Non-invasive prenatal cell-free fetal DNA testing for down syndrome and other chromosomal abnormalities
Background: Chorionic villus sampling and amniocentesis as definitive diagnostic procedures represent a gold standard for prenatal diagnosis of chromosomal abnormalities. The methods are invasive and lead to a miscarriage and fetal loss in approximately 0.5–1 %. Non-invasive prenatal DNA testing (NIPT) is based on the analysis of cell-free fetal DNA from maternal blood. It represents a highly accurate screening test for detecting the most common fetal chromosomal abnormalities. In our study we present the results of NIPT testing in the Diagnostic Center Strah, Slovenia, over the last 3 years.
Methods: In our study, 123 pregnant women from 11th to 18th week of pregnancy were included. All of them had First trimester assessment of risk for trisomy 21, done before NIPT testing.
Results: 5 of total 6 high-risk NIPT cases (including 3 cases of Down syndrome and 2 cases of Klinefelter’s syndrome) were confirmed by fetal karyotyping. One case–Edwards syndrome was false positive. Patau syndrome, triple X syndrome or Turner syndrome were not observed in any of the cases. Furthermore, there were no false negative cases reported. In general, NIPT testing had 100 % sensitivity (95 % confidence interval: 46.29 %–100.00 %) and 98.95 % specificity (95 % confidence interval: 93.44 %–99.95 %). In determining Down syndrome alone, specificity (95 % confidence interval: 95.25 %- 100.00 %) and sensitivity (95 % confidence interval: 31.00 %–100.00 %) turned out to be 100 %. In 2015, the average turnaround time for analysis was 8.3 days from the day when the sample was taken. Repeated blood sampling was required in 2 cases (redraw rate = 1.6 %).
Conclusions: Our results confirm that NIPT represents a fast, safe and highly accurate advanced screening test for most common chromosomal abnormalities. In current clinical practice, NIPT would significantly decrease the number of unnecessary invasive procedures and the rate of fetal loss caused by invasive diagnostics.
Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn 2011; 1: 7–15.
Strah DM, Pohar Perme M, Geršak K. Ultrazvočno presejanje za kromosomopatije v prvem trimesečju nosečnosti pri 13049 naključno izbranih nosečnicah. Med Razgl 2011; 50: S 2: 87–92.
Strah D, Bernik J. Neinvazivno predporodno presejanje za anevploidije na osnovi proste plodove DNA–pregled razvoja in priporočila za klinično prakso. Farmacevtski vestnik 2013; 64: 363–70.
Dan S, Wang W, Ren J, Li Y, Hu H, Xu Z, et al. Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11,105 pregnancies with mixed risk factors. Prenat Diagn 2012; 32: 1225–32.
Lo Y M, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, et al. Presence of fetal DNA in maternal plasma and serum. The Lancet 1997; 350: 485–7.
Bircl I, Dovč-Drnovšek T, Blejec T, Rožman P. Določanje plodovne krvne skupine med nosečnostjo. Zdrav Vestn 2004; 73: Suppl. I: 139–42
Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998; 62: 768–775.
Zhang H, Gao Y, Jiang F, Fu M, Yuan Y, Guo Y, et al. Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146 958 pregnencies. Ultrasound Obstet Gynecol 2015; 45: 530–583.
Zhou Q, Pan L, Chen S, Chen F, Hwang R, Yang X, e tal. Clinical appliaction of noninvasive prenatal testing for the detection of trisomies 21, 18, and 13: a hospital experience. Prenat Diagn 2014; 34: 1061–5
Shulman L P, Elias S. Amniocentesis and chorionic vilus sampling. West J Med 1993; 159: 260–8.