Cianfarani S, Germani D, Rossi P, Rossi L, Germani A, Ossicini C, Zuppa A, Argirò G, Holly J M, Branca F
Department of Pediatrics, Tor Vergata University, Rome, Italy.
Pediatr Res. 1998 Sep;44(3):374-80. doi: 10.1203/00006450-199809000-00018.
Thirty-seven children with intrauterine growth retardation (IUGR) were enrolled in a 3-mo longitudinal study. Weight, length, and knee-heel length (by knemometry) were measured at birth and at 7, 14, 30, 60, and 90 d. GH, IGF-I, IGF binding protein (BP)-3, IGFBP-1, and C-peptide were measured at birth and at 2 mo. IGFBP-3 Western immunoblotting and proteolytic activity assay were also performed. Twenty-five newborns with birth weight appropriate for gestational age were chosen as controls. At birth IUGR newborns showed levels of GH and IGFBP-1 significantly higher, and IGF-I, IGFBP-3, and C-peptide significantly lower than control subjects. At 2 mo GH and IGFBP-1 levels decreased, whereas IGF-I, IGFBP-3, and C-peptide rose, attaining the concentrations found in control subjects at birth. Baseline peptide levels as well as their 2-mo variations did not correlate with the gain in weight, supine length, and knee-heel length recorded at 3 mo. Fourteen of nineteen IUGR cord blood samples showed the presence of the intact approximately 42-39-kD IGFBP-3 doublet and the major approximately 29-kD fragment. At 2 mo the IGFBP-3 band pattern was characterized by the predominance of a approximately 18-kD fragment in 6 of 19 tested IUGR infants. The incubation of 2-mo IUGR samples with normal adult serum induced the appearance of the approximately 18-kD band, which was not modified by the addition of EDTA. These results suggest that: 1) the IGF-related growth-promoting mechanism is impaired in IUGR children at birth but is fully restored at 2 mo; 2) the cord blood levels of GH, IGF-I, IGFBP-3, IGFBP-1, and C-peptide are not predictive of the weight and length gain during the first 3 mo of life; 3) IUGR children have at least two different IGFBP-3 proteases, one cation-dependent protease that is present at birth and able to yield the major approximately 29-kD IGFBP-3 fragment and a second one, with a different activation timing, which exhibits cation independence and induces the formation of a approximately 18-kD IGFBP-3 form.
37名宫内生长受限（IUGR）儿童参与了一项为期3个月的纵向研究。在出生时以及出生后7天、14天、30天、60天和90天测量体重、身长和膝跟长度（通过测膝跟距法）。在出生时和2个月时测量生长激素（GH）、胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子结合蛋白（BP）-3、胰岛素样生长因子结合蛋白-1（IGFBP-1）和C肽。还进行了IGFBP-3的蛋白质免疫印迹分析和蛋白水解活性测定。选择25名出生体重与孕周相符的新生儿作为对照。出生时，IUGR新生儿的GH和IGFBP-1水平显著高于对照组，而IGF-I、IGFBP-3和C肽水平显著低于对照组。在2个月时，GH和IGFBP-1水平下降，而IGF-I、IGFBP-3和C肽水平上升，达到对照组出生时的浓度。基线肽水平及其2个月时的变化与3个月时记录的体重、仰卧身长和膝跟长度增加无关。19份IUGR脐血样本中的14份显示存在完整的约42 - 39kD的IGFBP-3双峰以及主要的约29kD片段。在2个月时，19名接受检测的IUGR婴儿中有6名的IGFBP-3条带模式以约18kD片段为主。将2个月时IUGR样本与正常成人血清孵育会诱导出现约18kD条带，添加乙二胺四乙酸（EDTA）对此无影响。这些结果表明：1）出生时IUGR儿童中与IGF相关的生长促进机制受损，但在2个月时完全恢复；2）出生时的GH、IGF-I、IGFBP-3、IGFBP-1和C肽水平不能预测生命最初3个月期间的体重和身长增加；3）IUGR儿童至少有两种不同的IGFBP-3蛋白酶，一种是出生时存在的阳离子依赖性蛋白酶，能够产生主要的约29kD的IGFBP-3片段，另一种具有不同的激活时间，表现出阳离子非依赖性并诱导形成约18kD的IGFBP-3形式。
