The advantages of using triple-marker screening for chromosomal abnormalities

Abstract

OBJECTIVE: Our purpose was to assess the utility of triple-marker serum screening for chromosomal abnormalities. STUDY DESIGN: Our laboratory received 10,605 samples that were between 15 and 22 weeks' gestation for maternal serum screening of chromosomal abnormalities. Triple-maker maternal serum screening consisted of α-fetoprotein, human chorionic gonadotropin, and unconjugated estriol in conjunction with maternal age. Women ≥35 years old were first offered amniocentesis. If they refused amniocentesis, they were offered the screening test. A second-trimester risk for trisomy 21 ≥ 1:270 was considered screen positive. Patients were screen positive for trisomy f8 if all three markers were low: α-fetoprotein ≤0.75 multiples of the median, unconjugated estriol ≤ 0.60 multiples of the median, and human chorionic gonadotropin ≤0.55 multiples of the median. RESULTS: The initial screen-positive rate was 8.3% (880 women); amniocentesis was offered to 766 (7.2%). Twelve of 16 ascertained cases of trisomy 21 (75%), two of three cases of trisomy 18 (67%), five cases of 45,X karyotype, and one case each of 45,X/46,XX, 47,XXY, 47,XYY, 46,XX,ins(2)(q21p13p15)mat, and 69,XXX karyotypes were identified in the screen-positive patients. All four known cases of trisomy 21 in the 886 women ≥35 years old who were screened were detected, with a 21% false-positive rate. Omitting unconjugated estriol from our screening program would have resulted in detecting nine of 16 trisomy 21 and six of 12 other chromosomal abnormalities. The false-positive rate would have remained the same. CONCLUSION: In our sample cohort addition of unconjugated estriol to the screening program resulted in an increased detection rate of chromosomal abnormalities with no change in the false-positive rate. Considering the advancement in screening for chromosomal abnormalities, maternal age alone as an indicatio for amniocentesis should be reevaluated.