Predicting the result of additional second-trimester markers from a woman's first-trimester marker profile: a new concept in Down syndrome screening.
OBJECTIVE
To describe a method for deciding whether an individual's first-trimester Down syndrome screening test result justifies further testing in the second trimester.


METHODS
Statistical modelling was used to estimate the distribution of second-trimester marker profiles for a given first-trimester profile and hence the probability of a final positive result, using a 1 in 250 term cut-off. A multi-variate log Gaussian model was used with published parameters. Markers were maternal serum pregnancy-associated plasma protein-A and free beta-human chorionic gonadotrophin (hCG) at 10 weeks, nuchal translucency at 11 weeks, and second-trimester maternal serum alpha-fetoprotein, total hCG, unconjugated estriol and inhibin-A. To illustrate the method, the model was applied to a published series of 24 Down syndrome and 367 unaffected pregnancies.


RESULTS
Modelling predicts that for 63% Down syndrome and 0.4% unaffected pregnancies having first-trimester tests, there is a 50% or more probability of a final positive result. A step-wise sequential screening policy based on immediate prenatal diagnosis for those with high probability and second-trimester testing for the remainder would have a 90% detection rate and 1.7% false-positive rate. Modelling also predicts 8.0% Down syndrome and 89% unaffected pregnancies with probabilities below 3%. A contingent screening policy restricting second-trimester testing to those with 3-49% probabilities would have an 88% detection rate and 1.4% false-positive rate.


CONCLUSIONS
Predicting the probability of a positive final result from the first-trimester marker profile has potential utility, either as a decision aide for individual women or as a formal part of screening policy in selecting a subset of women for second-trimester testing.
Maymon
Ron
R
Department of Obstetrics and Gynecology, Assaf Harofe Medical Center, Zerifin and Sackler Faculty of Medicine, Tel Aviv University, Israel. intposgr@post.tau.ac.il
Cuckle
Howard
H
Jones
Rick
R
Reish
Orit
O
Sharony
Reuven
R
Herman
Arie
A
D000328:Adult; D015415:Biomarkers / Q000097:blood; D006063:Chorionic Gonadotropin / Q000097:blood; D004314:Down Syndrome / Q000175:diagnosis* / Q000196:embryology; D004964:Estriol / Q000032:analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007265:Inhibins / Q000032:analysis; D016011:Normal Distribution; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011262:Pregnancy Trimester, Second / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D011296:Prenatal Diagnosis / Q000379:methods*; D000509:alpha-Fetoproteins / Q000032:analysis
D015415:Biomarkers; D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; D007265:Inhibins; D011266:Pregnancy-Associated Plasma Protein-A; D004964:Estriol