Cell-free DNA testing in the maternal blood in high-risk pregnancies after first-trimester combined screening

Abstract

Objective The objective of this study was to investigate a strategy for clinical implementation of cell-free DNA (cfDNA) testing in high-risk pregnancies after first-trimester combined screening.Methods In 259 singleton pregnancies undergoing invasive testing after first-trimester combined screening, a maternal blood sample was sent to the laboratory Natera for cfDNA testing using a single-nucleotide polymorphismbased methodology.Results The cfDNA test provided a result in 249 (96.1%) pregnancies and, among these, identified as being at high risk 35 of 36 cases of trisomy 21, 13 of 13 with trisomy 18, five of five with trisomy 13 and three of four with sex chromosome aneuploidies. A policy of performing an invasive test in women with a combined risk of ≥1 in 10 or NT ≥4 mm and offering cfDNA testing to the remaining cases would detect all cases of trisomy 21, 18 or 13, 80% of sex aneuploidies and 62.5% of other defects and would avoid an invasive procedure in 82.4% of euploid fetuses. ConclusionIn high-risk pregnancies after combined screening, a policy of selecting a subgroup for invasive testing and another for cfDNA testing would substantially reduce the number of invasive procedures and retain the ability to diagnose most of the observed aneuploidies.

Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

“…Alternatively to universal screening by cfDNA, some authors have suggested a strategy of cfDNA contingent to first‐line screening by CT as more cost effective . In this case, women with high risk at the CT are referred for invasive testing and women with intermediate risk (cut‐off depending on financial means) are offered cfDNA . This results in higher sensitivity and specificity at considerably lower costs.…”

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

“…In two of the 35 studies, some of the maternal blood samples for the cfDNA analysis were obtained after the invasive test 16,19 . In 18 studies, it was stated explicitly [7][8][9][10][11][12][13][14][15]18,[20][21][22]27,32,35,37,40 , and in 10 it was assumed on the basis of the described methodology 17,26,[28][29][30][31]33,34,36,38 , that, if an invasive test was carried out, the samples for cfDNA analysis were obtained before the invasive test. In five studies it was uncertain if invasive testing was before or after maternal blood sampling for the cfDNA test 6,[23][24][25]39 .…”

“…*Bivariate random-effects regression model. 7 8 8 (100.0, 63.1-100.0) 100 0 (0.00, 0.00-3.62) Liang (2013) 11 5 5 (100.0, 47.8-100.0) 401 1 (0.25, 0.01-1.38) Nicolaides (2013) 12 2 2 (100.0, 15.8-100.0) 227 0 (0.00, 0.00-1.61) Song (2013) 13 3 2 (66.7, 9.4-99.2) 1737 † 0 (0.00, 0.00-0.21) Comas (2014) 17 0 -315 1 (0.32, 0.01-1.76) Porreco (2014) 20 9 9 (100.0, 66.4-100.0) 3269 11 (0.34, 0.17-0.60) Shaw (2014) 21 3 3 (100.0, 29.2-100.0) 192 0 (0.00, 0.00-1.90) Song (2015) 27 0 -203 1 (0.49, 0.01-2.71) Persico (2016) 35 3 2 (66. 7, 9.4- Jiang (2012) 6 3 3 (100.0, 29.2-100.0) 900 0 (0.00, 0.00-0.41) Lau (2012) 7 1 1 (100.0, 2.5-100.0) 107 0 (0.00, 0.00-3.36) Liang (2013) 11 3 3 (100.0, 29.2-100.0) 403 1 (0.25, 0.01-1.37) Porreco (2014) 20 6 6 (100.0, 54.1-100.0) 3263 5 (0.15, 0.05-0.36) Shaw (2014) 21 1 1 (100.0, 2.5-100.0) 194 0 (0.00, 0.00-1.88) Song (2015) 27 1 0 (0.0, 0.0-97.5) 202 0 (0.00, 0.00-1.81) Persico (2016) 35 1 1 (100.0, 2.5-100.0) 248 0 (0.00, 0.00-1.48) Zhang (2016) 39 1 1 (100.0, 2.5-100.0) 86 0 (0.00, 0.00-4.20) Pooled analysis (% (95% CI))* 100 (83.6-100) 0.004 (0-0.08) I 2 (%) 0 0…”

Screening for Common Fetal Trisomies in Twin Pregnancies: First-Trimester Combined, Cell-Free DNA, or Both?

“…In this strategy, it was considered to offer an invasive procedure to patients with no results at cfDNA testing only if the CT was positive (risk ≥1: 250) for at least one twin. The implementation of cfDNA testing contingent to the results of combined screening has been shown to be effective in reducing the invasive testing rate in singleton pregnancies [11,12,20]. In addition, a recent study showed that the results of combined screening are useful in the clinical management of cases with a cfDNA test failure [21].…”