Alphafetoprotein (afp), free beta human chorionic gonadotrophin (fβhcg), and dimeric inhibin a (ih-a) produce the best results in a three-analyte multiple marker screening test for fetal down syndrome

OBJECTIVE: To determine the best three-analyte combination of six potential maternal serum markers in the multiple marker screening test (MMST) for fetal Down Syndrome (DS). STUDY DESIGN: From our bank of second trimester maternal serum stored at -70° C for ≤2 years, we randomly selected 313 samples from euploid pregnancies at 14 to 20 weeks' gestation (mean maternal age = 35.6 ± 5.2) and 33 samples from DS pregnancies. AFP, unconjugated estriol (E3), and Intact hCG (IhCG) levels had been determined prior to storage; after thawing, CA-125, FβhCG, and IH-A levels were determined by ELISA and converted to week-specific multiples of the median (MUM). Various combinations of three analytes were used in the MMST and the screen positive rates (DS risk ≥ 1:190) and DS detection rates were compared to those of the traditional MMST (AFP, E3, IhCG). RESULTS: Combinations including E3 and IhCG were rejected as a result of suboptimal performance. Other combinations included: ANALYTES SCREEN POSITIVE % * DS DETECTION % AFP, E3, IhCG 28 85 FβhCG, CA-125. IH-A 21 77 AFP, FβhCG, CA-125 20 84 AFP, CA-125, IH-A 20 85 AFP, FβhCG, IH-A 18 90 * High SP% reflect the high mean maternal age of the study population. CONCLUSIONS: The best combination of 3 analytes in the MMST appears to be AFP, FβhCG, and IH-A, resulting in the lowest screen positive rate (18%) and the highest DS detection rate (90%). This combination should be evaluated prospectively.