Meng Meng, Chen Jianping, Yang Yingjun, Zhang Yun, Zou Gang, Zhou Fenhe, Wei Xing, Ge Yuchun, Zhou Jia, Sun Luming
Department of Fetal Medicine & Prenatal Diagnosis Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Acta Obstet Gynecol Scand. 2024 Dec;103(12):2426-2432. doi: 10.1111/aogs.14958. Epub 2024 Oct 2.
Our objective was to evaluate the efficacy of expanded non-invasive prenatal testing (NIPT) that includes both trisomies and copy number variants (CNVs) in high-risk twin pregnancies.
A prospective, double-blinded cohort study was conducted, enrolling 73 high-risk twin pregnancies characterized by increased risk of genetic disorders due to factors such as increased nuchal translucency, structural anomalies, fetal growth restriction, and other factors associated with chromosomal abnormality. Participants underwent invasive karyotyping and chromosomal microarray analysis, alongside separate expanded NIPT for research purposes. The sensitivity, specificity, positive predictive value, and negative predictive value of expanded NIPT were calculated.
The cohort included 24 monochorionic and 49 dichorionic twin pregnancies. The median cell-free fetal DNA concentration in expanded NIPT was 16.7% (range 3.86%-49.1%), with a test failure rate of 1.4% (1/73). High-risk findings for trisomy 21/13/18 were identified in five cases (6.8%), Turner syndrome in one case (1.4%), and CNVs indicative of high risk for clinically significant microdeletion/microduplication syndromes (MMS) in ten cases (13.7%). Of these, 56 cases (76.7%) tested NIPT negative, revealing one false-negative for 45, X and five false-negatives for CNVs. Expanded NIPT achieved a detection rate of 100% (5/5) for trisomy 21/13/18 with a false-positive rate of 0% (0/5), a detection rate of 33.3% (1/3) for sex chromosome abnormalities with a false-positive rate of 0% (0/3), and a detection rate of 66.7% (4/6) for MMS with a false-positive rate of 3.0% (2/67). The positive predictive values for trisomy T21/13/18, sex chromosome abnormalities, and known MMS were 100% (5/5), 100% (1/1), and 66.7% (4/6) in the expanded NIPT, respectively.
The expanded NIPT demonstrated high detection rates for common trisomies and moderate detection rates for prenatal MMS in high-risk twin pregnancies. Further studies with large sample sizes in low-risk populations are needed.
我们的目的是评估扩展的无创产前检测（NIPT）在高危双胎妊娠中检测三体和拷贝数变异（CNV）的有效性。
进行了一项前瞻性、双盲队列研究，纳入73例高危双胎妊娠，这些妊娠因颈项透明层增厚、结构异常、胎儿生长受限等因素以及其他与染色体异常相关的因素而具有较高的遗传疾病风险。参与者接受了侵入性核型分析和染色体微阵列分析，同时为研究目的进行了单独的扩展NIPT。计算了扩展NIPT的敏感性、特异性、阳性预测值和阴性预测值。
该队列包括24例单绒毛膜双胎妊娠和49例双绒毛膜双胎妊娠。扩展NIPT中游离胎儿DNA浓度的中位数为16.7%（范围3.86%-49.1%），检测失败率为1.4%（1/73）。5例（6.8%）检测到21/13/18三体的高危结果，1例（1.4%）检测到特纳综合征，10例（13.7%）检测到提示临床显著微缺失/微重复综合征（MMS）高危的CNV。其中，56例（76.7%）NIPT检测为阴性，45，X有1例假阴性，CNV有5例假阴性。扩展NIPT对21/13/18三体的检测率为100%（5/5），假阳性率为0%（0/5）；对性染色体异常的检测率为33.3%（1/3），假阳性率为0%（0/3）；对MMS的检测率为66.7%（4/6），假阳性率为3.0%（2/67）。扩展NIPT中21/13/18三体、性染色体异常和已知MMS的阳性预测值分别为100%（5/5）、100%（1/1）和66.7%（4/6）。
扩展NIPT在高危双胎妊娠中对常见三体显示出高检测率，对产前MMS显示出中等检测率。需要在低风险人群中进行更大样本量的进一步研究。
