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

Introduction: 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). Objectives: To assess performance, patients’ uptake, and cost of contingent cfDNA screening and to compare them with those of the established FCT. Methods: 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. Results: 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. Conclusions: Contingent cfDNA screening shows high DR, low IT rate, and high uptake at a similar cost than traditional screening.

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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

Journal of Medical Screening ◽

10.1258/jms.2008.008049 ◽

2008 ◽

Vol 15 (4) ◽

pp. 204-206 ◽

Cited By ~ 16

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.

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

Fetal Diagnosis and Therapy ◽

10.1159/000442198 ◽

2015 ◽

Vol 40 (3) ◽

pp. 214-218 ◽

Cited By ~ 1

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.

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

LaboratoriumsMedizin ◽

10.1515/labmed-2015-0084 ◽

2016 ◽

Vol 0 (0) ◽

Cited By ~ 1

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.

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

10.22541/au.160726360.01844693/v1 ◽

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.

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

Fetal Diagnosis and Therapy ◽

10.1159/000434632 ◽

2015 ◽

Vol 39 (2) ◽

pp. 105-112 ◽

Cited By ~ 4

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.

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First trimester ultrasound screening of chromosomal abnormalities

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0704153t ◽

2007 ◽

Vol 135 (3-4) ◽

pp. 153-156 ◽

Cited By ~ 4

Author(s):

Aleksandra Trninic-Pjevic ◽

Aleksandra Novakov-Mikic

Keyword(s):

Maternal Age ◽

Detection Rate ◽

Chromosomal Abnormalities ◽

False Positive Rate ◽

First Trimester ◽

Nuchal Translucency ◽

Ultrasound Screening ◽

Positive Rate ◽

Chromosomal Defects ◽

First Trimester Ultrasound

Introduction: A retrocervical subcutaneous collection of fluid at 11-14 weeks of gestation, can be visualized by ultrasound as nuchal translucency (NT). Objective. To examine the distribution of fetal nuchal translucency in low risk population, to determine the detection rate of chromosomal abnormalities in the population of interest based on maternal age and NT measurement. Method. Screening for chromosomal defects, advocated by The Fetal Medicine Foundation (FMF), was performed in 1,341 pregnancies in the period January 2000 - April 2004. Initial risk for chromosomal defects (based on maternal and gestational age) and corrected risk, after the NT measurement, were calculated. Complete data were collected from 1,048 patients. Results. Out of 1,048 pregnancies followed, 8 cases of Down?s syndrome were observed, 7 were detected antenatally and 6 out of 7 were detected due to screening that combines maternal age and NT measurement. According to our results, sensitivity of the screening for aneuploidies based on maternal age alone was 12.5% and false positive rate 13.1%, showing that screening based on NT measurement is of great importance. Screening by a combination of maternal age and NT, and selecting a screening-positive group for invasive testing enabled detection of 75% of fetuses with trisomy 21. Conclusion. In screening for chromosomal abnormalities, an approach which combines maternal age and NT is effective and increases the detection rate compared to the use of any single test. .

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Ductus Venosus: A Love Story of 14 Years

Donald School Journal of Ultrasound in Obstetrics & Gynecology ◽

10.5005/jp-journals-10009-1190 ◽

2011 ◽

Vol 5 (2) ◽

pp. 141-149 ◽

Cited By ~ 1

Author(s):

Nuno Montenegro ◽

Alexandra Matias

Keyword(s):

Blood Flow ◽

Chromosomal Abnormalities ◽

False Positive Rate ◽

First Trimester ◽

Nuchal Translucency ◽

Ductus Venosus ◽

Love Story ◽

Positive Rate ◽

Trimester Screening ◽

Twin Pregnancies

ABSTRACT Ductus venosus is a tiny vessel with a central role in fetal circulation. Combining B-mode with color and pulsed Doppler is feasible to identify this vessel and evaluate the blood flow waveform at 11 to 13 weeks. The higher prevalence of abnormal A-wave in fetuses with abnormal karyotype and/or cardiac defects turned DV evaluation into a useful marker for chromosomal abnormalities and cardiopathies. Even when combined with nuchal translucency (NT) or biochemical markers, DV blood flow evaluation contributes to an increase in sensitivity and reduces false-positive rate. Abnormal ductal flow is also related to a worse fetal and perinatal outcome. In monochorionic twin pregnancies, in addition to NT measurement at 11 to 14 weeks, the Doppler assessment of DV blood flow increases relevantly the performance of screening for those at higher risk of developing twin-to-twin transfusion syndrome. This story of 14 years surely contributed to change the way first trimester screening is being implemented.

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First Trimester Genetic Sonogram for Screening Fetal Down Syndrome: a Population-based Study

10.21203/rs.3.rs-48430/v1 ◽

2020 ◽

Author(s):

Kuntharee Traisrisilp ◽

Supatra Sirichotiyakul ◽

Fuanglada Tongprasert ◽

Kasemsri Srisupun ◽

Suchaya Luewan ◽

...

Keyword(s):

Down Syndrome ◽

Pregnant Women ◽

False Positive ◽

Detection Rate ◽

False Positive Rate ◽

Nasal Bone ◽

First Trimester ◽

Nuchal Translucency ◽

Ductus Venosus ◽

Positive Rate

Abstract Background: To evaluate the performance of first trimester sonomarkers in the detection of fetal Down syndrome among Thai pregnant womenMethods: Pregnant women at 11-13+6 weeks’ gestation underwent ultrasound examination for assessment of nuchal translucency (NT), nasal bone (NB), tricuspid regurgitation (TR), and abnormal ductus venosus (aDV) Doppler waveforms. The women were followed up for final outcomes. Fetal abnormalities other than trisomy 21 were excluded. The performances of each sonomarker and their combinations in predicting fetal Down syndrome were calculated.Results: A total of 7,820 pregnant women meeting the inclusion criteria were available for analysis, including 20 cases with fetal Down syndrome and 7,800 unaffected cases. Of the four sonomarkers, NT, as a single sonomarker, had the highest detection rate (55.0% at a false positive rate of about 5%), whereas the remaining single sonomarkers had low detection rate (15-20%). The combination of all sonomarkers had the highest detection rate of 70% but the false positive rate was as high as 10.8%. The combination of NT and NB had a detection rate of 60% with an acceptable false positive rate of 6.9%, whereas the other combinations yielded relatively high false positive rates. Conclusion: The first trimester genetic sonogram in screening for Down syndrome among Asian women is acceptably effective and may be offered to some selected groups of the population. NT is the best sonomarker with a detection rate of 55% at 5% false positive rate and its combination with NB can improve performance with minimal increase in false positive rate.

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

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1210606k ◽

2012 ◽

Vol 140 (9-10) ◽

pp. 606-611 ◽

Cited By ~ 1

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.

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First-trimester presentation of ultrasound findings in trisomy 13 and validation of multiparameter ultrasound-based risk calculation models to detect trisomy 13 in the late first trimester

Journal of Perinatal Medicine ◽

10.1515/jpm-2020-0383 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Bartosz Rajs ◽

Agnieszka Nocuń ◽

Anna Matyszkiewicz ◽

Marcin Pasternok ◽

Michał Kołodziejski ◽

...

Keyword(s):

Heart Defects ◽

False Positive Rate ◽

Nasal Bone ◽

First Trimester ◽

Nuchal Translucency ◽

Trisomy 13 ◽

Ductus Venosus ◽

Patau Syndrome ◽

A Prospective Study ◽

Cns Anomalies

AbstractObjectivesTo identify the most common ultrasound patterns of markers and anomalies associated with Patau syndrome (PS), to explore the efficacy of multiparameter sonographic protocols in detecting trisomy 13 (T13) and to analyze the influence of maternal age (MA) on screening performance. Methods: The project was a prospective study based on singleton pregnancies referred for a first-trimester screening examination. The scan protocol included nuchal translucency (NT), fetal heart rate (FHR), secondary ultrasound markers [nasal bone (NB), tricuspid regurgitation (TR), ductus venosus reversed a-wave (revDV)] and major anomaly findings. Results: The study population comprised 6133 pregnancies: 6077 cases of euploidy and 56 cases of T13. Statistically significant differences were found in MA, FHR, NT, absence of NB, presence of revDV, TR and single umbilical artery. Fourteen cases of T13 (25%) demonstrated no markers of aneuploidy. The best general detection rate (DR) (DR of 78.6% with an false positive rate (FPR) of 1.2%) was obtained for a cutoff of 1/300 utilizing the “NT+T13” algorithm. The logistic regression model revealed that the central nervous system (CNS) anomalies had the greatest odds ratio (of 205.4) for T13. Conclusions: The effectiveness of the multiparameter sonographic protocol used for T13 screening showed promising results in patients older than 36 years and suboptimal results in patients between 26 and 36 years old. When screening for T13 left heart defects, CNS anomalies, abdominal anomalies, FHR above the 95th percentile, increased NT, revDV and lack of NB should receive specific attention.

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