Stepan Holger, Unversucht Angela, Wessel Niels, Faber Renaldo
Department of Obstetrics and Gynecology, University of Leipzig, Leipzig, Germany.
Hypertension. 2007 Apr;49(4):818-24. doi: 10.1161/01.HYP.0000258404.21552.a3. Epub 2007 Jan 29.
Angiogenic factors like placental growth factor and its antiangiogenic antagonist soluble fms-like tyrosine kinase 1 (sFlt1) are closely related to the pathogenesis of preeclampsia and intrauterine growth restriction. Because it is known that altered maternal sFlt1 and placental growth factor levels are detectable weeks before the onset of these pregnancy complications, it was the aim of the study to investigate the predictive value of these markers in high-risk second trimester pregnancies characterized by abnormal uterine perfusion. This prospective study includes 63 second trimester pregnant women with abnormal uterine perfusion. Twenty five of them developed a later complication (12 with preeclampsia, 11 with intrauterine growth restriction, and 2 with intrauterine death), whereas 38 had a normal course of pregnancy. Pregnancies with adverse pregnancy outcome showed in the second trimester significantly higher sFlt1 (1403.6+/-555 versus 451.8+/-42 pg/mL; P<0.05) and lower placental growth factor (139.6+/-24 versus 184.1+/-21 pg/mL) levels compared with those with normal outcome. These alterations were more pronounced in pregnancies with subsequent preeclampsia compared with intrauterine growth restriction and early onset diseases (delivery <34 weeks) compared with late-onset diseases. The combination of Doppler and sFlt1 increases the sensitivity of Doppler alone for iatrogenic preterm delivery from 64% up to 79% and the specificity from 63% up to 80%. Using both factors, sFlt1 and placental growth factor, early onset preeclampsia can be predicted with 83% sensitivity and 95% specificity. We conclude that the concurrent measurement of uterine perfusion and angiogenic factors allows an efficient prediction of early onset pregnancy complications, particularly preeclampsia.
胎盘生长因子等血管生成因子及其抗血管生成拮抗剂可溶性fms样酪氨酸激酶1(sFlt1)与子痫前期和胎儿生长受限的发病机制密切相关。由于已知在这些妊娠并发症发作前数周就能检测到母体sFlt1和胎盘生长因子水平的改变,本研究的目的是调查这些标志物在以子宫灌注异常为特征的高危孕中期妊娠中的预测价值。这项前瞻性研究纳入了63例子宫灌注异常的孕中期孕妇。其中25例随后出现了并发症(12例发生子痫前期,11例发生胎儿生长受限,2例发生宫内死亡),而38例妊娠过程正常。与妊娠结局正常的孕妇相比,不良妊娠结局的孕妇在孕中期sFlt1水平显著更高(1403.6±555 vs 451.8±42 pg/mL;P<0.05),胎盘生长因子水平更低(139.6±24 vs 184.1±21 pg/mL)。与胎儿生长受限相比,子痫前期后续妊娠中的这些改变更为明显;与晚发型疾病相比,早发型疾病(<34周分娩)中的这些改变更为明显。多普勒检查与sFlt1联合使用可使单独使用多普勒检查预测医源性早产的敏感性从64%提高到79%,特异性从63%提高到80%。同时使用sFlt1和胎盘生长因子这两个因素,预测早发型子痫前期的敏感性为83%,特异性为95%。我们得出结论,同时测量子宫灌注和血管生成因子能够有效预测早发型妊娠并发症,尤其是子痫前期。