Alpha-fetoprotein, free beta-human chorionic gonadotropin, and dimeric inhibin A produce the best results in a three-analyte, multiple-marker screening test for fetal Down syndrome.

Objective: The purpose of this study was to determine, among six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection.

Study Design: With use of commercially available assay kits, medians for free beta-human chorionic gonadotropin, CA 125, and dimeric inhibin A were established in stored sera from 45 to 50 euploid pregnancies at each week of gestation from 14 to 22 weeks and from 33 Down syndrome pregnancies. Maternal serum alpha-fetoprotein, unconjugated estriol, and intact human chorionic gonadotropin levels measured in each sample before storage were retrieved. All 20 possible three-analyte combinations were evaluated in the multiple-marker screening test for Down syndrome.

Results: The mean maternal age of the study population was 35.6 +/- 5.3 years. The best three-analyte combination was maternal serum alpha-fetoprotein, free beta-human chorionic gonadotropin, and dimeric inhibin A: 97% of Down syndrome cases were detected at a false-positive rate of 16%. At a slightly higher false-positive rate (18%) maternal serum alpha-fetoprotein, estriol, and intact human chorionic gonadotropin detected only 79% of cases.

Conclusions: Of six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection was maternal serum alpha-fetoprotein, free beta-human chorionic gonadotropin, and dimeric inhibin A. This retrospective analysis should now be confirmed prospectively.