Kajantie E, Hytinantti T, Koistinen R, Risteli J, Rutanen E M, Seppälä M, Andersson S
The Hospital for Children and Adolescents, Helsinki University Central Hospital, PL 280, FI-00029 HYKS, Helsinki, Finland.
Pediatr Res. 2001 Apr;49(4):481-9. doi: 10.1203/00006450-200104000-00008.
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.
影响胎儿生长的疾病通常与早产有关。胰岛素样生长因子（IGFs）及其结合蛋白（IGFBPs）是胎儿生长的有效调节因子。体外证据表明它们调节胶原蛋白周转。胶原蛋白周转可通过I型胶原蛋白合成（PINP）和降解（ICTP）的血清标志物以及III型胶原蛋白合成（PIIINP）的标志物来监测。我们研究了胎儿循环中的这些标志物是否反映宫内生长和成熟度，以及在妊娠32周前的早产儿中它们与胎儿IGFs和IGFBPs之间是否存在任何相互关系。测定了98例早产儿的脐血PINP、ICTP、PIIINP、IGF-I、IGF-II、IGFBP-1和IGFBP-3。为了以根据胎龄调整的单位表示出生体重，计算了出生体重标准差评分（SDS）。胎龄与PINP（r = -0.43；p < 0.0001）、ICTP（r = -0.34；p = 0.002）和PIIINP（r = -0.34；p = 0.0001）呈负相关。出生体重SDS与PINP（r = 0.40；p = 0.0002）和ICTP（r = 0.48；p < 0.0001）呈正相关，但与PIIINP无相关性。此外，出生体重SDS与IGF-I（r = 0.58；p < 0.0001）和IGFBP-3（r = 0.44；p < 0.0001）呈正相关，与IGF-II（r = -0.36；p = 0.003）和IGFBP-1（r = -0.50；p < 0.0001）呈负相关。胎龄与IGFBP-3相关（r = 0.25；p = 0.03）。在子痫前期，即使在调整胎儿大小后，IGF-I也较低（p = 0.002），IGFBP-1较高（p < 0.0001）。产前糖皮质激素治疗的次数与较低的ICTP（p = 0.04）、较高的IGF-I（p = 0.002）、较低的IGF-II（p = 0.02）、较低的IGFBP-1（p = 0.05）和较高的IGFBP-3（p = 0.004）相关，即使在调整潜在混杂因素后也是如此。在多元回归分析中，与PINP显著相关的因素（R² = 0.47）是胎龄和IGF-I，与ICTP显著相关的因素（R² = 0.54）是IGF-I、胎龄和产前糖皮质激素治疗。我们得出结论，IGF-I可能参与生长中胎儿I型胶原蛋白周转的调节。脐血PINP和ICTP反映胎儿生长和成熟度，作为早产儿出生后生长速度的潜在指标值得评估，而PIIINP反映胎儿成熟度。
