Biochemical screening for Down syndrome.

Maternal serum screening for Down syndrome is an established practise in many countries. In the second trimester human chorionic gonadotrophin (hCG) or free beta-hCG is the marker of first choice, with alpha-fetoprotein (AFP) as the second marker and unconjugated oestriol (uE(3)) the third. Statistical models with parameters derived by meta-analysis predict that a three marker combination will yield a 67% detection rate for a 5% false-positive rate. The model prediction have been confirmed in 21 large prospective intervention studies. A fourth marker, inhibin A, increases the detection rate by 7% for the same false-positive rate. In the first trimester, similar models predict that a combination of pregnancy associated plasma protein A, free beta-hCG, AFP and uE(3) will yield a 70% detection rate. This is increased to 88% if ultrasound nuchal translucency is used as an additional marker. Screening can also be extended to Edwards' syndrome, yielding high detection rates with little increase in the false-positive rate. Abnormal marker levels are also associated with a variety of adverse outcomes of pregnancy. High quality information and decision aids are needed to minimise anxiety among screenees.