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 birth. IGFs and their binding proteins (IGFBPs) are potent regulators of fetal growth. In vitro evidence suggests that they regulate collagen turnover. Collagen turnover can be monitored by serum markers of type I collagen synthesis (PINP) and degradation (ICTP) and a marker of type III collagen synthesis (PIIINP). We examined whether these markers in fetal circulation reflect intrauterine growth and maturity, and whether any interrelationship exists 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 IGFBP-3 were determined for 98 preterm infants. To express birth weight in units adjusted for gestational age, a birth weight SD score (SDS) was calculated. 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 < 0.0001) and IGFBP-3 (r = 0.44; p < 0.0001) and negatively correlated with IGF-II (r = -0.36; p = 0.003) and IGFBP-1 (r = -0.50; p < 0.0001). Gestational age 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 for fetal size. The number of antenatal glucocorticoid treatments was associated 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 after adjustment for potential confounders. In multiple regression analysis, the factors significantly associated with PINP (R:(2) = 0.47) were gestational age and IGF-I, and those associated with ICTP (R:(2) = 0.54) were IGF-I, gestational 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 postnatal growth velocity in preterm infants, whereas PIIINP reflects fetal maturity.
The Hospital for Children and Adolescents, Helsinki University Central Hospital, PL 280, FI-00029 HYKS, Helsinki, Finland. eero.kajantie@hus.fi
E
E
Kajantie
T
T
Hytinantti
R
R
Koistinen
J
J
Risteli
E M
EM
Rutanen
M
M
Seppälä
S
S
Andersson
D015415:Biomarkers; D001724:Birth Weight; D003094:Collagen / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy
D015415:Biomarkers; D005938:Glucocorticoids; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003094:Collagen