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

Palomaki, Glenn E.; Knight, George J.; Roberson, Marie; Cunningham, George C.; Lee, Jo Ellen; Strom, Charles M.; Pandian, Raj

doi:10.1373/clinchem.2003.023986

Cited by 23 publications

(8 citation statements)

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“…The Down syndrome screening performance was modeled for selected combinations of serum ITA and other secondtrimester serum markers, using the maternal age distribution in the United States for 2000 (16 ). The modeling methodology is based on overlapping gaussian distributions and has been described previously (11 ). Continuous variables were compared, after appropriate transformations, by the t-test at a two-tailed significance level of 0.05.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2004

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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 ␤-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

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Section: Methodsmentioning

confidence: 99%

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

et al. 2004

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“…A model for normalization of systematically changing concentrations during pregnancy has been developed for several analytes used in pregnancy screening, by calculation of the 'multiples of the median' (MoM) and its natural logarithm (lnMoM), 15 as the lnMoM values for these analytes are higher than that in normal pregnancies.…”

Section: Introductionmentioning

confidence: 99%

“…15,17 The model is exemplified here by studying D-dimer concentrations in pregnancy and the postpartum period and compared with concentrations found in non-pregnant women.…”

Section: Introductionmentioning

confidence: 99%

A model for calculating the within-subject biological variation and likelihood ratios for analytes with a time-dependent change in concentrations; exemplified with the use of D-dimer in suspected venous thromboembolism in healthy pregnant women

2012

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Background: Within-subject biological variation and reference change value (RCV) are difficult to calculate for an analyte with a changing concentration. The aim of this study was to develop a model to examine if it was possible to transform an analyte with a time-dependent change in concentration into a 'steady-state' situation by the use of 'multiples of the median' (MoM) and its natural logarithm (lnMoM). In addition, we wanted to extend the RCV concept, using likelihood and odds ratios, to calculate the post-test probabilities for disease. D-dimer in pregnancy is used as an example. Methods: Blood samples from 18 healthy pregnant and 18 healthy non-pregnant women were collected every fourth week. MoM of the D-dimer concentrations was calculated for each four-week interval to obtain a 'steady-state' situation for the D-dimer concentrations. The 'normalized' values were then transformed to the lnMoM to obtain a Gaussian distribution, used for the estimation of biological variation. Results: Median D-dimer concentrations increased six-fold during pregnancy. Within-subject variation (SD) of lnMoM D-dimer was 0.27 during pregnancy and 0.23 in non-pregnant women, with RCVs of 0.72 and 0.90, respectively. Conclusions: By using the lnMoM model, an increasing concentration of an analyte can be transformed to a steady-state situation and the within-subject biological variation and its derived parameters can be calculated.

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“…The modeling methodology is based on overlapping gaussian distributions and has been described previously (9,18 ). The maternal age distribution in the United States for 2000 (19 ) was used as the baseline population.…”

Section: Discussionmentioning

confidence: 99%

“…ITA is essentially equivalent to hyperglycosylated human chorionic gonadotropin (hCG). To date, studies have found that ITA is increased in Down syndrome pregnancies: in both maternal urine and serum in the second trimester, and in maternal urine in the first trimester (7)(8)(9)(10)(11)(12)(13)(14). There are 3 published reports of the Down syndrome screening performance of urine ITA in the first trimester, and all report detection rates at a 5% false-positive rate.…”

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

et al. 2005

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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 ␤-subunit of human chorionic gonadotropin (free ␤), 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 firsttrimester 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 firsttrimester 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 ␤ and PAPP-A combination; adding NT measurements reduces false positives for the 2 combinations to 2.0% and 1.8%, respectively.

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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

Cited by 23 publications

References 36 publications

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

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

A model for calculating the within-subject biological variation and likelihood ratios for analytes with a time-dependent change in concentrations; exemplified with the use of D-dimer in suspected venous thromboembolism in healthy pregnant women

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

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