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.

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.

Prenatal serum screening for Down syndrome and neural tube defects in the United States: Changes in utilization patterns from 2012 to 2020

2021 ◽  
pp. 096914132110316
Author(s):  
Nathalie Lepage ◽  
Philip Wyatt ◽  
Edward R Ashwood ◽  
Robert G Best ◽  
Thomas Long ◽  
...  
Keyword(s):  
United States ◽  
Down Syndrome ◽  
First Trimester ◽  
The United States ◽  
Maternal Serum ◽  
Second Trimester ◽  
Maternal Serum Screening ◽  
Cell Free Dna ◽  
Free Dna ◽  
Serum Screening

Objective To compile current usage of serum-based prenatal screening for Down syndrome in the United States and compare it with results from a similar 2011/2012 survey. Setting The College of American Pathologists maternal screening proficiency testing survey includes a supplemental question on the first of three yearly distributions. Methods Information regarding tests offered and the monthly number of pregnancies tested for US-based laboratories were reviewed. Results were stratified by size of laboratory, tests offered, and pregnancies tested. Findings were compared to an earlier survey. Results Fifty-six laboratories reported they will have screened 1,131,336 pregnancies in 2020. Of these, 36% are screened by stand-alone first trimester testing, 48% by stand-alone second trimester testing, and 16% using tests that integrate results from both trimesters. Eighty percent of all serum screens were provided by the five laboratories that performed the most screens (at least 50,000). These five performed similar proportions of first or second trimester screens (42.2% and 41.8%, respectively). Compared to eight years earlier, there are now 54% fewer laboratories. Pregnancies screened using the first trimester, second trimester, and integrated protocols were lower by 27%, 69%, and 72%, respectively. The serum screening activity in the US showed a 62% decrease from 2012 levels. During 2012–2020, the number of cell-free DNA tests increased from negligible to 1,492,332. Conclusions Maternal serum screening for common aneuploidies has changed significantly in eight years with fewer laboratories, a shift toward larger laboratories and a 2.5-fold reduction in pregnancies tested, likely due to the introduction of cell-free DNA screening.

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.

scholarly journals Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A

1998 ◽  
Vol 5 (3) ◽  
pp. 115-119 ◽  
Author(s):  
J E Haddow ◽  
G E Palomaki ◽  
G J Knight ◽  
D L Foster ◽  
L M Neveux
Keyword(s):  
Down's Syndrome ◽  
Down’S Syndrome ◽  
The United States ◽  
Serum Markers ◽  
Maternal Serum ◽  
Human Chorionic Gonadotrophin ◽  
Second Trimester ◽  
Serum Samples ◽  
Inhibin A ◽  
Screening Performance

Objectives To determine the second trimester Down's syndrome screening performance of maternal serum dimeric inhibin A, both alone and in combination with existing serum markers. Setting A case-control set of serum samples from patients with Down's syndrome (52) and subjects with matched unaffected pregnancies obtained in a previous cohort study before second trimester amniocentesis and karyotyping. The amniocenteses were performed for reasons other than a positive serum screening test result. Methods For each serum from a Down's syndrome pregnancy, five serum samples from pregnancies with a normal karyotype were matched for recruitment centre, gestational age, maternal age, and date of amniocentesis. A specific form of inhibin (dimeric inhibin A) was measured using monoclonal antibodies. Measurements of α fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin and its free β subunit were already available. Screening performance was modelled using distribution variables of the analytes coupled with the 1993 age distribution of pregnant women in the United States. Results The median dimeric inhibin A level was 2.10 times higher in Down's syndrome pregnancies. When dimeric inhibin A was combined with maternal age and three other serum markers (α fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin) the Down's syndrome detection rate increased to 75% (from 66%) at a 5% false positive rate. If dimeric inhibin A could be added for less than $31 (ranging from $16 to $39 depending on the detection rate, markers chosen, and method of dating), the cost of detecting each Down's syndrome pregnancy and the number of procedure related fetal losses would both be reduced. Conclusions The addition of dimeric inhibin A to prenatal screening programmes for Down's syndrome should be considered, or possibly it could be substituted for an existing serum marker. One barrier to implementation in the United States, however, is the unavailability of kits with Food and Drug Administration approval.

Maternal serum screening for Down syndrome in the United States: A 1995 survey

1997 ◽  
Vol 176 (5) ◽  
pp. 1046-1051 ◽  
Author(s):  
Glenn E. Palomaki ◽  
George J. Knight ◽  
Jane E. McCarthy ◽  
James E Haddow ◽  
John M Donhowe
Keyword(s):  
United States ◽  
Down Syndrome ◽  
The United States ◽  
Maternal Serum ◽  
Maternal Serum Screening ◽  
Serum Screening

scholarly journals Evaluation of Maternal Serum sHLA-G Levels for Trisomy 18 Fetuses Screening at Second Trimester

2021 ◽  
Vol 11 ◽  
Author(s):  
Danping Xu ◽  
Yiyang Zhu ◽  
Lanfang Li ◽  
Yingping Xu ◽  
Weihua Yan ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Prenatal Screening ◽  
Maternal Serum ◽  
Trisomy 18 ◽  
Second Trimester ◽  
Serum Samples ◽  
Predictive Values ◽  
Second Trimester Screening ◽  
Β Hcg ◽  
Screening Marker

Human leukocyte antigen-G (HLA-G) has been widely acknowledged to play critical roles in fetal-maternal maintenance. However, the significance of using maternal serum sHLA-G to detect prenatal chromosomal abnormality has not been investigated. In China, prenatal screening using maternal α-fetoprotein (AFP), unconjugated estriol (uE3), and free β subunit human chorionic gonadotropin (β-hCG) in the second trimester has been widely applied. In this study, we evaluated the use of sHLA-G as a screening marker, compared with traditional second trimester prenatal screening. Serum samples from 1,019 singleton women in their second trimester were assessed. Among them, 139 infants were confirmed with trisomy 21 (T21) by karyotyping, 83 were confirmed with trisomy 18 (T18), and the remaining 797 infants had no abnormalities. The sHLA-G levels in maternal sera were significantly lower in pregnant women with T18 fetuses (median: 47.8 U/ml, range: 9.8–234.2 U/ml) and significantly higher in those with T21 fetuses (median: 125.7 U/ml, range: 28.7–831.7 U/ml), compared with the normal controls (median: 106.3 U/ml, range: 50.5–1136.4 U/ml) (p < 0.001). The risk values of the screening of T21 or T18 fetuses were assessed using mean and standard deviation log10 analyte multiples of median (MoM) which showed that the predictive values of sHLA-G were the same as free β-hCG, and superior to AFP and uE3 for T18 screening. Logistic regression analysis revealed that sHLA-G MoM was the highest risk factor associated with pregnant women carrying T18 fetuses [Exp(B): 171.26, 95% CI: 36.30–807.97, p < 0.001]. Receiver operating characteristic (ROC) analysis revealed that the area under ROC curve for sHLA-G MoM was 0.915 (95% CI, 0.871–0.959, p < 0.001), for AFP MoM was 0.796 (95% CI, 0.730–0.861, p < 0.001), for free β-hCG MoM was 0.881 (95% CI, 0.829–0.934, p < 0.001), and for uE3 MoM was 0.876 (95% CI, 0.828–0.923, p < 0.001) in the T18 group. sHLA-G MoM demonstrated the best sensitivity and negative predictive value. For the first time, our findings reveal that sHLA-G is a better second trimester screening marker for the detection of T18 fetuses and the combined application of sHLA-G with AFP, free β-hCG, and uE3 could improve clinical screening for T18 fetuses.

Screening for Down Syndrome in the United States: Results of Surveys in 2011 and 2012

2013 ◽  
Vol 137 (7) ◽  
pp. 921-926 ◽  
Author(s):  
Glenn E. Palomaki ◽  
George J. Knight ◽  
Edward R. Ashwood ◽  
Robert G. Best ◽  
James E. Haddow
Keyword(s):  
United States ◽  
Down Syndrome ◽  
Best Practice ◽  
First Trimester ◽  
The United States ◽  
Second Trimester ◽  
Missing Responses ◽  
Testing Protocols ◽  
Better Than ◽  
Down Syndrome Screening

Context.—Participants in a College of American Pathologists external proficiency testing program for first and second trimester Down syndrome screening. Objectives.—To determine the number of women screened for Down syndrome in the United States, along with the type of test received and to compare those results to earlier surveys in 1988 and 1992. Design.—Questionnaires regarding the type and number of Down syndrome tests performed per month were completed by participants in early 2011 and again in early 2012. Results.—After accounting for some of the missing responses, data from up to 131 laboratories indicated that 67% (2 764 020 of 4 130 000) to 72% (2012: 2 963 592 of 4 130 000) of US pregnancies received prenatal screening for Down syndrome. Second trimester tests were most common (2012: 60%; 1 770 024 of 2 963 592), followed by integrated (2012: 21%; 627 876 of 2 963 592), and first trimester (2012: 19%; 565 692 of 2 963 592). The 6 largest laboratories tested 61% of screened pregnancies and offered the widest array of tests, while the smallest 32 tested 1% and almost always offered only second trimester tests. Conclusions.—The current population estimate of 72% pregnancies screened annually is higher than estimates from 1988 (25%) and 1992 (50%). Available testing choices are also more varied, and all testing methods perform better than those methods available 10 years ago. Clinicians should ensure that women are offered tests that follow recommended best-practice testing protocols, and screening laboratories should assess whether patient needs are being met.

Maternal serum screening for fetal down syndrome in the United States: A 1992 survey

1993 ◽  
Vol 169 (6) ◽  
pp. 1558-1562 ◽  
Author(s):  
Glenn E. Palomaki ◽  
George J. Knight ◽  
Jane McCarthy ◽  
James E. Haddow ◽  
John H. Eckfeldt
Keyword(s):  
United States ◽  
Down Syndrome ◽  
The United States ◽  
Maternal Serum ◽  
Maternal Serum Screening ◽  
Serum Screening

scholarly journals Maternal Serum Invasive Trophoblast Antigen and First-Trimester Down Syndrome Screening

2005 ◽  
Vol 51 (8) ◽  
pp. 1499-1504 ◽  
Author(s):  
Glenn E Palomaki ◽  
George J Knight ◽  
Louis M Neveux ◽  
Raj Pandian ◽  
James E Haddow
Keyword(s):  
Down Syndrome ◽  
False Positive Rate ◽  
First Trimester ◽  
The United States ◽  
Maternal Serum ◽  
Ultrasound Measurement ◽  
First Trimester Screening ◽  
Serum Samples ◽  
Trimester Screening ◽  
Down Syndrome Screening

Abstract Background: In the United States, Down syndrome screening is still performed mainly in the second trimester, using 3 or 4 markers. Moving screening into the first trimester has the advantage of earlier diagnosis. Currently, first-trimester screening typically includes maternal serum pregnancy-associated plasma protein-A (PAPP-A), the free β-subunit of human chorionic gonadotropin (free β), and ultrasound measurement of nuchal translucency thickness (NT). The current report describes a case–control study of serum invasive trophoblast antigen (ITA) and its possible inclusion in first-trimester screening for Down syndrome. Methods: As part of an earlier observational study, serum samples from 54 Down syndrome and 276 matched unaffected pregnancies were collected between 9 and 15 weeks of gestation. Samples had been aliquoted and stored at −20 °C for 8 years. ITA was measured and converted to weight-adjusted multiples of the median (MoM). The distributions of other first-trimester markers are from a single published study. Results: Median ITA MoM in Down syndrome pregnancies increase as gestational age increases (2.02 MoM at 11 and 2.44 MoM at 13 completed weeks). At 75% detection, maternal age in combination with ITA and PAPP-A measurements have an 8.0% false-positive rate, slightly lower than the 8.8% found for the free β and PAPP-A combination; adding NT measurements reduces false positives for the 2 combinations to 2.0% and 1.8%, respectively. Conclusion: Serum ITA appears to be a useful first-trimester Down syndrome marker that could replace free β measurements while maintaining performance.

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