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Abstract：
Patients with atypical values of HCG and/or PAPP-A are at higher risk of chromosomal abnormality and vascular complications of pregnancy. The performance of cfDNA in this particular population has not yet been evaluated.
The primary objective was to evaluate the usefulness and reliability of cfDNA in screening for trisomy 21, 18 and 13 for patients with HCG < 0.25 multiple of median (MoM), HCG > 5.0 MoM and/or PAPP-A < 0.25 MoM, PAPP-A > 2.5 MoM. The secondary objective was to evaluate the contribution of cfDNA assay for the prediction of pregnancy\'s vascular complications.
Between June 2016 and July 2017, we analysed a women cohort from all over France who had at least one first trimester serum biomarker outside of normal range, in a retrospective, observational and multicentre study. Patients were included if they had a single pregnancy, normal first trimester ultrasound examination, whatever the result of the combined first trimester screening test was. The cfDNA was analysed by massive parallel sequencing technique. The accuracy of cfDNA assay was evaluated by calculation of sensitivity and specificity, and multivariate regression analysis was used to search for predictive factors for pregnancy\'s vascular complications.
Among the 498 patients who underwent a cfDNA assay in this context, twenty-one (4.2%) were excluded because of loss to follow-up. Out of 477, test failure occurred for four patients initially, reduced to two patients (0.4%) after redrawn. CfDNA was positive for Trisomy 21 (n = 19), Trisomy 18 (n = 6) and Trisomy 13 (n = 1) and negative in 449. The sensitivity of cfDNA assay for trisomy 21 screening was 100% (19/19) (IC 95% 82.4-100) and specificity 100% (458/458) (IC 95% 99.2-100). Among the 447 patients included for prediction of vascular complications, there were four cases of pregnancy induced hypertension and 10 cases of preeclampsia, for which no predictive factor was identified. Intra Uterine growth restriction under 5th percentile (n = 44, 9.8%) was significantly associated with a low fetal fraction (OR = 0.87, IC 95% 0.79-0.96, p = 0.006).
cfDNA assay is an effective and reliable tool for women with atypical profile of first trimester serum biomarkers.
The primary objective was to evaluate the usefulness and reliability of cfDNA in screening for trisomy 21, 18 and 13 for patients with HCG < 0.25 multiple of median (MoM), HCG > 5.0 MoM and/or PAPP-A < 0.25 MoM, PAPP-A > 2.5 MoM. The secondary objective was to evaluate the contribution of cfDNA assay for the prediction of pregnancy\'s vascular complications.
Between June 2016 and July 2017, we analysed a women cohort from all over France who had at least one first trimester serum biomarker outside of normal range, in a retrospective, observational and multicentre study. Patients were included if they had a single pregnancy, normal first trimester ultrasound examination, whatever the result of the combined first trimester screening test was. The cfDNA was analysed by massive parallel sequencing technique. The accuracy of cfDNA assay was evaluated by calculation of sensitivity and specificity, and multivariate regression analysis was used to search for predictive factors for pregnancy\'s vascular complications.
Among the 498 patients who underwent a cfDNA assay in this context, twenty-one (4.2%) were excluded because of loss to follow-up. Out of 477, test failure occurred for four patients initially, reduced to two patients (0.4%) after redrawn. CfDNA was positive for Trisomy 21 (n = 19), Trisomy 18 (n = 6) and Trisomy 13 (n = 1) and negative in 449. The sensitivity of cfDNA assay for trisomy 21 screening was 100% (19/19) (IC 95% 82.4-100) and specificity 100% (458/458) (IC 95% 99.2-100). Among the 447 patients included for prediction of vascular complications, there were four cases of pregnancy induced hypertension and 10 cases of preeclampsia, for which no predictive factor was identified. Intra Uterine growth restriction under 5th percentile (n = 44, 9.8%) was significantly associated with a low fetal fraction (OR = 0.87, IC 95% 0.79-0.96, p = 0.006).
cfDNA assay is an effective and reliable tool for women with atypical profile of first trimester serum biomarkers.
摘要：
HCG和/或PAPP-A值不典型的患者染色体异常和妊娠血管并发症的风险较高。尚未评估cfDNA在该特定群体中的性能。
主要目的是评估cfDNA在HCG<0.25中位数倍数（MoM）的21、18和13三体性筛查中的有用性和可靠性。HCG>5.0MoM和/或PAPP-A<0.25MoM，PAPP-A>2.5MoM。次要目的是评估cfDNA测定对预测妊娠血管并发症的贡献。
在2016年6月至2017年7月之间，我们分析了来自法国各地的女性队列，这些女性队列中至少有一个孕早期血清生物标志物超出正常范围。在回顾中，观察性和多中心研究。如果患者有一次怀孕，正常的孕早期超声检查，无论合并的孕早期筛查测试结果如何。通过大规模平行测序技术分析cfDNA。通过计算灵敏度和特异性来评估cfDNA测定的准确性，多因素回归分析用于寻找妊娠血管并发症的预测因素。
在这种情况下接受cfDNA检测的498名患者中，21例(4.2%)因失访而被排除.在477人中，最初有四名患者出现测试失败，重新绘制后减少到两名患者（0.4％）。CfDNA对21三体阳性（n=19），18三体（n=6）和13三体（n=1），阴性449。cfDNA测定对21三体筛查的敏感性为100％（19/19）（IC95％82.4-100），特异性为100％（458/458）（IC95％99.2-100）。在用于预测血管并发症的447例患者中，妊娠高血压4例,子痫前期10例,没有确定预测因素。第5百分位数（n=44，9.8％）下的子宫内生长受限与低胎儿分数显着相关（OR=0.87，IC95％0.79-0.96，p=0.006）。
cfDNA测定是一种有效且可靠的工具，适用于妊娠早期血清生物标志物非典型的女性。
主要目的是评估cfDNA在HCG<0.25中位数倍数（MoM）的21、18和13三体性筛查中的有用性和可靠性。HCG>5.0MoM和/或PAPP-A<0.25MoM，PAPP-A>2.5MoM。次要目的是评估cfDNA测定对预测妊娠血管并发症的贡献。
在2016年6月至2017年7月之间，我们分析了来自法国各地的女性队列，这些女性队列中至少有一个孕早期血清生物标志物超出正常范围。在回顾中，观察性和多中心研究。如果患者有一次怀孕，正常的孕早期超声检查，无论合并的孕早期筛查测试结果如何。通过大规模平行测序技术分析cfDNA。通过计算灵敏度和特异性来评估cfDNA测定的准确性，多因素回归分析用于寻找妊娠血管并发症的预测因素。
在这种情况下接受cfDNA检测的498名患者中，21例(4.2%)因失访而被排除.在477人中，最初有四名患者出现测试失败，重新绘制后减少到两名患者（0.4％）。CfDNA对21三体阳性（n=19），18三体（n=6）和13三体（n=1），阴性449。cfDNA测定对21三体筛查的敏感性为100％（19/19）（IC95％82.4-100），特异性为100％（458/458）（IC95％99.2-100）。在用于预测血管并发症的447例患者中，妊娠高血压4例,子痫前期10例,没有确定预测因素。第5百分位数（n=44，9.8％）下的子宫内生长受限与低胎儿分数显着相关（OR=0.87，IC95％0.79-0.96，p=0.006）。
cfDNA测定是一种有效且可靠的工具，适用于妊娠早期血清生物标志物非典型的女性。
