Analysis of the results of chromosomal trisomies 21, 18 and 13 screening among 40 628 women by non-invasive prenatal testing / 中华医学遗传学杂志

OBJECTIVE@#To assess the clinical value of non-invasive prenatal testing (NIPT) for the screening of trisomy and copy number variations (CNVs) of chromosomes 21, 18 and 13.@*METHODS@#From January 2015 to December 2019, 40 628 pregnant women underwent NIPT testing using high-throughput sequencing and bioinformatics analysis to test the cell-free fetal DNA in maternal plasma. High-risk pregnant women underwent invasive prenatal diagnosis, while low-risk ones were followed up by telephone.@*RESULTS@#The three most common indications included intermediate risk of serological screening, high risk of serological screening and advanced maternal age. Among all pregnant women, 257 cases were detected as trisomy 21, 18 and 13 (170, 49 and 38 cases, respectively). 227 cases chose invasive prenatal diagnosis, with respectively 122, 28 and 10 cases confirmed. The positive predictive value (PPV) was 81.33% (122/150), 65.12% (28/43), 29.41% (10/34), respectively. Two false negative cases of trisomy 18 were found during follow-up. Meanwhile, NIPT has detected 46 cases (15, 16 and 15 cases, respectively) CNVs on chromosomes 21, 18 and 13, among which 37 cases underwent invasive prenatal diagnosis. There were 5, 3 and 5 positive cases, which yielded a PPV of 41.67% (5/12), 25%(3/12) and 33.33%(5/15), respectively. Two other chromosome CNVs were accidentally discovered among the false positive samples.@*CONCLUSION@#The incidence of chromosomal abnormalities in the serological screening high-risk group was 52.02%, which was significantly higher than other groups. NIPT has a high sensitivity and specificity for the screening of trisomies 21, 18 and 13, while its accuracy for detecting CNVs of chromosomes 21, 18 and 13 needs to be improved. As a screening method, NIPT has a great clinical value, though there are still limitations of false positive and false negative results.Comprehensive pre- and post-test genetic counseling should be provided to the patients.

Application of non-invasive prenatal genetic testing in prenatal anomaly index screening / 中华检验医学杂志

Objective@#To evaluate the value of non-invasive prenatal testing (NIPT) in pregnancies with anomaly in prenatal screening. @*Methods@#This was a retrospective study of 2 837 singleton pregnancies who performed NIPT indicated by isolated anomaly in prenatal screening at Guangdong Women and Children Hospital between November 2014 and August 2016. All pregnancies were divided into 3 groups by single indication: advanced maternal age ( AMA, ≥35), abnormal multiples of the median (MoM) in standard screening, increased nuchal translucency thickness (NT, 2.5-3.0 mm). High risk results were verified by prenatal diagnosis. Low risk cases were followed by a 22-26 week anatomical ultrasound examination. All of the cases were followed up and the performance of NIPT for every single indication was evaluated. @*Results@#There were total of 2 837 pregnant women who underwent NIPT. Twenty-five of 2 448 pregnancies indicated by AMA had high risk results, among which 17 were confirmed by invasive genetic testing, except 1 case rejecting prenatal diagnosis. In 351 pregnant women with abnormal MoM, NIPT found 3 cases of sex chromosome aneuploidies (SCA) and 2 of them were validated by invasive prenatal diagnosis. Increased NT group included 38 cases, NIPT found 1 case of trisomy 21 which was consistent with karyotype analysis. For common aneuploidies and SCA, the performance of NIPT in the pregnant women who indicated by AMA, abnormal MoM and increased NT were as the follows: the sensitivity were 17/17, 2/2 and 1/1 respectively, the specificity were 99.7% (2 423/2 431), 99.7% (348/349) and 100%(37/37), the positive predictive value were 68% (17/25), 2/3 and 1/1, the negative predictive value were 100% (2 423/2 423), 100% (348/348) and 100% (38/38), respectively. By follow-up survey, a total of 8 cases of abnormal fetus were recorded in NIPT low-risk women, including 5 cases of termination of pregnancy due to abnormal ultrasound findings, 2 cases of abortion as a result of severe obstetric complications and 1 case of stillbirth. @*Conclusions@#To the pregnant women who indicated by advanced maternal age, abnormal MoM and increased NT (2.5-3.0 mm), NIPT had satisfactory performance for common aneuploidies, and also had potential value for SCA, resulting in a significant reduction in diagnostic procedures. However, for NIPT low-risk pregnancies, routine antenatal examination and anatomical ultrasound detection would be highly necessary to avoid missing abnormal fetuses.(Chin J Lab Med, 2018, 41: 509-513)