Placental growth factor predicts time to delivery in women with signs or symptoms of early preterm preeclampsia: a prospective multicenter study.
Placental growth factor predicts time to delivery in women with signs or symptoms of early preterm preeclampsia: a prospective multicenter study.
复制标题
胎盘生长因子可预测有早期早产先兆子痫体征或症状的女性的分娩时间：一项前瞻性多中心研究。
DOI：
10.1097/01.ogx.0000695060.26788.2f
复制
发表时间：
2020
影响因子：
6.2
通讯作者：
Petra Trial
中科院分区：
文献类型：
--
作者：
J. Barton;D. Woelkers;R. Newman;C. Combs;H. How;K. Boggess;J. Martin;K. Kupfer;B. Sibai;Petra Trial
背景
血管生成因子浓度改变（包括胎盘生长因子）与临床公认的先兆子痫之间存在强相关性。血管生成因子浓度的改变先于先兆子痫临床发作数周。然而，在妊娠35周以下的疑似先兆子痫妇女中，测量的血管生成因子与分娩时间之间的时间关系仍有待澄清。
目标
研究胎盘生长因子（PlGF）与妊娠<35周、有先兆子痫体征或症状的妇女分娩时间之间的关系，并比较PlGF与其他临床标志物预测先兆子痫分娩时间的性能。
研究设计
在24个中心进行的一项前瞻性观察性研究中，纳入了20.0至35.0周之间有先兆子痫体征或症状的妇女。在出现PlGF时采集血液，并根据当地方案对受试者进行评价和管理。获得临床结局，所有最终诊断均由独立专家小组根据2013年ACOG妊娠高血压标准进行裁定。在Alere，Inc.上回顾性测量PlGF。分诊平台。正常PlGF定义为>100 pg/ml，测定的检测限为12 pg/ml。构建2x2表格，用于比较包括阴性预测值（NPV）在内的试验结果;通过生存曲线和考克斯回归分析分娩时间。
结果
753例受试者入组; 538例（71%）最终诊断为先兆子痫。542例（72%）分娩<37周，358例（47%）<34周。在279名（37%）PlGF正常的妇女中，先兆子痫在14天内或7天内分娩的NPV分别为90%和93%。与PlGF正常的妇女相比，在校正入组时的胎龄和先兆子痫的最终诊断后，PlGF < 100 pg/mL的妇女在分娩时间的考克斯回归中的风险比为7.17（5.08，10.13）。正常（>100 pg/mL）、低（12至100 pg/mL）和非常低（<12 pg/mL）的PlGF水平具有良好分离的递送时间分布，中值分别为45、10和2天。PlGF < 100 pg/mL的受试者具有5.7%的围产期死亡率和51.7%的SGA率，而PlGF > 100 pg/mL的受试者具有0%的围产期死亡率（在该群组中没有观察结果）和16.8%的SGA率。
结论
在< 35.0周时疑似先兆子痫的妇女中，低PlGF与早产密切相关，与先兆子痫的诊断或就诊时的胎龄无关，而正常PlGF与妊娠延长相关，即使在最终诊断为先兆子痫的患者中也是如此。这表明PlGF水平在预测患有疑似先兆子痫的妇女的不良妊娠方面优于临床标志物上级。
BACKGROUND
There is a robust association between altered angiogenic factor concentrations, including placental growth factor and clinically recognized preeclampsia. Alterations in concentrations of angiogenic factors precede the clinical onset of preeclampsia by several weeks. The temporal relationship between the measured angiogenic factors and the time to delivery in women presenting with suspected preeclampsia at <35weeks gestation, however remains to be clarified.
OBJECTIVES
To examine the relationship between placental growth factor (PlGF) and time-to-delivery in women <35 weeks' gestation presenting with signs or symptoms of preeclampsia, and to compare the performance of PlGF to other clinical markers for prediction of time-to-delivery in preeclampsia.
STUDY DESIGN
Women with signs or symptoms of preeclampsia between 20.0 and 35.0 weeks were enrolled in a prospective, observational study at 24 centers. Blood was collected at presentation for PlGF, and subjects were evaluated and managed according to local protocols. Clinical outcomes were obtained and all final diagnoses were adjudicated by an independent expert panel according to 2013 ACOG Hypertension in Pregnancy criteria. PlGF was measured retrospectively on the Alere, Inc. Triage platform. A normal PlGF was defined as >100 pg/ml and the assay's limit of detection is 12 pg/ml. 2x2 tables were constructed for comparison of test outcomes including negative predictive value (NPV); time-to-delivery was analyzed by survival curves and Cox regression.
RESULTS
753 subjects were enrolled; 538 (71%) had a final diagnosis of preeclampsia. 542 (72%) delivered <37 weeks and 358 (47%) <34 weeks. Among the 279 (37%) women with a normal PlGF at presentation, the NPV for preeclampsia delivered within 14 days, or within 7 days was 90% and 93%, respectively. As compared to women with normal PlGF, women with PlGF < 100 pg/mL have a hazard ratio of 7.17 (5.08, 10.13) in Cox regression for time-to-delivery after adjusting for both gestational age at enrollment and the final diagnosis of preeclampsia. The PlGF levels of normal (>100 pg/mL), low (12 to 100 pg/mL), and very low (<12 pg/mL), have well separated distributions of time-to-delivery with median values of 45, 10, and 2 days, respectively. Subjects with PlGF < 100 pg/mL have a perinatal death rate of 5.7% and an SGA rate of 51.7%, while subjects with PlGF > 100 pg/mL have a perinatal death rate of 0% (no observations in this cohort) and an SGA rate of 16.8%.
CONCLUSIONS
In women with suspected preeclampsia at < 35.0 weeks, a low PlGF was strongly correlated with preterm delivery independent of a diagnosis of preeclampsia or gestational age at presentation, whereas a normal PlGF was associated with pregnancy prolongation, even in patients who ultimately had a final diagnosis of preeclampsia. This suggests that PlGF levels are superior to clinical markers in predicting adverse pregnancy in women presenting with suspected preeclampsia.