Translational Obstetrics Group, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
PLoS One. 2012;7(2):e32509. doi: 10.1371/journal.pone.0032509. Epub 2012 Feb 28.
Miscarriage is the most common complication of pregnancy. Pre-clinical miscarriage has an estimated incidence of 30%, whilst clinical miscarriage has an incidence of 12-15%. Two thirds of pregnancies lost to miscarriage are believed to be attributable to defective placentation, thus a number of studies have sought to identify markers of defective placentation that could be used as clinical biomarkers of miscarriage. Decreased soluble FMS-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF), and soluble endoglin (sEng) in the maternal circulation during the first trimester have recently been proposed as potential markers of pregnancy loss. However, in these studies clinical samples were only obtained once women had presented with symptoms of miscarriage. In this study we prospectively screened serum samples collected from asymptomatic women with a viable fetus. We assessed maternal serum levels of sFlt1, PlGF and sEng across the first trimester of normal pregnancy and compared levels between women who continued to a live birth, to those who subsequently miscarried. Both sFlt1 and PlGF significantly (p≤0.05) increased across gestation in normal pregnancy with serum levels rising from 0.65±0.12 ng/ml at 6 weeks to 1.85±0.24 ng/ml at 12 weeks for sFlt1, and 57.2±19.2 pg/ml to 106±22.7 pg/ml for PlGF. sEng remained unchanged throughout the the first trimester. Importantly we detected a significant (35%, p≤0.05) decrease in sFlt1 levels between our control and miscarriage cohort, however there was significant overlap between cases and controls, suggesting serum sFlt1 is unlikely to be useful as a clinical biomarker in asymptomatic women. Nevertheless, our data suggests a dysregulation of angiogenic factors may be involved in the pathophysiology of miscarriage.
流产是妊娠最常见的并发症。临床前流产的估计发生率为 30%，而临床流产的发生率为 12-15%。三分之二的流产归因于胎盘缺陷，因此许多研究试图识别胎盘缺陷的标志物，这些标志物可作为流产的临床生物标志物。最近提出，妊娠早期母体循环中可溶性 FMS 样酪氨酸激酶-1（sFlt1）、胎盘生长因子（PlGF）和可溶性内皮素（sEng）减少可能是妊娠丢失的潜在标志物。然而，在这些研究中，仅在女性出现流产症状时才获得临床样本。在这项研究中，我们前瞻性地筛选了来自有存活胎儿的无症状女性的血清样本。我们评估了正常妊娠早期母体血清中 sFlt1、PlGF 和 sEng 的水平，并比较了继续活产和随后流产的女性之间的水平。在正常妊娠中，sFlt1 和 PlGF 均随着妊娠而显著（p≤0.05）增加，血清水平从 6 周时的 0.65±0.12ng/ml 升高至 12 周时的 1.85±0.24ng/ml，PlGF 从 57.2±19.2pg/ml 升高至 106±22.7pg/ml。sEng 在整个第一孕期保持不变。重要的是，我们在对照组和流产组之间检测到 sFlt1 水平显著（35%，p≤0.05）降低，但病例和对照组之间存在显著重叠，表明血清 sFlt1 不太可能作为无症状女性的临床生物标志物有用。尽管如此，我们的数据表明，血管生成因子的失调可能参与了流产的病理生理学。
