Free beta-hCG subunit versus intact hCG in Down syndrome screening.
OBJECTIVE
To assess the ability of second-trimester maternal serum free beta-hCG to detect fetal Down syndrome and to compare free beta-hCG to intact hCG in the multiple-marker screening test for Down syndrome.


METHODS
From our bank of stored maternal sera, we selected 40-50 samples from euploid pregnancies at each week of gestation from 14 to 20 weeks and 31 samples from Down syndrome pregnancies. Free beta-hCG was measured by enzyme-linked immunosorbent assay, and week-specific multiples of the median (MoM) were derived. The free beta-hCG Down syndrome detection and false-positive rates were determined. Free beta-hCG was then substituted for intact hCG in the multiple-marker screening test, and the Down syndrome detection and false-positive rates at various risk cutoffs were compared.


RESULTS
The mean (+/-standard deviation) maternal age of all study samples was 35.6 +/- 5.3 years. The mean Down syndrome free beta-hCG MoM was significantly higher than the mean euploid MoM (2.4 +/- 1.1 versus 1.2 +/- 1.0; P < .001). A free beta-hCG level of at least 1.7 MoM identified 68% of Down syndrome pregnancies at a false-positive rate of 20%. When intact hCG was replaced with free beta-hCG in the multiple-marker screening test, a higher Down syndrome detection rate was achieved at a lower false-positive rate at each of several screen positive risk cutoffs.


CONCLUSIONS
Elevated free beta-hCG levels identify Down syndrome pregnancies. Replacing intact hCG with free beta-hCG in the multiple-marker screening test results in a higher Down syndrome detection rate at a lower false-positive rate.
Wenstrom
K D
KD
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, USA.
Owen
J
J
Chu
D C
DC
Boots
L
L
D000328:Adult; D006063:Chorionic Gonadotropin / Q000097:blood*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D011933:Reagent Kits, Diagnostic
D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011933:Reagent Kits, Diagnostic