Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study
Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study
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DOI：
10.1111/1471-0528.12195
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发表时间：
2013-09-01
影响因子：
5.8
通讯作者：
North, R. A.
中科院分区：
文献类型：
--
作者：
Myers, J. E.;Kenny, L. C.;North, R. A.
目的评价临床危险因素、子宫动脉多普勒及血管生成指标对未产妇女早产子痫的预测作用。设计预测测试准确性研究。设定前瞻性多中心队列研究妊娠终点筛查（SCOPE）。方法招募低危未生育的单胎妊娠妇女。获得临床危险因素数据，并于妊娠14-16周测定血浆胎盘生长因子（PlGF）、可溶性内啡肽和可溶性膜样酪氨酸激酶-1 （sFlt-1）。采用多变量逐步逻辑回归建立预测模型。主要观察指标早产先兆子痫（妊娠37 + 0周前分娩）。结果在招募的3529名妇女中，187名（5.3%）发生先兆子痫，其中47名（1.3%）早产。对照组（n = 188）从没有早产先兆子痫的妇女和有其他妊娠并发症的妇女中随机选择。使用先前报道的临床风险变量，观察到受试者工作特征曲线下面积（AUC）为0.76 （95% CI 0.67-0.84）。1416周时添加PlGF后AUC有所改善（0.84;95% CI 0.77-0.91），但添加子宫动脉多普勒或其他血管生成标志物后未见进一步改善。使用临床风险变量和PlGF测量，观察到敏感性为45% (95% CI 0.310.59)（假阳性率5%），检测后概率为11% （95% CI 9-13）。结论：在临床风险评估中加入妊娠14-16周血浆PlGF可提高对未产妇女发生早产子痫前期风险增加的识别，但其性能尚不足以作为临床筛查试验。这些发现依赖于标记，而不是依赖于测定；需要额外的标记物来实现临床应用。
Objectives To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women. Design Predictive test accuracy study. Setting Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE). Methods Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression. Main outcome measure Preterm pre-eclampsia (delivered before 37 + 0 weeks of gestation). Results Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 1416 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.310.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and PlGF measurement. Conclusions Addition of plasma PlGF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm preeclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility.