The advantages of using triple-marker screening for chromosomal abnormalities

Our purpose was to assess the utility of triple-marker serum screening for chromosomal abnormalities.

Our laboratory received 10,605 samples that were between 15 and 22 weeks' gestation for maternal serum screening of chromosomal abnormalities. Triple-marker maternal serum screening consisted of alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol in conjunction with maternal age. Women > or = 35 years old were first offered amniocentesis. If they refused amniocentesis, they were offered the screening test. A second-trimester risk for trisomy 21 > or = 1:270 was considered screen positive. Patients were screen positive for trisomy 18 if all three markers were low: alpha-fetoprotein < or = 0.75 multiples of the median, unconjugated estriol < or = 0.60 multiples of the median, and human chorionic gonadotropin < or = 0.55 multiples of the median.

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 > or = 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.

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 indication for amniocentesis should be reevaluated.