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

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.

ADAM 12 may be used to reduce the false positive rate of first trimester combined screening for Down syndrome

2009 ◽  
Vol 30 (2) ◽  
pp. 110-114 ◽  
Author(s):  
Michael Christiansen ◽  
Kasper Pihl ◽  
Paula L. Hedley ◽  
Anne-Cathrine Gjerris ◽  
Pia Ø. Lind ◽  
...  
Keyword(s):  
Down Syndrome ◽  
False Positive ◽  
False Positive Rate ◽  
First Trimester ◽  
Positive Rate ◽  
Adam 12

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.

MATERNAL SERUM PAPP-A LEVELS AT 11+0 TO 13+6 WEEKS OF GESTATION IN THE PREDICTION OF HYPERTENSION DISORDER

2015 ◽  
pp. 143-152
Author(s):  
Ngoc Thanh Cao ◽  
Van Duc Vo ◽  
Vu Quoc Huy Nguyen ◽  
Quang Vinh Truong ◽  
Viet Nhan Nguyen ◽  
...  
Keyword(s):  
False Positive ◽  
Gestational Hypertension ◽  
False Positive Rate ◽  
First Trimester ◽  
Outcome Data ◽  
Maternal Serum ◽  
Control Group ◽  
Detection Rates ◽  
Screening Study ◽  
Positive Rate

Objective: To detect maternal serum PAPP-A levels at 11-13 weeks 6 day of gestation in pregnancies who subsequently develop pre-eclampsia and to evaluating the role of these screening PAPP-A in the prediction of pre-eclampsia. Materials and methods: Prospective screening study for preeclampsia in pregnant attending their first hospital visit at 11-13 weeks 6 of gestation. The performance of screening for PE by serum PAPP-A and free βhCG were determined. Results: Of 2,998 patients with complete outcome data, there were 3.74% of hypertension disorder, and 2.84% cases of pre-eclampsia. free βhCG levels were no different significantly in pregnancy who developed pre-eclampsia compared to the control group. PAPP-A levels were significantly lower in pregnants who developed early pre-eclampsia (0.653 MoM) and late pre-eclampsia (0.744 MoM) compared to the control group (1.039 MoM).In screening for PE by combinematernal factors and PAPP-A,at false positive rate of 5%, the estimateddetection rates were 36.4% and the detection rates were 54.6%, at at false positive rate of 10%. Conclusion: Low PAPP-A levels are associated with the development of preeclampsia; however, it should be combined with other tests to increase effectiveness of hypertension disorder screening at the first trimester. Key words: preeclampsia; gestational hypertension; screening; PAPP-A.

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.

Predicting Fetal Chromosome Anomalies in the First Trimester Using Pregnancy Associated Plasma Protein-A: A Comparison of Statistical Methods

1993 ◽  
Vol 32 (02) ◽  
pp. 175-179 ◽  
Author(s):  
B. Brambati ◽  
T. Chard ◽  
J. G. Grudzinskas ◽  
M. C. M. Macintosh
Keyword(s):  
Logistic Regression ◽  
General Population ◽  
Likelihood Ratio ◽  
False Positive ◽  
False Positive Rate ◽  
Ratio Method ◽  
Detection Rates ◽  
Gaussian Distributions ◽  
Positive Rate ◽  
Likelihood Ratio Method

Abstract:The analysis of the clinical efficiency of a biochemical parameter in the prediction of chromosome anomalies is described, using a database of 475 cases including 30 abnormalities. A comparison was made of two different approaches to the statistical analysis: the use of Gaussian frequency distributions and likelihood ratios, and logistic regression. Both methods computed that for a 5% false-positive rate approximately 60% of anomalies are detected on the basis of maternal age and serum PAPP-A. The logistic regression analysis is appropriate where the outcome variable (chromosome anomaly) is binary and the detection rates refer to the original data only. The likelihood ratio method is used to predict the outcome in the general population. The latter method depends on the data or some transformation of the data fitting a known frequency distribution (Gaussian in this case). The precision of the predicted detection rates is limited by the small sample of abnormals (30 cases). Varying the means and standard deviations (to the limits of their 95% confidence intervals) of the fitted log Gaussian distributions resulted in a detection rate varying between 42% and 79% for a 5% false-positive rate. Thus, although the likelihood ratio method is potentially the better method in determining the usefulness of a test in the general population, larger numbers of abnormal cases are required to stabilise the means and standard deviations of the fitted log Gaussian distributions.

scholarly journals Hyperglycosylated Human Chorionic Gonadotropin (Invasive Trophoblast Antigen) Immunoassay: A New Basis for Gestational Down Syndrome Screening

1999 ◽  
Vol 45 (12) ◽  
pp. 2109-2119 ◽  
Author(s):  
Laurence A Cole ◽  
Shohreh Shahabi ◽  
Utku A Oz ◽  
Ray O Bahado-Singh ◽  
Maurice J Mahoney
Keyword(s):  
Down Syndrome ◽  
False Positive ◽  
False Positive Rate ◽  
Normal Karyotype ◽  
Screen Test ◽  
Β Subunit ◽  
Second Trimester ◽  
Marker Test ◽  
Positive Rate ◽  
Down Syndrome Screening

Abstract Background: Serum human chorionic gonadotropin (hCG) and hCG free β-subunit tests are used in combination with unconjugated estriol and α-fetoprotein in the triple screen test, and with the addition of inhibin-A in the quadruple marker test for detecting Down syndrome in the second trimester of pregnancy. These tests have a limited detection rate for Down syndrome: ∼40% for hCG or free β-subunit alone, ∼60% for the triple screen test, and ∼70% for the quadruple marker test, all at 5%, or a relatively high, false-positive rate. New tests are needed with higher detection and lower false rates. Hyperglycosylated hCG (also known as invasive trophoblast antigen or ITA) is a new test. It specifically detects a unique oligosaccharide variant of hCG associated with Down syndrome pregnancies. We evaluated this new Down syndrome-directed test in prenatal diagnosis. Methods: Hyperglycosylated hCG was measured in urine samples from women undergoing amniocentesis for advanced maternal age concerns at 14–22 weeks of gestation, 1448 with normal karyotype and 39 with Down syndrome fetuses. Results: The median hyperglycosylated hCG value was 9.5-fold higher in Down syndrome cases (9.5 multiples of the normal karyotype median). The single test detected 80% of Down syndrome cases at a 5% false-positive rate. Urine hyperglycosylated hCG was combined with urine β-core fragment (urine breakdown product of serum hCG free β-subunit), serum α-fetoprotein, and maternal age-related risk. This urine-serum combination detected 96% of Down syndrome cases at a 5% false-positive rate, 94% of cases at a 3% false-positive rate, and 71% of cases at a 1% false-positive rate. These detection rates exceed those of any previously reported combination of biochemical markers. Conclusions: Hyperglycosylated hCG is a new base marker for Down syndrome screening in the second trimester of pregnancy. The measurement of hyperglycosylated hCG can fundamentally improve the performance of Down syndrome screening protocols.

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.

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