Chapter 3

#### KEY POINTS

Key Points

• Quad marker serum screening is the most effective form of Down syndrome screening in the second trimester (81% detection rate at a 5% false-positive rate).

• Presence of a major structural malformation at second trimester sonographic fetal anatomy survey is an indication for genetic amniocentesis.

• A range of minor markers at second trimester sonographic fetal anatomy survey can be utilized with likelihood ratios to adjust the risk of Down syndrome.

• Absence of major or minor markers at second trimester sonographic fetal anatomy survey reduces the risk of fetal Down syndrome by 60%.

• Combinations of screening tests in both first and second trimesters, such as integrated, stepwise, and contingency screening, may be more efficient than screening in either trimester alone.

#### INTRODUCTION

While tremendous advances have been made in recent years regarding screening for fetal aneuploidy in the first trimester of pregnancy, the mainstay of screening for aneuploidy has been second trimester serum and sonographic screening. Despite the increasing popularity of first trimester screening, there will always be a role for second trimester aneuploidy screening given that some patients do not present for antenatal care sufficiently early in pregnancy to avail of nuchal translucency and given that a second trimester fetal anatomical survey has become an almost routine aspect of general antenatal care. Additionally, since first trimester screening requires the availability of chorionic villus sampling (CVS) to provide a first trimester diagnosis, in areas in which CVS is not available there will be a continued requirement for second trimester screening protocols leading to amniocentesis.

Options for second trimester screening include serum screening using the Quad test (alphafetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin-A), sonographic screening using the so-called Genetic Sonogram, and combinations of serum and sonographic screening.

#### SECOND TRIMESTER SERUM SCREENING

Maternal serum levels of alphafetoprotein (AFP) and unconjugated estriol (uE3) are both approximately 25% lower in pregnancies complicated by Down syndrome, compared with euploid pregnancies (Wald et al., 1994; Malone et al., 2005). By contrast, levels of hCG and inhibin-A are approximately twice as high in pregnancies complicated by Down syndrome (Wald et al., 1994; Malone et al., 2005). Maternal serum levels of AFP, uE3, and hCG all tend to be decreased in pregnancies complicated by trisomy 18. The combination of AFP, uE3, and hCG, commonly known as the triple screen, can detect 69% of cases of Down syndrome, for a 5% false-positive rate (Wald et al., 2003; Malone et al., 2005). When inhibin-A is added to this test, commonly known as the Quad screen, the Down syndrome detection rate increases to 81%, for a 5% false-positive rate (Wald et al., 2003; Malone et al., 2005). Based on these results, if a second trimester serum sample is obtained for aneuploidy risk assessment, optimal performance will be obtained by measuring the four ...

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