The clinical usefulness of non-invasive prenatal testing in pregnancies with abnormal ultrasound findings

PURPOSE: This study aimed to evaluate the clinical usefulness of non-invasive prenatal testing (NIPT) as an alternative testing of invasive diagnostic testing in pregnancies with ultrasound abnormalities. MATERIALS AND METHODS: This was a retrospective study of pregnant women with abnormal ultrasound findings before 24 weeks of gestation between April 2016 and March 2017. Abnormal ultrasound findings included isolated increased nuchal translucency, structural anomalies, and soft markers. The NIPT or diagnostic test was conducted and NIPT detected trisomy 21 (T21), T18, T13 and sex chromosomal abnormalities. We analyzed the false positive and residual risks of NIPT based on the ultrasound findings. RESULTS: During the study period, 824 pregnant women had abnormal ultrasound findings. Among the study population, 139 patients (16.9%) underwent NIPT. When NIPT was solely performed in the patients with abnormal ultrasound findings, overall false positive risk was 2.2% and this study found residual risks of NIPT. However, the discordant results of NIPT differed according to the type of abnormal ultrasound findings. Discordant results were significant in the group with structural anomalies with 4.4% false positive rate. However, no discordant results were found in the group with single soft markers. CONCLUSION: This study found different efficacy of NIPT according to the ultrasound findings. The results emphasize the importance of individualized counseling for prenatal screening or diagnostic test based on the type of abnormal ultrasound.

Non-invasive prenatal test in 2 949 intermediate risk women after traditional Down syndrome screening / 天津医药

Objective To explore the value of non-invasive prenatal test (NIPT) in pregnant women with intermediate risk after traditional Down syndrome screening. Methods From March 1 2015 to March 31 2016, a total of 2 949 pregnant women with intermediate risk after traditional Down syndrome screening who received NIPT as the second-line screening method at Shenzhen Maternity and Child Healthcare Hospital after informed consent were recruited for this study. Retrospective data analysis including the results of traditional Down syndrome screening, ultrasound, NIPT and invasive amniocentesis to fetal karyotype analysis were conducted, and pregnant outcomes were followed up. Results NIPT results were all obtained in 2 949 pregnant women with intermediate risk after traditional Down syndrome screening. Of 25 NIPT-positive cases, 24 cases received invasive amniocentesis to fetal karyotype analysis. Thirteen cases were confirmed with fetal chromosomal abnormalities including 5 cases of trisomy 21, 2 cases of trisomy 13, 4 cases of sex chromosomal abnormalities and 2 cases of other chromosomal abnormalities. In addition, 1 NIPT-positive case refused prenatal diagnosis was confirmed normal result after birth. The postnatal follow-up in NIPT-negative women did not find any newborn with chromosomal abnormality. The incidence of fetal chromosomal abnormalities in women with intermediate risk was 0.44% (13/2 949). Conclusion NIPT can be used as second-line screening method in pregnant women with intermediate risk after Down syndrome screening, which could lead to the prenatal detection of a higher proportion of fetal chromosomal abnormalities and a lower invasive-testing rate.

Influence of cell free fetal fraction DNA for noninvasive prenatal test / 国际检验医学杂志

Objective To explore the influence of lower concentration of cell free fetal fraction DNA in maternal plasma on non-invasive prenatal test(NIPT) .Methods A total of 3240 pregnant women accepted NIPT in Foshan Maternal and Children′s Hos-pital from April ,2015 to March ,2016 were analyzed retrospectively ,and 150 samples of which were male fetus judged by Z score of Y chromosome and the cell free fetal fraction DNA were lower than 8% were selected .The cell free fetal fraction DNA were in-creased by agarose gel electrophoresis ,then conducted NIPT ,compared with the results of aneuploidy screening .Results The cell free fetal fraction DNA were increased from 5% to 9 .2% by agarose gel electrophoresis .The result of NIPT after increasing fetal fraction was consistent with it before .Conclusion Concentration of cell free fetal fraction DNA has no influence on the result of NIPT when cell free fetal fraction DNA is above 5% .

Influence of cell free fetal fraction DNA for noninvasive prenatal test / 国际检验医学杂志

Objective To explore the influence of lower concentration of cell free fetal fraction DNA in maternal plasma on non-invasive prenatal test(NIPT) .Methods A total of 3240 pregnant women accepted NIPT in Foshan Maternal and Children′s Hos-pital from April ,2015 to March ,2016 were analyzed retrospectively ,and 150 samples of which were male fetus judged by Z score of Y chromosome and the cell free fetal fraction DNA were lower than 8% were selected .The cell free fetal fraction DNA were in-creased by agarose gel electrophoresis ,then conducted NIPT ,compared with the results of aneuploidy screening .Results The cell free fetal fraction DNA were increased from 5% to 9 .2% by agarose gel electrophoresis .The result of NIPT after increasing fetal fraction was consistent with it before .Conclusion Concentration of cell free fetal fraction DNA has no influence on the result of NIPT when cell free fetal fraction DNA is above 5% .

Analysis on Policy and Ethics of Non-Invasive Prenatal Test / 中国医学伦理学

This paper comprehensively reviewed the practice and meanings of non-invasive prenatal test (NIPT) in China and discussed the ethical issues.NIPT,as a step of prenatal diagnosis,brought conflicting values and moral economic influences.Its widely application also imposes higher requirements on policy regulation and lead to some ethical issues,including whether the client really informed consent.Genetic counselling is also crucial before and after the test.However,the subjects,doctors and medical staff have not yet fully prepared.Furthermore,this technique is relatively simple and cheap,and its application relates to many aspects.It is necessary to discuss the influence at the early stage and put forward the ethical issues that need to be paid attention to.Therefore,life ethics expert participation is extremely important,and to some extent will leadfetal and maternal supervision,management and supervision to a new level,especially with the development of NIPT and the application of whole genome sequencing (WGS).

The clinical application and follow-up study of f non-invasive prenatal testing / 重庆医学

Objective To provide valid data and useful genetic counseling in the clinical application of non‐invasive prenatal test (NIPT) ,fetal chromosomal disorder were screened by massive parallel sequencing and made a follow‐up study .Methods Preg‐nant women with Down screening in high‐risk were screened by NIPT ;NIPT verified high‐risk individuals were suggested for kary‐otyping ;and we follow up on whoever showed low risk by NIPT before and after their deliveries .Results (1)Totally 1 676 cases of pregnant women were tested by NIPT ,25 cases prompted to be abnormal ,with an abnormal rate of 1 .49% ,karyotype analysis re‐sults in 12 cases of abnormalit ,the accuracies of NIPT for T21 ,T18 ,XO ,XXY ,and XYY were 99 .93% ,100 .00% ,99 .66% , 100 .00% ,100 .00% respectively ;the accuracy of NIPT for women with advanced paternal age and twins were both 100 .00% ;kary‐otyping positive individuals underwent abortion ,which gives a prenatal intervention rate of 100 .00% .(2)Out of 1 651 cases of NIPT low risk testers ,1 468 cases were successfully followed up ,with a 88 .91% success rate .We found chromosome abnormality with one case of inversion of chromosome 9 (maternal) .(3)Ultrasound‐detection possessed 98 .17% accuracy and 7 .69% in detec‐tion rate;in high‐risk pregnant woman ,Down screening had an accuracy of 0 .88% and false positive rate of 99 .12% ;98 .71%women were avoided prenatal diagnosis via NIPT .Conclusion Compare to ultrasound and maternal plasma screening ,NIPT is a far more accurate prenatal screening approach .To build effective follow‐up and service systems of NIPT is necessary to reduce birth de‐fects in medical institutions .

Non-invasive prenatal test using cell free DNA

Although conventional prenatal screening tests for Down syndrome have been developed over the past 20 years, the positive predictive value of these tests is around 5%. Through these tests, many pregnant women have taken invasive tests including chorionic villi sampling and amniocentesis for confirming Down syndrome. Invasive test carries the risk of fetal loss at a low but significant rate. There is a large amount of evidence that non-invasive prenatal test (NIPT) using cell free DNA in maternal serum is more sensitive and specific than conventional maternal serum and/or ultrasound screening. Therefore implementing NIPT will increase aneuploidy detection rate and concurrently decrease fetal loss rate accompanying invasive test. More than 1,000,000 NIPT were performed globally since 2011. The uptake rate of NIPT is expected to increase more rapidly in the future. Moreover, as a molecular genetic technique advances, NIPT can be used for not only common aneuploidy screening but single gene disorder, microdeletion, and whole fetal genome sequencing. In this review, I will focus on the NIPT for common aneuploidies such as trisomy 13, 18, and 21.

Clinical Study of Non-Invasive Prenatal Testing Using Next-Generation Sequencing

BACKGROUND: Serological prenatal screening tests are widely used to detect fetal chromosomal abnormalities such as Down and Edward syndromes. After determining the presence of fetal cell-free DNA in maternal blood, the non-invasive prenatal test (NIPT) coupled with next-generation sequencing has been performed in other countries, therefore, we developed a domestic NIPT technology. METHODS: The results of genomics-based NIPT performed between April and May, 2015 were analyzed. Maternal blood samples were collected in a specific Cell-Free DNA BCT tube. The samples were then massively sequenced using MiSeq and NextSeq 500 (Illumina Inc., USA) using LabGenomics laboratory-developed libraries. Chromosomal abnormalities were analyzed using a bioinfomatics algorithm. RESULTS: A total of 464 cases were analyzed. The samples of 12 subjects had to be collected again because of a low fetal DNA fraction in the initially obtained samples. Among the 456 cases for which fetal genome results were obtained, 436 had a low risk of trisomy, 12 had a high risk for Down syndrome, two had a high risk for Edward syndrome, and four had sex chromosomal aneuploidy, showing that the positive percentage of chromosomal abnormalities was 4.4%. All 12 cases with high risk for Down syndrome were confirmed as having trisomy 21 by amniocentesis. CONCLUSIONS: Our laboratory-developed genomics-based NIPT showed high positive predictive value, therefore, NIPT may be replaced by our own developed method.

An Experience of Using the Harmony Test for Genomics-Based Non-Invasive Prenatal Testing / 임상검사와정도관리

Serological prenatal screening tests are widely used to detect fetal chromosomal abnormalities such as Down and Edward syndromes. Amniocentesis is conducted as a confirmatory test in the screening-positive case. After discovering of presence of fetal cell-free DNA in maternal blood, non-invasive prenatal test (NIPT) coupled with next generation sequencing are performed in abroad. Results of genomics-based NIPT results supplied to Labgenomics laborotory from June, 2013 to August, 2014 were analyzed. Maternal blood samples were collected into specific Cell-Free DNA BCT tube and were transported. The samples were then delivered to Ariosa Diagnostics by FEDEX. Fetal cell-free DNA samples were analyzed using the Harmony test with sequencing of relevant chromosomes and by using the FORTE (fetal-fraction optimized risk of trisomy evaluation) algorism at Ariosa Diagnostics. In all, 149 cases from 28 medical clinics were analyzed. Six subjects were required recollection of samples because of a low fetal DNA fraction in the initially obtained samples. Of these 6 subjects, no sample could be collected from one. Of the remaining 148 cases, 144 had a low risk of trisomy, and 4 had a high risk for Down syndrome, thus providing a positivity percentage of 2.7%. Fetal DNA fraction in the maternal blood samples ranged from 4.2% to 23.7% with a mean value of 12.0%. We have experienced cases with a high risk for Down syndrome with genomics-based NIPT referred to abroad.