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

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 ␤-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

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

“…One area of concern is that the logarithmic SD for ITA measurements in Down syndrome pregnancies (0.2326) is much tighter than in unaffected pregnancies (0.3064). In our previous study of ITA in second-trimester serum samples, the SD in unaffected pregnancies was similar to that found in the current study (0.3088) (12 ), suggesting that this estimate is reliable. The SD of ITA measurements in second-trimester Down syndrome pregnancies, however, was broader (0.4640), suggesting that one of these estimates may not be reliable.…”

“…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.…”

Specific Measurement of O-Linked Core 2 Sugar-Containing Isoforms of Hyperglycosylated Human Chorionic Gonadotropin by Antibody B152

“…The laboratories of L. Cole as well as that of Nichols Institute Diagnostics (which produces a commercial measurement system based on B152 on its 'Advantage' automated platform) and Palomaki at the Blood Foundation have done a series of studies showing that measurement of the core 2 hCG isoforms by B152 can provide an improved Down syndrome screening test over that obtained using standard hCG isoform measurements [3,[7][8][9][10][11][12] . This fi nding may relate to the correspondence of secretion of these early pregnancy isoforms with the state of differentiation of the placenta.…”

“…Measurements of these variant forms of hCG have applications in prenatal diagnosis, specifi cally Down syndrome [1][2][3][6][7][8][9][10][11][12] , in assessment of the health and likely success of early pregnancy in the fertility clinic [4,13] , and for both diagnosis and management of hCG-secreting cancers [14][15][16] . The purpose of this review is to defi ne what is known about the hCG isoforms being measured, to detail the characteristics of the antibody which is used to defi ne these hCG isoforms and to describe the variety of potential clinical applications and complications in making these measurements.…”

Administrative Optimization of Proteomics Networks for Drug Development

“…• Screening markers: allow indication of the transit from health to disease [e.g., maternal serum invasive trophoblast antigen for Down syndrome during the second trimester (Palomaki et al, 2004)]. …”