Maternidade Dr. Alfredo da Costa, Lisbon, Portugal.
Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK.
Acta Obstet Gynecol Scand. 2023 May;102(5):635-643. doi: 10.1111/aogs.14546. Epub 2023 Mar 18.
The velocity of fetal deterioration in fetal growth restriction is extremely variable, which makes monitoring and counseling very challenging. The soluble fms-like tyrosine kinase to placental growth factor (sFlt1/PlGF) ratio provides a readout of the vasoactive environment that correlates with preeclampsia and fetal growth restriction and that could be useful to predict fetal deterioration. Previous studies showed a correlation between higher sFlt1/PlGF ratios and lower gestational ages at birth, although it is unclear whether this is due to the increased incidence of preeclampsia. Our goal was to evaluate whether the sFlt1/PlGF ratio predicts faster fetal deterioration in early fetal growth restriction.
This was a historical cohort study in a tertiary maternity hospital. Data from singleton pregnancies with early fetal growth restriction (diagnosed before 32 gestational weeks) confirmed after birth monitored between January 2016 and December 2020 were retrieved from clinical files. Cases of chromosomal/fetal abnormalities, infection and medical terminations of pregnancy were excluded. The sFlt1/PlGF ratio was acquired at diagnosis of early fetal growth restriction in our unit. The correlation of log10 sFlt1/PlGF with latency to delivery/fetal demise was assessed with linear, logistic (positive sFlt1/PlGF if >85) and Cox regression excluding deliveries for maternal conditions and controlling for preeclampsia, gestational age at time of ratio test, maternal age and smoking during pregnancy. Receiver-operating characteristic (ROC) analysis tested the performance of sFlt1/PlGF ratio in predicting delivery for fetal reasons in the following week.
125 patients were included. Mean sFlt1/PlGF ratio was 91.2 (SD 148.7) and 28% of patients had a positive ratio. A higher log10 sFlt1/PlGF ratio predicted shorter latency for delivery/fetal demise in linear regression after controlling for confounders, β = -3.001, (-3.713 to -2.288). Logistic regression with ratio positivity confirmed these findings (latency for delivery 5.7 ± 3.32 weeks for ratios ≤85 vs 1.9 ± 1.52 weeks for ratios >85); β = -0.698 (-1.064 to -0.332). Adjusted Cox regression showed that a positive ratio confers a significantly positive hazard ratio (HR) for earlier delivery/fetal demise, HR 9.869 (5.061-19.243). ROC analysis showed an area under the curve of 0.847 (SE ± 0.06).
sFlt1/PlGF ratio is correlated with faster fetal deterioration in early fetal growth restriction, independently of preeclampsia.
胎儿生长受限（FGR）中胎儿恶化的速度变化非常大，这使得监测和咨询极具挑战性。可溶性 fms 样酪氨酸激酶与胎盘生长因子（sFlt1/PlGF）比值可反映与子痫前期和胎儿生长受限相关的血管活性环境，这可能有助于预测胎儿恶化。先前的研究表明，较高的 sFlt1/PlGF 比值与较低的出生胎龄之间存在相关性，尽管尚不清楚这是否是由于子痫前期发病率增加所致。我们的目标是评估 sFlt1/PlGF 比值是否可以预测早期胎儿生长受限中胎儿恶化的速度更快。
这是在一家三级妇产医院进行的历史队列研究。从 2016 年 1 月至 2020 年 12 月出生后确诊的胎龄小于 32 周的单胎胎儿生长受限患者的临床档案中检索数据。排除了染色体/胎儿异常、感染和终止妊娠的病例。sFlt1/PlGF 比值在我们单位确诊为早期胎儿生长受限时获得。使用线性、逻辑（阳性 sFlt1/PlGF 比值>85）和 Cox 回归评估 log10 sFlt1/PlGF 与分娩/胎儿死亡的潜伏期之间的相关性，排除了因母亲疾病和控制子痫前期、比值检测时的胎龄、母亲年龄和妊娠期间吸烟而导致的分娩，并进行了调整。受试者工作特征（ROC）分析测试了 sFlt1/PlGF 比值在预测下周因胎儿原因分娩的性能。
共纳入 125 例患者。sFlt1/PlGF 比值的平均值为 91.2（标准差 148.7），28%的患者比值阳性。在控制混杂因素后，线性回归显示较高的 log10 sFlt1/PlGF 比值预测分娩/胎儿死亡的潜伏期更短，β=-3.001（-3.713 至-2.288）。阳性比值的逻辑回归证实了这些发现（比值≤85 的分娩潜伏期为 5.7±3.32 周，比值>85 的分娩潜伏期为 1.9±1.52 周）；β=-0.698（-1.064 至-0.332）。调整后的 Cox 回归显示，阳性比值对更早的分娩/胎儿死亡具有显著的正风险比（HR），HR 9.869（5.061-19.243）。ROC 分析显示曲线下面积为 0.847（SE±0.06）。
sFlt1/PlGF 比值与早期胎儿生长受限中胎儿恶化速度相关，独立于子痫前期。
