Markers of type I and type III collagen turnover, insulin-like growth factors, and their binding proteins in cord plasma of small premature infants: Relationships with fetal growth, gestational age, preeclampsia, and antenatal glucocorticoid treatment

Disorders affecting fetal growth are commonly associated with premature bir th. IGFs and their binding proteins (IGFBPs) are potent regulators of fetal growth. In vitro evidence suggests that they regulate collagen turnover. C ollagen turnover can be monitored by serum markers of type I collagen synth esis (PINP) and degradation (ICTP) and a marker of type III collagen synthe sis (PIIINP). We examined whether these markers in fetal circulation reflec t intrauterine growth and maturity, and whether any interrelationship exist s between them and fetal IGFs and IGFBPs in preterm infants before 32 wk of gestation. Cord plasma PINP, ICTP, PIIINP, IGF-I, IGF-II, IGFBP-1, and IGF BP-3 were determined for 98 preterm infants. To express birth weight in uni ts adjusted for gestational age, a birth weight SD score (SDS) was calculat ed. Negative correlations existed between gestational age and PINP (r = -0. 43; p < 0.0001), ICTP (r = -0.34; p = 0.002), and PIIINP (r = -0.34; p = 0. 0001). Positive correlations existed between birth weight SDS and PINP (r = 0.40; p = 0.0002) and ICTP (r = 0.48; p < 0.0001) but not PIIINP. Moreover , birth weight SDS was positively correlated with IGF-I (r = 0.58; p < 0.00 01) and IGFBP-3 (r = 0.44; p < 0.0001) and negatively correlated with IGF-I I (r = -0.36; p = 0.003) and IGFBP-1 (r = -0.50; p < 0.0001). Gestational a ge correlated with IGFBP-3 (r = 0.25;p = 0.03). In preeclampsia, IGF-I was lower (p = 0.002) and IGFBP-1 higher (p < 0.0001), also after adjustment fo r fetal size. The number of antenatal glucocorticoid treatments was associa ted with lower ICTP (p, = 0.04), higher IGF-I (p = 0.002), lower IGF-II (p, = 0.02), lower IGFBP-1 (p = 0.05), and higher IGFBP-3 (p = 0.004), also af ter adjustment for potential confounders. In multiple regression analysis, the factors significantly associated with PINP (R-2 = 0.47) were gestationa l age and IGF-I, and those associated with ICTP (R-2 = 0.54) were IGF-I, ge stational age, and antenatal glucocorticoid treatment. We conclude that IGF -I may be involved in regulation of type I collagen turnover in the growing fetus. Cord blood PINP and ICTP reflect both fetal growth and maturity and deserve evaluation as potential indicators of post natal growth velocity i n preterm infants, whereas PIIINP reflects fetal maturity.