Maternal serum-integrated screening for trisomy 18 using both first- and second-trimester markers

To estimate the prenatal screening performance of an integrated serum test for detecting trisomy 18, which combines measurements of first- and second-trimester markers with maternal age to assign patient-specific risks.

Published and new observations of maternal serum marker levels in trisomy 18 and unaffected pregnancies are used to derive population parameters. These parameters are then combined in a multivariate Gaussian model to assign patient-specific risks for trisomy 18.

The best combination of serum markers includes pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein, unconjugated estriol and human chorionic gonadotropin in the second trimester. At a second-trimester risk cutoff of 1 : 100, these 4 markers, in combination with maternal age, detect 90% of trisomy 18 pregnancies at a false-positive rate of 0.1%. The odds of a trisomy 18 pregnancy among screen-positive women are 1 : 4. Without the first-trimester marker, detection is reduced to 67% at about the same false-positive rate.

The algorithm described here is highly efficient for detecting trisomy 18 and should be considered by programs that offer serum-integrated screening for Down syndrome.