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.
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.
Palomaki
Glenn E
GE
Foundation for Blood Research, PO Box 190, Scarborough, ME 04070-0190, USA. palomaki@fbr.org
Knight
George J
GJ
Roberson
Marie M
MM
Cunningham
George C
GC
Lee
Jo Ellen
JE
Strom
Charles M
CM
Pandian
Raj
R
D000328:Adult; D015415:Biomarkers / Q000652:urine; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000652:urine*; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008423:Maternal Age; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D018566:Pregnancy, High-Risk; D014327:Trophoblasts / Q000378:metabolism*
D015415:Biomarkers; D006063:Chorionic Gonadotropin; C024889:glycosylated HCG