First-Trimester PlGF and PAPP-A and the Risk of Placenta-Mediated Complications: PREDICTION Prospective Study

Objectives: This study aimed to estimate the association between low first-trimester maternal serum PlGF (placental growth factor) and PAPP-A (pregnancy-associated plasma protein A) and the risk of placenta-mediated complications. Methods: We performed a secondary analysis of the PREDICTION study, including nulliparous participants recruited at 11 to 14 weeks of pregnancy. First-trimester PlGF and PAPP-A levels were reported in multiples of the median (MoM) adjusted for maternal characteristics and gestational age. Participants were stratified into 4 groups based on absence/presence of low (<0.4 MoM) PlGF and PAPP-A values. A composite of adverse pregnancy outcomes (including preeclampsia, fetal growth restriction, fetal death, and placental abruption) was calculated for deliveries occurring before 34 weeks, before 37 weeks, and at or after 37 weeks. Results: Out of the 7262 participants, 86 (1.2%) experienced the composite outcome before 37 weeks of gestation, including 35 (0.4%) before 34 weeks. The combination of low PAPP-A and low PlGF levels was associated with the greatest risk of adverse outcomes before 37 weeks (21%) and before 34 weeks (12%) compared with low PlGF alone (7% and 3%), low PAPP-A alone (2% and 1%), or neither marker (1% and 0.4%, respectively; P < 0.001). For preterm preeclampsia specifically, the combination of low PAPP-A and low PlGF was also associated with a greater risk (12%) compared with low PlGF alone (6%), low PAPP-A alone (0.5%), or neither marker (0.7%; P < 0.001). Conclusions: The combination of low PAPP-A and low PlGF levels is associated with a very high risk for adverse outcomes before 34 and 37 weeks. An isolated low PAPP-A should not be considered a risk factor for adverse pregnancy outcomes.