Second-Trimester Maternal Serum Invasive Trophoblast Antigen: A Marker for Down Syndrome Screening

More than 2 million pregnancies in the United States are screened for Down syndrome each year, most often in the second trimester, by a test using three biochemical markers in combination with maternal age (1). The “triple” test includes measurements of serum α-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG). In the general pregnancy population, the triple test can identify ∼65% of Down syndrome pregnancies at a 5% false-positive rate (2)(3). Recently, a fourth test, dimeric inhibin-A (DIA), was added to form the “quadruple” test, which has a higher sensitivity of up to 75% (4)(5). Combining first-trimester biochemistry (free β-subunit of hCG and pregnancy-associated plasma protein A) and ultrasound markers can yield higher performance (6)(7)(8), but the highest performance reported to date is from a combination of both first- and second-trimester markers into the “integrated” test (9). The search continues for even better markers that can be used to both increase the detection rate and reduce false positives. One such marker was originally identified as hyperglycosylated hCG. Cole et al. (10) used a specific antibody to measure hyperglycosylated hCG [recently called invasive trophoblast antigen (ITA)] in random urine specimens from women with Down syndrome pregnancies. When these authors used only the creatinine-corrected ITA multiple of the median (MoM), 78% of cases were detected at a false-positive rate of 5% (10). The current practice of Down syndrome screening is based on serum samples. Although collecting random urine is not difficult, the additional sample type may be inconvenient and adds expense beyond the measurements of ITA and creatinine. In addition, obtaining a serum sample for AFP analysis would still be required to screen for open neural tube defects. We therefore investigated the possibility of using maternal serum ITA as a Down syndrome …