First-Trimester Screening for Trisomies 21, 18 and 13 by Ultrasound and Biochemical Testing

Abstract

Objective: To examine the performance of screening for trisomies 21, 18 and 13 at 11-13 weeks' gestation using specific algorithms for these trisomies based on combinations of fetal nuchal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index for veins (DV PIV), and serum free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Methods: Model-based estimates of screening performance were produced for the distribution of maternal ages in England and Wales in 2011, and prospectively collected data on fetal NT, FHR, DV PIV, β-hCG, PAPP-A, PLGF and AFP from singleton pregnancies undergoing aneuploidy screening. Results: In screening by NT, FHR, free β-hCG and PAPP-A, using specific algorithms for trisomy 21 and trisomies 18 and 13 at the risk cutoff of 1:100, the estimated detection rate (DR) was 87.0% for trisomy 21 and 91.8% for trisomies 18 and 13, at a false-positive rate (FPR) of 2.2%. Addition of PLGF, AFP and DV PIV increased the DR to 93.3% for trisomy 21 and 95.4% for trisomies 18 and 13 and reduced the FPR to 1.3%. Conclusions: Effective screening for trisomies can be achieved using specific algorithms based on NT, FHR, DV PIV, β-hCG, PAPP-A, PLGF and AFP.

Screening for trisomy 21 based on maternal age, nuchal translucency measurement, first trimester biochemistry and quantitative and qualitative assessment of the flow in the DV — the assessment of efficacy

“…The ultrasound examination performed at 11 to 13 + 6 weeks of pregnancy allows for the assessment of the fetal structure, but also identification of fetuses at increased risk of chromosomal defects [1][2][3]. Nuchal translucency (NT) is considered to be the strongest marker of chromosomal defects, but in order to increase sensitivity and specificity some additional ultrasound markers are also assessed, including the nasal bone (NB), flow through the tricuspid valve (Tricuspid Regurgitation, TR), and flow through the ductus venosus (DV) [3,4].…”

“…Nuchal translucency (NT) is considered to be the strongest marker of chromosomal defects, but in order to increase sensitivity and specificity some additional ultrasound markers are also assessed, including the nasal bone (NB), flow through the tricuspid valve (Tricuspid Regurgitation, TR), and flow through the ductus venosus (DV) [3,4]. The use of the last marker is increasing in screening for chromosomal defects and cardiac defects [3,5,6].…”

Influence of first trimester biochemistry methodology on detection rate in screening for trisomy 21

“…The efficacy of screening may be increased, with a simultaneous reduction of invasive testing rate, by addition of ultrasound markers of trisomy 21 (NB, DV PI, TR, FMA-angle) to the risk calculation algorithm. It should be noted that the use of additional markers should only be considered when the risk based on Maternal Age (MA), NT and the biochemistry test falls within the range of 1/50-1/1000 [3][4][5][6].…”

“…PAPP-A level increases throughout the whole duration of uncomplicated pregnancy. In trisomy 21 PAPP-A level drops during the first trimester and in the second trimester appears normal or slightly reduced [1,5]. Expressing free β-hCG and PAPP-A in MoMs allowed creating efficient risk calculation algorithm [7].…”

Cell-free fetal DNA in maternal blood – an update of the method and clinical practice

“…Continuous research had the aim to further increase detection rate, especially for Down syndrome, and reduce the false positive rate. This can be achieved by including into the assessment the entire panel of ultrasound markers and by adding new maternal biomarkers, such as serum placental growth factor (PLGF) and first trimester alpha fetoprotein (AFP) (5). This extended screening algorithm, according to authors, would increase the detection rate of Down syndrome as high as 95% with a false positive rate of 2% or even better, by choosing a cut-off risk of 1:100.…”