Hill D J, Tevaarwerk G J, Caddell C, Arany E, Kilkenny D, Gregory M
Medical Research Council Group in Fetal and Neonatal Health and Development, Lawson Research Institute, St. Joseph's Health Center, London, Ontario, Canada.
J Clin Endocrinol Metab. 1995 Sep;80(9):2626-32. doi: 10.1210/jcem.80.9.7673405.
We previously detected immunoreactive fibroblast growth factor 2 (FGF-2) in maternal and fetal circulations. Here, we determined whether the amounts of FGF-2 in term maternal serum, cord serum, and amniotic fluid were altered in pregnancies complicated by diabetes, as these are associated with a higher incidence of fetal macrosomia and increased placental size. Serum and amniotic fluid were collected at term from normal pregnancies (n = 17), women with pregestational insulin-dependent diabetes (n = 37; group A), patients with previously undiagnosed diabetes (n = 32; group B), women with gestational diabetes (n = 85; group C), and women with a milder form of glucose intolerance in pregnancy (n = 16; group D). Mean newborn weight and length, and placental weight did not significantly differ between normal and diabetic pregnancies, although the placental weight tended to be higher in the latter. However, 24% of the infants in group A and 19% in group B had a birth weight in excess of the 90th percentile. Levels of insulin in cord serum and amniotic fluid in groups A and B were significantly elevated compared to control values. FGF-2 was extracted from serum and amniotic fluid by heparin-Sepharose affinity chromatography and subjected to Western blot analysis or quantified by specific RIA. Western blot analysis of maternal serum, cord serum, and amniotic fluid from diabetic pregnant patients revealed, in each case, a single immunoreactive FGF-2 species of 18 kilodaltons; this was absent from nonpregnancy serum. In normal term pregnancies, the mean immunoreactive FGF-2 level in cord serum was 119 +/- 28 pmol/L, and that in amniotic fluid was 91 +/- 35 pmol/L. Values were significantly increased (2- to 4-fold) in both cord serum and amniotic fluid for all groups of diabetic patients. The mean FGF-2 level in normal term maternal serum was 104 +/- 24 pmol/L, and this was significantly increased in diabetic patients in groups B and C. The amount of FGF-2 in maternal serum showed a positive correlation with newborn weight and length, and placental weight (P < 0.05 or better, by Spearman rank correlation), and significant positive correlations also existed between the amounts of FGF-2 in cord serum and newborn or placental weight. The results suggest that the FGF-2 levels in maternal serum, cord serum, and amniotic fluid at term are elevated in pregnancies complicated by diabetes, and that the amounts of FGF-2 in maternal serum and cord serum are correlated with fetal and placental size.
我们之前在母血和胎儿循环中检测到了免疫反应性成纤维细胞生长因子2（FGF - 2）。在此，我们确定了在合并糖尿病的妊娠中，足月孕妇血清、脐血血清和羊水中FGF - 2的含量是否发生改变，因为这些情况与胎儿巨大儿发生率较高及胎盘增大有关。在足月时从正常妊娠（n = 17）、孕前胰岛素依赖型糖尿病女性（n = 37；A组）、既往未诊断糖尿病患者（n = 32；B组）、妊娠期糖尿病女性（n = 85；C组）以及妊娠期间糖耐量轻度异常的女性（n = 16；D组）中采集血清和羊水。正常妊娠和糖尿病妊娠之间新生儿平均体重、身长及胎盘重量无显著差异，尽管后者胎盘重量有升高趋势。然而，A组24%的婴儿和B组19%的婴儿出生体重超过第90百分位数。与对照值相比，A组和B组脐血血清和羊水中胰岛素水平显著升高。通过肝素 - 琼脂糖亲和层析从血清和羊水中提取FGF - 2，并进行蛋白质免疫印迹分析或通过特异性放射免疫分析进行定量。对糖尿病孕妇的母血血清、脐血血清和羊水进行蛋白质免疫印迹分析，在每种情况下均显示出一种18千道尔顿的单一免疫反应性FGF - 2条带；非妊娠血清中不存在此条带。在正常足月妊娠中，脐血血清中免疫反应性FGF - 2的平均水平为119±28 pmol/L，羊水中为91±35 pmol/L。所有糖尿病患者组的脐血血清和羊水中的值均显著升高（2至4倍）。正常足月孕妇血清中FGF - 2的平均水平为104±24 pmol/L，B组和C组糖尿病患者中该值显著升高。母血血清中FGF - 2的含量与新生儿体重、身长及胎盘重量呈正相关（Spearman等级相关，P < 0.05或更佳），脐血血清中FGF - 2的含量与新生儿或胎盘重量之间也存在显著正相关。结果表明，在合并糖尿病的妊娠中，足月时母血血清、脐血血清和羊水中的FGF - 2水平升高，且母血血清和脐血血清中FGF - 2的含量与胎儿及胎盘大小相关。
