Elsevier

Seminars in Perinatology

Volume 29, Issue 4, August 2005, Pages 203-208
Seminars in Perinatology

Second Trimester Serum Markers

https://doi.org/10.1053/j.semperi.2005.05.011Get rights and content

Prenatal screening for Down syndrome in the early second trimester with multiple maternal serum markers has been available for more than 15 years. The multiple marker combination with the highest screening performance currently available is alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and inhibin A, together with maternal age (so-called quad marker test). With this combination, a detection rate of 80% at a 5% false positive rate is achieved. Inhibin A, the newest addition to second trimester serum screening, is an alpha-beta subunit hormone of placental origin, and is measured using a monoclonal two-site ELISA validated for use in prenatal screening. Quality control parameters for inhibin A measurement are acceptable and are monitored through the proficiency testing program administered by the College of American Pathologists. Research into other possible second trimester screening markers has included studies on the maternal urine and serum levels of an hCG variant, hyperglosylated hCG (h-hCG; invasive trophoblast antigen). Recent data indicate that h-hCG is similar to hCG itself, although its measurement in maternal urine may improve the performance of the established serum marker combinations. With the introduction of first trimester screening markers and their use in an integrated first and second trimester marker approach to screening, and with the fact that many women do not seek prenatal care until the early second trimester, prenatal screening for Down syndrome using second trimester serum markers remains a major resource in obstetrical care.

Section snippets

Addition of Inhibin A

Inhibin is a family of alpha-beta subunit glycoproteins named in the 1930s for their ability to selectively inhibit the secretion of the anterior pituitary gonadotropin, follicle stimulating hormone. In 1992, van Lith and coworkers, using an immunoassay that measured all forms of inhibin and its alpha subunit, reported that second trimester maternal serum total inhibin levels tended to be elevated in Down syndrome pregnancy.9 By 1994 through 1996, with the advent of a specific immunoassay that

Reliability of the Inhibin A Assay

The assay currently available to measure inhibin A is in one format, an enzyme-linked immunosorbent assay (ELISA) produced by Diagnostic Systems Laboratories, Inc. (DSL), Webster, TX. The monoclonal antibodies used in the assay (one directed against the alpha-subunit and one against the beta-subunit) were developed by Nigel Groome at Oxford Brookes University, UK. The assay can be performed manually or by using an automated immunoassay platform. The DSL assay has been validated for use in Down

Hyperglycosylated HCG

A more recent research finding of some interest has been the observation that a specific variant of hCG, hyperglycosylated hCG (h-hCG), also called invasive trophoblast antigen (ITA), has potential value as a screening marker for fetal Down syndrome. H-hCG is a variant with an increased carbohydrate content, making it structurally more complex. Rather than having predominantly biantenary (two branches) carbohydrate side chains, h-hCG has a proportion of triantenary (three branched) side chains.

Conclusions

In the United States and Canada, second trimester serum screening is transitioning from the measurement of triple markers to quad markers. Maternal serum inhibin A, measured in the second trimester, is an important clinical marker, and the available assay performs properly. Recent studies on the clinical utility of hyperglycosylated hCG as a second trimester marker have not replicated the impressive results seen in the initial reports. However, maternal urine measurement of h-hCG may improve

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