A summary analysis of Down syndrome markers in the late first trimester

Prenatal screening for Down syndrome in the late first trimester involves the measurement of maternal serum markers and the fetal ultrasound marker, nuchal translucency (NT). In addition to the established first trimester maternal serum markers, pregnancy-associated plasma protein-A (PAPP-A), and the free beta-subunit of hCG (free beta), studies have indicated that the known second trimester markers, total hCG and inhibin-A (DIA), are also useful in screening in the late first trimester. In this chapter, we review the existing literature on first trimester biochemical and ultrasound markers for Down syndrome, develop week-specific marker parameters, and combine the results via modeling in a comprehensive overview of screening performance. All first trimester markers vary in their usefulness during the 11 through 13 completed week-screening window and the literature is reasonably consistent. NT is the best single marker for Down syndrome in the first trimester of pregnancy (weighted summary detection rate is 60% at a constant 5% false positive rate). The two best maternal serum markers, taken individually, are PAPP-A and free beta (weighted summary detection rates of 36% and 37%, respectively). Combining maternal age, NT and PAPP-A, with either free beta, total hCG, or DIA gives similar screening performance (weighted summary detection rates of 83%, 81%, and 81%, respectively). When both free beta and DIA, or total hCG and DIA are combined with maternal age, NT and PAPP-A, weighted summary detection rates are 85% and 83%, respectively.