Non-invasive Prenatal Testing For Trisomy Research Articles

432: A cost-effective analysis of non-invasive prenatal testing for trisomy 21 in low-risk women

432: A cost-effective analysis of non-invasive prenatal testing for trisomy 21 in low-risk women

Non-Invasive Prenatal Testing of Trisomy 18 by an Epigenetic Marker in First Trimester Maternal Plasma

BackgroundQuantification of cell-free fetal DNA by methylation-based DNA discrimination has been used in non-invasive prenatal testing of fetal chromosomal aneuploidy. The maspin (Serpin peptidase inhibitor, clade B (ovalbumin), member 5; SERPINB5) gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells. The objective of this study was to evaluate the accuracy of non-invasive detection of fetal trisomy 18 using the unmethylated-maspin (U-maspin) gene as a cell-free fetal DNA marker and the methylated-maspin (M-maspin) gene as a cell-free total DNA marker in the first trimester of pregnancy.Methodology/Principal FindingsA nested case-control study was conducted using maternal plasma collected from 66 pregnant women, 11 carrying fetuses with trisomy 18 and 55 carrying normal fetuses. Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001). Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001). The specificities of U-maspin and M-maspin concentrations for non-invasive fetal trisomy 18 detection were 96.4% and 74.5%, respectively, with a sensitivity of 90.9%.ConclusionsOur results suggest that U-maspin and M-maspin concentrations may be useful as potential biomarkers for non-invasive detection of fetal trisomy 18 in the first trimester of pregnancy, irrespective of the sex and genetic variations of the fetus.

Noninvasive prenatal testing for trisomy 21: Challenges for implementation in Australia

The term 'Non invasive prenatal testing' is used to describe the rapidly emerging molecular technologies related to cell free DNA assessment that are being applied to prenatal screening for Down syndrome and other chromosomal abnormalities. This technology is now available to Australian women through a number of off-shore laboratories. We review the basis of this method of testing, the literature describing the effectiveness of NIPT in screening for trisomy 21 and the potential methods by which this tool could be incorporated into current screening strategies.

Patient acceptance of non-invasive testing for fetal aneuploidy via cell-free fetal DNA

Objective: To evaluate factors associated with patient acceptance of noninvasive prenatal testing for trisomy 21, 18 and 13 via cell-free fetal DNA.Methods: This was a retrospective study of all patients who were offered noninvasive prenatal testing at a single institution from 1 March 2012 to 2 July 2012. Patients were identified through our perinatal ultrasound database; demographic information, testing indication and insurance coverage were compared between patients who accepted the test and those who declined. Parametric and nonparametric tests were used as appropriate. Significant variables were assessed using multivariate logistic regression. The value p < 0.05 was considered significant.Results: Two hundred thirty-five patients were offered noninvasive prenatal testing. Ninety-three patients (40%) accepted testing and 142 (60%) declined. Women who accepted noninvasive prenatal testing were more commonly white, had private insurance and had more than one testing indication. There was no statistical difference in the number or the type of testing indications. Multivariable logistic regression analysis was then used to assess individual variables. After controlling for race, patients with public insurance were 83% less likely to accept noninvasive prenatal testing than those with private insurance (3% vs. 97%, adjusted RR 0.17, 95% CI 0.05–0.62).Conclusion: In our population, having public insurance was the factor most strongly associated with declining noninvasive prenatal testing.

Trisomy 13 detection in the first trimester of pregnancy using a chromosome‐selective cell‐free DNA analysis method

To assess the performance of chromosome-selective sequencing of maternal plasma cell-free DNA (cfDNA) in non-invasive prenatal testing for trisomy 13. Two-phase case-control study on a single plasma sample per case. The first phase was used to optimize the trisomy 13 algorithm, which was then applied to a second dataset to determine the risk score for trisomy 13 by laboratory personnel who were blinded to the fetal karyotype. In the first phase, trisomy 13 risk scores were given for 11 cases of trisomy 13 and 145 euploid cases at 11-13 weeks' gestation. The test identified seven (63.6%) cases of trisomy 13 with no false positives. The trisomy 13 algorithm was subsequently modified and the trisomy 13 risk score was > 99% in all 11 cases of trisomy 13 and < 0.01% in all 145 euploid cases. In the second phase, the new algorithm was used to generate trisomy 13 risk scores for 10 cases of trisomy 13 and 1939 euploid cases. The trisomy 13 risk scores were > 99% in eight (80.0% (95% confidence interval (CI), 49.0-94.3%)) cases of trisomy 13. In the 1939 euploid cases the risk score for trisomy 13 was < 0.01% in 1937 (99.9%), 0.79% in one, and > 99% in one. Therefore, at the predefined risk cut-off of 1% for classifying a sample as high or low risk, the false-positive rate (FPR) was 0.05% (95% CI, 0.0-0.3%). Chromosome-selective sequencing of cfDNA can detect the majority of cases of trisomy 13 at an FPR of less than 0.1%.