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

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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In combined first-trimester Down syndrome screening, the false-positive rate is not higher in pregnancies conceived after assisted reproduction compared with spontaneous pregnancies

Fertility and Sterility ◽

10.1016/j.fertnstert.2010.07.1048 ◽

2011 ◽

Vol 95 (1) ◽

pp. 378-381 ◽

Cited By ~ 15

Author(s):

Maarit Matilainen ◽

Sini Peuhkurinen ◽

Paivi Laitinen ◽

Ilkka Jarvela ◽

Laure Morin-Papunen ◽

...

Keyword(s):

Down Syndrome ◽

Assisted Reproduction ◽

False Positive ◽

False Positive Rate ◽

First Trimester ◽

Positive Rate ◽

Down Syndrome Screening

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Improved first-trimester Down syndrome screening performance by lowering the false-positive rate: a prospective study of 9941 low-risk women

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.1834 ◽

2005 ◽

Vol 25 (3) ◽

pp. 227-233 ◽

Cited By ~ 41

Author(s):

K. R. Wøjdemann ◽

A. C. Shalmi ◽

M. Christiansen ◽

S. O. Larsen ◽

K. Sundberg ◽

...

Keyword(s):

Down Syndrome ◽

Prospective Study ◽

False Positive ◽

False Positive Rate ◽

First Trimester ◽

Screening Performance ◽

Positive Rate ◽

A Prospective Study ◽

Low Risk Women ◽

Down Syndrome Screening

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

Clinical Chemistry ◽

10.1093/clinchem/45.12.2109 ◽

1999 ◽

Vol 45 (12) ◽

pp. 2109-2119 ◽

Cited By ~ 80

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.

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Predicting first-trimester outcome of embryos with cardiac activity in women with recurrent spontaneous abortion

Journal of International Medical Research ◽

10.1177/0300060520911829 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006052091182

Author(s):

Huixian Li ◽

Shuang Qin ◽

Fanfan Xiao ◽

Yuhong Li ◽

Yunhe Gao ◽

...

Keyword(s):

Pregnant Women ◽

False Positive ◽

Detection Rate ◽

False Positive Rate ◽

Cardiac Activity ◽

First Trimester ◽

Clinical Indicators ◽

Early Outcome ◽

Heart Motion ◽

Positive Rate

Objective This study was performed to evaluate the capability of routine clinical indicators to predict the early outcome of embryos with cardiac activity in women with recurrent spontaneous abortion (RSA). Methods A retrospective cohort study of pregnant women with a history of RSA in a Chinese tertiary hospital was performed using unadjusted and multivariable logistic regression. Results Of 789 pregnant women with RSA, 625 (79.21%) had ongoing pregnancy, whereas 164 (20.79%) developed abortion before 20 full weeks of gestational age even after embryonic heart motion was detected. The final model had an area under the curve of 0.81 (95% confidence interval, 0.78–0.84) with a sensitivity of 74.39%, a specificity of 76.00%, and a false-positive rate of 52.32% at a fixed detection rate of 90%. Conclusions The combination of multiple routine clinical indicators was valuable in predicting the early outcome of embryos with cardiac activity in viable pregnancies with RSA. However, this model might result in a high false-positive rate with a fixed detection rate of 90%; other markers must be investigated to identify first-trimester RSA once positive embryonic heart motion is established.

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Impaired renal function in the mother may result in a high false positive rate in Down Syndrome screening

Journal of Obstetrics and Gynaecology ◽

10.1080/01443610600618671 ◽

2006 ◽

Vol 26 (4) ◽

pp. 376-377 ◽

Cited By ~ 3

Author(s):

L. M. Byrd ◽

P. Baker

Keyword(s):

Renal Function ◽

Down Syndrome ◽

False Positive ◽

Impaired Renal Function ◽

False Positive Rate ◽

High False Positive Rate ◽

Positive Rate ◽

Down Syndrome Screening

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New screen on the block: non-invasive prenatal testing for fetal chromosomal abnormalities

Journal of Primary Health Care ◽

10.1071/hc16055 ◽

2017 ◽

Vol 9 (4) ◽

pp. 248 ◽

Cited By ~ 1

Author(s):

Sara Filoche ◽

Beverley Lawton ◽

Angela Beard ◽

Anthony Dowell ◽

Peter Stone

Keyword(s):

False Positive ◽

Chromosomal Abnormalities ◽

False Positive Rate ◽

Prenatal Testing ◽

Diagnostic Procedures ◽

First Trimester ◽

Maternal Blood ◽

Non Invasive ◽

Positive Rate ◽

Trimester Screening

ABSTRACT Non-invasive prenatal testing (NIPT) is a new screen for fetal chromosomal abnormalities. It is a screening test based on technology that involves the analysis of feto-placental DNA that is present in maternal blood. This DNA is then analysed for abnormalities of specific chromosomes (eg 13, 18, 21, X, Y). NIPT has a much higher screening capability for chromosomal abnormalities than current combined first trimester screening, with ~99% sensitivity for trisomy 21 (Down syndrome) and at least a 10-fold higher positive predictive value. The low false-positive rate (1–3%) is one of the most advertised advantages of NIPT. In practice, this could lead to a significant reduction in the number of false-positive tests and the need for invasive diagnostic procedures. NIPT is now suitable for singleton and twin pregnancies and can be performed from ~10 weeks in a pregnancy. NIPT is not currently publicly funded in most countries. However, the increasing availability of NIPT commercially will likely lead to an increase in demand for this as a screening option. Given the high numbers of women who visit a general practitioner (GP) in their first trimester, GPs are well-placed to also offer NIPT as a screening option. A GP’s role in facilitating access to this service will likely be crucial in ensuring equity in access to this technology, and it is important to ensure that they are well supported to do so.

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