Biology of pregnancy‐associated plasma protein‐A in relation to prenatal diagnostics: an overview

Pregnancy-associated plasma protein-A (PAPP-A) is highly efficient as a serum marker in first-trimester screening for chromosomal abnormalities. Furthermore, there is increasing evidence that low levels of PAPP-A in the first trimester are associated with adverse pregnancy outcomes such as preterm delivery, intrauterine growth retardation, preeclampsia, and stillbirth. PAPP-A is a glycoprotein, produced in the placenta, and it is present in the maternal circulation in increasing concentrations during pregnancy. By means of its proteolytic activity, PAPP-A functions as a regulatory protein in the insulin-like growth factor system, known to be important for placental formation and regulation of fetal growth. This overview describes aspects of biochemistry, synthesis, and biological functions of PAPP-A, with a focus on information of importance to clinicians. The clinical applications of PAPP-A are summarized, and new insights regarding the analyses of PAPP-A discussed.