Inhibin A parameters and prenatal screening for Down's syndrome
Purpose: Assays specific for dimeric inhibin A (InhA) have allowed its potential as a screening marker for Down's syndrome pregnancies to be identified but concerns over assay variability have limited the use of InhA as a routine screening marker for Down's syndrome (DS). As a result there is a relative paucity of data on the performance of the assay within a routine service setting and information on the effect of several maternal and pregnancy variables is sparse.
Methods: InhA was analysed prospectively in 18,000 second trimester serum samples received for routine prenatal screening and retrospectively in a series of chromosomally abnormal pregnancies selected from frozen storage (99 DS, 25 trisomy 18 (T18), and 9 trisomy 13 (T13)). InhA was assayed using an enzyme linked immunosorbent assay (Diagnostic Systems Laboratories) on a robotic analyser. The median InhA concentration and the median gestation in days were calculated for each week of gestation between 15 and 21 weeks and regressed medians at each day of gestation calculated. Results were expressed as multiples of the appropriate regressed median (MoM).
Results: The median InhA MoM in the DS cases was 2.11, in the T18 cases 0.90, and T13 cases 1.99. Median inhA MoM was higher in non-smokers (NS) than in smokers (S) in all groups. For unaffected pregnancies the InhA MoM was 0.88 in NS (n=9577) and 1.44 in S (n=3484). For DS pregnancies the InhA MoM was 2.00 in NS (n=69) and 2.41 in S (n= 20). For T18 the InhA MoM was 0.87 in NS (n=15) and 1.19 in S (n=6). In IDDM pregnancies (n=148) the InhA median MoM was 0.98 and in twin pregnancies (n= 47) 2.75.
Conclusions: On this data set, mathematical modelling predicts 77% detection of DS pregnancies at a 5% false positive rate when InhA is added to a second trimester triple marker screening protocol.