Maternal Serum Invasive Trophoblast Antigen and First-Trimester 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 ␤-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.

Human choriogonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights

“…In this syndrome, its levels, given in MoM, are 3.5 -9.5 higher when compared with those levels verified in normal pregnancies. hCGh may detect up to 78% of Down syndrome cases at a 5-8% false-positive rate (Palomaki et al, 2005), but in the first trimester its performance is lower, with a reported 63% Down syndrome detection rate at a 10% false-positive rate (Weinans et al, 2005). The measurement of urinary hCGh as a test for tracking the Down syndrome seems promising (Wald et al, 2003).…”

An audit of the detection of trisomy 18 in prenatal screening for Down syndrome using the Combined test

“…In the prenatal screening programme for Down syndrome at the Wolfson Institute of Preventive Medicine, women who have the first trimester Combined test (nuchal translucency, free ß-human chorionic gonadotrophin, and pregnancy associated plasma protein-A) also have an assessment of their risk of having a pregnancy with trisomy 18 (Edwards syndrome), using a trisomy 18 algorithm based on published parameters (Palomaki et al (2004) or Tul et al (1999) prior to November 2007. Risks were calculated using the medical screening software, αlpha (Logical Medical Systems), and a risk cut-off of 1 in 100 (at term) was used to classify a pregnancy as screen-positive.…”