Natera, San Carlos, CA.
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Am J Obstet Gynecol. 2015 Jan;212(1):79.e1-9. doi: 10.1016/j.ajog.2014.10.012. Epub 2014 Oct 15.
We sought to determine the ability of single-nucleotide polymorphism-based noninvasive prenatal testing (NIPT) to identify triploid, unrecognized twin, and vanishing twin pregnancies.
The study included 30,795 consecutive reported clinical cases received for NIPT for fetal whole-chromosome aneuploidies; known multiple gestations were excluded. Cell-free DNA was isolated from maternal blood samples, amplified via 19,488-plex polymerase chain reaction, and sequenced. Sequencing results were analyzed to determine fetal chromosome copy number and to identify the presence of additional fetal haplotypes.
Additional fetal haplotypes, indicative of fetal triploidy, vanishing twin, or undetected twin pregnancy, were identified in 130 (0.42%) cases. Clinical confirmation (karyotype for singleton pregnancies, ultrasound for multifetal pregnancies) was available for 58.5% (76/130) of cases. Of the 76 cases with confirmation, 42.1% were vanishing twin, 48.7% were viable twin, 5.3% were diandric triploids, and 3.9% were nontriploid pregnancies that lacked evidence of co-twin demise. One pregnancy had other indications suggesting triploidy but lacked karyotype confirmation. Of the 5 vanishing twin cases with a known date of demise, 100% of losses occurred in the first trimester; up to 8 weeks elapsed between loss and detection by NIPT.
This single-nucleotide polymorphism-based NIPT successfully identified vanished twin, previously unrecognized twin, and triploid pregnancies. As vanishing twins are more likely to be aneuploid, and undetected residual cell-free DNA could bias NIPT results, the ability of this method to identify additional fetal haplotypes is expected to result in fewer false-positive calls and prevent incorrect fetal sex calls.
我们旨在确定基于单核苷酸多态性的无创产前检测（NIPT）识别三倍体、未识别的双胎和消失的双胎妊娠的能力。
这项研究纳入了 30795 例连续报告的接受胎儿全染色体非整倍体 NIPT 的临床病例；已知多胎妊娠被排除在外。从母体血液样本中提取游离 DNA，通过 19488 plex 聚合酶链反应扩增，并进行测序。对测序结果进行分析，以确定胎儿染色体拷贝数，并识别额外的胎儿单倍型。
在 130 例（0.42%）病例中鉴定出额外的胎儿单倍型，提示胎儿三倍体、消失的双胎或未检测到的双胎妊娠。有 58.5%（76/130）的病例可获得临床确认（单胎妊娠的核型，多胎妊娠的超声）。在 76 例有确认结果的病例中，42.1%为消失的双胎，48.7%为存活的双胎，5.3%为二倍体三倍体，3.9%为无三体妊娠且缺乏同胞死亡证据。有 1 例妊娠有其他提示三倍体的迹象，但缺乏核型确认。在 5 例已知死亡日期的消失的双胎妊娠中，100%的丢失发生在孕早期；从丢失到通过 NIPT 检测到，最多相隔 8 周。
这种基于单核苷酸多态性的 NIPT 成功地识别了消失的双胎、以前未识别的双胎和三倍体妊娠。由于消失的双胎更可能是非整倍体，并且未检测到的游离 DNA 可能会影响 NIPT 结果，因此该方法识别额外胎儿单倍型的能力有望减少假阳性结果，并防止错误的胎儿性别结果。
