Eline S. de Vos, A. H. Jan Danser, Anton H. J. Koning, Sten P. Willemsen, Lotte E. van der Meeren, Eric. A. P. Steegers, Régine P. M. Steegers-Theunissen, Annemarie G. M. G. J. Mulders
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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.</p><h3>Methods</h3><p>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<sup>3</sup>. 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.</p><h3>Results</h3><p>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. 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引用次数: 0
摘要
目的：循环血管生成因子可用于预测胎盘相关并发症，但它们与第一胎胎盘发育的关系尚不清楚。本研究探讨了母体血管生成因子与子宫胎盘血管体积（uPVV）和子宫胎盘血管骨架（uPVS）之间的关系，它们是第一孕期子宫胎盘血管体积和形态（分支）发育的新型成像标记：VIRTUAL胎盘研究是鹿特丹前瞻性围孕期队列的一个子队列，在该研究的185名孕妇中，于胎龄7-9-11周时进行了胎盘三维动力多普勒超声检查。uPVV作为体积发育参数进行测量，并报告以立方厘米为单位的血管数量。uPVS是作为形态（分支）发育参数生成的，报告了血管末端、分叉交叉点或血管点的数量以及血管总长度。怀孕 11 周时，评估了反映胎盘（血管）发育的母体血清生物标志物：胎盘生长因子（PlGF）、可溶性酪氨酸激酶-1（sFlt-1）和可溶性内胚叶素（sEng）。使用调整后的多变量线性回归估计血清生物标志物与uPVV和uPVS轨迹之间的关系：结果：血清 PlGF 与 uPVV 和 uPVS 的发展呈正相关（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；血管总长度：β = 13.33，95% CI = 3.09;23.58，所有 p 值 结论：血清 PlGF 与 uPVV 和 uPVS 的发展呈正相关：母体血清中 PlGF 浓度越高，胎儿第一妊娠期子宫胎盘血管发育就越快，uPVV 和 uPVS 反映了这一点。临床试验注册号：荷兰试验注册 NTR6854。
Maternal serum PlGF associates with 3D power doppler ultrasound markers of utero-placental vascular development in the first trimester: the rotterdam periconception cohort
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.
Methods
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 cm3. 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.
Results
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.
期刊介绍：
Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.
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