Pregnancy‑associated plasma protein‑A beyond the first trimester: Predictive value for adverse pregnancy outcomes (Review)

Pregnancy-associated plasma protein-A (PAPP-A) is a placentally-derived metalloproteinase that serves a key role in trophoblast invasion and fetal growth through the regulation of insulin-like growth factor bioavailability.Since its introduction into first-trimester aneuploidy screening, low maternal serum PAPP-A concentrations have been consistently associated with adverse pregnancy outcomes, including preeclampsia, preterm birth, fetal growth restriction, low birth weight and stillbirth.Although the clinical importance of reduced first-trimester PAPP-A concentrations is well established, the predictive value of PAPP-A measurements beyond the first trimester, particularly during the second trimester, remains less clearly defined.The present review summarizes the current research regarding the association between maternal serum PAPP-A concentrations throughout pregnancy and adverse obstetric outcomes, with a particular emphasis on second-trimester findings.Available evidence suggests that persistently low maternal serum PAPP-A concentrations from the first into the second trimester are associated with placental dysfunction-related complications.However, despite statistically significant associations, the predictive performance of PAPP-A as a standalone biomarker remains limited.Future prospective studies are required to determine whether incorporating second-trimester PAPP-A into multimarker prediction models can improve risk stratification, clinical decision-making and pregnancy outcomes.