Department of Obstetrics and Gynecology, Erasmus MC University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Department of Pharmacology, Erasmus MC University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Angiogenesis. 2024 Nov;27(4):797-808. doi: 10.1007/s10456-024-09939-3. Epub 2024 Aug 14.
OBJECTIVE (S): Circulating angiogenic factors are used for prediction of placenta-related complications, but their associations with first-trimester placental development is unknown. This study investigates associations between maternal angiogenic factors and utero-placental vascular volume (uPVV) and utero-placental vascular skeleton (uPVS) as novel imaging markers of volumetric and morphologic (branching) development of the first-trimester utero-placental vasculature.
In 185 ongoing pregnancies from the VIRTUAL Placenta study, a subcohort of the ongoing prospective Rotterdam Periconception cohort, three-dimensional power Doppler ultrasounds of the placenta were obtained at 7-9-11 weeks gestational age (GA). The uPVV was measured as a parameter of volumetric development and reported the vascular quantity in cm. The uPVS was generated as a parameter of morphologic (branching) development and reported the number of end-, bifurcation- crossing- or vessel points and total vascular length. At 11 weeks GA, maternal serum biomarkers suggested to reflect placental (vascular) development were assessed: placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). sFlt-1/PlGF and sEng/PlGF ratios were calculated. Multivariable linear regression with adjustments was used to estimate associations between serum biomarkers and uPVV and uPVS trajectories.
Serum PlGF was positively associated with uPVV and uPVS development (uPVV: β = 0.39, 95% CI = 0.15;0.64; bifurcation points: β = 4.64, 95% CI = 0.04;9.25; crossing points: β = 4.01, 95% CI = 0.65;7.37; total vascular length: β = 13.33, 95% CI = 3.09;23.58, all p-values < 0.05). sEng/PlGF ratio was negatively associated with uPVV and uPVS development. We observed no associations between sFlt-1, sEng or sFlt-1/PlGF ratio and uPVV and uPVS development.
CONCLUSION(S): Higher first-trimester maternal serum PlGF concentration is associated with increased first-trimester utero-placental vascular development as reflected by uPVV and uPVS. Clinical trial registration number Dutch Trial Register NTR6854.
循环血管生成因子用于预测胎盘相关并发症，但它们与早期胎盘发育的关系尚不清楚。本研究旨在探讨母体血管生成因子与子宫胎盘血管容积(uPVV)和子宫胎盘血管骨架(uPVS)之间的关系，uPVS 是反映子宫胎盘血管容积和形态（分支）发育的新型影像学标志物。
在 VIRTUAL Placenta 研究的 185 例持续妊娠中，前瞻性鹿特丹围孕期队列的一个亚组，在妊娠 7-9-11 周时对胎盘进行三维能量多普勒超声检查。uPVV 作为体积发育的参数进行测量，并以 cm 为单位报告血管数量。uPVS 作为形态（分支）发育的参数生成，并报告末端、分叉、交叉或血管点数量和总血管长度。在 11 周 GA 时，评估了提示反映胎盘（血管）发育的母体血清生物标志物：胎盘生长因子(PlGF)、可溶性 fms 样酪氨酸激酶-1(sFlt-1)和可溶性内皮糖蛋白(sEng)。计算 sFlt-1/PlGF 和 sEng/PlGF 比值。采用多元线性回归调整模型来估计血清生物标志物与 uPVV 和 uPVS 轨迹之间的关系。
血清 PlGF 与 uPVV 和 uPVS 发育呈正相关(uPVV：β=0.39，95%CI=0.15；0.64；分叉点：β=4.64，95%CI=0.04；9.25；交叉点：β=4.01，95%CI=0.65；7.37；总血管长度：β=13.33，95%CI=3.09；23.58，所有 p 值均<0.05)。sEng/PlGF 比值与 uPVV 和 uPVS 发育呈负相关。我们没有观察到 sFlt-1、sEng 或 sFlt-1/PlGF 比值与 uPVV 和 uPVS 发育之间的关系。
孕早期母体血清 PlGF 浓度较高与 uPVV 和 uPVS 反映的早期子宫胎盘血管发育增加有关。临床试验注册号 Dutch Trial Register NTR6854。
