Table1_Maternal, neonatal, pregnancy outcome characteristics of pregnant women with high plasma cell-free DNA concentration in non-invasive prenatal screening: a retrospective analysis.xls

ObjectiveCell-free DNA (cfDNA) is a useful biomarker in various clinical contexts. Herein, we aimed to identify maternal characteristics and pregnancy outcomes associated with a failed NIPS test due to high cfDNA concentrations.
MethodsA retrospective study of cases with high plasma cfDNA concentration in pregnant women in which NIPS test was performed (from 174,318 cases). We reported the detection of 126 cases (118 with complete clinical information) in which the high amount of cfDNA did not allow the performance of NIPS and study the possible causes of this result.
Results622 (0.35%) of 174,318 pregnant women had failed the NIPS test, including 126 (20.3%) cases with high plasma cfDNA concentrations. The failed NIPS due to high plasma cfDNA concentrations was associated with maternal diseases and treatment with low-molecular-weight heparin (LMWH). Further follow-up of the 118 pregnant women in the case group revealed that the pregnancy outcomes included 31 premature deliveries, 21 abortions. The cfDNA concentrations of pregnant women with preterm deliveries were 1.15 (0.89, 1.84), which differed significantly from those who had full-term deliveries.
ConclusionsAmong pregnant women with high cfDNA concentrations, systemic autoimmune diseases, pregnancy complications and LMWH were associated with increased incidence of failed NIPS test. High maternal cfDNA concentrations may not be associated with chromosomal abnormalities in the fetus. However, they should be alerted to the possibility of preterm births and stillbirths. Further clinical studies on pregnant women with high cfDNA concentrations are required.

研究目的：无细胞脱氧核糖核酸（cell-free DNA, cfDNA）是多种临床场景中极具应用价值的生物标志物。本研究旨在探究因血浆cfDNA浓度过高导致无创产前筛查（Non-invasive Prenatal Screening, NIPS）失败的产妇特征及相关妊娠结局。
研究方法：本研究为回顾性研究，纳入174318例行NIPS的孕妇中血浆cfDNA浓度偏高的病例。本研究共检出126例（其中118例具备完整临床信息）因cfDNA含量过高无法完成NIPS的病例，并对该结果的潜在诱因展开分析。
研究结果：174318名孕妇中，共计622名（占比0.35%）NIPS失败，其中126例（占失败病例的20.3%）因血浆cfDNA浓度过高所致。因血浆cfDNA浓度过高引发的NIPS失败与产妇基础疾病及低分子肝素（low-molecular-weight heparin, LMWH）治疗存在显著关联。对病例组中的118名孕妇进行后续随访发现，其妊娠结局包括31例早产、21例流产。早产孕妇的cfDNA浓度中位数为1.15（四分位距为0.89, 1.84），该水平与足月分娩孕妇的cfDNA浓度存在显著差异。
研究结论：在血浆cfDNA浓度偏高的孕妇群体中，全身性自身免疫性疾病、妊娠并发症及低分子肝素治疗与NIPS失败发生率升高显著相关。母体血浆cfDNA浓度偏高可能与胎儿染色体异常并无关联，但需警惕此类孕妇出现早产及死产的风险。未来仍需针对血浆cfDNA浓度偏高的孕妇开展进一步的临床研究。