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.