First trimester screening for Down syndrome using free beta hCG, total hCG and PAPP-A: an exploratory study.
OBJECTIVE
To investigate the potential utility of first trimester screening for Down syndrome using Free beta-hCG, total hCG and PAPP-A.


METHODS
Using estimates from the literature, a simulation study was undertaken to estimate the performance of tests incorporating, Free beta-hCG, total hCG and PAPP-A at gestations of 8-12 weeks. We used sensitivity analysis to assess the effect of departures from the assumed model.


RESULTS
We estimate that detection rates in excess of 75% for a false positive rate (FPR) of 3% can be achieved with first trimester measures of PAPP-A, total hCG and Free beta-hCG at 8 weeks-the addition of total hCG adding 11%. Detection rates of around 90% for a FPR of 3% can be achieved through the inclusion of nuchal translucency (NT) at 12 weeks to these early first trimester biochemical markers. Our analysis indicates that the marginal benefit of adding total hCG diminishes rapidly with gestational age and that there is little benefit from adding total hCG later than 10 weeks of gestation.


CONCLUSIONS
The performance of first trimester screening using early combinations of total hCG, Free beta-hCG and PAPP-A should be assessed in further studies.
Wright
Dave
D
University of Plymouth, Plymouth, UK. dave.wright@plymouth.ac.uk
Spencer
Kevin
K
Nix
Barry
B
D006063:Chorionic Gonadotropin / Q000032:analysis; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000032:analysis* / Q000097:blood; D003198:Computer Simulation; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D005333:Fetus; D006801:Humans; D009010:Monte Carlo Method; D010865:Pilot Projects; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011296:Prenatal Diagnosis / Q000379:methods*
D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A