University Clinic of Obstetrics and Gynecology, Skopje, Republic of Macedonia.
Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland.
Am J Obstet Gynecol. 2018 Dec;219(6):610.e1-610.e9. doi: 10.1016/j.ajog.2018.09.016. Epub 2018 Sep 18.
Placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 have been studied in patients at risk for preterm birth with signs and symptoms of preterm labor. However, a direct comparison between these 2 biomarkers, alone or in combination with cervical length measurement with an adequate sample size, has been lacking to date.
The purpose of this study was to compare the placental alpha microglobulin-1 test and the phosphorylated insulin-like growth factor-binding protein-1 test alone and in combination with cervical length measurement for the prediction of imminent spontaneous preterm birth of testing in pregnant women with symptoms of preterm labor in a tertiary care setting.
Four hundred three patients with intact amniotic membranes and cervical dilation ≤3 cm, without recent intercourse or cerclage, between gestational weeks of 20 and 36 were recruited prospectively from 3 international centers. Placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 tests were conducted before cervical length measurement via transvaginal ultrasound scanning. Caregivers were blinded to the biomarker test results. Medically indicated deliveries within 14 days of testing were excluded. Standard performance statistics with 95% confidence intervals were calculated and compared based on pairwise estimates from a generalized model.
Of 403 subjects who were enrolled in the study cohort, 94% (383/403 women) met the inclusion criteria. Median gestational age and cervical length at presentation were 30 weeks and 27 mm, respectively; 6.8% women (26/383 women) had spontaneous birth ≤7 days from testing. The placental alpha microglobulin-1 test was positive in 7.8% of the women (30/383 women); the phosphorylated insulin-like growth factor-binding protein-1 test was positive in 29.5% women (113/383 women). Positive predictive value for placental alpha microglobulin-1, phosphorylated insulin-like growth factor-binding protein-1, and cervical length <25 mm for the prediction of spontaneous preterm birth in the overall cohort was 60.0% (18/30 women), 18.6% (21/113 women), 11.8% (18/152 women), respectively. The negative predictive value was 97.7% (345/353 women), 98.2% (265/270 women), 96.5% (223/231 women), respectively. The prevalence of spontaneous preterm birth in this group was 6.8% (26/383 women). The positive likelihood ratios were 20.6, 3.1, and 1.8, respectively. The negative likelihood ratio were 0.3, 0.3, and 0.5, respectively. Positive predictive values for placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 tests in patients with cervical length shortening of 15-30 mm for the prediction of spontaneous preterm birth were 60.9% (14/23 women) and 28.1% (16/57 women), respectively. The negative predictive values were 97.1% (168/173 women) and 97.8% (136/139 women), respectively. The prevalence of spontaneous preterm birth in the 15-30 mm cohort was 9.7% (19/196 women). The positive likelihood ratios were 14.5 and 3.6, respectively. The negative likelihood ratios were 0.3 and 0.2, respectively.
Placental alpha microglobulin-1 is significantly more specific than phosphorylated insulin-like growth factor-binding protein-1 for the prediction of spontaneous preterm birth ≤7 days (P<.0001), whereas both tests have comparable sensitivity. In patients with cervical length 15-30 mm, although placental alpha microglobulin-1 has a significantly higher positive predictive value and specificity compared with phosphorylated insulin-like growth factor-binding protein-1 for the prediction of spontaneous preterm birth at ≤7 days (P<.01), both tests have a comparable sensitivity and negative predictive value. In conclusion, placental alpha microglobulin-1 is a better predictor of imminent spontaneous preterm birth when compared with phosphorylated insulin-like growth factor-binding protein-1 alone or in combination with cervical length measurement. In patients with shortening of cervical length of 15-30 mm, the placental alpha microglobulin-1 test is a significantly better predictor of imminent spontaneous preterm birth within 7 days of testing than is phosphorylated insulin-like growth factor-binding protein-1.
胎盘α微球蛋白-1 和磷酸化胰岛素样生长因子结合蛋白-1 已在有早产迹象和症状的早产风险患者中进行了研究。然而，目前还缺乏单独或联合宫颈长度测量对这 2 种生物标志物进行直接比较的研究，样本量也不足。
本研究的目的是比较胎盘α微球蛋白-1 检测和磷酸化胰岛素样生长因子结合蛋白-1 检测单独和联合宫颈长度测量在预测有早产迹象和症状的孕妇中即将发生自发性早产的价值，这些孕妇在 3 家国际中心就诊时胎膜完整，宫颈扩张≤3cm，最近无性生活或宫颈环扎术。通过经阴道超声扫描在进行宫颈长度测量之前进行胎盘α微球蛋白-1 和磷酸化胰岛素样生长因子结合蛋白-1 检测。医护人员对生物标志物检测结果不知情。排除了在检测后 14 天内有医学指征的分娩。根据广义模型的成对估计值计算并比较了标准性能统计数据和 95%置信区间。
在纳入的研究队列中，403 名患者的胎膜完整，宫颈扩张≤3cm，最近无性生活或宫颈环扎术，孕龄在 20-36 周之间。中位数孕龄和就诊时的宫颈长度分别为 30 周和 27mm；6.8%（26/383 名女性）的女性在检测后 7 天内自然分娩。胎盘α微球蛋白-1 检测阳性率为 7.8%（30/383 名女性）；磷酸化胰岛素样生长因子结合蛋白-1 检测阳性率为 29.5%（113/383 名女性）。在整个队列中，胎盘α微球蛋白-1、磷酸化胰岛素样生长因子结合蛋白-1 和宫颈长度<25mm 对自发性早产的阳性预测值分别为 60.0%（30/30 名女性）、18.6%（21/113 名女性）和 11.8%（18/152 名女性）。阴性预测值分别为 97.7%（345/353 名女性）、98.2%（265/270 名女性）和 96.5%（223/231 名女性）。该组自发性早产的发生率为 6.8%（26/383 名女性）。阳性似然比分别为 20.6、3.1 和 1.8。阴性似然比分别为 0.3、0.3 和 0.5。宫颈长度缩短 15-30mm 的患者中，胎盘α微球蛋白-1 和磷酸化胰岛素样生长因子结合蛋白-1 检测对自发性早产的阳性预测值分别为 60.9%（14/23 名女性）和 28.1%（16/57 名女性）。阴性预测值分别为 97.1%（168/173 名女性）和 97.8%（136/139 名女性）。15-30mm 组的自发性早产发生率为 9.7%（19/196 名女性）。阳性似然比分别为 14.5 和 3.6。阴性似然比分别为 0.3 和 0.2。
胎盘α微球蛋白-1 预测≤7 天的自发性早产的特异性明显优于磷酸化胰岛素样生长因子结合蛋白-1（P<.0001），而这两种检测方法的敏感性相当。在宫颈长度为 15-30mm 的患者中，虽然胎盘α微球蛋白-1在预测≤7 天的自发性早产方面的阳性预测值和特异性均明显高于磷酸化胰岛素样生长因子结合蛋白-1（P<.01），但两种检测方法的敏感性和阴性预测值相当。总之，与单独使用磷酸化胰岛素样生长因子结合蛋白-1 或联合宫颈长度测量相比，胎盘α微球蛋白-1 是更能预测即将发生的自发性早产的指标。在宫颈长度缩短为 15-30mm 的患者中，胎盘α微球蛋白-1 检测在检测后 7 天内预测即将发生自发性早产的能力明显优于磷酸化胰岛素样生长因子结合蛋白-1。
