scholarly journals Evaluation of Cell-free Fetal DNA as a Second-Trimester Maternal Serum Marker of Down Syndrome Pregnancy

2003 ◽  
Vol 49 (2) ◽  
pp. 239-242 ◽  
Author(s):  
Antonio Farina ◽  
Erik S LeShane ◽  
Geralyn M Lambert-Messerlian ◽  
Jacob A Canick ◽  
Thomas Lee ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Detection Rate ◽  
False Positive Rate ◽  
Maternal Serum ◽  
Second Trimester ◽  
Fetal Dna ◽  
Screening Performance ◽  
Cell Free Fetal Dna ◽  
Positive Rate ◽  
Screening Marker

Abstract Background: Second-trimester cell-free fetal DNA (studied only in pregnancies with male fetuses) is higher in maternal serum samples from women carrying Down syndrome fetuses than in unaffected pregnancies. In this study we evaluated the potential performance of fetal DNA as a screening marker for Down syndrome. Methods: Data on maternal serum fetal DNA concentrations and the corresponding concentrations of the quadruple serum markers were available from 15 Down syndrome cases, each matched for gestational age and length of freezer storage, with 5 control samples. Analyte values were expressed as multiple(s) of the control or population median. Screening performance of fetal DNA, both alone and when added to estimates of quadruple marker performance, was determined after modeling using univariate and multivariate gaussian distribution analysis. Results: The median fetal DNA concentration in Down syndrome cases was 1.7 times higher than in controls. In univariate analysis, fetal DNA gave a 21% detection rate at a 5% false-positive rate. When added to quadruple marker screening, fetal DNA increased the estimated detection rate from 81% to 86% at a 5% false-positive rate. Conclusions: Cell-free fetal DNA, measured in maternal serum, can modestly increase screening performance above what is currently available in the second trimester. If and when maternal serum fetal DNA can be measured in pregnancies with both male and female fetuses, the utility and cost-effectiveness of adding it as a Down syndrome screening marker should be assessed.

scholarly journals Maternal Serum Invasive Trophoblast Antigen (Hyperglycosylated hCG) as a Screening Marker for Down Syndrome during the Second Trimester

2004 ◽  
Vol 50 (10) ◽  
pp. 1804-1808 ◽  
Author(s):  
Glenn E Palomaki ◽  
Louis M Neveux ◽  
George J Knight ◽  
James E Haddow ◽  
Raj Pandian
Keyword(s):  
United States ◽  
Down Syndrome ◽  
False Positive Rate ◽  
The United States ◽  
Maternal Serum ◽  
Second Trimester ◽  
Marker Panel ◽  
Screening Performance ◽  
Β Hcg ◽  
Screening Marker

Abstract Background: Approximately two million pregnancies in the United States are screened for Down syndrome annually by use of second-trimester maternal serum markers. At present, a combination of four markers can identify 75% of affected pregnancies when 5% of screened women are classified as candidates for amniocentesis. Although not currently included in screening panels, invasive trophoblast antigen (ITA) is a promising screening marker in serum or urine in both the second and first trimesters. This study aims at better defining the screening performance of serum ITA in the second trimester. Methods: In an earlier study, serum samples from an unbiased sampling of 45 Down syndrome (cases) and 238 unaffected (control) pregnancies between 14 and 20 weeks of gestation were collected from various centers in the United States. Samples were aliquoted and stored at −20 °C for 8 years. We measured ITA in these samples and determined the screening performance both univariately and in combination with other screening markers. Results: The median ITA in Down syndrome pregnancies was >3.00 multiples of the median, higher than that found for human chorionic gonadotropin (hCG) or free β-hCG. At a 5% false-positive rate, ITA univariately detected 38% and 40% of Down syndrome pregnancies, respectively, when assigned by date of last menstrual period or ultrasound date. Modeling yielded rates of 45% and 48%. ITA correlated strongly with hCG and free β-hCG. When substituted for either of these in a multiple marker panel, ITA performed comparably. Conclusions: This study indicates that serum ITA is an effective marker for Down syndrome. It is highly correlated with both hCG and free β-hCG and could replace either of them in a multiple marker panel.

Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia

2017 ◽  
Vol 56 (1) ◽  
Author(s):  
Carin P. De Villiers ◽  
Paula L. Hedley ◽  
Sophie Placing ◽  
Karen R. Wøjdemann ◽  
Anne-Cathrine Shalmi ◽  
...  
Keyword(s):  
Detection Rate ◽  
False Positive Rate ◽  
First Trimester ◽  
Serum Marker ◽  
Maternal Serum ◽  
Maternal Serum Screening ◽  
Discriminatory Ability ◽  
Screening Performance ◽  
Positive Rate ◽  
Placental Protein

AbstractBackground:Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified.Methods:PP13 was measured in first trimester (week 10Results:In severe PE (including HELLP) cases (n=26) the median PP13 concentration was 35.8 pg/mL (range: 17.8–85.5 pg/mL) and in PE pregnancies (n=10) with birth prior to week 34, the median PP13 concentration was 30.6 pg/mL (13.1–50.1 pg/mL), compared to controls with a median of 54.8 pg/mL (range: 15.4–142.6 pg/mL) (p<0.04). The population screening detection rate (DR) for a false-positive rate of 10% for severe PE and HELLP was 26% for PP13, 28% for PP13+PAPP-A, 33% for PP13+fLI, and 40% for PP13+PAPP-A+fLI.Conclusions:PP13 is a marker of severe PE and HELLP syndrome. The screening performance of PP13 can be markedly improved by combining it with fLI and PAPP-A.

Down syndrome and cell-free fetal DNA in archived maternal serum

2002 ◽  
Vol 187 (5) ◽  
pp. 1217-1221 ◽  
Author(s):  
Thomas Lee ◽  
Erik S. LeShane ◽  
Geralyn M. Messerlian ◽  
Jacob A. Canick ◽  
Antonio Farina ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Maternal Serum ◽  
Fetal Dna ◽  
Cell Free Fetal Dna

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 Invasive Trophoblast Antigen (Hyperglycosylated Human Chorionic Gonadotropin) in Second-Trimester Maternal Urine as a Marker for Down Syndrome: Preliminary Results of an Observational Study on Fresh Samples

2004 ◽  
Vol 50 (1) ◽  
pp. 182-189 ◽  
Author(s):  
Glenn E Palomaki ◽  
George J Knight ◽  
Marie M Roberson ◽  
George C Cunningham ◽  
Jo Ellen Lee ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Observational Study ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
False Positive Rate ◽  
Serum Markers ◽  
Maternal Serum ◽  
Second Trimester ◽  
Preliminary Results ◽  
Hyperglycosylated Human Chorionic Gonadotropin

Abstract Background: Down syndrome screening is commonly performed in the US using maternal age and three or four second-trimester maternal serum markers that can identify up to 75% of affected pregnancies by offering diagnostic studies to 5% of women. Invasive trophoblast antigen [ITA; hyperglycosylated human chorionic gonadotropin (hCG)] is a promising marker that can be measured in urine or serum in the first or second trimester. We report preliminary results for urinary ITA in an ongoing observational study. Methods: Women undergoing second-trimester amniocentesis for reasons not associated with biochemical testing provided consent and a urine (and possibly serum) sample that was tested within a few days. Demographic and pregnancy-related information was collected, along with karyotype. Screening performance was modeled for ITA alone and in combination with serum markers Results: Twelve recruitment centers collected urine from 2055 women with singleton pregnancies between 15 and 20 weeks of gestation (2023 unaffected, 28 Down syndrome, and 4 pregnancies with other chromosome abnormalities). After correction for gestational age, urine concentration, and maternal race and weight, the ITA measurements were higher in women with a Down syndrome pregnancy (median ITA, 4.33 multiples of the median). At a 75% detection rate, the false-positive rate could be reduced by substituting ITA for hCG measurements (from 5.6% to 2.6% for the triple test) or by adding ITA measurements to existing combinations (from 3.3% to 2.0% for the quadruple test). Conclusions: Our data provide preliminary confirmation of the potential usefulness of urinary ITA measurements in detecting Down syndrome in a setting that simulates routine usage.

22 Fetal down syndrome is associated with increased cell-free fetal DNA levels in archived maternal serum samples

2001 ◽  
Vol 185 (6) ◽  
pp. S79 ◽  
Author(s):  
Thomas Lee ◽  
Erik Leshane ◽  
Geralyn Messerlian ◽  
Jacob Canick ◽  
Marshall Carpenter ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Maternal Serum ◽  
Serum Samples ◽  
Fetal Dna ◽  
Cell Free Fetal Dna

The efficacy of combining several risk factors as a screening test

2005 ◽  
Vol 12 (4) ◽  
pp. 197-201 ◽  
Author(s):  
Nicholas J Wald ◽  
Joan K Morris ◽  
Simon Rish
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
False Positive ◽  
Detection Rate ◽  
False Positive Rate ◽  
Individual Risk ◽  
Detection Rates ◽  
Screening Performance ◽  
Positive Rate ◽  
The Individual

Objective: To determine the quantitative effect on overall screening performance (detection rate for a given false-positive rate) of using several moderately strong, independent risk factors in combination as screening markers. Setting: Theoretical statistical analysis. Methods: For the purposes of this analysis, it was assumed that all risk factors were independent, had Gaussian distributions with the same standard deviation in affected and unaffected individuals and had the same screening performance. We determined the overall screening performance associated with using an increasing number of risk factors together, with each risk factor having a detection rate of 10%, 15% or 20% for a 5% false-positive rate. The overall screening performance was estimated as the detection rate for a 5% false-positive rate. Results: Combining the risk factors increased the screening performance, but the gain in detection at a constant false-positive rate was relatively modest and diminished with the addition of each risk factor. Combining three risk factors, each with a 15% detection rate for a 5% false-positive rate, yields a 28% detection rate. Combining five risk factors increases the detection rate to 39%. If the individual risk factors have a detection rate of 10% for a 5% false-positive rate, it would require combining about 15 such risk factors to achieve a comparable overall detection rate (41%). Conclusion: It is intuitively thought that combining moderately strong risk factors can substantially improve screening performance. For example, most cardiovascular risk factors that may be used in screening for ischaemic heart disease events, such as serum cholesterol and blood pressure, have a relatively modest screening performance (about 15% detection rate for a 5% false-positive rate). It would require the combination of about 15 or 20 such risk factors to achieve detection rates of about 80% for a 5% false-positive rate. This is impractical, given the risk factors so far discovered, because there are too few risk factors and their associations with disease are too weak.

Screening for Diabetic Retinopathy in Primary Care: Retinal Photography Alone can Be Used Efficiently and Effectively to Exclude Those with Sight Threatening Lesions

1997 ◽  
Vol 4 (3) ◽  
pp. 174-176 ◽  
Author(s):  
P M S Evans ◽  
T S Purewal ◽  
A Hopper ◽  
H Slater ◽  
D R L Jones ◽  
...  
Keyword(s):  
Primary Care ◽  
Diabetic Retinopathy ◽  
Gold Standard ◽  
Detection Rate ◽  
False Positive Rate ◽  
Poor Quality ◽  
Background Retinopathy ◽  
Screening Performance ◽  
Positive Rate ◽  
Retinal Photography

Background— Good screening performance of retinal photography and ophthalmoscopy together in screening for diabetic retinopathy in primary care have been reported. This study reanalysed the data to evaluate the screening performance of photography alone. Methods— One thousand and ten patients screened by fundal photography and ophthalmoscopy were studied retrospectively. Fundal photographs were quality graded with poor quality pictures being excluded from the analysis. Each patient was reviewed initially by both retinal photographs and ophthalmoscopy by an ophthalmologist, the “gold standard”. Six months later the fundal photographs were reviewed and reported in a blinded manner by the ophthalmologist. Results— Two thousand and fourteen photographs were obtained, of which 162 (8%) had to be excluded because of poor quality. On review of the remaining 18S2 photographs in isolation, of 77 cases of severe retinopathy as determined by the “gold standard”, 67 had severe changes on photography—detection rate 87%. Of the 1775 cases without sight threatening retinopathy only five were judged to have sight threatening changes on photography—false positive rate 0.3%. Considering sight threatening and background retinopathy together, the detection rate was 69% (2S7 of 375) and the false positive rate 1.6% (23 of 1477). Conclusion— Good quality fundal photographs alone seem specific enough to screen for sight threatening diabetic retinopathy, but will underdetect background retinopathy.

scholarly journals The effect of correlations between screening markers on screening performance

2007 ◽  
Vol 14 (3) ◽  
pp. 151-157 ◽  
Author(s):  
J K Morris ◽  
N J Wald
Keyword(s):  
Computer Simulation ◽  
Detection Rate ◽  
Prenatal Screening ◽  
False Positive Rate ◽  
Strong Correlations ◽  
Computer Simulation Study ◽  
Opposite Pattern ◽  
Screening Performance ◽  
Positive Rate ◽  
Highly Correlated

Objectives: It is widely thought that correlations between screening markers will tend to degrade screening performance. We performed a computer simulation study to investigate the quantitative effect of correlations between two markers on screening performance, using prenatal screening for Down's syndrome as an example, although the results apply generally. Methods: Monte Carlo simulation was used to generate values of two hypothetical markers, A and B, in 1000 affected and 1000 unaffected pregnancies. The means, standard deviations and correlations of A and B were varied in five different examples. Results: If markers A and B are, on average, higher in affected than unaffected pregnancies and each marker, individually, has the same detection rate for a given false-positive rate (i.e. the same screening performance), then the screening performance of A and B together tends to decrease as A and B become more positively correlated with each other (within affected or unaffected categories) and tends to increase as A and B become more negatively correlated. If A is, on average, higher in affected pregnancies and B is, on average, lower in affected pregnancies (but again each marker has the same screening performance), the opposite pattern is observed; screening performance increases as A and B become more positively correlated and screening performance decreases as they become more negatively correlated. If A and B have unequal screening performances, modest correlations between A and B have little effect on the screening performance of A and B together, but when the correlations are strong whether positive or negative (with r values greater than about 0.45 or less than −0.45) screening performance progressively increases. Conclusion: Correlations between screening markers considered separately in affected and unaffected pregnancies can either decrease or increase screening performance. In practice, these effects are usually modest, because most screening markers are not highly correlated with each other and the effects become important only with strong correlations, whether positive or negative.

Combining Carotid Intima-media Thickness with Carotid Plaque on Screening for Coronary Heart Disease

2009 ◽  
Vol 16 (3) ◽  
pp. 155-159 ◽  
Author(s):  
David S Wald ◽  
Jonathan P Bestwick ◽  
Geraint Morton ◽  
Linda Drummond ◽  
Nick Jenkins ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
False Positive ◽  
Carotid Plaque ◽  
Detection Rate ◽  
False Positive Rate ◽  
Intima Media Thickness ◽  
Carotid Imt ◽  
Percentage Points ◽  
Screening Performance ◽  
Positive Rate

Background Ultrasound-detected carotid artery intima-media thickness (IMT) and carotid plaque are possible screening tests for coronary heart disease (CHD) among asymptomatic individuals. Objective To assess the increase in screening performance of combining carotid IMT and plaque compared with each measurement alone in the identification of individuals with CHD. Methods Ultrasound examination of left and right carotid arteries was performed on 100 individuals (median age 57), 55 with a history of CHD (unstable angina or myocardial infarction) and 45 without. IMT measurements were taken from the common carotid artery and plaque was identified above, at and below the carotid bifurcation. Associations between IMT and plaque were determined using logistic regression, and screening performance was assessed from the distributions of IMT and plaque among cases and controls. Results At a false-positive rate of 5%, IMT (cut-off >0.75 mm) identified 30% (95% CI 14–58) of affected individuals. There was an increase in the detection rate of 8 percentage points (1–33%) using IMT and plaque combined compared with IMT alone. As the false-positive increased, the difference in the detection rate increased, up to a maximum of 20 percentage points (5–38%) at a false-positive rate of 20%. The comparison of IMT and plaque combined with plaque alone could only be estimated for the false-positive rate observed using plaque alone (18%); at this point the detection rate was 72% for plaque and 75% for plaque and IMT combined, an increase of 3 percentage points (0–4%). Conclusion In screening for CHD, combining carotid IMT measurement with plaque assessment is better than using either measurement alone, but the improvement in discrimination is not sufficient to make carotid ultrasound screening for CHD worthwhile.

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