Giorgione Veronica, Ramnarine Stephan, Malik Amna, Bhide Amarnath
Maternity Department, St George's University Hospitals NHS Foundation Trust, London, UK.
Maternity Department, St George's University Hospitals NHS Foundation Trust, London, UK; Vascular Biology Research Center, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
Eur J Obstet Gynecol Reprod Biol. 2024 Aug;299:91-95. doi: 10.1016/j.ejogrb.2024.05.036. Epub 2024 May 29.
The identification of fetal growth restriction (FGR) due to uteroplacental insufficiency is important to improve perinatal outcomes. To distinguish FGR from small for gestational age (SGA), FGR consensus definition is currently based on biometry and/or additional biophysical parameters. This study aims to verify if this definition might be modified by including circulating angiogenic factors.
This historical cohort study included singleton pregnancies with SGA fetuses after 20 weeks. All patients underwent detailed ultrasound and measurements of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) at first assessment. ISUOG criteria for FGR were applied. Total PlGF was calculated using free PlGF, sFlt-1 and a receptor pharmacology model, and multiple of the median (MoM) values for sFlt-1, free PlGF, total PlGF and sFlt-1/PlGF ratio were calculated to adjust for gestational age.
72 pregnancies with SGA were first evaluated at median (IQR) of 28 (26 -31) weeks' gestation, and 51 fetuses (70.8 %) satisfied the FGR consensus definition. Pregnancies with FGR showed significantly lower levels of free and total PlGF MoM (0.12, 95 % IQR: 0.07-0.36 vs 0.32, 95 % IQR: 0.20-0.53, p = 0.008) and 0.26, 95 % CI: 0.16-0.55 vs 0.43, 95 % IQR: 0.23-0.53, p = 0.028) respectively; and higher sFlt-1 MoM (4.62, 95 % IQR: 1.80-7.30 vs 1.74, 95 % IQR:1.11-3.61, p = 0.014) than pregnancies not classified as FGR. Free and total PlGF MoM correlated significantly with gestational age at delivery (r = 0.776, p < 0.001 and r = 0.707, p < 0.001, respectively). sFlt-1 MoM and sFlt-1/PlGF ratio MoM also correlated with gestational age at delivery (r = -0.681, p < 0.001 and r = -0.823, p < 0.001). Six cases identified as FGR at first ultrasound were not confirmed at birth showing significantly higher levels of free PlGF MoM (0.77, 95 % IQR: 0.27-3.07 vs 0.17, 95 % IQR: 0.08-0.43, p = 0.022).
These findings show that total as well as free PlGF levels are lower in pregnancies affected with placental growth restriction. Angiogenic biomarkers might improve the differentiation between placental growth restriction and constitutional smallness. Further studies are needed to determine how to integrate them into the current definitions of FGR.
识别因子宫胎盘功能不全导致的胎儿生长受限（FGR）对于改善围产期结局很重要。为了将FGR与小于胎龄儿（SGA）区分开来，目前FGR的共识定义基于生物测量和/或其他生物物理参数。本研究旨在验证是否可以通过纳入循环血管生成因子来修改该定义。
这项历史性队列研究纳入了孕20周后单胎SGA胎儿的妊娠。所有患者在首次评估时均接受了详细的超声检查，并测量了可溶性fms样酪氨酸激酶1（sFlt-1）和胎盘生长因子（PlGF）。应用FGR的国际妇产科超声学会（ISUOG）标准。使用游离PlGF、sFlt-1和受体药理学模型计算总PlGF，并计算sFlt-1、游离PlGF、总PlGF和sFlt-1/PlGF比值的中位数倍数（MoM）值，以校正孕周。
72例SGA妊娠在妊娠中位数（四分位间距）为28（26 - 31）周时首次评估，51例胎儿（70.8%）符合FGR共识定义。FGR妊娠的游离和总PlGF MoM水平显著较低（分别为0.12，95%四分位间距：0.07 - 0.36 vs 0.32，95%四分位间距：0.20 - 0.53，p = 0.008）和0.26，95%置信区间：0.16 - 0.55 vs 0.43，95%四分位间距：0.23 - 0.53，p = 0.028）；sFlt-1 MoM高于未分类为FGR的妊娠（4.62，95%四分位间距：1.80 - 7.30 vs 1.74，95%四分位间距：1.11 - 3.61，p = 0.014）。游离和总PlGF MoM与分娩时的孕周显著相关（分别为r = 0.776，p < 0.001和r = 0.707，p < 0.001）。sFlt-1 MoM和sFlt-1/PlGF比值MoM也与分娩时的孕周相关（r = -0.681，p < 0.001和r = -0.823，p < 0.001）。6例在首次超声检查时被诊断为FGR的病例在出生时未得到证实，其游离PlGF MoM水平显著较高（0.77，95%四分位间距：0.27 - 3.07 vs 0.17，95%四分位间距：0.08 - 0.43，p = 0.022）。
这些发现表明，胎盘生长受限的妊娠中总PlGF和游离PlGF水平均较低。血管生成生物标志物可能会改善胎盘生长受限与体质性小体型之间的区分。需要进一步研究以确定如何将它们纳入FGR的当前定义中。
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