Maternal serum invasive trophoblast antigen and first-trimester Down syndrome screening.
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 beta-subunit of human chorionic gonadotropin (free beta), 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 first-trimester 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 degrees C for 8 years. ITA was measured and converted to weight-adjusted multiples of the median (MoM). The distributions of other first-trimester 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 beta and PAPP-A combination; adding NT measurements reduces false positives for the 2 combinations to 2.0% and 1.8%, respectively.


CONCLUSIONS
Serum ITA appears to be a useful first-trimester Down syndrome marker that could replace free beta measurements while maintaining performance.
Palomaki
Glenn E
GE
Foundation for Blood Research, Scarborough, ME, USA. gpalomaki@wihri.org
Knight
George J
GJ
Neveux
Louis M
LM
Pandian
Raj
R
Haddow
James E
JE
D001322:Autoanalysis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D006063:Chorionic Gonadotropin / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006031:Glycosylation; D006801:Humans; D007118:Immunoassay; D008163:Luminescent Measurements; D008403:Mass Screening / Q000379:methods; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D014327:Trophoblasts / Q000378:metabolism*
D015415:Biomarkers; D006063:Chorionic Gonadotropin; C024889:glycosylated HCG; D011266:Pregnancy-Associated Plasma Protein-A