Pregnancy-associated plasma protein A (PAPP-A): Measurement by highly sensitive and specific enzyme immunoassay, importance of first-trimester serum determinations, and stability studies

It has recently been established that maternal serum pregnancy-associated plasma protein A (PAPP-A) was reduced in pregnancies with fetal Down syndrome in the first but not in the second trimester of gestation. In comparison with two other placental proteins, human chorionic gonadotrophin and pregnancy-specific beta(1)-glycoprotein, an explanation for this can be formulated based on the large molecular weight of PAPP-A. With the increasing clinical demand for fetal abnormalities to be diagnosed in the first rather than in the second trimester of pregnancy, maternal serum PAPP-A is a strong potential candidate for being used in routine trisomy screening. We have developed a sensitive enzyme immunoassay (ELISA) intended at smaller laboroatories due to its long shelf life. Here we show that repeated freezing and thawing, or the addition of iodoacetate (5 mM) did not affect the results, at both high or low concentration of PAPP-A. It is also possible to introduce the serum into the test as a dry sample on blotting paper, easily posted in an envelope. A decrease of 21% was observed after such dry storage for three weeks at room temperature, which can be compensated for by the inclusion of a dried control serum, mailed with the sample(s).