Women's Health and Genetics, Laboratory Corporation of America, La Jolla, California, USA.
Augustana University, Sioux Falls, South Dakota, USA.
Prenat Diagn. 2021 Oct;41(11):1372-1379. doi: 10.1002/pd.5918. Epub 2021 Mar 8.
To evaluate cell-free DNA (cfDNA) redraws and pregnancy outcomes following low fetal fraction (FF) cfDNA failures, as it has been suggested that a failed cfDNA screen due to insufficient FF carries increased risk for fetal aneuploidy.
Here >200,000 consecutive samples were reviewed and >1,100 patients were identified with a failed cfDNA due to low FF using genome-wide massively parallel sequencing. Redraw results following the initial low FF failure were analyzed, as well as pregnancy outcomes for patients with repeated low FF failure on redraw.
Upon redraw 84.2% of samples yielded a reportable result with no enrichment of aneuploidy observed (p = 0.332). Higher maternal weights and multifetal pregnancy rates were observed in samples with insufficient FF. In patients with repeated low FF failure on redraw, almost all pregnancies resulted in apparently healthy liveborns.
Insufficient FF was not an indicator of aneuploidy risk or adverse pregnancy outcomes in this study. Caution should be taken in generalizing aneuploidy risk to all low FF cfDNA failures. Redrawing may be an appropriate next step, as proceeding directly with diagnostic testing for aneuploidy may be unwarranted for most patients.
评估由于胎儿游离 DNA（cfDNA）片段含量低而导致 cfDNA 检测失败后的游离 DNA 重抽结果和妊娠结局，因为有研究表明，由于 cfDNA 片段含量低而导致 cfDNA 筛查失败可能会增加胎儿非整倍体的风险。
对超过 20 万例连续样本进行了回顾性分析，发现有 1100 多例患者由于 cfDNA 片段含量低而导致 cfDNA 检测失败。分析了初始 cfDNA 片段含量低而导致检测失败后的游离 DNA 重抽结果，以及在重抽时多次出现 cfDNA 片段含量低而导致检测失败的患者的妊娠结局。
在游离 DNA 重抽时，84.2%的样本得出了可报告的结果，未观察到非整倍体的富集（p=0.332）。在 cfDNA 片段含量低的样本中，母亲体重较高和多胎妊娠率较高。在重复 cfDNA 片段含量低而导致检测失败的患者中，几乎所有的妊娠都导致了明显健康的活产儿。
在本研究中，cfDNA 片段含量低并不是非整倍体风险或不良妊娠结局的指标。在一般情况下，cfDNA 片段含量低的所有 cfDNA 检测失败都不能被认为是非整倍体风险高。重抽可能是一个合适的下一步，因为对于大多数患者来说，直接进行非整倍体的诊断性检测可能是不必要的。
