Irvine Katharine M, Bligh Larissa N, Kumar Sailesh
Mater Research Institute, University of Queensland, Australia.
Mater Research Institute, University of Queensland, Australia; Faculty of Medicine, The University of Queensland, Australia.
Eur J Obstet Gynecol Reprod Biol. 2020 Feb;245:198-204. doi: 10.1016/j.ejogrb.2019.11.018. Epub 2019 Nov 21.
A low fetal cerebroplacental ratio (CPR) in late pregnancy is a marker of a fetus that has failed to reach its growth potential and is associated with a variety of perinatal and pregnancy complications. It is not known if it is also correlated with aberrations in angiogenic, hypoxia-responsive or inflammatory cytokine levels in the maternal circulation. We investigated if there were any differences in levels of biomarkers of angiogenesis, endothelial cell dysfunction, hypoxia and/or inflammation in term pregnancies with a low fetal CPR compared to controls. We hypothesized that as the CPR is a marker of suboptimal growth, this would be reflected in a shift towards upregulation of hypoxia-responsive factors even in non-small for gestational age fetuses.
We used Multiplex ELISA to measure a panel of 28 candidate biomarkers of angiogenesis and/or hypoxia in pre-labour maternal plasma from 113 women at term, stratified for CPR <10th centile vs. CPR >10th centile. Plasma levels of the biomarkers were measured using 2 multiplex Luminex assays - a commercially available human angiogenesis/growth factor panel (R&D Systems®), comprising 15 analytes and an in-house custom panel of a further 13 candidate biomarkers.
Of the 28 candidate biomarkers investigated, we found significantly elevated levels of Carbonic Anhydrase 9 and soluble Fms-like tyrosine kinase (Vascular Endothelial Growth Factor Receptor 1), and lower levels of Placental Growth Factor in plasma from women with a low fetal CPR. The soluble Fms-like tyrosine kinase-1/Placental Growth Factor ratio was also markedly elevated in this cohort. We also demonstrated significant inverse correlations between the fetal CPR and Carbonic Anydrase 9, soluble Fms-like tyrosine kinase and Hepatocyte Growth Factor.
A low fetal CPR is associated with changes in some hypoxia-responsive and angiogenesis factors in the maternal circulation in pregnancies with normally grown fetuses.
妊娠晚期胎儿脑胎盘比值（CPR）低是胎儿未达到其生长潜能的一个标志物，与多种围产期和妊娠并发症相关。目前尚不清楚它是否也与母体循环中血管生成、缺氧反应或炎症细胞因子水平的异常有关。我们调查了与对照组相比，胎儿CPR低的足月妊娠中血管生成、内皮细胞功能障碍、缺氧和/或炎症生物标志物水平是否存在差异。我们假设，由于CPR是生长欠佳的一个标志物，即使在非小于胎龄儿中，这也会反映在缺氧反应因子上调的转变上。
我们使用多重酶联免疫吸附测定法（Multiplex ELISA），对113名足月孕妇临产前母血血浆中的一组28种血管生成和/或缺氧候选生物标志物进行测量，根据CPR＜第10百分位数与CPR＞第10百分位数进行分层。使用两种多重Luminex测定法测量生物标志物的血浆水平——一种市售的人血管生成/生长因子检测板（R&D Systems®），包含15种分析物，以及另外13种候选生物标志物的内部定制检测板。
在所研究的28种候选生物标志物中，我们发现胎儿CPR低的女性血浆中碳酸酐酶9和可溶性Fms样酪氨酸激酶（血管内皮生长因子受体1）水平显著升高，胎盘生长因子水平较低。该队列中可溶性Fms样酪氨酸激酶-1/胎盘生长因子比值也显著升高。我们还证明胎儿CPR与碳酸酐酶9、可溶性Fms样酪氨酸激酶和肝细胞生长因子之间存在显著的负相关。
在胎儿生长正常的妊娠中，胎儿CPR低与母体循环中一些缺氧反应和血管生成因子的变化有关。
