Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, USA.
Am J Obstet Gynecol. 2013 Apr;208(4):310.e1-310.e11. doi: 10.1016/j.ajog.2013.01.017. Epub 2013 Jan 17.
Massive perivillous fibrin deposition (MPFD) is associated with serious complications of pregnancy including recurrent spontaneous abortion, fetal growth restriction, and fetal demise. The aim of this study was to determine whether maternal plasma concentrations of angiogenic/antiangiogenic factors in MPFD differ from those of uncomplicated pregnancies.
This retrospective longitudinal case-control study included MPFD cases (n = 10) and control patients (n = 175) with uncomplicated pregnancies who were enrolled in a longitudinal study and delivered at term. Serial plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor (sVEGFR)-1 and -2 were determined by an enzyme-linked immunosorbent assay (cases, n = 28 samples; controls, n = 723 samples). Individual analyte concentrations were averaged across gestational age at specimen collection intervals. Linear mixed models were used to test for differences in log-transformed mean analyte concentrations both overall and as a function of time.
The following results were found: (1) patients with MPFD had a lower mean plasma PlGF concentration (P = .03) and higher mean plasma concentrations of sVEGFR-1 and sEng (both P < .01) than controls, adjusted for potential confounders; (2) the mean plasma concentration of PlGF differed further among cases and controls as a function of gestational age interval (P < .0001); however, mean sVEGFR-1 and sEng group differences as a function of gestational age interval approached but did not reach significance (P = .09 and P = .11, respectively); (3) patients with MPFD had lower mean plasma concentrations of PlGF/sVEGFR-1 (P < .0001) and PlGF/sEng (P < .001): both of these relationships differed further as a function of gestational age interval (both P < .0001); and (4) differences in mean sVEGFR-1, sEng, and the ratios of PlGF to sVEGFR-1 and PlGF to sEng were observed before 20 weeks of gestation.
An imbalance of angiogenic/antiangiogenic factors is present in patients with MPFD prior to the diagnosis. We propose that these changes participate in the mechanisms responsible for adverse pregnancy outcomes in patients with MPFD.
绒毛膜外大量纤维蛋白沉积（MPFD）与妊娠的严重并发症有关，包括复发性自然流产、胎儿生长受限和胎儿死亡。本研究的目的是确定 MPFD 产妇血浆中血管生成/抗血管生成因子的浓度是否与无并发症的妊娠不同。
本回顾性纵向病例对照研究纳入了 10 例 MPFD 病例（病例组）和 175 例无并发症的对照患者（对照组），这些患者参与了一项纵向研究并在足月时分娩。通过酶联免疫吸附试验（病例组：n=28 个样本；对照组：n=723 个样本）测定胎盘生长因子（PlGF）、可溶性内皮因子（sEng）和可溶性血管内皮生长因子受体（sVEGFR）-1 和 -2 的血浆浓度。在标本采集间隔时间内，将个体分析物浓度取平均值。使用线性混合模型检验对数转换后的平均分析物浓度的总体差异以及作为时间函数的差异。
发现以下结果：（1）与对照组相比，MPFD 患者的平均血浆 PlGF 浓度较低（P=0.03），sVEGFR-1 和 sEng 的平均血浆浓度较高（均 P<0.01），调整了潜在的混杂因素；（2）PlGF 的平均血浆浓度在病例组和对照组之间进一步随妊娠间隔时间的不同而不同（P<0.0001）；然而，sVEGFR-1 和 sEng 组之间的差异随妊娠间隔时间的不同接近但未达到显著性（P=0.09 和 P=0.11）；（3）MPFD 患者的平均血浆 PlGF/sVEGFR-1（P<0.0001）和 PlGF/sEng（P<0.001）浓度较低：这两种关系进一步随妊娠间隔时间的不同而不同（均 P<0.0001）；（4）在 20 周妊娠之前，观察到平均 sVEGFR-1、sEng 和 PlGF 与 sVEGFR-1 和 PlGF 与 sEng 的比值存在差异。
在 MPFD 患者被诊断之前，就存在血管生成/抗血管生成因子的失衡。我们提出，这些变化参与了 MPFD 患者不良妊娠结局的发生机制。
