Pregnancy-associated plasma protein A (PAPP-A)
Human pregnancy‑associated plasma protein A (PAPP‑A) is a large glycoprotein with a molecular weight of 200 kDa, which belongs to the metzincin superfamily of zinc peptidases. PAPP‑A was first isolated from the serum of pregnant women, where its concentration increases steadily until term. PAPP‑A is produced by the trophoblast and secreted into the maternal serum, where it mainly circulates as a heterotetrameric 2:2 complex, together with two subunits of the proform of eosinophil major basic protein (proMBP).
It is now well established that the PAPP‑A concentration in the serum is a reliable marker for fetal aneuploidy. In a number of studies it could be confirmed that PAPP‑A, in combination with free βhCG and the sonografic determination of nuchal translucency (NT), is the serum marker of choice to identify women at increased risk of carrying a fetus affected with Down syndrome during the first trimester (week 8‑14) of pregnancy. Using this marker combination, detection rates of up to 70 % (serum markers only) and 90 % (combined with NT) have been described at a false positive rate of 5 %.
Median maternal serum PAPP‑A levels in affected pregnancy are lower, compared to the median of non‑affected pregnancies. Based on the maternal age, the risk for having a Down syndrome pregnancy can be calculated using a specific algorithm e.g. based on likelihood ratios.
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