Abstract：
To determine whether maternal serum glycosylated fibronectin (GlyFn) level in the first trimester increases the sensitivity of the Fetal Medicine Foundation (FMF) triple test, which incorporates mean arterial pressure, uterine artery pulsatility index and placental growth factor, when screening for pre-eclampsia (PE) in an Asian population.
This was a nested case-control study of Chinese women with a singleton pregnancy who were screened for PE at 11-13 weeks\' gestation as part of a non-intervention study between December 2016 and June 2018. GlyFn levels were measured retrospectively in archived serum from 1685 pregnancies, including 101 with PE, using an enzyme-linked immunosorbent assay (ELISA), and from 448 pregnancies, including 101 with PE, using a point-of-care (POC) device. Concordance between ELISA and POC tests was assessed using Lin\'s correlation coefficient and Passing-Bablok and Bland-Altman analyses. GlyFn was transformed into multiples of the median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM was compared between PE and non-PE pregnancies, and the association between GlyFn MoM and gestational age at delivery with PE was assessed. Risk for developing PE was estimated using the FMF competing-risks model. Screening performance for preterm and any-onset PE using different biomarker combinations was quantified by area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed false-positive rate (FPR). Differences in AUC between biomarker combinations were compared using the DeLong test.
The concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was independent of gestational age at screening (P = 0.11), but significantly dependent on maternal age (P < 0.003), weight (P < 0.0002), height (P = 0.001), parity (P < 0.02) and smoking status (P = 0.002). Compared with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was elevated significantly in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery with PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE increased significantly the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively.
Adding GlyFn to the FMF triple test increased the screening sensitivity for both preterm and any-onset PE in an Asian population. Prospective non-intervention studies are needed to confirm these initial findings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
This was a nested case-control study of Chinese women with a singleton pregnancy who were screened for PE at 11-13 weeks\' gestation as part of a non-intervention study between December 2016 and June 2018. GlyFn levels were measured retrospectively in archived serum from 1685 pregnancies, including 101 with PE, using an enzyme-linked immunosorbent assay (ELISA), and from 448 pregnancies, including 101 with PE, using a point-of-care (POC) device. Concordance between ELISA and POC tests was assessed using Lin\'s correlation coefficient and Passing-Bablok and Bland-Altman analyses. GlyFn was transformed into multiples of the median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM was compared between PE and non-PE pregnancies, and the association between GlyFn MoM and gestational age at delivery with PE was assessed. Risk for developing PE was estimated using the FMF competing-risks model. Screening performance for preterm and any-onset PE using different biomarker combinations was quantified by area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed false-positive rate (FPR). Differences in AUC between biomarker combinations were compared using the DeLong test.
The concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was independent of gestational age at screening (P = 0.11), but significantly dependent on maternal age (P < 0.003), weight (P < 0.0002), height (P = 0.001), parity (P < 0.02) and smoking status (P = 0.002). Compared with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was elevated significantly in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery with PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE increased significantly the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively.
Adding GlyFn to the FMF triple test increased the screening sensitivity for both preterm and any-onset PE in an Asian population. Prospective non-intervention studies are needed to confirm these initial findings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
摘要：
目的：确定母体的糖基化纤连蛋白（GlyFn）水平是否会增加胎儿医学基金会（FMF）三重测试对平均动脉压的敏感性，子宫动脉搏动指数和胎盘生长因子对亚洲人群子痫前期（PE）的影响。
方法：这是一项巢式病例对照研究，在2016年12月至2018年6月进行的一项非干预性研究中，使用中国单胎妊娠女性的血清，最初在11-13周时筛查PE。在1792例妊娠中对血清GlyFn水平进行了回顾性测量，包括112与PE，使用LumellaTM酶联免疫测定法（ELISA），在448例妊娠中，包括112与PE，使用LumellaTM定点护理(POC)装置。使用Lins相关性和Passing-Bablok（PB）分析评估ELISA和POC测量水平之间的一致性。将GlyFn转化为预期中位数(MoM)的倍数以调整母体和妊娠特征。评估了PE和非PE妊娠中的GlyFnMoM以及GlyFnMoM与PE分娩时的胎龄之间的关联。使用FMF竞争风险模型估计PE的风险。筛选性能，根据受试者工作特征曲线下面积(AUC)和检出率(DR)以10%的固定假阳性率(FPR)测定早产PE和任何发作PE.使用Delong检验比较不同生物标志物组合之间的AUC差异(AAUC)。
结果：ELSIA和POC测量之间的一致性相关性为0.86（95％置信区间[CI]：0.83-0.88）。PB分析显示比例偏差(斜率=1.08;95CI:1.04-1.14),POCGlyFn显著高于ELISA。非PE妊娠中的GlyFn水平与筛查时的孕龄无关（p>0.11），但与母亲年龄（p<0.003）显着相关。体重（p<0.0002），身高（p=0.001），奇偶校验（p<0.02），吸烟状况（p=0.002）。与非PE妊娠相比，平均ELISA和POCGlyFnMoM水平在早产PE（分别为1.23vs1.00;p<0.0001和1.18vs1.00;p<0.0001）和足月PE（分别为1.26vs1.00;p<0.0001和1.221.00;p<0.0001）妊娠中显著增加。GlyFnMoM与分娩时的胎龄没有显着相关（p=0.989）。在FMF三联试验中添加GlyFn进行早产PE筛查，可将AUC从0.859显着增加到0.896（ΔAUC=0.037；p=0.012），并将DR从64.86％（95CI：48.65％-81.08％）增加到82.86％（95CI：66.35％-93.44％）对于10％的FPR。在同一个FPR，当通过添加GlyFn筛查任何起病PE时，DR从52.48％（95CI：42.30％-62.51％）增加到65.35％（95CI：55.23％-74.54％）。
结论：在亚洲人群中，添加GlyFn可以提高FMF三联试验对早产和任何发作性PE的筛查敏感性。需要前瞻性的非干预性研究来证实我们的初步发现。本文受版权保护。保留所有权利。
方法：这是一项巢式病例对照研究，在2016年12月至2018年6月进行的一项非干预性研究中，使用中国单胎妊娠女性的血清，最初在11-13周时筛查PE。在1792例妊娠中对血清GlyFn水平进行了回顾性测量，包括112与PE，使用LumellaTM酶联免疫测定法（ELISA），在448例妊娠中，包括112与PE，使用LumellaTM定点护理(POC)装置。使用Lins相关性和Passing-Bablok（PB）分析评估ELISA和POC测量水平之间的一致性。将GlyFn转化为预期中位数(MoM)的倍数以调整母体和妊娠特征。评估了PE和非PE妊娠中的GlyFnMoM以及GlyFnMoM与PE分娩时的胎龄之间的关联。使用FMF竞争风险模型估计PE的风险。筛选性能，根据受试者工作特征曲线下面积(AUC)和检出率(DR)以10%的固定假阳性率(FPR)测定早产PE和任何发作PE.使用Delong检验比较不同生物标志物组合之间的AUC差异(AAUC)。
结果：ELSIA和POC测量之间的一致性相关性为0.86（95％置信区间[CI]：0.83-0.88）。PB分析显示比例偏差(斜率=1.08;95CI:1.04-1.14),POCGlyFn显著高于ELISA。非PE妊娠中的GlyFn水平与筛查时的孕龄无关（p>0.11），但与母亲年龄（p<0.003）显着相关。体重（p<0.0002），身高（p=0.001），奇偶校验（p<0.02），吸烟状况（p=0.002）。与非PE妊娠相比，平均ELISA和POCGlyFnMoM水平在早产PE（分别为1.23vs1.00;p<0.0001和1.18vs1.00;p<0.0001）和足月PE（分别为1.26vs1.00;p<0.0001和1.221.00;p<0.0001）妊娠中显著增加。GlyFnMoM与分娩时的胎龄没有显着相关（p=0.989）。在FMF三联试验中添加GlyFn进行早产PE筛查，可将AUC从0.859显着增加到0.896（ΔAUC=0.037；p=0.012），并将DR从64.86％（95CI：48.65％-81.08％）增加到82.86％（95CI：66.35％-93.44％）对于10％的FPR。在同一个FPR，当通过添加GlyFn筛查任何起病PE时，DR从52.48％（95CI：42.30％-62.51％）增加到65.35％（95CI：55.23％-74.54％）。
结论：在亚洲人群中，添加GlyFn可以提高FMF三联试验对早产和任何发作性PE的筛查敏感性。需要前瞻性的非干预性研究来证实我们的初步发现。本文受版权保护。保留所有权利。
