Normative Values of Second-Trimester Maternal Serum Markers Using an Automated Assay Platform for Down Syndrome Screening

Objective. To evaluate the agreement of risk categorization for Down syndrome screening between ultrasound scan-based gestational age (GA) and last menstrual period-based gestational age in both first and second trimesters by maternal serum markers. Methods. Data comprising 4,055 and 4,016 cases of first and second trimester screening were used. The maternal serum markers were analyzed using the ultrasound-based GA and menstrual age. The subjects whose menstrual age and ultrasound-based GA fell in different trimesters were excluded because the risk could not be calculated due to the different serum markers used in each trimester. The agreement of risk categorization for fetal Down syndrome was evaluated. Results. The agreement of Down syndrome screening in the first and the second trimesters were 92.7% and 89%, respectively. The study found a good agreement of risk categorization by Kappa index, which was 0.615 for the overall screening. The menstrual age had a slight decrease in the detection rate and a lower false-positive rate. Conclusion. Menstrual age is acceptable in cases of accurate last menstrual period. However, in places where ultrasonography is not readily available, gestational age estimation by menstrual age along with clinical examination that corresponds to the gestational age can be reliable.

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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

Clinical Chemistry ◽

10.1373/clinchem.2003.023986 ◽

2004 ◽

Vol 50 (1) ◽

pp. 182-189 ◽

Cited By ~ 17

Author(s):

Glenn E Palomaki ◽

George J Knight ◽

Marie M Roberson ◽

George C Cunningham ◽

Jo Ellen Lee ◽

...

Keyword(s):

Down Syndrome ◽

Observational Study ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

False Positive Rate ◽

Serum Markers ◽

Maternal Serum ◽

Second Trimester ◽

Preliminary Results ◽

Hyperglycosylated Human Chorionic Gonadotropin

Abstract Background: Down syndrome screening is commonly performed in the US using maternal age and three or four second-trimester maternal serum markers that can identify up to 75% of affected pregnancies by offering diagnostic studies to 5% of women. Invasive trophoblast antigen [ITA; hyperglycosylated human chorionic gonadotropin (hCG)] is a promising marker that can be measured in urine or serum in the first or second trimester. We report preliminary results for urinary ITA in an ongoing observational study. Methods: Women undergoing second-trimester amniocentesis for reasons not associated with biochemical testing provided consent and a urine (and possibly serum) sample that was tested within a few days. Demographic and pregnancy-related information was collected, along with karyotype. Screening performance was modeled for ITA alone and in combination with serum markers Results: Twelve recruitment centers collected urine from 2055 women with singleton pregnancies between 15 and 20 weeks of gestation (2023 unaffected, 28 Down syndrome, and 4 pregnancies with other chromosome abnormalities). After correction for gestational age, urine concentration, and maternal race and weight, the ITA measurements were higher in women with a Down syndrome pregnancy (median ITA, 4.33 multiples of the median). At a 75% detection rate, the false-positive rate could be reduced by substituting ITA for hCG measurements (from 5.6% to 2.6% for the triple test) or by adding ITA measurements to existing combinations (from 3.3% to 2.0% for the quadruple test). Conclusions: Our data provide preliminary confirmation of the potential usefulness of urinary ITA measurements in detecting Down syndrome in a setting that simulates routine usage.

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