Department of Women's and Children's Health, University of Liverpool and The Liverpool Women's Hospital, Members of Liverpool Health Partners, United Kingdom.
Liverpool Clinical Trials Unit, University of Liverpool, United Kingdom.
Eur J Obstet Gynecol Reprod Biol. 2019 Oct;241:109-118. doi: 10.1016/j.ejogrb.2019.08.007. Epub 2019 Aug 16.
Severe early-onset fetal growth restriction (FGR) predisposes to fetal death, neonatal death, neonatal morbidity and neurodisability. The use of placental biomarkers has been proposed for risk stratification in pre-eclampsia, but they could be equally useful in fetal growth restriction in aiding management.
To determine the efficacy of angiogenic biomarkers at predicting adverse pregnancy outcome in severe early-onset fetal growth restriction.
This is a secondary analysis of the multicentre, placebo-controlled STRIDER UK randomised controlled trial of singleton pregnancies with severe early-onset fetal growth restriction. Women with FGR pregnancies between 22 and 29 weeks of gestation were randomly assigned to receive either sildenafil 25 mg three times daily or placebo until 32 weeks' gestation or delivery. We developed prediction models based upon maternal demographics (age, parity, blood pressure, preeclampsia, gestational hypertension), fetal biometric (estimated fetal weight) and Doppler measurements (Middle Cerebral Artery (MCA), Umbilical Artery (UA)) and maternal angiogenic biomarkers [placental growth factor (PlGF), soluble endoglin (sEng), soluble fms-like tyrosine kinase 1 (sFlt-1) and sFlt-1:PlGF ratio) using both univariate and multivariate analysis.
A complete data set was available for 105 of 135 randomised women. Multivariate regression analysis identified estimated fetal weight (EFW) and sFlt-1:PlGF as independent predictors of livebirth (EFW OR: 1.01 (1.008, 1.021); p < 0.001 and lower sFlt-1:PlGF ratio OR: 0.53 (0.284, 0.994); p = 0.048) and overall survival (EFW OR: 1.01 (1.006, 1.015); p < 0.001 and lower sFlt-1/PlGF ratio OR: 0.51 (0.286, 0.904); p = 0.021). EFW was a consistent predictor for all outcomes other than gestation at delivery. sFlt-1:PlGF ratio was a consistent predictor for all outcomes other than neonatal morbidity.
In severe early-onset FGR pregnancies livebirth and overall survival can be predicted using a model involving EFW and sFlt-1:PlGF ratio. This model require validation in a larger cohort but may allow informed decision making about pregnancy management, especially in previable cases.
严重的早发性胎儿生长受限（FGR）易导致胎儿死亡、新生儿死亡、新生儿发病率和神经发育障碍。胎盘生物标志物的应用已被提出用于子痫前期的风险分层，但它们在胎儿生长受限的辅助管理中同样有用。
确定血管生成生物标志物在预测严重早发性胎儿生长受限不良妊娠结局中的功效。
这是一项多中心、安慰剂对照的 STRIDER UK 随机对照试验的二次分析，该试验纳入了严重早发性胎儿生长受限的单胎妊娠。22 至 29 孕周的 FGR 妊娠孕妇被随机分配接受西地那非 25mg，每日 3 次或安慰剂，直至 32 孕周或分娩。我们基于母体人口统计学（年龄、产次、血压、子痫前期、妊娠期高血压）、胎儿生物测量（估计胎儿体重）和多普勒测量（大脑中动脉（MCA）、脐动脉（UA））以及母体血管生成生物标志物[胎盘生长因子（PlGF）、可溶性内皮素（sEng）、可溶性 fms 样酪氨酸激酶 1（sFlt-1）和 sFlt-1：PlGF 比值]，使用单变量和多变量分析建立预测模型。
135 名随机分配的孕妇中，有 105 名孕妇的完整数据集可用。多变量回归分析确定估计胎儿体重（EFW）和 sFlt-1：PlGF 是活产（EFW OR：1.01（1.008，1.021）；p<0.001）和总体生存（EFW OR：1.01（1.006，1.015）；p<0.001）的独立预测因素，以及较低的 sFlt-1：PlGF 比值（OR：0.53（0.284，0.994）；p=0.048）。EFW 是除分娩时孕周外所有结局的一致预测因素，而 sFlt-1：PlGF 比值是除新生儿发病率外所有结局的一致预测因素。
在严重的早发性 FGR 妊娠中，可以使用涉及 EFW 和 sFlt-1：PlGF 比值的模型来预测活产和总体生存。该模型需要在更大的队列中进行验证，但可能允许对妊娠管理做出知情决策，特别是在可行的情况下。
