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- Title
Impact of bias in serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A multiples of the median levels on first-trimester screening for trisomy 21.
- Authors
Wright, D.; Abele, H.; Baker, A.; Kagan, K. O.
- Abstract
Objective To examine the effect of bias in median multiples of the median (MoM) levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG) on first-trimester combined screening for trisomy 21. Methods The effects of deviations in the MoM levels of free β-hCG and PAPP-A were investigated by simulating nuchal translucency (NT) at 12 weeks and MoM values for PAPP-A and free β-hCG for 500 000 euploid and 500 000 trisomy 21 pregnancies at 9 and at 12 weeks of gestation. Likelihoods were calculated using the mixture model for NT and the standard Gaussian model for log MoM PAPP-A and free β-hCG values. Deviations in MoM marker levels were simulated by applying percentage changes of 5% to 20% to MoM values. Detection and false-positive rates were calculated with and without adjustments of the maternal serum marker levels by taking the proportion of euploid and aneuploid cases above given thresholds for each maternal age and then taking a weighted average with respect to the maternal age distribution. Results With median MoM levels on target, the modeled detection and false-positive rates in combined screening for trisomy 21 at 12 weeks of gestation with a fixed risk cut-off of 1 in 100 were 85% and 2.5%, respectively. For median MoM levels of free β-hCG and PAPP-A between 0.8 and 1.2 MoM, detection rates ranged from 77% to 91%, with corresponding false-positive rates ranging from 1.0% to 6.1%. Conclusion In first-trimester screening for trisomy 21, biases in the serum marker MoM levels of 10% can increase false-positive rates by over 50%, whilst biases of 20% can more than double false-positive rates. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
- Subjects
FIRST trimester of pregnancy; CHORIONIC gonadotropins; DOWN syndrome; MATERNAL age; BLOOD proteins
- Publication
Ultrasound in Obstetrics & Gynecology, 2011, Vol 38, Issue 3, p309
- ISSN
0960-7692
- Publication type
Article
- DOI
10.1002/uog.8987