Currently, the only second-trimester multiple marker test widely used in the United States is the quadruple marker or "quad" screening test. It is performed from 15 to 21 weeks' gestation, and inclusive gestational age ranges vary according to individual laboratories. Pregnancies with fetal Down syndrome are characterized by lower maternal serum AFP, higher hCG, lower unconjugated estriol, and higher dimeric inhibin levels. When the quad screen was initially described, the Down syndrome detection rate approximated 70 percent. But, by the early 2000s, the reported detection rate in two large prospective trials had improved to 81 to 83 percent, with a 5-percent screen-positive rate (Malone, 2005b; Wald, 1996, 2003). The improved detection rate is attributable, at least in part, to accurate gestational age assessment with sonography. In a review of more than 500,000 pregnancies receiving quadruple-marker screening through the statewide California Prenatal Screening Program, trisomy 21 detection was 78 percent with sonographic gestational age assessment but only 67 percent when the screen was calculated based on last menstrual period alone (Kazerouni, 2011). As with first-trimester screening, aneuploidy detection rates are lower in younger women and higher in women older than 35 years at delivery. If second-trimester serum screening is used in twin pregnancies, aneuploidy detection rates are significantly lower (Vink, 2012). With trisomy 18, the levels of the first three analytes are all decreased, and inhibin is not part of the calculation. Trisomy 18 detection is similar to that for Down syndrome, with a false-positive rate of only 0.5 percent (Benn, 1999).
Although the quadruple-marker screening test is used to screen for Down syndrome and trisomy 18, pregnancies with other chromosomal abnormalities may be identiied as well.
The California Prenatal Screening Program found that the of those with triploidy, in 75 percent with Turner syndrome (45,X), in 44 percent with trisomy 13, and in more than 40 percent of those with other major chromosomal abnormalities (Kazerouni, 2011). Although a speciic risk for these aneuploi dies cannot be provided based on the test result, the informa tion may be relevant for women considering amniocentesis.
Quadruple-marker screening ofers no beneit over irsttrimester screening from the standpoint of trisomy 21 or trisomy 18 detection. As a stand-alone test, it is generally used if women do not begin care until the second trimester or if irst-trimester screening is not available. In 2011, women who initiated prenatal care beyond the irst trimester made up nearly 25 percent of pregnancies in the United States. As subsequently discussed, combining irst-and second-trimester screening yields an even greater aneuploidy detection rate.