OBJECTIVE: To determine the ability of second-trimester maternal serum CA-125 levels to detect fetal Down syndrome. METHODS: From stored, second-trimester maternal serum analyzed previously with the multiple-marker screening test for fetal Down syndrome, we selected 306 samples from euploid pregnancies and 22 samples from Down syndrome pregnancies at 14-20 weeks' gestation. CA-125 levels were measured by enzyme-linked immunosorbent assay and converted to gestational week-specific multiples of the median (MoM). RESULTS: The mean maternal age (+/- standard deviation) of the study population was 35.5 +/- 5.3 years. The Down syndrome group CA-125 mean MoM was significantly higher than the euploid group mean MoM (1.47 +/- 0.51 MoM versus 1.05 +/- 0.44 MoM; P < .001). CA-125 at or above 1.5 MoM identified 10 of 22 (45%) Down syndrome cases. Substituting CA-125 for estriol (E3) in the multiple-marker screening test resulted in a lower screen-positive rate (67 of 328, 20% [95% confidence interval {CI} 16, 25] versus 91 of 328, 28% [95% CI 23, 33]) with a similar Down syndrome detection rate (18 of 22, 82%). Alternatively, when the screen-positive rate was held constant, the Down syndrome detection rate improved (20 of 22, 91% [95% CI 71, 99] versus 18 of 22, 82% [95% CI 60, 95]). CONCLUSIONS: Down syndrome pregnancies have higher second-trimester maternal serum CA-125 levels than euploid pregnancies. CA-125 may be superior to E3 in the multiple-marker screening test for fetal Down syndrome.
