Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea.
PLoS One. 2013;8(2):e56787. doi: 10.1371/journal.pone.0056787. Epub 2013 Feb 15.
Cell-free fetal DNA and cell-free total DNA in maternal circulation have been proposed as potential markers for noninvasive monitoring of the placental condition during the pregnancy. However, the correlation of and change in cell-free fetal DNA and cell-free total DNA in spontaneous abortion (SA) with fetal chromosomal aneuploidy have not yet been reported. Therefore, we investigated cell-free fetal DNA and cell-free total DNA levels in SA women with fetal chromosomal aneuploidy.
METHODOLOGY/PRINCIPAL FINDINGS: A nested case-control study was conducted with maternal plasma collected from 268 women in their first trimester of pregnancy. Subjects included 41 SA with normal fetal karyotype, 26 SA with fetal chromosomal aneuploidy, and 201 normal controls. The unmethylated PDE9A gene was used to measure the maternal plasma levels of cell-free fetal DNA. The GAPDH gene was used to measure the maternal plasma levels of cell-free total DNA. The diagnostic accuracy was measured using receiver-operating characteristic (ROC) curves. Levels of cell-free fetal DNA and cell-free total DNA were significantly higher in both SA women with normal fetal karyotype and SA women with fetal chromosomal aneuploidy in comparison with the normal controls (P<0.001 in both). The correlation between cell-free fetal DNA and cell-free total DNA levels was stronger in the normal controls (r = 0.843, P<0.001) than in SA women with normal karyotype (r = 0.465, P = 0.002) and SA women with fetal chromosomal aneuploidy (r = 0.412, P = 0.037). The area under the ROC curve for cell-free fetal DNA and cell-free total DNA was 0.898 (95% CI, 0.852-0.945) and 0.939 (95% CI, 0.903-0.975), respectively.
Significantly high levels of cell-free fetal DNA and cell-free total DNA were found in SA women with fetal chromosomal aneuploidy. Our findings suggest that cell-free fetal DNA and cell-free total DNA may be useful biomarkers for the prediction of SA with fetal chromosomal aneuploidy, regardless of fetal gender.
游离胎儿 DNA 和母体循环中的游离总 DNA 已被提议作为监测妊娠期间胎盘状况的潜在无创标志物。然而，自然流产（SA）中游离胎儿 DNA 和游离总 DNA 的相关性及其与胎儿染色体非整倍体的变化尚未报道。因此，我们研究了 SA 妇女中游离胎儿 DNA 和游离总 DNA 水平与胎儿染色体非整倍体的关系。
方法/主要发现：采用巢式病例对照研究，对 268 例妊娠早期妇女的血浆进行了检测。研究对象包括 41 例正常胎儿核型的 SA 妇女、26 例胎儿染色体非整倍体的 SA 妇女和 201 例正常对照。使用非甲基化 PDE9A 基因测量母体血浆中游离胎儿 DNA 的水平。使用 GAPDH 基因测量母体血浆中游离总 DNA 的水平。使用受试者工作特征（ROC）曲线测量诊断准确性。与正常对照组相比，正常胎儿核型和胎儿染色体非整倍体的 SA 妇女的游离胎儿 DNA 和游离总 DNA 水平均显著升高（均 P<0.001）。在正常对照组中，游离胎儿 DNA 和游离总 DNA 水平之间的相关性更强（r=0.843，P<0.001），而在正常核型的 SA 妇女（r=0.465，P=0.002）和胎儿染色体非整倍体的 SA 妇女（r=0.412，P=0.037）中较弱。游离胎儿 DNA 和游离总 DNA 的 ROC 曲线下面积分别为 0.898（95%CI，0.852-0.945）和 0.939（95%CI，0.903-0.975）。
发现胎儿染色体非整倍体的 SA 妇女中游离胎儿 DNA 和游离总 DNA 水平显著升高。我们的研究结果表明，游离胎儿 DNA 和游离总 DNA 可能是预测胎儿染色体非整倍体 SA 的有用生物标志物，而与胎儿性别无关。
