Thadhani Ravi, Mutter Walter P, Wolf Myles, Levine Richard J, Taylor Robert N, Sukhatme Vikas P, Ecker Jeffrey, Karumanchi S Ananth
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
J Clin Endocrinol Metab. 2004 Feb;89(2):770-5. doi: 10.1210/jc.2003-031244.
An imbalance of pro- and antiangiogenic factors may lead to preeclampsia (PE). In this prospective nested case-control study, we investigated whether first trimester serum levels of placental growth factor (PlGF), a potent angiogenic factor, and its soluble inhibitor, soluble fms-like tyrosine kinase 1 (sFlt1), distinguished women who developed PE (n = 40) from those who developed gestational hypertension (n = 40), delivered a small for gestational age (SGA) newborn (n = 40), or completed a full term normal pregnancy (n = 80). Compared with controls, serum PlGF levels were lower among women who developed PE (23 +/- 24 pg/ml vs. 63 +/- 145 pg/ml; P < 0.01) or gestational hypertension (27 +/- 19 pg/ml; P = 0.03), or who delivered a SGA newborn (21 +/- 16 pg/ml; P < 0.01). In contrast, serum sFlt1 levels did not markedly differ between the groups: PE, 1048 +/- 657 pg/ml; gestational hypertension, 942 +/- 437 pg/ml; SGA newborns, 1011 +/- 479 pg/ml; and normal controls, 973 +/- 490 pg/ml. Multivariable analysis adjusting for potential confounders and serum sFlt1 levels demonstrated a 3.7-fold (95% confidence interval, 1.2-12.5) increase in risk for PE for every log unit decrease in serum levels of PlGF compared with controls. Analyses for gestational hypertension and SGA were not significant. Examined in tertiles, the risk for PE was increased 28.7-fold (95% confidence interval, 2.3-351.0) in the third (<12 pg/ml) compared with the first (>39 pg/ml) PlGF tertile. First trimester serum levels of PlGF and sFlt1 may identify women at high risk for PE.
促血管生成因子和抗血管生成因子的失衡可能导致先兆子痫（PE）。在这项前瞻性巢式病例对照研究中，我们调查了孕早期血清中强效血管生成因子胎盘生长因子（PlGF）及其可溶性抑制剂可溶性fms样酪氨酸激酶1（sFlt1）的水平，能否区分发生PE的女性（n = 40）与发生妊娠期高血压的女性（n = 40）、分娩小于胎龄（SGA）新生儿的女性（n = 40）或完成足月正常妊娠的女性（n = 80）。与对照组相比，发生PE的女性（23±24 pg/ml vs. 63±145 pg/ml；P < 0.01）、发生妊娠期高血压的女性（27±19 pg/ml；P = 0.03）或分娩SGA新生儿的女性（21±16 pg/ml；P < 0.01）血清PlGF水平较低。相比之下，各组之间血清sFlt1水平无明显差异：PE组为1048±657 pg/ml；妊娠期高血压组为942±437 pg/ml；SGA新生儿组为1011±479 pg/ml；正常对照组为973±490 pg/ml。在对潜在混杂因素和血清sFlt1水平进行校正的多变量分析中，与对照组相比，血清PlGF水平每降低一个对数单位，PE风险增加3.7倍（95%置信区间，1.2 - 12.5）。对妊娠期高血压和SGA的分析无统计学意义。按三分位数分析，与PlGF三分位数的第一组（>39 pg/ml）相比，第三组（<12 pg/ml）发生PE的风险增加28.7倍（95%置信区间，2.3 - 351.0）。孕早期血清PlGF和sFlt1水平可能有助于识别PE高危女性。
