IGF‐I levels were 2.4 ± 1.8ng ml‐1, median 1.8 ng ml‐1, range 0.4–7.8ng ml‐1. The concentration of IGFBP‐1 was 144± 110 ng ml‐1, median 113 ng ml‐1, range 20–626 ng ml‐1; that of IGFBP‐2 was 1165 ± 455ng ml‐1, median 1119ng ml‐1, range 440–3466 ng ml‐1. IGFBP‐3 levels were 1272 ± 280 ng ml‐1, median 1272ng ml‐1, range 600–1966 ng ml‐1. IGF‐I levels correlated significantly with IGFBP‐3 levels (r= 0.71). birthweight (r= 0.48) and birth length (r= 0.37). There were significant inverse correlations between IGF‐I and both IGFBP‐I (r= ‐ 0.45) and IGFBP‐2 (r= ‐ 0.62). Although free IGF‐I levels correlated (r= 0.71) with total IGF‐I, only marginally significant correlations were found between free IGF‐I and birthweight (r= 0.25). According to multiple regression analysis free IGF‐I levels were only dependent upon total IGF‐I, IGFBP‐2 and IGFBP‐1, whereas IGFBP‐3 levels did not contribute to the variance of free IGF‐1 concentrations in venous cord blood. There was no significant correlation between IGF‐II and auxologic data at birth. When IGF‐I and IGFBP‐3 levels were analysed with respect to gestational age a biphasic pattern with maxima at 270 d was observed. IGFBP‐2 exhibited a reversed pattern with a minimum at 265 d of gestation. In conclusion, these data suggest that IGF‐I and the IGFBPs, but not IGF‐II, play a role in the regulation of late fetal growth and development.

Exploring the Underlying Hormonal Mechanisms of Prenatal Risk Factors for Breast Cancer: A Review and Commentary

“…Most studies addressing the associations of the IGF system with birth size have focused on differences between small for gestational age neonates resulting from a variety of etiologies and appropriate for gestational age neonates; however, the greatest breast cancer risks are observed for women born heavy. In studies conducted in normal pregnancies with a range of birth weights, the positive association between birth size and cord IGF-I concentrations is well established (89)(90)(91)(92)(93)(94)(95)(96)(97)(98). IGFBP-3 has also been positively associated with birth size in most studies (75,95,96,99), whereas IGFBP-1 may be inversely associated (90,95).…”

“…IGFBP-3 has also been positively associated with birth size in most studies (75,95,96,99), whereas IGFBP-1 may be inversely associated (90,95). Associations of IGF-2 with birth size are unclear (92,93,99), as is the role of IGFBP-2, the main IGFBP in the fetal circulation (99). In contrast, birth weight is generally not associated with concentrations of IGF-I (100, 101), IGFBP-1 (100-102), or IGFBP-3 in the maternal circulation (103).…”

Early postnatal alteration of body composition in preterm and small-for-gestational-age infants: implications of catch-up fat

“…Previous studies have shown that IGF-I has a more critical role than the other factors (56)(57)(58), and growth hormone is not an important regulator of IGF-I secretion during perinatal life (57,58). In addition, children with IGF-I gene deletion are characterized by severe prenatal and postnatal growth retardation (59).…”

Maternal growth factor regulation of human placental development and fetal growth

“…weight is positively correlated with cord blood IGF1 levels (Osorio et al 1996, Klauwer et al 1997, and so levels are low in small-for-gestational-age (SGA) infants and are enhanced in large-for-gestational-age babies (Table 1). Evidence for the importance of IGF2 in this regard comes from the observation that the IGF2 gene is maternally imprinted (Giannoukakis et al 1993).…”