Signore Caroline, Mills James L, Qian Cong, Yu Kai, Lam Chun, Epstein Franklin H, Karumanchi S Ananth, Levine Richard J
Epidemiology Branch and the Biometry and Mathematical Statistics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
Obstet Gynecol. 2006 Aug;108(2):338-44. doi: 10.1097/01.AOG.0000216014.72503.09.
Abnormalities in circulating angiogenic factors have been reported in diseases of abnormal placentation, such as preeclampsia and intrauterine growth restriction. Our objective was to determine whether circulating angiogenic factors are altered in another placental vascular disease, abruptio placentae.
In a nested case-control study of nulliparous pregnancies, we examined levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in serum collected prospectively from 31 women who later developed placental abruption and from 31 normal control subjects. All serum specimens were collected before the onset of hypertension or abruption and before labor or delivery. Serum angiogenic factors were compared within 3 gestational age windows: early (20 weeks or less), middle (21-32 weeks), and late (33 weeks or more) pregnancy.
During early pregnancy women who developed placental abruption had lower PlGF and higher sFlt-1 concentrations and higher sFlt-1/PlGF ratios than women with normal pregnancies. In mid-pregnancy these differences became greater, reaching statistical significance for PlGF concentration (431 versus 654 pg/mL, P<.01) and the sFlt-1/PlGF ratio (25.3 versus 2.5, P<.01). When the women with placental abruption were subdivided into those who did (n=10) and those who did not (n=21) develop preeclampsia or gestational hypertension, significant alterations in angiogenic factors were noted only in women who later developed hypertension in pregnancy. Among these women, PlGF concentrations were decreased in mid-pregnancy (160 versus 723 pg/mL, P<.001), and the mid-pregnancy sFlt-1/PlGF ratio was increased (70.1 versus 2.3, P=.001).
Serum levels of the proangiogenic factor PlGF were decreased, and those of the antiangiogenic ratio sFlt-1/PlGF were increased in nulliparous women who subsequently developed hypertension and placental abruption.
已有报道称,在胎盘异常的疾病中,如子痫前期和胎儿生长受限,循环血管生成因子存在异常。我们的目的是确定在另一种胎盘血管疾病——胎盘早剥中,循环血管生成因子是否发生改变。
在一项针对初产妇妊娠的巢式病例对照研究中,我们检测了前瞻性收集的31例后来发生胎盘早剥的女性和31例正常对照受试者血清中的胎盘生长因子(PlGF)和可溶性fms样酪氨酸激酶1(sFlt-1)水平。所有血清标本均在高血压或胎盘早剥发作前、分娩或临产前提取。在三个孕周窗口内比较血清血管生成因子:孕早期(20周及以内)、孕中期(21 - 32周)和孕晚期(33周及以上)。
在孕早期,发生胎盘早剥的女性与正常妊娠女性相比,PlGF水平较低,sFlt-1浓度较高,sFlt-1/PlGF比值也较高。在孕中期,这些差异变得更大,PlGF浓度(431对654 pg/mL,P<0.01)和sFlt-1/PlGF比值(25.3对2.5,P<0.01)达到统计学显著差异。当将发生胎盘早剥的女性分为发生(n = 10)和未发生(n = 21)子痫前期或妊娠高血压的两组时,仅在后来发生妊娠高血压的女性中发现血管生成因子有显著改变。在这些女性中,孕中期PlGF浓度降低(160对723 pg/mL,P<0.001),孕中期sFlt-1/PlGF比值升高(70.1对2.3,P = 0.001)。
在随后发生高血压和胎盘早剥的初产妇中,促血管生成因子PlGF的血清水平降低,而抗血管生成比值sFlt-1/PlGF升高。