Zhang Bin, Shen Cong, Wang Huiyan, Cai Zhengmao, Lu Beiyi, Zhang Xiaoqing, Yu Bin, Wang Ting
Center of Prenatal Diagnosis, Changzhou Woman and Children's Health Care Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu 213003, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2018 Jun 10;35(3):329-333. doi: 10.3760/cma.j.issn.1003-9406.2018.03.005.
To explore the cause of failure of non-invasive prenatal testing (NIPT) using cell-free fetal DNA from peripheral maternal blood.
A total of 31 832 cases of NIPT were retrospectively analyzed. The clinical data of pregnant women were analyzed and the outcome of pregnancy was followed up.
Among the 31 832 cases, 200 patients have failed for the first NIPT test. Second test has succeeded in 171 (85.9%) of 199 cases, while 28 cases (14.1%) still yielded no effective results. This gave rise for a total failure rate of 0.088%. Of the 28 cases, 11 (39.2%) were due to high content of total free DNA and could not be sequenced, 17 (60.7%) were found to have the fetal DNA content of less than 4%. Among the 171 cases which have obtained a valid result, NIPT showed that there were 4 patients with high risk of trisomy 21, 18 cases with high risk of 18 trisomy and 1 case with high risk of 13 trisomy. Karyotyping analysis of the amniocytic chromosomes has identified 3 cases with 47,XN,+21, 1 case with 46,XN,rob(21;21), 1 case with 47,XN,+18, while the 13 trisomy case was found to be false positive. For the 28 cases with failed NIPT retest, 14 had normal delivery, with no anomaly noticed in the neonates. Nine patients had opted for artificial abortion during middle or late pregnancy due to maternal factors (4 cases) or fetal factors (5 cases). Four patients developed complications of pregnancy. One case was in good condition upon follow-up. Four cases were lost during follow-up. Of the 11 pregnant women who had failed the NIPT test due to high content of total free DNA, 6 (54.5%) had opted for artificial abortion during midterm pregnancy, which was significantly higher than that of pregnant women with low free DNA content (17.6%).
Failure of NIPT testing should attract attention from researchers. Failure of single NIPT test should not be regarded as a high risk signal for fetal chromosomal aneuploidies. For those where the test has failed again, genetic counseling and strengthened perinatal care should be provided for the pregnant women.
探讨利用孕妇外周血中游离胎儿DNA进行无创产前检测（NIPT）失败的原因。
回顾性分析31832例NIPT病例。分析孕妇的临床资料并随访妊娠结局。
在31832例病例中，200例首次NIPT检测失败。199例中的171例（85.9%）第二次检测成功，而28例（14.1%）仍未得到有效结果。总失败率为0.088%。在这28例中，11例（39.2%）是由于总游离DNA含量过高无法测序，17例（60.7%）胎儿DNA含量低于4%。在获得有效结果的171例中，NIPT显示有4例21三体高风险、18例18三体高风险和1例13三体高风险。羊水细胞染色体核型分析鉴定出3例47,XN,+21、1例46,XN,rob(21;21)、1例47,XN,+18，而13三体病例为假阳性。对于28例NIPT复测失败的病例，14例顺产，新生儿未见异常。9例孕妇因母体因素（4例）或胎儿因素（5例）在妊娠中晚期选择人工流产。4例孕妇出现妊娠并发症。1例随访时情况良好。4例失访。在因总游离DNA含量高而NIPT检测失败的11例孕妇中，6例（54.5%）在中期妊娠时选择人工流产，显著高于游离DNA含量低的孕妇（17.6%）。
NIPT检测失败应引起研究人员的关注。单次NIPT检测失败不应被视为胎儿染色体非整倍体的高风险信号。对于再次检测失败的孕妇，应提供遗传咨询并加强围产期护理。
