Performance characteristics of Elecsys free βhCG and PAPP-A for first trimester trisomy 21 risk assessment in gestational weeks 8+0 to 14+0

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Niels Tørring ◽  
Carlos Aulesa ◽  
Bernd Eiben ◽  
Mª José Ferri ◽  
Kypros H. Nicolaides ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Trisomy 21 ◽  
False Positive Rate ◽  
Protein A ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Serological Markers ◽  
Cross Sectional ◽  
Positive Rate ◽  
Technical Validation

AbstractScreening for fetal trisomy 21 (T21) in the first trimester includes analysis of the serological markers pregnancy-associated plasma protein A (PAPP-A) and free β-choriogonadotropin (free βhCG). With the recent launch of these assays on the cobas e and Elecsys platforms, we investigated their clinical and analytical performance.We conducted a multicenter study in 5397 pregnancies including 108 cross-sectional collected repository cases with verified fetal T21 at 8–14 weeks of gestation. A technical validation of the Roche ElecsysThe imprecision of the Elecsys free βhCG and PAPP-A assays was between 1.0% and 2.8%, and both assays showed correlation to Kryptor (free βhCG 0.981; PAPP-A 0.987), AutoDELFIA (free βhCG 0.995; PAPP-A 0.979) and IMMULITE assays (free βhCG 0.983; PAPP-A 0.983). With a cut off at 1:300 the overall sensitivity of the screening including nuchal translucency reached 94% for a 3% false positive rate.The Roche Elecsys free βhCG and PAPP-A are suitable and reliable assays for first trimester T21 risk assessment. Both assays were approved and recommended by the FMF.

First trimester Down's syndrome screening marker values and cigarette smoking: new data and a meta-analysis on free β human chorionic gonadotophin, pregnancy-associated plasma protein-A and nuchal translucency

2008 ◽  
Vol 15 (4) ◽  
pp. 204-206 ◽  
Author(s):  
Jonathan P Bestwick ◽  
Wayne J Huttly ◽  
Nicholas J Wald
Keyword(s):  
Meta Analysis ◽  
False Positive Rate ◽  
Protein A ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Screening Performance ◽  
Combined Test ◽  
Positive Rate ◽  
Trimester Screening ◽  
Β Hcg

Objectives To examine the effect of smoking on three first trimester screening markers for Down's syndrome that constitute the Combined test, namely nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A) and free β human chorionic gonadotophin (free β-hCG) and to use the results to determine which of these markers need to be adjusted for smoking and by how much. Methods The difference in the median multiple of the median (MoM) values in smokers compared to non-smokers was determined for NT, PAPP-A and free β-hCG in 12,517 unaffected pregnancies that had routine first trimester Combined test screening. These results were then included in a meta-analysis of published studies and the effect of adjusting for smoking on screening performance of the Combined test was estimated. Results The results using the routine screening data were similar to the summary estimates from the meta-analysis of all studies. The results from the meta-analysis were; median MoM in smokers compared to non-smokers: 1.06 NT (95% confidence interval 1.03 to 1.10), 0.81 PAPP-A (0.80 to 0.83) and 0.94 free β-hCG (0.89 to 0.99). The effect of adjusting for smoking on the Combined test is small, with an estimated less than half percentage point increase in the detection rate (the proportion of affected pregnancies with a positive result) for a 3% false-positive rate (the proportion of unaffected pregnancies with a positive result) and less than 0.2 percentage point decrease in the false-positive rate for an 85% detection rate. Conclusion Adjusting first trimester screening markers for smoking has a minimal favourable effect on screening performance, but it is simple to implement and this paper provides the adjustment factors needed if a decision is made to make such an adjustment.

How Effective Is First-Trimester Screening for Trisomy 21 Based on Ultrasound Only?

2015 ◽  
Vol 39 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Marcin Wiechec ◽  
Anna Knafel ◽  
Agnieszka Nocun ◽  
Anna Matyszkiewicz ◽  
Magdalena Juszczak ◽  
...  
Keyword(s):  
Trisomy 21 ◽  
False Positive Rate ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Cardiac Anomaly ◽  
Screening Methods ◽  
Detection Rates ◽  
Comparable Performance ◽  
Positive Rate ◽  
A Prospective Study

Objective: To evaluate the most common first-trimester ultrasound features of fetuses with trisomy 21 (T21) and to examine the screening performance for Down syndrome (DS) using only ultrasound-based protocols. To investigate whether maternal age (MA) has an impact on the efficacy of the ultrasound-based screening methods. Methods: In a prospective study, 6,265 patients were examined. Two ultrasound-based risk calculation protocols were applied: ‘NT' (based on nuchal translucency) and ‘NT+' (based on NT and secondary markers). Results: A total of 5,696 patients were enrolled for analysis; 84 subjects with T21 were identified. Combinations of abnormal ultrasound markers were observed in only 1.2% of euploid fetuses compared to 71.5% of fetuses with T21. Among 17.9% of DS cases with cardiac anomaly, 14.3% comprised atrioventricular septal defects. For a false-positive rate of 3%, the detection rates of T21 were 73.8 and 91.7% for the ‘NT' and ‘NT+' protocols, respectively. The efficacy of both methods was affected by MA. Conclusions: Most of the fetuses with DS demonstrate a combination of ultrasound markers of aneuploidy in the first trimester. The ‘NT+' protocol is efficient and provides comparable performance as a combined screening test. It is a valuable method, especially when the access to biochemical analysis is restricted.

scholarly journals Screening for aneuploidies by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-13+6 gestational weeks

2012 ◽  
Vol 140 (9-10) ◽  
pp. 606-611 ◽  
Author(s):  
Natasa Karadzov-Orlic ◽  
Amira Egic ◽  
Dejan Filimonovic ◽  
Maja Marinkovic ◽  
Barbara Damnjanovic-Pazin ◽  
...  
Keyword(s):  
False Positive ◽  
Trisomy 21 ◽  
Maternal Age ◽  
False Positive Rate ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Maternal Serum ◽  
Trisomy 18 ◽  
Serum Free ◽  
Positive Rate

Introduction. Aneuploidies are the major cause of perinatal death and early psychophysical disorders. Objective. In this study, we analyzed detection and false-positive rates of screening for aneuploidies in the first trimester by the combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotrophin (?-hCG), and pregnancy-associated plasma protein-A (PAPP-A) at 11-13+6 weeks of gestation, using the appropriate software developed by the Fetal Medicine Foundation. Methods. Our screening study for aneuploidies analyzed 4172 singleton pregnancies from January 2006 to December 2010. The sensitivities and false-positive rates using the combined aneuploidies determination for the risk cut-off of 1:275 were evaluated. Results. In the trisomy 21 pregnancies, the fetal NT was higher than 95th centile, in 72.8%, serum free b-hCG concentration it was above the 95th centile in 55% and serum PAPP-A was below the 5th centile in 47% of the cases. In the trisomy 18 and 13, the fetal NT was above 95th centile in 66.6% and 44.4% of the cases, respectively. The serum free b-hCG concentration was above the 95th centile in 0 and 10%, but serum PAPP-A was below 5th centile in 80.9% and 88.8% of pregnancies. In the trisomy 21 pregnancies the median free beta-hCG was 2.3 MoM and the median PAPP-A was 0.45 MoM. Chromosomal abnormalities were detected in 169 fetuses: trisomy 21 (97), Turner syndrome (19), trisomy 18 (28), trisomy 13 (11) and others (14). Detection rate of combined screening for aneuploides were 86.0% with false positive rate of 5.3% (mean age 33?4.9 years, >35 years in 35% of pregnancies). Conclusion. Our study suggests that the strategy of first-trimester combined screening of biochemical values and ultrasonographic parameters at 12 gestational weeks identifies higher percentage of aneuploidies with a lower false-positive rate than a single parameter strategy.

scholarly journals Clinical and Economic Evaluation after Adopting Contingent Cell-Free DNA Screening for Fetal Trisomies in South Spain

2020 ◽  
Vol 47 (10) ◽  
pp. 749-756
Author(s):  
José A. Sainz ◽  
María R. Torres ◽  
Ignacio Peral ◽  
Reyes Granell ◽  
Manuel Vargas ◽  
...  
Keyword(s):  
False Positive Rate ◽  
Cost Effective ◽  
First Trimester ◽  
Nuchal Translucency ◽  
University Hospitals ◽  
Combined Test ◽  
Positive Rate ◽  
Fetal Malformations ◽  
Cfdna Screening ◽  
Singleton Pregnancies

<b><i>Introduction:</i></b> Contingent cell-free (cf) DNA screening on the basis of the first-trimester combined test (FCT) results has emerged as a cost-effective strategy for screening of trisomy 21 (T21). <b><i>Objectives:</i></b> To assess performance, patients’ uptake, and cost of contingent cfDNA screening and to compare them with those of the established FCT. <b><i>Methods:</i></b> This is a prospective cohort study including all singleton pregnancies attending to their FCT for screening of T21 at 2 university hospitals in South Spain. When the FCT risk was ≥1:50, there were major fetal malformations, or the nuchal translucency was ≥3.5 mm, women were recommended invasive testing (IT); if the risk was between 1:50 and 1:270, women were recommended cfDNA testing; and for risks bellow 1:270, no further testing was recommended. Detection rate (DR), false-positive rate (FPR), patients’ uptake, and associated costs were evaluated. <b><i>Results:</i></b> We analyzed 10,541 women, including 46 T21 cases. DR of our contingent strategy was 89.1% (41/46) at 1.4% (146/10,541) FPR. Uptake of cfDNA testing was 91.2% (340/373), and overall IT rate was 2.0%. The total cost of our strategy was €1,462,895.7, similar to €1,446,525.7 had cfDNA testing not been available. <b><i>Conclusions:</i></b> Contingent cfDNA screening shows high DR, low IT rate, and high uptake at a similar cost than traditional screening.

Impact of Including or Removing Nuchal Translucency Measurement on the Detection and False-Positive Rates of First-Trimester Down Syndrome Screening

2015 ◽  
Vol 40 (3) ◽  
pp. 214-218 ◽  
Author(s):  
Emmanuel Spaggiari ◽  
Isabelle Czerkiewicz ◽  
Corinne Sault ◽  
Sophie Dreux ◽  
Armelle Galland ◽  
...  
Keyword(s):  
Down Syndrome ◽  
False Positive ◽  
False Positive Rate ◽  
Method Comparison ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Routine Practice ◽  
Detection Rates ◽  
Significant Difference ◽  
Positive Rate

Introduction: First-trimester Down syndrome (DS) screening combining maternal age, serum markers (pregnancy-associated plasma protein-A and beta-human chorionic gonadotropin) and nuchal translucency (NT) gives an 85% detection rate for a 5% false-positive rate. These results largely depend on quality assessment of biochemical markers and of NT. In routine practice, despite an ultrasound quality control organization, NT images can be considered inadequate. The aim of the study was to evaluate the consequences for risk calculation when NT measurement is not taken into account. Material and Method: Comparison of detection and false-positive rates of first-trimester DS screening (PerkinElmer, Turku, Finland), with and without NT, based on a retrospective study of 117,126 patients including 274 trisomy 21-affected fetuses. NT was measured by more than 3,000 certified sonographers. Results: There was no significant difference in detection rates between the two strategies including or excluding NT measurement (86.7 vs. 81.8%). However, there was a significant difference in the false-positive rates (2.23 vs. 9.97%, p < 0.001). Discussion: Sonographers should be aware that removing NT from combined first-trimester screening would result in a 5-fold increase in false-positive rate to maintain the expected detection rates. This should be an incentive for maintaining quality in NT measurement.

scholarly journals First Trimester Biochemical Screening for Trisomy 21: The Role of Free Beta hCG, Alpha Fetoprotein and Pregnancy Associated Plasma Protein A

1994 ◽  
Vol 31 (5) ◽  
pp. 447-454 ◽  
Author(s):  
K Spencer ◽  
D A Aitken ◽  
J A Crossley ◽  
G McCaw ◽  
E Berry ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Plasma Protein ◽  
Human Chorionic Gonadotropin ◽  
Trisomy 21 ◽  
False Positive Rate ◽  
Protein A ◽  
First Trimester ◽  
Serum Markers ◽  
Maternal Serum ◽  
Detection Rates

The potential efficacy of screening for trisomy 21 in the first trimester, using maternal serum markers α fetoprotein, free β human chorionic gonadotropin, unconjugated oestriol and pregnancy associated plasma protein A, was studied in an unselected population of women between the seventh and fourteenth week of gestation. Using a combination of α fetoprotein and free β human chorionic gonadotropin, 53% of affected pregnancies could be identified at a false positive rate of 5%. Unconjugated oestriol and pregnancy associated plasma protein A levels were lower in cases of trisomy 21, but their inclusion with other markers did not significantly improve detection rate. Monitoring the same pregnancies also in the second trimester showed that screening in the first trimester identified the same cases as in the second. We conclude that first trimester screening using free β human chorionic gonadotropin and α fetoprotein, is a viable possibility and will lead to detection rates in excess of 50%. Prospective studies are needed to confirm these observations.

scholarly journals First-Trimester Risk Calculation for Trisomy 13, 18, and 21: Comparison of the Screening Efficiency between 2 Locally Developed Programs and Commercial Software

2011 ◽  
Vol 57 (7) ◽  
pp. 1023-1031 ◽  
Author(s):  
Steen Sørensen ◽  
Günther Momsen ◽  
Karin Sundberg ◽  
Lennart Friis-Hansen ◽  
Finn Stener Jørgensen
Keyword(s):  
False Positive Rate ◽  
Protein A ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Maternal Plasma ◽  
Trisomy 13 ◽  
Individual Risk ◽  
Risk Calculation ◽  
Commercial Program ◽  
Screening Efficiency

BACKGROUND Reliable individual risk calculation for trisomy (T) 13, 18, and 21 in first-trimester screening depends on good estimates of the medians for fetal nuchal translucency thickness (NT), free β-subunit of human chorionic gonadotropin (hCGβ), and pregnancy-associated plasma protein-A (PAPP-A) in maternal plasma from unaffected pregnancies. Means and SDs of these parameters in unaffected and affected pregnancies are used in the risk calculation program. Unfortunately, our commercial program for risk calculation (Astraia) did not allow use of local medians. We developed 2 alternative risk calculation programs to assess whether the screening efficacies for T13, T18, and T21 could be improved by using our locally estimated medians. METHODS We established these estimates from 19 594 women with singleton pregnancies and from 100 pregnant women carrying a fetus affected with trisomy (11 with T13, 23 with T18, and 66 with T21). All measured values were recalculated to a multiple of the median (MoM) and log10 transformed; the mean and SD were calculated for each group. RESULTS At a given risk cutoff value, we observed a slight improvement in detection rate (DR) for T13, T18, and T21 for a slightly higher false-positive rate (FPR) compared with the commercial program. The lower FPR in the commercial program was caused mainly by an inaccuracy in the PAPP-A median. CONCLUSIONS Center-specific medians for NT, hCGβ, and PAPP-A should be used in risk calculation programs to ensure high DRs and low FPRs for all 3 trisomies at a given risk cutoff.

scholarly journals Impact of replacing or adding placental growth factor on Down syndrome screening: a prospective cohort study

2020 ◽  
Author(s):  
Wing To Angela Sin ◽  
Liona Poon ◽  
Piya Chaemsaithong ◽  
Yi Man Wah ◽  
Shuk Yi Annie Hui ◽  
...  
Keyword(s):  
Growth Factor ◽  
Test Performance ◽  
Trisomy 21 ◽  
Detection Rate ◽  
False Positive Rate ◽  
First Trimester ◽  
Placental Growth Factor ◽  
Singleton Pregnancy ◽  
Combined Test ◽  
Positive Rate

Objectives: To assess whether adding placental growth factor (PlGF) or replacing pregnancy-associated plasma protein-A (PAPP-A) improves the first trimester combined test performance for trisomy 21. Design: Prospective observation Cohort Setting: The Chinese University of Hong Kong, China Sample: 11,518 women having a singleton pregnancy screened for trisomy 21 between December 2016 and December 2019 using the first trimester combined test. Methods: PlGF was prospectively measured and estimated term risk for trisomy 21 was calculated by 1) replacing PAPP-A with PlGF and 2) adding PlGF to the combined test which includes nuchal translucency, PAPP-A and free β-human chorionic gonadotropin (hCG). Main Outcome Measure: Screening performance, area under curve (AUC), detection rate (DR), screen positive rate (SPR) and false positive rate (FPR) Results: 29 women had trisomy 21. The combined tests DR, FPR and SPR were 89.7%, 5.7% and 6% respectively. DR when replacing PAPP-A or adding PlGF to the combined test remained unchanged. Replacing PAPP-A by PlGF increased FPR and SPR to 6.2% and 6.4% respectively. Adding PlGF to the combined test gave FPR and SPR rates of 5.5% and 5.7% respectively. Adding or replacing PlGF did not give a significant increase in AUC (p>0.48) over that of the combined test. Conclusion: Adding PlGF to the combined test or replacing PAPP-A with PlGF in the combined test did not improve trisomy 21 detection rate. Replacing PAPP-A by PlGF increased SPR, whilst adding PlGF resulted in only a marginal reduction in SPR.

scholarly journals Early Prediction of Preeclampsia

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Leona C. Poon ◽  
Kypros H. Nicolaides
Keyword(s):  
Early Onset ◽  
False Positive Rate ◽  
Protein A ◽  
First Trimester ◽  
Maternal Serum ◽  
Uterine Artery Doppler ◽  
Maternal Risk ◽  
Positive Rate ◽  
First Trimester Of Pregnancy ◽  
Early Onset Preeclampsia

Effective screening for the development of early onset preeclampsia (PE) can be provided in the first-trimester of pregnancy. Screening by a combination of maternal risk factors, uterine artery Doppler, mean arterial pressure, maternal serum pregnancy-associated plasma protein-A, and placental growth factor can identify about 95% of cases of early onset PE for a false-positive rate of 10%.

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