Elevated second trimester dimeric inhibin a levels identify down syndrome pregnancies

OBJECTIVE: To determine if second trimester dimeric inhibin A (IH-A) levels distinguish Down syndrome (DS) from euploid pregnancies. STUDY DESIGN: We utilized second trimester maternal serum samples obtained prior to genetic amniocentesis, subjected to the multiple marker screening test for DS (MMST, maternal serum alphafetoprotein, unconjugated estriol, hCG, and maternal age), and then stored at -70° C for <2 years. We randomly selected 313 samples from euploid pregnancies evenly distributed from 14 to 20 weeks (mean maternal age = 35.6 ±5.2 years), and also analyzed 33 samples from DS pregnancies. IH-A levels were measured by ELISA (Serotec, Oxford) and converted to week specific MOMs. The screen positive rate (DS risk s 1:190), DS detection rate, and IH-A's performance in the MMST were determined. RESULTS: The mean IH-A MOM was significantly higher in the DS group than in the euploid group (2.8 ±2.0 vs 1.2 ±1.0, p = 0.0001). An IH-A level > 2.0 MOM identified 55% of all DS pregnancies at a screen positive rate of 16.5%. {The relatively high screen positive rate reflects the high maternal age of the study population.) IH-A correlated better with hCG (r = 0.65) than with MSAFP (r - 0.29) or estriol (r = -0.10). Replacing estriol with IH-A in the MMST resulted in a higher DS detection rate (91% vs 85%) at a lower screen positive rate (23% vs 28%). At a cut-off chosen to produce the same DS detection rate (1:150, 85%), the screen positive rate with IH-A was even lower (20% vs 28%). CONCLUSIONS: Elevated second trimester maternal serum IH-A levels identify DS pregnancies; replacing estriol with IH-A in the MMST results in a lower screen positive (amniocentesis) rate while maintaining a high DS detection rate.