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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Palomaki
Glenn E
GE
Foundation for Blood Research, PO Box 190, Scarborough, Maine 04070-0190, USA. palomaki@fbr.org
Neveux
Louis M
LM
Knight
George J
GJ
Haddow
James E
JE
D000465:Algorithms; D015415:Biomarkers / Q000097:blood*; D006063:Chorionic Gonadotropin / Q000097:blood; D002887:Chromosomes, Human, Pair 18; D004964:Estriol / Q000097:blood; D005189:False Positive Reactions; D005260:Female; D005865:Gestational Age; D006801:Humans; D008423:Maternal Age; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D011296:Prenatal Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity; D014314:Trisomy; D000509:alpha-Fetoproteins / Q000032:analysis
D015415:Biomarkers; D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; D011266:Pregnancy-Associated Plasma Protein-A; D004964:Estriol