Noninvasive Prenatal Testing for Whole Fetal Chromosomal Aneuploidies: A Multicenter Prospective Cohort Trial in Taiwan

Abstract

Objective: To evaluate the performance of noninvasive prenatal testing for all fetal chromosomal aneuploidies in an extremely high-risk group undergoing first trimester combined Down syndrome screening. Method: A multicenter cohort prospective study in Taiwan was performed between June and December 2012. Maternal plasma was collected and shotgun massive parallel sequencing was performed on each fetal chromosome. 201 Taiwanese pregnant women at >12 weeks' gestation from 11 medical centers were enrolled in this trial. The extremely high-risk group was defined as a Down syndrome risk cutoff >1:30 or nuchal translucency >3.0 mm (n = 100), while the low-risk group was defined as a Down syndrome cutoff <1:1,500 (n = 101). Amniocentesis confirmation was performed and birth outcome was also recorded. Results: There were 11 cases of trisomy 21, 8 cases of trisomy 18, 3 cases of trisomy 13, 1 case of trisomy 16, 3 cases of 45,X, and 1 case of 47,XYY detected prenatally in 100 extremely high-risk gravidas [n = 27/100 (27%)]. The overall autosomal or sex chromosome aneuploidy detection rate was 96% (27/28) because of an insufficient amount maternal plasma for one fetus with Turner syndrome. In the low-risk group, no chromosomal abnormalities were detected (specificity = 100%). There were no false-positive cases in this study. Conclusions: This first trial in Taiwan shows that noninvasive prenatal testing for whole chromosome aneuploidies can be efficiently applied in extremely high- and low-risk populations.

Analysis of cell‐free DNA in maternal blood in screening for fetal aneuploidies: updated meta‐analysis

“…CSS, chromosome-specific sequencing; GA, gestational age; MPSS, massively parallel shotgun sequencing; SNP, single nucleotide polymorphism-based method. 73 MPSS > 12 1 1 (100, 2.5-100) 191 0 (0.00, 0.00-1.91) Song (2015) 76 Only the first author of each study is given. All monosomy-X pregnancies have been excluded from these data.…”

Population‐based trends in the prenatal diagnosis of sex chromosome aneuploidy before and after non‐invasive prenatal testing

“…Until recently, fetal sex chromosome abnormalities were usually detected incidentally in the context of a diagnostic test for an increased risk of autosomal aneuploidy . However, cell‐free DNA‐based screening has created novel opportunities for targeted screening for sex chromosome aneuploidy (SCA) …”

“…2 However, cell-free DNA-based screening has created novel opportunities for targeted screening for sex chromosome aneuploidy (SCA). [3][4][5][6][7] The most common SCAs include 45,X (monosomy X or Turner syndrome) and the sex chromosome trisomies: 47,XXY (Klinefelter syndrome), 47,XXX (triple X syndrome) and 47,XYY (XYY syndrome).…”

The implications of non-invasive prenatal testing failures: a review of an under-discussed phenomenon

“…In a recent meta‐analysis on NIPT, including 37 studies, Gil et al analyzed failure rates: Two studies did not report on any laboratory failures, and 24 others did not specify the reason for failure to obtain a result. Among these, the total laboratory failure rate ranged from as low as 0% to as high as 8.8% for the common trisomies.…”

“…It is of note, however, that in certain laboratories administrative issues may be higher than in others because of specific laboratory requirements such as high blood volume or unique 'out of specification' instances such as multiple gestations and pregnancies in which the mother and fetus are genetically unrelated, as with egg donation and surrogacy. 11 In a recent meta-analysis on NIPT, including 37 studies, Gil et al analyzed failure rates 10 : Two studies did not report on any laboratory failures, 12,13 and 24 others 14-37 did not specify the reason for failure to obtain a result. Among these, the total laboratory failure rate ranged from as low as 0% [14][15][16][17]22,26,27,31 to as high as 8.8% 19 for the common trisomies.…”