Combined first‐ and second‐trimester screening for Down syndrome: an evaluation of proMBP as a marker

Objectives To estimate the screening performance of different combinations of first‐ and second‐trimester markers, including a new marker, the proform of eosinophil major basic protein (proMBP). Methods The population comprised 195 singleton pregnancies with a normal outcome enrolled in the Copenhagen First Trimester Study, in which a serum sample was available from both the first and the second trimester. The performance of different marker combinations was estimated by receiver–operator–characteristics (ROC) analysis using a Monte Carlo simulation and distributions of log 10 MoM markers and their correlations, derived from our normal material and Down syndrome cases from the literature. Results Using a fixed screen‐positive rate (SPR) of 5%, the first‐trimester combined test [nuchal translucency (NT), PAPP‐A and free β‐hCG] yielded a detection rate (DR) of 76%, and the integrated test (NT, PAPP‐A, AFP, hCG, uE3 and inhibin A) yielded a DR of 86%. With a DR of 90%, the best combination was the first‐trimester β‐hCG and NT with the second‐trimester proMBP and AFP. ProMBP combined with the triple test increased the DR from 62 to 83%, whereas the addition of inhibin A only increased the DR to 69%. Conclusion These results suggest that proMBP may be an important new marker in Down syndrome screening and, in particular, a good substitute for inhibin A. Copyright © 2003 John Wiley & Sons, Ltd.