Grati Francesca Romana, Bajaj Komal, Malvestiti Francesca, Agrati Cristina, Grimi Beatrice, Malvestiti Barbara, Pompilii Eva, Maggi Federico, Gross Susan, Simoni Giuseppe, Ferreira Jose Carlos P
Toma Advanced Biomedical Assays, Busto Arsizio, Varese, Italy.
Department of Obstetrics, Gynecology and Women's Health at Albert Einstein College of Medicine, Bronx, NY, USA.
Prenat Diagn. 2015 Oct;35(10):994-8. doi: 10.1002/pd.4659. Epub 2015 Sep 11.
Cell-free DNA (cfDNA) screening can provide false positive/negative results because the fetal fraction originates primarily from trophoblast. Consequently, invasive diagnostic testing is recommended to confirm a high-risk result. Currently, there is debate about the most appropriate invasive method. We sought to estimate the frequency in which a chorionic villus sampling (CVS) performed after a high-risk cfDNA result would require a follow-up amniocentesis due to placental mosaicism.
Analyses of the frequencies of the different types of mosaicism involving cytotrophoblasts, for trisomies 21 (T21), 18 (T18), 13 (T13) and monosomy X (MX) among 52,673 CVS karyotypes obtained from cytotrophoblast, mesenchyme and confirmatory amniocentesis.
After a high-risk cfDNA result for T21, 18, 13 and MX, the likelihood of finding CVS mosaicism and need for amniocentesis is, respectively, 2%, 4%, 22% and 59%. When mosaicism is detected by CVS, the likelihood of fetal confirmation by amniocentesis is, respectively, 44%, 14%, 4% and 26%.
In cases of high-risk cfDNA results for T21/T18, CVS (combining cytotrophoblast and mesenchyme analysis) can be considered, but with the caveat of 2-4% risk of an inconclusive result requiring further testing. In high-risk results for MX/T13, amniocentesis would appear to be the most appropriate follow-up diagnostic test, especially in the absence of sonographic findings.
游离DNA（cfDNA）筛查可能会出现假阳性/阴性结果，因为胎儿游离DNA主要来源于滋养层细胞。因此，对于高危结果建议进行侵入性诊断检测以确诊。目前，关于最合适的侵入性检测方法存在争议。我们试图评估在cfDNA检测结果为高危后进行绒毛取样（CVS）时，因胎盘嵌合现象而需要后续进行羊膜腔穿刺术的频率。
对从滋养层细胞、间充质细胞获得的52673例CVS核型以及用于确诊的羊膜腔穿刺术样本进行分析，统计21三体（T21）、18三体（T18）、13三体（T13）和X单体（MX）中涉及细胞滋养层的不同类型嵌合现象的频率。
在cfDNA检测结果显示T21、T18、T13和MX为高危后，发现CVS嵌合现象并需要进行羊膜腔穿刺术的可能性分别为2%、4%、22%和59%。当通过CVS检测到嵌合现象时，通过羊膜腔穿刺术确诊胎儿情况的可能性分别为44%、14%、4%和26%。
对于cfDNA检测结果显示T21/T18为高危的情况，可以考虑采用CVS（结合滋养层细胞和间充质细胞分析），但需注意有2%-4%的风险可能出现无法确诊的结果而需要进一步检测。对于MX/T13高危结果，羊膜腔穿刺术似乎是最合适的后续诊断检测方法，尤其是在没有超声检查结果的情况下。
